Arsenic poisoning is a toxic disorder caused by clinically significant exposure to inorganic arsenic. Acute high-dose ingestion can produce severe gastrointestinal illness, hemodynamic compromise, cardiac repolarization abnormalities, multisystem toxicity, and death; peripheral neuropathy can appear after a delay. Chronic exposure, most often through contaminated drinking water, is classically associated with hyperpigmentation and palmoplantar keratosis. Total urinary arsenic can be misleading after seafood consumption because arsenobetaine can raise the total, so arsenic speciation is central to exposure assessment. Long-latency arsenic-related malignancies are modeled separately in Arsenic Related Cancers; this entry does not infer cancer from short-term poisoning findings.
Ask a research question about Arsenic Poisoning. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
name: Arsenic Poisoning
creation_date: '2026-02-11T21:06:43Z'
category: Environmental
categories:
- Toxic Exposure Disorder
- Heavy Metal Poisoning
- Environmental Health Disorder
synonyms:
- arsenicosis
- arsenic intoxication
- inorganic arsenic poisoning
description: >-
Arsenic poisoning is a toxic disorder caused by clinically significant
exposure to inorganic arsenic. Acute high-dose ingestion can produce severe
gastrointestinal illness, hemodynamic compromise, cardiac repolarization
abnormalities, multisystem toxicity, and death; peripheral neuropathy can
appear after a delay. Chronic exposure, most often through contaminated
drinking water, is classically associated with hyperpigmentation and
palmoplantar keratosis. Total urinary arsenic can be misleading after seafood
consumption because arsenobetaine can raise the total, so arsenic speciation
is central to exposure assessment. Long-latency
arsenic-related malignancies are modeled separately in Arsenic Related
Cancers; this entry does not infer cancer from short-term poisoning findings.
definitions:
- name: Clinical framing of acute inorganic arsenic poisoning
definition_type: CASE_DEFINITION
description: >-
A compatible acute exposure followed by gastrointestinal and cardiovascular
toxicity, with exposure supported by appropriately interpreted arsenic
measurements, defines the acute clinical syndrome.
scope: Acute high-dose inorganic arsenic exposure
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: >-
This acute arsenic-trioxide case directly documents the characteristic
gastrointestinal, cardiac, and hepatic presentation.
- name: Clinical framing of chronic inorganic arsenicosis
definition_type: CASE_DEFINITION
description: >-
Chronic arsenicosis is a clinical toxicity syndrome in a person with
sustained inorganic arsenic exposure, commonly identified by characteristic
melanosis and keratotic skin lesions rather than by exposure alone.
scope: Chronic environmental inorganic arsenic exposure
evidence:
- reference: PMID:11218669
reference_title: Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes.
explanation: >-
The human biopsy series directly identifies melanosis and keratosis as
predominant manifestations of chronic arsenic toxicity.
parents:
- heavy metal poisoning
has_subtypes:
- name: Acute
display_name: Acute inorganic arsenic poisoning
description: >-
Toxicity following a large, usually ingested, dose of inorganic arsenic,
with early gastrointestinal and hemodynamic manifestations and possible
delayed neuropathy.
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide.
explanation: Directly supports the acute high-dose ingestion subtype.
- name: Chronic
display_name: Chronic inorganic arsenicosis
description: >-
Clinical toxicity arising during sustained inorganic arsenic exposure,
particularly through drinking water, with characteristic cutaneous lesions.
evidence:
- reference: PMID:21576319
reference_title: A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).
explanation: >-
The prospective cohort supports chronic drinking-water exposure as a cause
of incident arsenical skin lesions.
progression:
- phase: Early acute gastrointestinal and hemodynamic toxicity
subtype: Acute
notes: >-
Gastrointestinal symptoms and hemodynamic compromise can occur early after a
large ingestion and require immediate stabilization and monitoring.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Initially, the patient developed signs of acute hemodynamic compromise with tachycardia, hypertension, gastrointestinal symptoms, and poor urine output.
explanation: The case directly establishes the early acute phase.
- phase: Delayed peripheral neuropathy after a single acute exposure
subtype: Acute
duration: Neurologic abnormalities can persist for years
notes: >-
Peripheral neuropathy can begin 10 days to 3 weeks after ingestion and may
improve only slowly and incompletely.
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic. All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs.
explanation: >-
The longitudinal case series directly supplies the onset window and
persistent course of delayed neuropathy.
- phase: Chronic cutaneous disease during sustained exposure and after mitigation
subtype: Chronic
duration: Years
notes: >-
Skin lesions arise during sustained drinking-water exposure. Providing
arsenic-safe water can improve lesion scores over several years, although
severe lesions and systemic disease may persist.
evidence:
- reference: PMID:25161968
reference_title: 'Effect of Safe Water on Arsenicosis: A Follow-up Study.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In participants belonging to Cohort-I, the skin score was found to improve significantly at the end of each year, and it was found to be reduced significantly from 2.17 ± 1.09 to 1.23 ± 1.17; P < 0.001 at the end of 3 year's intervention study indicating beneficial effect of safe water on skin lesions.
explanation: >-
The three-year intervention follow-up supports improvement after exposure
mitigation without implying that all established disease reverses.
clinical_burden:
burden_level: HIGH
rationale: >-
Severe acute poisoning can be fatal despite intensive care, and delayed
neurologic or chronic cutaneous injury can remain clinically important for
years.
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
He died within 37 hours despite intensive treatment that included intramuscular dimercaprol and hemodialysis.
explanation: Documents the mortality risk of severe acute ingestion.
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs.
explanation: Documents long-term neurologic burden among survivors.
pathophysiology:
- name: Systemic inorganic arsenic exposure
biological_scale: ORGANISM
mechanism_confidence: ESTABLISHED
description: >-
Absorbed inorganic arsenic is the initiating toxic exposure. Dose, chemical
species, route, and duration distinguish severe acute poisoning from chronic
arsenicosis; exposure itself is not equivalent to clinical disease.
chemical_entities:
- preferred_term: arsenic atom
term:
id: CHEBI:27563
label: arsenic atom
triggers:
- preferred_term: exposure to arsenic
term:
id: ECTO:9000032
label: exposure to arsenic
downstream:
- target: AS3MT-linked arsenic biotransformation
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- cellular uptake and enzymatic methylation of inorganic arsenic
description: >-
In exposed humans, variation near AS3MT strongly influences the urinary
distribution of methylated arsenic species.
evidence:
- reference: PMID:22383894
reference_title: Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10(-8)) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations.
explanation: >-
The human GWAS links AS3MT-region variation to arsenic metabolite
proportions under exposure.
- target: Arsenite-generated oxidative and nitrosative stress
causal_link_type: DIRECT
description: Cellular arsenite exposure generates reactive oxygen and nitrogen species.
evidence:
- reference: PMID:23602911
reference_title: Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells.
explanation: Directly supports arsenite-triggered cellular ROS/RNS generation.
- target: Acute gastrointestinal and hemodynamic toxicity
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: >-
Large acute ingestions produce gastrointestinal illness and cardiovascular
compromise through multiple incompletely resolved intermediates.
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: >-
The acute ingestion case directly links arsenic trioxide to the retained
gastrointestinal syndrome.
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide.
explanation: Directly links acute arsenic-trioxide ingestion to shock.
- target: Cardiac repolarization disturbance
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Arsenic intoxication can markedly prolong repolarization and trigger torsade de pointes.
evidence:
- reference: PMID:1689832
reference_title: Torsade de pointes and T-U wave alternans associated with arsenic poisoning.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Reported in this study are two cases of arsenic poisoning causing torsade de pointes. Furthermore, marked prolongation of the QT-U interval and the rarely observed phenomenon of T-U wave alternans are demonstrated.
explanation: The two cases directly support arsenic-associated repolarization toxicity.
- target: Delayed peripheral axonopathy
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Peripheral nerve injury may appear after a symptom-free interval following acute ingestion.
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication.
explanation: >-
Human biopsy evidence directly links the post-ingestion neuropathy to
peripheral axonal degeneration.
- target: Chronic cutaneous toxicity
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Sustained drinking-water arsenic exposure increases incident arsenical skin lesions.
evidence:
- reference: PMID:21576319
reference_title: A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).
explanation: The prospective cohort directly supports the exposure-to-skin-lesion edge.
- target: Hepatic biochemical injury
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Higher chronic exposure is associated with increased serum hepatic enzyme activities.
evidence:
- reference: PMID:21740555
reference_title: 'Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates.
explanation: >-
The exposure-stratified human study directly supports a dose-related
biochemical liver-injury association.
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Hemodynamic and laboratory data are presented illustrating the multisystem toxicities of inorganic arsenic.
explanation: Supports inorganic arsenic as the initiating exposure in acute multisystem toxicity.
- reference: PMID:21576319
reference_title: A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The authors aimed to evaluate the association between arsenic exposure and skin lesion incidence among participants in the Health Effects of Arsenic Longitudinal Study (HEALS).
explanation: Supports the initiating exposure in the chronic human cohort.
- name: AS3MT-linked arsenic biotransformation
biological_scale: MOLECULAR
mechanism_confidence: PROVISIONAL
description: >-
AS3MT-region variation changes the distribution of urinary MMA and DMA in
exposed humans. This establishes a human exposure-response modifier but does
not make AS3MT a monogenic cause of arsenicosis.
gene:
preferred_term: AS3MT
term:
id: hgnc:17452
label: AS3MT
biological_processes:
- preferred_term: detoxification of arsenic-containing substance
modifier: ABNORMAL
term:
id: GO:0071722
label: detoxification of arsenic-containing substance
downstream:
- target: MMA(III)-sensitive pyruvate dehydrogenase inhibition
causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
intermediate_mechanisms:
- production of trivalent monomethylated arsenic species
description: >-
Methylation can generate MMA(III), which inhibited pyruvate dehydrogenase
more potently than arsenite in the studied systems.
evidence:
- reference: PMID:11409934
reference_title: 'Monomethylarsonous acid (MMA(III)) and arsenite: LD(50) in hamsters and in vitro inhibition of pyruvate dehydrogenase.'
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
These data demonstrate that MMA(III) is more toxic than inorganic arsenite, both in vivo and in vitro, and call into question the hypothesis that methylation of inorganic arsenic is a detoxication process.
explanation: >-
The comparative animal and enzyme data support toxicity of the
methylated trivalent intermediate rather than uniform detoxification.
evidence:
- reference: PMID:22383894
reference_title: Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005).
explanation: >-
Human association data connect the AS3MT-region signal to both metabolite
proportions and arsenical skin-lesion susceptibility.
- name: MMA(III)-sensitive pyruvate dehydrogenase inhibition
biological_scale: MOLECULAR
mechanism_confidence: PROVISIONAL
description: >-
Pyruvate dehydrogenase is among the purified enzymes sensitive to micromolar
arsenic, and MMA(III) inhibited PDH in animal tissue and purified-enzyme
assays. These data do not justify a universal sulfhydryl-enzyme blockade
model for human poisoning.
biological_processes:
- preferred_term: pyruvate metabolic process
modifier: DECREASED
term:
id: GO:0006090
label: pyruvate metabolic process
evidence:
- reference: PMID:9806419
reference_title: Arsenic toxicity is enzyme specific and its affects on ligation are not caused by the direct inhibition of DNA repair enzymes.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Only pyruvate dehydrogenase, one of eight purified enzymes examined so far, is inhibited by micromolar arsenic.
explanation: Supports selective PDH sensitivity while constraining broader enzyme-inhibition claims.
- reference: PMID:11409934
reference_title: 'Monomethylarsonous acid (MMA(III)) and arsenite: LD(50) in hamsters and in vitro inhibition of pyruvate dehydrogenase.'
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
To inhibit activity of purified porcine heart PDH activity by 50%, the concentrations (mean +/- SE) of MMA(III) as methylarsine oxide and arsenite were 17.6 +/- 4.1 and 106.1 +/- 19.8 microM, respectively.
explanation: Quantifies greater PDH inhibition by MMA(III) than arsenite in the purified-enzyme assay.
- name: Arsenite-generated oxidative and nitrosative stress
biological_scale: CELLULAR
mechanism_confidence: PROVISIONAL
description: >-
In cultured cells, arsenite-generated reactive oxygen and nitrogen species
mediate downstream loss of PARP-1 zinc and activity.
biological_processes:
- preferred_term: response to oxidative stress
modifier: INCREASED
term:
id: GO:0006979
label: response to oxidative stress
downstream:
- target: PARP-1 zinc loss and activity impairment
causal_link_type: DIRECT
description: Arsenite-generated ROS/RNS decrease PARP-1 zinc content, DNA binding, and enzymatic activity.
evidence:
- reference: PMID:23602911
reference_title: Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding.
explanation: Directly supports the ROS/RNS-to-PARP-1 impairment edge in cells.
evidence:
- reference: PMID:23602911
reference_title: Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine.
explanation: >-
Reversal by antioxidant and NOS-directed interventions supports a mediated
role for ROS/RNS in this cellular model.
- name: PARP-1 zinc loss and activity impairment
biological_scale: MOLECULAR
mechanism_confidence: PROVISIONAL
description: >-
Arsenite-induced ROS/RNS reduce PARP-1 zinc content, DNA binding, and
enzymatic activity in cells. This is a mechanistic observation relevant to
DNA-repair impairment, not direct proof of a clinical cancer trajectory.
biological_processes:
- preferred_term: DNA repair
modifier: DECREASED
term:
id: GO:0006281
label: DNA repair
evidence:
- reference: PMID:23602911
reference_title: Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity.
explanation: Supports the retained PARP-1 impairment mechanism and its model-system boundary.
- name: Acute gastrointestinal and hemodynamic toxicity
biological_scale: ORGANISM
mechanism_confidence: ESTABLISHED
subtypes:
- Acute
description: >-
Large acute inorganic arsenic ingestions can produce cramps, vomiting,
diarrhea, oliguria, shock, and multisystem toxicity.
downstream:
- target: Vomiting
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Acute inorganic arsenic ingestion produces vomiting.
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: Directly supports vomiting after acute arsenic-trioxide ingestion.
- target: Diarrhea
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Acute inorganic arsenic ingestion produces diarrhea.
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: Directly supports diarrhea after acute arsenic-trioxide ingestion.
- target: Shock
causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
description: Severe acute arsenic ingestion can cause shock.
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide.
explanation: Directly supports shock after severe acute ingestion.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Initially, the patient developed signs of acute hemodynamic compromise with tachycardia, hypertension, gastrointestinal symptoms, and poor urine output.
explanation: Supports combined gastrointestinal and hemodynamic toxicity in acute poisoning.
- name: Cardiac repolarization disturbance
biological_scale: ORGANISM
mechanism_confidence: ESTABLISHED
subtypes:
- Acute
description: >-
Arsenic intoxication can markedly prolong the QT-U interval and cause torsade
de pointes.
downstream:
- target: Prolonged QTc interval
causal_link_type: DIRECT
description: Arsenic-associated repolarization disturbance manifests as marked QT-U prolongation.
evidence:
- reference: PMID:1689832
reference_title: Torsade de pointes and T-U wave alternans associated with arsenic poisoning.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thus, arsenic intoxication may be complicated by prolongation of the QT-U interval and torsade de pointes.
explanation: Directly supports the electrocardiographic phenotype.
evidence:
- reference: PMID:1689832
reference_title: Torsade de pointes and T-U wave alternans associated with arsenic poisoning.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Reported in this study are two cases of arsenic poisoning causing torsade de pointes.
explanation: Supports clinically consequential repolarization toxicity.
- name: Delayed peripheral axonopathy
biological_scale: TISSUE
mechanism_confidence: ESTABLISHED
subtypes:
- Acute
description: >-
A delayed axonal peripheral neuropathy can follow a single acute dose, with
sensory nerve action-potential abnormalities and incomplete long-term
recovery.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
locations:
- preferred_term: nerve
term:
id: UBERON:0001021
label: nerve
downstream:
- target: Delayed peripheral neuropathy
causal_link_type: DIRECT
description: Peripheral axonal degeneration manifests as delayed neuropathy.
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials.
explanation: Electrophysiology directly supports the clinical neuropathy phenotype.
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication.
explanation: Human nerve biopsies establish axonal degeneration after acute intoxication.
- name: Chronic cutaneous toxicity
biological_scale: TISSUE
mechanism_confidence: ESTABLISHED
subtypes:
- Chronic
description: >-
Sustained inorganic arsenic exposure causes melanotic and keratotic skin
lesions with epidermal proliferative changes.
cell_types:
- preferred_term: keratinocyte
term:
id: CL:0000312
label: keratinocyte
- preferred_term: melanocyte
term:
id: CL:0000148
label: melanocyte
locations:
- preferred_term: skin of body
term:
id: UBERON:0002097
label: skin of body
downstream:
- target: Chronic hyperpigmentation
causal_link_type: DIRECT
description: Chronic arsenical cutaneous toxicity manifests as melanosis and increased basal pigmentation.
evidence:
- reference: PMID:11218669
reference_title: Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases.
explanation: Directly supports increased basal pigmentation in chronic arsenical skin lesions.
- target: Arsenical palmar keratosis
causal_link_type: DIRECT
description: Chronic arsenical cutaneous toxicity can manifest as keratotic lesions on the palms.
evidence:
- reference: PMID:40583662
reference_title: Comparison between Combination of Neem, Propylene Glycol and Salicylic Acid with Salicylic Acid Alone Topically in Arsenical Palmar Keratosis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thirty patients of moderate palmar arsenical keratosis from an arsenic-affected area at Cumilla in Bangladesh were recruited randomly based on inclusion and exclusion criteria.
explanation: Directly documents palmar arsenical keratosis in a primary human treatment cohort.
evidence:
- reference: PMID:21576319
reference_title: A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Multivariate-adjusted hazard ratios for incident skin lesions comparing 10.1-50.0, 50.1-100.0, 100.1-200.0, and ≥200.1 μg/L with ≤10.0 μg/L of well water arsenic exposure were 1.17 (95% confidence interval (CI): 0.92, 1.49), 1.69 (95% CI: 1.33, 2.14), 1.97 (95% CI: 1.58, 2.46), and 2.98 (95% CI: 2.40, 3.71), respectively (P(trend) = 0.0001).
explanation: Prospective dose-response data support chronic arsenical cutaneous toxicity.
- name: Hepatic biochemical injury
biological_scale: TISSUE
mechanism_confidence: PROVISIONAL
subtypes:
- Chronic
description: >-
Higher chronic arsenic exposure is associated with increased ALP, AST, and
ALT activities. These cross-sectional biochemical associations do not by
themselves establish chronic liver failure or fibrosis.
locations:
- preferred_term: liver
term:
id: UBERON:0002107
label: liver
evidence:
- reference: PMID:21740555
reference_title: 'Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Further, this study revealed a novel exposure- and dose- response relationship between arsenic exposure metrics and serum hepatic enzyme activity.
explanation: Supports a biochemical exposure-response relationship while preserving the study's cross-sectional boundary.
phenotypes:
- name: Vomiting
category: Acute gastrointestinal
subtype: Acute
description: Vomiting can occur early after a large inorganic arsenic ingestion.
phenotype_term:
preferred_term: Vomiting
temporality: ACUTE
term:
id: HP:0002013
label: Vomiting
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: Directly supports vomiting in acute poisoning.
- name: Diarrhea
category: Acute gastrointestinal
subtype: Acute
description: Diarrhea can occur early after a large inorganic arsenic ingestion.
phenotype_term:
preferred_term: Diarrhea
temporality: ACUTE
term:
id: HP:0002014
label: Diarrhea
evidence:
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Classical symptoms of an acute arsenicum (As) poisoning such as gastrointestinal cramps, vomiting, diarrhea, ECG changes and disturbed liver function tests were observed.
explanation: Directly supports diarrhea in acute poisoning.
- name: Shock
category: Acute cardiovascular
subtype: Acute
severity: SEVERE
description: Cardiovascular shock can dominate severe acute poisoning.
phenotype_term:
preferred_term: Shock
temporality: ACUTE
term:
id: HP:0031273
label: Shock
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide.
explanation: Directly supports shock after severe acute ingestion.
- name: Prolonged QTc interval
category: Acute cardiovascular
subtype: Acute
description: >-
Marked QT-U prolongation can precede torsade de pointes in arsenic
intoxication.
phenotype_term:
preferred_term: Prolonged QTc interval
temporality: ACUTE
term:
id: HP:0005184
label: Prolonged QTc interval
evidence:
- reference: PMID:1689832
reference_title: Torsade de pointes and T-U wave alternans associated with arsenic poisoning.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Furthermore, marked prolongation of the QT-U interval and the rarely observed phenomenon of T-U wave alternans are demonstrated.
explanation: Directly supports marked repolarization-interval prolongation.
- name: Delayed peripheral neuropathy
category: Neurologic
subtype: Acute
description: >-
Peripheral neuropathy may begin days to weeks after a single exposure and
can remain abnormal years later.
phenotype_term:
preferred_term: Peripheral neuropathy
temporality: SUBACUTE
term:
id: HP:0009830
label: Peripheral neuropathy
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic.
explanation: Directly supports the delayed peripheral neuropathy phenotype.
- name: Chronic hyperpigmentation
category: Cutaneous
subtype: Chronic
description: Melanosis and increased basal pigmentation are characteristic chronic cutaneous findings.
phenotype_term:
preferred_term: Hyperpigmentation of the skin
temporality: CHRONIC
term:
id: HP:0000953
label: Hyperpigmentation of the skin
evidence:
- reference: PMID:11218669
reference_title: Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Chronic arsenic toxicity (CAT) manifests predominantly as cutaneous lesions in the form of melanosis, keratosis and neoplastic changes.
explanation: Directly supports melanosis in chronic arsenic toxicity.
- name: Arsenical palmar keratosis
category: Cutaneous
subtype: Chronic
description: Keratotic lesions of the palms are a characteristic chronic cutaneous manifestation.
phenotype_term:
preferred_term: Palmoplantar keratoderma
temporality: CHRONIC
term:
id: HP:0000982
label: Palmoplantar keratoderma
evidence:
- reference: PMID:40583662
reference_title: Comparison between Combination of Neem, Propylene Glycol and Salicylic Acid with Salicylic Acid Alone Topically in Arsenical Palmar Keratosis.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thirty patients of moderate palmar arsenical keratosis from an arsenic-affected area at Cumilla in Bangladesh were recruited randomly based on inclusion and exclusion criteria.
explanation: Directly documents palmar arsenical keratosis in a primary human treatment cohort.
histopathology:
- name: Hyperkeratotic and proliferative epidermal change
subtype: Chronic
diagnostic: true
description: >-
Biopsied arsenical skin lesions can show hyperkeratosis, parakeratosis,
acanthosis, papillomatosis, rete-ridge elongation, increased basal
pigmentation, and sometimes dysplasia; the pattern is supportive rather
than independently pathognomonic.
finding_term:
preferred_term: Hyperkeratosis
term:
id: NCIT:C35541
label: Hyperkeratosis
evidence:
- reference: PMID:11218669
reference_title: Histopathology of skin lesions in chronic arsenic toxicity--grading of changes and study of proliferative markers.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Histological study of H/E stained sections showed--hyperkeratosis in 13, parakeratosis in 13, acanthosis in 12, papillomatosis in 24, elongation of reteridges in 21, increased basal pigmentation in 27 and dysplastic changes in 8 cases.
explanation: Directly supports the retained histopathologic features in 42 human biopsies.
biochemical:
- name: Total and speciated urinary arsenic
presence: INCREASED
context: >-
Total urinary arsenic reflects recent exposure but can rise markedly after
seafood because of arsenobetaine. Speciation of inorganic arsenic, MMA, DMA,
and arsenobetaine is necessary when the total is elevated; no universal
diagnostic threshold is asserted here.
biomarker_term:
preferred_term: arsenic atom
term:
id: CHEBI:27563
label: arsenic atom
readouts:
- target: Systemic inorganic arsenic exposure
relationship: READOUT_OF
direction: THRESHOLD_DEPENDENT
endpoint_context: DIAGNOSTIC
interpretation: >-
The inorganic and methylated species support recent inorganic exposure,
whereas arsenobetaine-dominant elevation can reflect seafood.
evidence:
- reference: PMID:18430299
reference_title: 'Fast determination of arsenic species and total arsenic in urine by HPLC-ICP-MS: concentration ranges for unexposed german inhabitants and clinical case studies.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Two case studies underline the need for As speciation, especially when total urinary arsenic concentrations are elevated.
explanation: Directly supports species-level interpretation of an elevated total.
evidence:
- reference: PMID:18430299
reference_title: 'Fast determination of arsenic species and total arsenic in urine by HPLC-ICP-MS: concentration ranges for unexposed german inhabitants and clinical case studies.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A maximum enhancement of total As from 1 up to 2,200 microg/L (2,000 microg/L for As-B) was observed after a normal fish meal.
explanation: Demonstrates the magnitude of seafood-related confounding of total urinary arsenic.
- name: Serum ALP, AST, and ALT activities
presence: INCREASED
subtype: Chronic
context: >-
Increased activities correlate with higher chronic exposure in the cited
cross-sectional cohort; they are nonspecific injury markers, not a diagnosis
of arsenicosis or liver failure.
readouts:
- target: Hepatic biochemical injury
relationship: CORRELATES_WITH
direction: POSITIVE
endpoint_context: DIAGNOSTIC
interpretation: Higher hepatic enzyme activities track a biochemical liver-injury association in exposed populations.
evidence:
- reference: PMID:21740555
reference_title: 'Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the respective activities of ALP, AST and ALT were found to be significantly increased in the high-exposure groups compared to the lowest-exposure groups before and after adjustments were made for different covariates.
explanation: Directly supports the exposure-stratified biochemical association.
evidence:
- reference: PMID:21740555
reference_title: 'Dose-response relationship between arsenic exposure and the serum enzymes for liver function tests in the individuals exposed to arsenic: a cross sectional study in Bangladesh.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Elevated serum hepatic enzyme activities in the higher exposure gradients provided new insights into arsenic-induced liver toxicity that might be helpful for the early prognosis of arsenic-induced liver diseases.
explanation: Supports increased hepatic enzyme activity as an exposure-associated biochemical finding.
genetic:
- name: AS3MT
gene_term:
preferred_term: AS3MT
term:
id: hgnc:17452
label: AS3MT
relationship_type: SUSCEPTIBILITY
association: Exposure-response modifier of arsenic metabolism and arsenical skin-lesion risk
notes: >-
Common variation near AS3MT changes MMA and DMA proportions and modifies
skin-lesion risk in exposed people; it is neither necessary nor sufficient
to cause arsenic poisoning.
evidence:
- reference: PMID:22383894
reference_title: Genome-wide association study identifies chromosome 10q24.32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005).
explanation: Directly supports an AS3MT-region susceptibility association under arsenic exposure.
environmental:
- name: Chronic ingestion of arsenic-contaminated drinking water
exposure_term:
preferred_term: exposure to arsenic in water via ingestion
term:
id: ECTO:0080000
label: exposure to arsenic in water via ingestion
description: >-
Sustained ingestion of inorganic arsenic in groundwater is the central
exposure context for chronic arsenicosis.
evidence:
- reference: PMID:21576319
reference_title: A prospective study of arsenic exposure from drinking water and incidence of skin lesions in Bangladesh.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Chronic arsenic exposure from drinking water was associated with increased incidence of skin lesions, even at low levels of arsenic exposure (<100 μg/L).
explanation: Prospective human data support contaminated drinking water as a chronic causal exposure.
- name: Acute high-dose inorganic arsenic ingestion
exposure_term:
preferred_term: exposure to arsenic
term:
id: ECTO:9000032
label: exposure to arsenic
description: >-
Accidental or intentional ingestion of a concentrated inorganic arsenic
compound can produce life-threatening acute poisoning.
evidence:
- reference: PMID:3578979
reference_title: Acute arsenic ingestion.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 21-year-old man presented in shock after ingesting 2 g of arsenic trioxide.
explanation: Directly supports concentrated inorganic arsenic ingestion as an acute exposure.
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A 22-month-old boy ingested approximately twice the estimated lethal dose of arsenic trioxide (As(2)O(3)) ant bait.
explanation: Directly supports accidental pediatric ingestion of an arsenical insecticide.
treatments:
- name: Exposure cessation and arsenic-safe water
action_category: THERAPEUTIC
description: >-
Remove the exposure source. For chronic drinking-water arsenicosis, provide
reliably arsenic-safe water and prevent renewed exposure. Skin lesions can
improve over years, but established severe disease may persist.
treatment_term:
preferred_term: chemical exposure avoidance
term:
id: NCIT:C15900
label: Lifestyle Therapy
target_mechanisms:
- target: Systemic inorganic arsenic exposure
treatment_effect: INHIBITS
description: Preventing further ingestion reduces ongoing systemic arsenic exposure.
evidence:
- reference: PMID:25161968
reference_title: 'Effect of Safe Water on Arsenicosis: A Follow-up Study.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All the participants who had arsenic contaminated drinking water source in their houses were supplied with arsenic removal filters for getting arsenic-free water during the follow-up period.
explanation: Directly documents exposure mitigation in the human follow-up study.
evidence:
- reference: PMID:25161968
reference_title: 'Effect of Safe Water on Arsenicosis: A Follow-up Study.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In participants belonging to Cohort-I, the skin score was found to improve significantly at the end of each year, and it was found to be reduced significantly from 2.17 ± 1.09 to 1.23 ± 1.17; P < 0.001 at the end of 3 year's intervention study indicating beneficial effect of safe water on skin lesions.
explanation: Supports clinical improvement after provision of arsenic-safe water.
- name: Early supportive resuscitation and intensive monitoring
action_category: THERAPEUTIC
description: >-
Acute severe poisoning requires immediate restoration and maintenance of
cardiac output and renal perfusion, with continuous cardiovascular,
electrolyte, urine-output, and acid-base monitoring.
treatment_term:
preferred_term: supportive care
term:
id: NCIT:C15747
label: Supportive Care
target_mechanisms:
- target: Acute gastrointestinal and hemodynamic toxicity
treatment_effect: RESTORES
description: Resuscitation restores organ perfusion during early hemodynamic compromise.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Recovery from arsenic poisoning was attributable to the restoration and maintenance of adequate cardiac output and renal perfusion in early shock, which allowed depot intramuscular British anti-Lewisite to circulate and eliminate the poison.
explanation: Directly supports early restoration of perfusion in this acute survivor.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Continuous monitoring in the pediatric intensive care unit included continuous electrocardiogram, arterial blood pressure, urine output, vital signs, arterial blood gases, serum and urine arsenic concentrations, electrolytes, electromyography, and determination of arsenic toxicokinetics.
explanation: Directly supports the intensive monitoring components retained here.
- name: Early dithiol chelation for severe acute poisoning
action_category: THERAPEUTIC
therapeutic_modality: SMALL_MOLECULE
description: >-
Dimercaprol, succimer, or DMPS may be considered early for severe acute
inorganic arsenic poisoning with toxicology consultation. Human evidence is
largely multi-intervention case experience, so this entry does not rank the
agents or assert controlled outcome benefit.
treatment_term:
preferred_term: chelator agent therapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: dimercaprol
term:
id: CHEBI:64198
label: dimercaprol
- preferred_term: succimer
term:
id: CHEBI:63623
label: succimer
- preferred_term: 2,3-disulfanylpropane-1-sulfonic acid
term:
id: CHEBI:888
label: 2,3-disulfanylpropane-1-sulfonic acid
target_mechanisms:
- target: Systemic inorganic arsenic exposure
treatment_effect: INHIBITS
description: Dithiol ligands can bind arsenic species and promote urinary excretion.
evidence:
- reference: PMID:12387631
reference_title: Determination of arsenic metabolic complex excreted in human urine after administration of sodium 2,3-dimercapto-1-propane sulfonate.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The finding of the DMPS-MMA(III) complex in human urine after DMPS treatment provides an explanation for the inhibition of arsenic methylation by DMPS.
explanation: Demonstrates a human urinary DMPS-arsenic complex supporting the chelation mechanism.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
He was stabilized with fluid resuscitation, placed on a sodium bicarbonate intravenous drip, and treated with intramuscular dimercaprol (British anti-Lewisite), 5 mg/kg every 6 hrs for 3 days.
explanation: >-
Documents early dimercaprol use in a survivor but cannot isolate chelation
efficacy from simultaneous resuscitation and other treatment.
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
Forced diuresis, BAL (2,3-dimercaptopropanol) and DMSA (meso-2,3-dimercaptosuccinic acid) were started and therapy to enhance the formation of methylated As derivatives, which are potentially less toxic and which can be excreted more easily, was then administered.
explanation: >-
Documents BAL and DMSA within a successful multi-intervention case, not a
controlled estimate of benefit.
diagnosis:
- name: Total urinary arsenic with species-level interpretation
diagnosis_term:
preferred_term: urine chemistry measurement
term:
id: NCIT:C61044
label: Urine Chemistry Measurement
description: >-
Measure urinary arsenic after a compatible exposure and obtain speciation
when total arsenic is elevated. Interpret inorganic species and MMA/DMA
separately from arsenobetaine, which can increase substantially after
seafood. A universal diagnostic cutoff is not asserted.
evidence:
- reference: PMID:18430299
reference_title: 'Fast determination of arsenic species and total arsenic in urine by HPLC-ICP-MS: concentration ranges for unexposed german inhabitants and clinical case studies.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Two case studies underline the need for As speciation, especially when total urinary arsenic concentrations are elevated.
explanation: Directly supports urinary speciation when total arsenic is elevated.
- name: Acute electrocardiographic and physiologic monitoring
diagnosis_term:
preferred_term: electrocardiography
term:
id: NCIT:C38053
label: Electrocardiography
description: >-
In severe acute poisoning, continuously monitor electrocardiography,
perfusion, urine output, acid-base status, and electrolytes because
hemodynamic compromise and malignant ventricular arrhythmia can occur.
evidence:
- reference: PMID:12793928
reference_title: 'Treatment and toxicokinetics of acute pediatric arsenic ingestion: danger of arsenic insecticides in children.'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Continuous monitoring in the pediatric intensive care unit included continuous electrocardiogram, arterial blood pressure, urine output, vital signs, arterial blood gases, serum and urine arsenic concentrations, electrolytes, electromyography, and determination of arsenic toxicokinetics.
explanation: Directly supports the retained acute monitoring strategy.
- reference: PMID:1689832
reference_title: Torsade de pointes and T-U wave alternans associated with arsenic poisoning.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
T-U wave alternans occurs in the presence of a long QT-U interval and may be an electrocardiographic warning sign of torsade de pointes.
explanation: Supports ECG monitoring for repolarization warning signs.
- name: Nerve conduction study for delayed neuropathy
diagnosis_term:
preferred_term: nerve conduction study
term:
id: NCIT:C88502
label: Nerve Conduction Velocity Test
description: >-
Electrophysiologic testing can document motor-conduction slowing and marked
sensory nerve action-potential abnormalities when delayed neuropathy follows
acute exposure.
evidence:
- reference: PMID:196051
reference_title: Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials.
explanation: Directly supports nerve-conduction testing for arsenic-associated neuropathy.
discussions:
- discussion_id: gap_arsenic_acute_chelation_outcomes
prompt: >-
Which dithiol chelator, timing, and regimen improve patient-centered outcomes
in severe acute inorganic arsenic poisoning beyond modern supportive care?
kind: KNOWLEDGE_GAP
status: OPEN
attaches_to:
- treatments#Early dithiol chelation for severe acute poisoning
rationale: >-
Acute treatment reports combine chelation with resuscitation,
gastrointestinal decontamination, and other interventions, preventing a
clean estimate of comparative efficacy. Chronic arsenicosis should not be
used as a proxy indication: a randomized placebo-controlled DMSA trial did
not show clinical, biochemical, or histopathologic benefit.
evidence:
- reference: PMID:9865236
reference_title: Randomized placebo-controlled trial of 2,3-dimercaptosuccinic acid in therapy of chronic arsenicosis due to drinking arsenic-contaminated subsoil water.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Under the conditions of this study, 2,3-dimercaptosuccinic acid was not effective in producing any clinical or biochemical benefit or any histopathological improvement of skin lesions in patients with chronic arsenicosis.
explanation: >-
The randomized trial directly establishes that chronic DMSA treatment did
not provide the asserted benefits under the studied regimen.
- reference: PMID:15533028
reference_title: Survival after a lethal dose of arsenic trioxide.
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
The patient survived this massive dose of ingested inorganic As with only polyneuropathy one year later.
explanation: >-
Survival after multiple simultaneous interventions motivates study but
does not isolate chelator efficacy.
- discussion_id: gap_arsenic_molecular_human_translation
prompt: >-
To what extent do PDH inhibition and ROS/RNS-mediated PARP-1 impairment drive
the acute and chronic organ syndromes in exposed humans at clinically
relevant internal doses?
kind: HUMAN_MODEL_MISMATCH
status: OPEN
attaches_to:
- pathophysiology#MMA(III)-sensitive pyruvate dehydrogenase inhibition
- pathophysiology#Arsenite-generated oxidative and nitrosative stress
- pathophysiology#PARP-1 zinc loss and activity impairment
rationale: >-
The retained proximal mechanisms are supported by purified-enzyme, cell,
and animal experiments, while the direct quantitative bridge to human organ
injury remains unresolved. The graph therefore does not connect these
molecular nodes directly to cancer, neuropathy, or cutaneous lesions.
evidence:
- reference: PMID:9806419
reference_title: Arsenic toxicity is enzyme specific and its affects on ligation are not caused by the direct inhibition of DNA repair enzymes.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Our results show that direct enzyme inhibition is not a common toxic effect of As and that only a few sensitive enzymes are responsible for arsenic-induced cellular toxicity.
explanation: Directly supports limiting the breadth of the enzyme-inhibition model.
- reference: PMID:23602911
reference_title: Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity.
explanation: >-
Supports an indirect ROS/RNS-mediated cellular mechanism and the need to
test its relevance in human tissues.
Arsenic poisoning refers to adverse clinical outcomes resulting from exposure to arsenic compounds, most importantly inorganic arsenic (iAs). Acute intoxication often follows ingestion of iAs and can present within ~30 minutes to 2 hours with severe gastroenteritis, hypotension, cardiac conduction abnormalities (including QT prolongation), neurologic toxicity (delirium, seizures), and acute kidney injury. (balalimood2025recentadvancesin pages 12-13)
Chronic arsenic poisoning is commonly termed arsenicosis and results from long-term low-dose exposure, typically via contaminated drinking water and/or diet. It features characteristic dermatologic findings (hyperpigmentation with “raindrop” pattern, palmoplantar hyperkeratosis), peripheral neuropathy, vascular disease, and increased risk of cancers (skin, bladder, lung, and others). (ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13)
Chronic arsenic toxicity is explicitly described as arsenicosis, historically also called arseniasis, arsenism, arsenicism. (ganie2024arsenictoxicitysources pages 2-3)
The information summarized here is derived from aggregated disease-level resources (systematic reviews, regulatory assessments, narrative reviews) and mechanistic/model-system studies, rather than individual EHR extractions. (balalimood2025recentadvancesin pages 12-13, visciano2025arsenicinwater pages 10-12, issanov2023arsenicindrinking pages 1-2)
A structured phenotype-to-HPO mapping is provided in Artifact-01.
| Clinical feature | Acute/Chronic | Description/onset notes | Suggested HPO term(s) | Evidence (citation IDs) |
|---|---|---|---|---|
| Nausea and vomiting | Acute | Common early gastrointestinal manifestations; acute symptoms may begin within ~30 minutes to 2 hours after ingestion | Nausea (HP:0002018); Vomiting (HP:0002013) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Diarrhea | Acute | Prominent early gastroenteritis in acute inorganic arsenic ingestion | Diarrhea (HP:0002014) | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Abdominal pain | Acute | Early abdominal pain/cramping as part of acute gastroenteritis syndrome | Abdominal pain (HP:0002027) | (balalimood2025recentadvancesin pages 12-13) |
| Dehydration / hypovolemia | Acute | Follows severe vomiting and diarrhea; contributes to shock and mortality | Dehydration (HP:0001944); Hypovolemia | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Hypotension | Acute | Reported in severe poisoning, often secondary to fluid loss and systemic toxicity | Hypotension (HP:0002615) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| QT prolongation / arrhythmia | Acute | ECG abnormalities include prolonged QT and other conduction disturbances; can progress to torsades/serious arrhythmia | Prolonged QT interval (HP:0005184); Cardiac arrhythmia (HP:0011675) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13, pereira2025arsenomearsenobolomeand pages 19-20) |
| Tremor | Acute | Neurologic sign reported in acute intoxication | Tremor (HP:0001337) | (balalimood2025recentadvancesin pages 12-13) |
| Delirium / encephalopathy | Acute | Severe neurotoxicity may include delirium and central nervous system dysfunction | Delirium (HP:0031258); Encephalopathy (HP:0001298) | (balalimood2025recentadvancesin pages 12-13, pereira2025arsenomearsenobolomeand pages 19-20) |
| Seizures | Acute | Can occur in severe poisoning as part of CNS involvement | Seizure (HP:0001250) | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Proteinuria / hematuria | Acute | Renal involvement in acute poisoning may include urinary abnormalities and acute tubular injury | Proteinuria (HP:0000093); Hematuria (HP:0000790) | (balalimood2025recentadvancesin pages 12-13) |
| Acute kidney injury | Acute | Severe poisoning may cause acute tubular necrosis/renal failure | Acute kidney injury (HP:0031270) | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Peripheral neuropathy | Subacute/Chronic | Characteristic sensory > motor neuropathy; may appear 2-4 weeks after acute exposure or develop with chronic exposure | Peripheral neuropathy (HP:0009830); Sensory neuropathy (HP:0000763); Motor neuropathy | (balalimood2025recentadvancesin pages 12-13, ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13, pereira2025arsenomearsenobolomeand pages 20-22) |
| Hyperpigmentation | Chronic | Classic skin manifestation, often diffuse or spotted; chronic arsenicosis hallmark | Hyperpigmentation of the skin (HP:0000953) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13, pereira2025arsenomearsenobolomeand pages 20-22) |
| Raindrop-pattern pigmentation | Chronic | Characteristic mottled hyper/hypopigmented skin change in chronic arsenic toxicity | Mottled pigmentation | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Palmoplantar hyperkeratosis | Chronic | Typical chronic dermal lesion; affects palms and soles | Palmoplantar hyperkeratosis (HP:0000982) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13, pereira2025arsenomearsenobolomeand pages 20-22) |
| Desquamation | Chronic | Reported with chronic arsenic-related dermal injury | Desquamation (HP:0001029) | (pereira2025arsenomearsenobolomeand pages 20-22) |
| Mees lines | Chronic | Transverse white nail bands associated with chronic exposure | Leukonychia striata / Mees lines | (balalimood2025recentadvancesin pages 12-13) |
| Cognitive / attention impairment | Chronic | Chronic exposure linked to learning, memory, and attention deficits | Cognitive impairment (HP:0100543); Abnormality of attention | (ganie2024arsenictoxicitysources pages 2-3) |
| Hypertension / vascular disease | Chronic | Chronic exposure associated with peripheral vascular disease and hypertension; Blackfoot disease is a classic severe vascular manifestation | Hypertension (HP:0000822); Peripheral vascular disease; Blackfoot disease | (ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 20-22) |
| Skin cancer | Chronic complication | Chronic inorganic arsenic exposure increases skin cancer risk | Skin neoplasm (HP:0012126) | (balalimood2025recentadvancesin pages 12-13, ganie2024arsenictoxicitysources pages 1-2) |
| Bladder cancer | Chronic complication | Strong epidemiologic association with long-term exposure | Bladder neoplasm (HP:0100747) | (chakif2026heavymetaltoxicity pages 12-13, pereira2025arsenomearsenobolomeand pages 20-22) |
| Lung cancer | Chronic complication | Established chronic carcinogenic outcome of inorganic arsenic exposure | Lung neoplasm (HP:0100526) | (chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 20-22) |
| Kidney or liver cancer | Chronic complication | Reported among internal malignancies linked to chronic exposure | Renal neoplasm; Hepatic neoplasm | (ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 20-22) |
Table: This table maps major acute and chronic clinical manifestations of arsenic poisoning to suggested HPO terms for knowledge-base annotation. It emphasizes timing, characteristic arsenicosis features, and long-term cancer complications supported by recent review evidence.
Key time-course features: - Acute: Symptoms begin ~30 min–2 h after ingestion (GI symptoms prominent) with possible cardiovascular collapse and multi-organ injury. (balalimood2025recentadvancesin pages 12-13) - Subacute neurologic: Sensory deficits may appear 2–4 weeks post-exposure. (balalimood2025recentadvancesin pages 12-13) - Chronic: Dermatologic and neurologic manifestations plus long-term cancer risks. (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13)
Arsenic poisoning is not a Mendelian genetic disease; however, genes that govern arsenic metabolism and response modify susceptibility. Strongly implicated genes/pathways include: - AS3MT (arsenic methyltransferase) for methylation of iAs to methylated metabolites. (ganie2024arsenictoxicitysources pages 2-3, singh2024arsenicexposurein pages 1-5) - Detoxification/transport and oxidative stress response genes highlighted in genetic mapping screens under MMA(III) exposure (Abcc4, Txnrd1) and DNA repair candidates (Xrcc2). (o’connor2024unravelingthegenetics pages 1-2)
Specific human variant pathogenicity classifications (ACMG/ClinVar) were not present in retrieved sources.
Chronic iAs exposure is described as producing epigenetic alterations, including promoter hypermethylation (e.g., MLH1/MSH2), altered DNMT expression (↑DNMT1/DNMT3B, ↓DNMT3A), and global methylation changes linked to SAM depletion. (pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41)
A structured mechanism table with ontology mapping is provided in Artifact-03.
| Mechanism (high level) | Molecular details/chain | Example genes/proteins | Suggested GO biological process terms | Suggested CL cell types | Suggested UBERON organs/tissues | Suggested CHEBI entities/arsenic species | Evidence (citation IDs) |
|---|---|---|---|---|---|---|---|
| Toxicokinetic uptake, biotransformation, and distribution | Ingested/inhaled inorganic arsenic is absorbed, distributed systemically, and methylated mainly in liver to MMA and DMA; As(V) enters via phosphate transporters, As(III) via aquaglyceroporins, then binds thiols and undergoes reduction/methylation using GSH, thioredoxin systems, SAM, and AS3MT. Urinary excretion is the main clearance route; skin, hair, nails, bone, and teeth can accumulate arsenic. | AS3MT, TXNRD1, thioredoxin, glutathione-related proteins, aquaglyceroporins, phosphate transporters | GO:0006730 one-carbon metabolic process; GO:0017144 drug metabolic process; GO:0042493 response to drug; GO:0055085 transmembrane transport | hepatocyte; erythrocyte; renal tubular epithelial cell | liver (UBERON:0002107); kidney (UBERON:0002113); skin (UBERON:0002097); blood (UBERON:0000178) | inorganic arsenic; arsenite(3+) / As(III); arsenate(V) / As(V); monomethylarsonous acid (MMAIII); dimethylarsinic acid (DMA) | (ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2, pullella2024elucidatingtherelationship pages 37-41) |
| Thiol binding and enzyme inhibition | Trivalent arsenicals bind sulfhydryl/lipoic-acid–dependent enzymes, disrupting central metabolism and redox homeostasis. MMA(III) binds lipoic acid and inhibits pyruvate dehydrogenase; As(V) can substitute for phosphate in metabolic intermediates, impairing ATP-generating reactions. | pyruvate dehydrogenase complex, lipoic acid–dependent enzymes, glyceraldehyde-3-phosphate dehydrogenase | GO:0006099 tricarboxylic acid cycle; GO:0006096 glycolytic process; GO:0046034 ATP metabolic process; GO:0055114 oxidation-reduction process | hepatocyte; cardiomyocyte; neuron | liver (UBERON:0002107); heart (UBERON:0000948); nervous system (UBERON:0001016) | arsenite(3+); arsenate(V); MMAIII; ADP-arsenate; glucose-6-arsenate | (pereira2025arsenomearsenobolomeand pages 19-20, ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13) |
| Oxidative and nitrosative stress | A central initiating event is ROS/RNS generation with lipid, protein, and DNA oxidation; reported biomarkers include MDA, protein carbonyls, and 8-hydroxydeoxyguanosine. MMA(III) and As(III) also interfere with nitric oxide biology, including NOS inhibition and peroxynitrite-related injury. | TXNRD1, Nrf2 pathway components, nitric oxide synthase, heme oxygenase, ferritin, metallothionein | GO:0006979 response to oxidative stress; GO:1903409 reactive oxygen species metabolic process; GO:0051409 response to nitrosative stress; GO:0034599 cellular response to oxidative stress | fibroblast; endothelial cell; keratinocyte; neuron | skin (UBERON:0002097); vasculature (UBERON:0004535); lung (UBERON:0002048); kidney (UBERON:0002113) | arsenite(3+); MMAIII; inorganic arsenic | (balalimood2025recentadvancesin pages 12-13, pereira2025arsenomearsenobolomeand pages 19-20, pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| NRF2-mediated antioxidant response and detoxification | Genetic and experimental studies identify NRF2-linked antioxidant defense, detoxification, and stress-response programs as major regulated responses to arsenic metabolites. Cellular morphology QTL mapped loci including Abcc4 and Txnrd1, supporting genetically controlled variability in response to MMAIII. | ABCC4, TXNRD1, NRF2 pathway genes, metallothioneins | GO:0034599 cellular response to oxidative stress; GO:0042744 hydrogen peroxide catabolic process; GO:0006805 xenobiotic metabolic process; GO:0046677 response to antibiotic | fibroblast; hepatocyte; renal epithelial cell | liver (UBERON:0002107); kidney (UBERON:0002113); skin (UBERON:0002097) | MMAIII; inorganic arsenic; arsenite(3+) | (pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| DNA damage and impaired DNA repair | Arsenic increases chromosomal abnormalities, sister chromatid exchange, oxidative DNA damage, and genomic instability. It inhibits DNA mismatch repair and broader DNA repair responses; cmQTL work highlighted DNA repair candidate Xrcc2. Chronic exposure is linked to 8-oxo-dG elevation and repair gene dysregulation. | XRCC2, MLH1, MSH2, p53-related pathways | GO:0006281 DNA repair; GO:0006974 cellular response to DNA damage stimulus; GO:0036297 interstrand cross-link repair; GO:0006302 double-strand break repair | fibroblast; keratinocyte; urothelial cell | skin (UBERON:0002097); urinary bladder (UBERON:0001255); lung (UBERON:0002048) | inorganic arsenic; arsenite(3+); MMAIII | (pereira2025arsenomearsenobolomeand pages 19-20, pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| Epigenetic dysregulation and methyl-donor depletion | Arsenic perturbs epigenetic control through SAM depletion, global hypomethylation, locus-specific hypermethylation (e.g., MLH1, MSH2), altered DNMT expression, mitochondrial D-loop hypomethylation, miRNA changes, and m6A-related signaling. Nutritional methyl-donor status (folate, choline, methionine, betaine, B vitamins) modifies toxicity. | DNMT1, DNMT3A, DNMT3B, MLH1, MSH2, METTL3, YTHDF2, JAK2, STAT3, AS3MT | GO:0006306 DNA methylation; GO:0016573 histone acetylation; GO:0032776 DNA methylation on cytosine; GO:0010608 post-transcriptional regulation of gene expression | keratinocyte; hepatocyte; stem/progenitor-like epithelial cell | skin (UBERON:0002097); liver (UBERON:0002107); urinary bladder (UBERON:0001255) | inorganic arsenic; arsenite(3+); methylated arsenicals | (pereira2025arsenomearsenobolomeand pages 20-22, pereira2025arsenomearsenobolomeand pages 19-20, pullella2024elucidatingtherelationship pages 37-41, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) |
| Mitochondrial dysfunction and apoptosis | Arsenic disrupts mitochondrial respiration and oxidative phosphorylation, lowers ATP production, activates JNK/ERK and GRP78/CHOP stress pathways, and promotes apoptosis/cell death trajectories. These events link upstream redox injury to organ dysfunction and neuro/cardiotoxicity. | JNK, ERK, GRP78, CHOP, pyruvate dehydrogenase complex | GO:0007005 mitochondrion organization; GO:0008635 activation of apoptotic process; GO:1902600 proton transmembrane transport; GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | neuron; cardiomyocyte; hepatocyte | brain (UBERON:0000955); heart (UBERON:0000948); liver (UBERON:0002107) | MMAIII; arsenite(3+); inorganic arsenic | (pereira2025arsenomearsenobolomeand pages 19-20, ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13) |
| Inflammation, angiogenesis, and malignant transformation | Chronic exposure activates inflammatory signaling (including NF-kB-related and CD14-linked profiles), VEGF/angiogenesis, EMT-like programs, and altered signal transduction, helping connect long-term exposure to skin, bladder, lung, kidney, and liver cancers. | NFkB, VEGF, EGFR, CD14, p38 MAPK pathway components | GO:0006954 inflammatory response; GO:0001525 angiogenesis; GO:0001837 epithelial to mesenchymal transition; GO:0008284 positive regulation of cell population proliferation | endothelial cell; macrophage/monocyte; keratinocyte; urothelial cell | skin (UBERON:0002097); lung (UBERON:0002048); urinary bladder (UBERON:0001255); kidney (UBERON:0002113) | inorganic arsenic; arsenite(3+); methylated arsenicals | (pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2) |
| Electrophysiologic cardiotoxicity | Arsenic blocks repolarizing potassium currents (IKr, IKs), prolonging QT and predisposing to torsades/arrhythmias; this is a key downstream mechanism in acute severe poisoning. | IKr channel, IKs channel | GO:0086001 cardiac muscle cell action potential; GO:1903779 regulation of cardiac conduction; GO:0006813 potassium ion transport | cardiomyocyte | heart (UBERON:0000948) | arsenite(3+); inorganic arsenic | (pereira2025arsenomearsenobolomeand pages 19-20, balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Population genetic susceptibility and gene-by-environment interaction | Toxic response varies with arsenic methylation phenotype and genetic background. Human and model-system evidence implicates AS3MT genotype in methylation/toxicity variability, while cell-based QTL mapping identified response loci including Abcc4, Txnrd1, and Xrcc2 under MMAIII exposure. | AS3MT, ABCC4, TXNRD1, XRCC2 | GO:0006805 xenobiotic metabolic process; GO:0042221 response to chemical; GO:0006974 cellular response to DNA damage stimulus | fibroblast; hepatocyte | liver (UBERON:0002107); skin (UBERON:0002097); kidney (UBERON:0002113) | MMAIII; inorganic arsenic; arsenite(3+) | (ganie2024arsenictoxicitysources pages 2-3, pullella2024elucidatingtherelationship pages 37-41, abuawad2023thefolicacid pages 8-9, abuawad2023thefolicacid pages 1-2) |
Table: This table summarizes major molecular and cellular mechanisms of arsenic poisoning and links them to suggested ontology terms for knowledge-base curation. It integrates toxicokinetics, oxidative stress, DNA damage, epigenetic dysregulation, mitochondrial injury, carcinogenic signaling, and genetic susceptibility.
Suggested UBERON targets are included in Artifact-03.
A structured diagnostics table is provided in Artifact-02.
| Category | Item | What it indicates/when used | Key quantitative thresholds or notes | Evidence |
|---|---|---|---|---|
| Diagnostic | Urine total arsenic (24-hour) | Main biomarker for recent arsenic exposure; used in suspected acute or ongoing exposure | 24-hour urinary arsenic >100 µg/L reported as elevated/toxic in retrieved evidence; chelation follow-up target <50 µg/L in 24-hour urine; seafood can confound total urinary arsenic unless speciation is done (pullella2024elucidatingtherelationship pages 37-41, balalimood2025recentadvancesin pages 13-14, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, balalimood2025recentadvancesin pages 13-14, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Spot urine arsenic | Practical alternative to 24-hour collection for recent exposure assessment | Spot urine >50 µg/L reported as elevated in retrieved evidence; should be interpreted with hydration correction (e.g., creatinine adjustment) and ideally with speciation (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Urine arsenic speciation (iAs, MMA, DMA) | Best test to distinguish toxic inorganic exposure from seafood-derived organic arsenic; also used to assess methylation phenotype and susceptibility | Requires seafood avoidance before testing; elevated urinary MMA or higher MMA/DMA ratio suggests less complete methylation and potentially higher cancer susceptibility; recent exposure window roughly several days because biologic half-life is about 2-4 days (chakif2026heavymetaltoxicity pages 12-13, pullella2024elucidatingtherelationship pages 37-41) | (chakif2026heavymetaltoxicity pages 12-13, pullella2024elucidatingtherelationship pages 37-41) |
| Diagnostic | Blood arsenic | Reflects very recent exposure and acute poisoning; less useful after rapid clearance | Blood arsenic >130 nmol/L reported as elevated/toxic in retrieved evidence; blood half-life about 2-6 h, so sensitivity falls quickly after exposure (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Serum arsenic | Limited clinical utility because arsenic clears rapidly from blood | Not considered reliable for diagnosis once time has elapsed after exposure (balalimood2025recentadvancesin pages 12-13) | (balalimood2025recentadvancesin pages 12-13) |
| Diagnostic | Hair arsenic | Marker of longer-term past exposure | Can become positive about 30 h after exposure; reflects longer-term exposure but is nondiscriminatory for source/species and is not ideal for acute decision-making (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41) | (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41) |
| Diagnostic | Nail arsenic (especially toenail) | Marker of chronic exposure over prior months | Toenail arsenic >0.5 µg/g reported as elevated in retrieved evidence; nails reflect long-term exposure over about 3-6 months (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Imaging (abdominal/chest X-ray) | Supportive test in acute poisoning to identify radiopaque ingested arsenic material or evaluate complications | Used selectively in acute ingestion; not a biomarker of body burden (balalimood2025recentadvancesin pages 12-13) | (balalimood2025recentadvancesin pages 12-13) |
| Diagnostic | ECG monitoring | Detects cardiotoxicity in acute poisoning | Important because acute arsenic can prolong QT/QRS and trigger torsades/arrhythmias (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Treatment | Exposure cessation/source removal | First-line intervention in all cases, especially chronic/subacute arsenicosis | Removal from contaminated water/food/occupational source is the primary treatment for chronic poisoning (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Succimer / DMSA | Oral chelator used for arsenic poisoning, especially when prolonged treatment is needed or less invasive therapy is preferred | Named as a key chelator; preferred for prolonged chronic/subacute cases in retrieved evidence; most effective when started minutes to hours after exposure (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | DMPS | Water-soluble chelator used in arsenic poisoning | Named as a key arsenic chelator; most useful early after exposure; use varies by region/regulatory approval (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Dimercaprol / BAL | Traditional parenteral chelator for severe acute arsenic poisoning | Named as a key chelator; most effective when given soon after exposure, typically minutes to hours (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | IV fluids and electrolyte replacement | Core supportive therapy for acute poisoning with severe vomiting/diarrhea and shock | Critical because deaths often result from hypovolemia, renal failure, or cardiac complications (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Treatment | GI decontamination / bowel irrigation / NG suction | Used in selected acute ingestions, especially if arsenic is still in the GI tract or radiopaque material is seen | Activated charcoal adsorbs arsenic poorly; whole-bowel irrigation or continued NG suction may be considered in severe ingestion (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Antiarrhythmic management and magnesium | Supportive management for QT prolongation/torsades and other arrhythmias | Magnesium sulfate, amiodarone, or lidocaine reported as options; avoid class IA/IC/III antiarrhythmics in this context per retrieved review (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Benzodiazepines for seizures | Symptom-directed treatment in acute neurotoxicity | Used when seizures occur during severe intoxication (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Hemodialysis | Adjunctive/supportive therapy in severe poisoning with kidney failure or oliguria | Recommended in acute kidney injury/oliguria; supportive rather than stand-alone antidotal therapy (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Exchange transfusion | Special situation therapy for arsine gas poisoning with massive hemolysis | Can help remove arsine-related toxic burden in severe hemolytic presentations (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Antioxidant/nutritional adjuncts | Investigational or supportive approaches to mitigate toxicity or improve methylation/detoxification | Selenium, zinc, folate, vitamins A/C/E, and phytochemicals have been proposed; clinical evidence remains limited (balalimood2025recentadvancesin pages 13-14, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) | (balalimood2025recentadvancesin pages 13-14, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) |
Table: This table summarizes clinically relevant diagnostic biomarkers and current treatment approaches for arsenic poisoning, including practical interpretation notes and quantitative thresholds reported in the retrieved evidence. It is useful for distinguishing recent versus chronic exposure and for mapping acute management options to the evidence base.
Key points: - Urine arsenic speciation (iAs/MMA/DMA) is emphasized as essential to distinguish inorganic exposure from seafood-related organic arsenic and to evaluate methylation phenotype. (chakif2026heavymetaltoxicity pages 12-13, pullella2024elucidatingtherelationship pages 37-41) - Quantitative cutoffs reported in retrieved sources include blood arsenic >130 nmol/L, 24‑h urinary total arsenic >100 µg/L, spot urine >50 µg/L, and toenail As >0.5 µg/g (noting these are presented in a review context and should be interpreted clinically). (pullella2024elucidatingtherelationship pages 41-44)
Suggested MAXO terms (names only): chelation therapy; hemodialysis; gastrointestinal decontamination; nutritional supplementation; exposure avoidance/remediation.
The retrieved sources did not provide well-documented naturally occurring “arsenicosis” case series in companion animals; however, the toxicant is relevant across species and arsenic exposure is discussed in livestock contexts in broader heavy-metal reviews (not specific to arsenic-only disease characterization).
| Concept | Definition/notes | Synonyms | Key exposure route(s) | Identifier(s) explicitly available in retrieved evidence | Key citation ID |
|---|---|---|---|---|---|
| Acute arsenic poisoning | Rapid-onset toxicity, usually after ingestion of inorganic arsenic; symptoms may begin within ~30 min to 2 h and commonly include severe gastroenteritis, hypotension, QT prolongation/arrhythmia, neurologic toxicity, renal injury, and hepatic/hematologic abnormalities. | Acute arsenic toxicity | Ingestion; less commonly inhalation in occupational settings | Not found in retrieved sources | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Chronic arsenic poisoning / arsenicosis | Slow accumulation of low-dose exposure over time causing multisystem disease, especially skin lesions, peripheral neuropathy, vascular disease, and elevated cancer risk; explicitly named “arsenicosis.” | Arsenicosis; arseniasis; arsenism; arsenicism | Chronic ingestion via drinking water/food; inhalation in some occupational settings | Not found in retrieved sources | (ganie2024arsenictoxicitysources pages 2-3, ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 20-22) |
| Inorganic arsenic (iAs) | Toxicologically most important arsenic category; includes pentavalent arsenate and trivalent arsenite, undergoes hepatic methylation to MMA and DMA, and is associated with carcinogenic, vascular, neurologic, and dermatologic effects. | iAs; inorganic As | Ingestion from contaminated water/food; inhalation | Not found in retrieved sources | (ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2) |
| Arsenite As(III) | Trivalent inorganic arsenic; generally more toxic than As(V), strongly interacts with sulfhydryl-containing proteins and key enzymes, and is central to oxidative stress and mitochondrial dysfunction mechanisms. | Arsenite; As3+; trivalent arsenic; meta-arsenite | Ingestion; inhalation; some dermal absorption of trivalent forms | Not found in retrieved sources | (ganie2024arsenictoxicitysources pages 2-3, ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 19-20) |
| Arsenate As(V) | Pentavalent inorganic arsenic; enters cells via phosphate transporters and can substitute for phosphate in biochemical reactions, disrupting cellular energetics before reduction/methylation. | Arsenate; As5+; pentavalent arsenic | Ingestion; inhalation | Not found in retrieved sources | (ganie2024arsenictoxicitysources pages 2-3, ganie2024arsenictoxicitysources pages 1-2, pereira2025arsenomearsenobolomeand pages 19-20) |
| Arsine gas AsH3 | Extremely toxic gaseous arsenic species; inhalational exposure is a classic occupational hazard and can be rapidly lethal, with reported lethality above ~10 ppm in retrieved evidence. | Arsine; arsenic hydride | Inhalation | Not found in retrieved sources | (balalimood2025recentadvancesin pages 12-13) |
Table: This table summarizes the main clinical and chemical concepts relevant to arsenic poisoning, including acute and chronic disease forms and major inorganic arsenic species. It is useful as a compact reference for terminology, exposure routes, and evidence-backed definitions from the retrieved literature.
| Category | Item | What it indicates/when used | Key quantitative thresholds or notes | Evidence |
|---|---|---|---|---|
| Diagnostic | Urine total arsenic (24-hour) | Main biomarker for recent arsenic exposure; used in suspected acute or ongoing exposure | 24-hour urinary arsenic >100 µg/L reported as elevated/toxic in retrieved evidence; chelation follow-up target <50 µg/L in 24-hour urine; seafood can confound total urinary arsenic unless speciation is done (pullella2024elucidatingtherelationship pages 37-41, balalimood2025recentadvancesin pages 13-14, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, balalimood2025recentadvancesin pages 13-14, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Spot urine arsenic | Practical alternative to 24-hour collection for recent exposure assessment | Spot urine >50 µg/L reported as elevated in retrieved evidence; should be interpreted with hydration correction (e.g., creatinine adjustment) and ideally with speciation (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Urine arsenic speciation (iAs, MMA, DMA) | Best test to distinguish toxic inorganic exposure from seafood-derived organic arsenic; also used to assess methylation phenotype and susceptibility | Requires seafood avoidance before testing; elevated urinary MMA or higher MMA/DMA ratio suggests less complete methylation and potentially higher cancer susceptibility; recent exposure window roughly several days because biologic half-life is about 2-4 days (chakif2026heavymetaltoxicity pages 12-13, pullella2024elucidatingtherelationship pages 37-41) | (chakif2026heavymetaltoxicity pages 12-13, pullella2024elucidatingtherelationship pages 37-41) |
| Diagnostic | Blood arsenic | Reflects very recent exposure and acute poisoning; less useful after rapid clearance | Blood arsenic >130 nmol/L reported as elevated/toxic in retrieved evidence; blood half-life about 2-6 h, so sensitivity falls quickly after exposure (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Serum arsenic | Limited clinical utility because arsenic clears rapidly from blood | Not considered reliable for diagnosis once time has elapsed after exposure (balalimood2025recentadvancesin pages 12-13) | (balalimood2025recentadvancesin pages 12-13) |
| Diagnostic | Hair arsenic | Marker of longer-term past exposure | Can become positive about 30 h after exposure; reflects longer-term exposure but is nondiscriminatory for source/species and is not ideal for acute decision-making (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41) | (balalimood2025recentadvancesin pages 12-13, pullella2024elucidatingtherelationship pages 37-41) |
| Diagnostic | Nail arsenic (especially toenail) | Marker of chronic exposure over prior months | Toenail arsenic >0.5 µg/g reported as elevated in retrieved evidence; nails reflect long-term exposure over about 3-6 months (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) | (pullella2024elucidatingtherelationship pages 37-41, pullella2024elucidatingtherelationship pages 41-44) |
| Diagnostic | Imaging (abdominal/chest X-ray) | Supportive test in acute poisoning to identify radiopaque ingested arsenic material or evaluate complications | Used selectively in acute ingestion; not a biomarker of body burden (balalimood2025recentadvancesin pages 12-13) | (balalimood2025recentadvancesin pages 12-13) |
| Diagnostic | ECG monitoring | Detects cardiotoxicity in acute poisoning | Important because acute arsenic can prolong QT/QRS and trigger torsades/arrhythmias (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) | (balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Treatment | Exposure cessation/source removal | First-line intervention in all cases, especially chronic/subacute arsenicosis | Removal from contaminated water/food/occupational source is the primary treatment for chronic poisoning (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Succimer / DMSA | Oral chelator used for arsenic poisoning, especially when prolonged treatment is needed or less invasive therapy is preferred | Named as a key chelator; preferred for prolonged chronic/subacute cases in retrieved evidence; most effective when started minutes to hours after exposure (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | DMPS | Water-soluble chelator used in arsenic poisoning | Named as a key arsenic chelator; most useful early after exposure; use varies by region/regulatory approval (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Dimercaprol / BAL | Traditional parenteral chelator for severe acute arsenic poisoning | Named as a key chelator; most effective when given soon after exposure, typically minutes to hours (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | IV fluids and electrolyte replacement | Core supportive therapy for acute poisoning with severe vomiting/diarrhea and shock | Critical because deaths often result from hypovolemia, renal failure, or cardiac complications (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 12-13, balalimood2025recentadvancesin pages 13-14) |
| Treatment | GI decontamination / bowel irrigation / NG suction | Used in selected acute ingestions, especially if arsenic is still in the GI tract or radiopaque material is seen | Activated charcoal adsorbs arsenic poorly; whole-bowel irrigation or continued NG suction may be considered in severe ingestion (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Antiarrhythmic management and magnesium | Supportive management for QT prolongation/torsades and other arrhythmias | Magnesium sulfate, amiodarone, or lidocaine reported as options; avoid class IA/IC/III antiarrhythmics in this context per retrieved review (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Benzodiazepines for seizures | Symptom-directed treatment in acute neurotoxicity | Used when seizures occur during severe intoxication (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Hemodialysis | Adjunctive/supportive therapy in severe poisoning with kidney failure or oliguria | Recommended in acute kidney injury/oliguria; supportive rather than stand-alone antidotal therapy (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Exchange transfusion | Special situation therapy for arsine gas poisoning with massive hemolysis | Can help remove arsine-related toxic burden in severe hemolytic presentations (balalimood2025recentadvancesin pages 13-14) | (balalimood2025recentadvancesin pages 13-14) |
| Treatment | Antioxidant/nutritional adjuncts | Investigational or supportive approaches to mitigate toxicity or improve methylation/detoxification | Selenium, zinc, folate, vitamins A/C/E, and phytochemicals have been proposed; clinical evidence remains limited (balalimood2025recentadvancesin pages 13-14, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) | (balalimood2025recentadvancesin pages 13-14, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) |
Table: This table summarizes clinically relevant diagnostic biomarkers and current treatment approaches for arsenic poisoning, including practical interpretation notes and quantitative thresholds reported in the retrieved evidence. It is useful for distinguishing recent versus chronic exposure and for mapping acute management options to the evidence base.
| Mechanism (high level) | Molecular details/chain | Example genes/proteins | Suggested GO biological process terms | Suggested CL cell types | Suggested UBERON organs/tissues | Suggested CHEBI entities/arsenic species | Evidence (citation IDs) |
|---|---|---|---|---|---|---|---|
| Toxicokinetic uptake, biotransformation, and distribution | Ingested/inhaled inorganic arsenic is absorbed, distributed systemically, and methylated mainly in liver to MMA and DMA; As(V) enters via phosphate transporters, As(III) via aquaglyceroporins, then binds thiols and undergoes reduction/methylation using GSH, thioredoxin systems, SAM, and AS3MT. Urinary excretion is the main clearance route; skin, hair, nails, bone, and teeth can accumulate arsenic. | AS3MT, TXNRD1, thioredoxin, glutathione-related proteins, aquaglyceroporins, phosphate transporters | GO:0006730 one-carbon metabolic process; GO:0017144 drug metabolic process; GO:0042493 response to drug; GO:0055085 transmembrane transport | hepatocyte; erythrocyte; renal tubular epithelial cell | liver (UBERON:0002107); kidney (UBERON:0002113); skin (UBERON:0002097); blood (UBERON:0000178) | inorganic arsenic; arsenite(3+) / As(III); arsenate(V) / As(V); monomethylarsonous acid (MMAIII); dimethylarsinic acid (DMA) | (ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2, pullella2024elucidatingtherelationship pages 37-41) |
| Thiol binding and enzyme inhibition | Trivalent arsenicals bind sulfhydryl/lipoic-acid–dependent enzymes, disrupting central metabolism and redox homeostasis. MMA(III) binds lipoic acid and inhibits pyruvate dehydrogenase; As(V) can substitute for phosphate in metabolic intermediates, impairing ATP-generating reactions. | pyruvate dehydrogenase complex, lipoic acid–dependent enzymes, glyceraldehyde-3-phosphate dehydrogenase | GO:0006099 tricarboxylic acid cycle; GO:0006096 glycolytic process; GO:0046034 ATP metabolic process; GO:0055114 oxidation-reduction process | hepatocyte; cardiomyocyte; neuron | liver (UBERON:0002107); heart (UBERON:0000948); nervous system (UBERON:0001016) | arsenite(3+); arsenate(V); MMAIII; ADP-arsenate; glucose-6-arsenate | (pereira2025arsenomearsenobolomeand pages 19-20, ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13) |
| Oxidative and nitrosative stress | A central initiating event is ROS/RNS generation with lipid, protein, and DNA oxidation; reported biomarkers include MDA, protein carbonyls, and 8-hydroxydeoxyguanosine. MMA(III) and As(III) also interfere with nitric oxide biology, including NOS inhibition and peroxynitrite-related injury. | TXNRD1, Nrf2 pathway components, nitric oxide synthase, heme oxygenase, ferritin, metallothionein | GO:0006979 response to oxidative stress; GO:1903409 reactive oxygen species metabolic process; GO:0051409 response to nitrosative stress; GO:0034599 cellular response to oxidative stress | fibroblast; endothelial cell; keratinocyte; neuron | skin (UBERON:0002097); vasculature (UBERON:0004535); lung (UBERON:0002048); kidney (UBERON:0002113) | arsenite(3+); MMAIII; inorganic arsenic | (balalimood2025recentadvancesin pages 12-13, pereira2025arsenomearsenobolomeand pages 19-20, pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| NRF2-mediated antioxidant response and detoxification | Genetic and experimental studies identify NRF2-linked antioxidant defense, detoxification, and stress-response programs as major regulated responses to arsenic metabolites. Cellular morphology QTL mapped loci including Abcc4 and Txnrd1, supporting genetically controlled variability in response to MMAIII. | ABCC4, TXNRD1, NRF2 pathway genes, metallothioneins | GO:0034599 cellular response to oxidative stress; GO:0042744 hydrogen peroxide catabolic process; GO:0006805 xenobiotic metabolic process; GO:0046677 response to antibiotic | fibroblast; hepatocyte; renal epithelial cell | liver (UBERON:0002107); kidney (UBERON:0002113); skin (UBERON:0002097) | MMAIII; inorganic arsenic; arsenite(3+) | (pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| DNA damage and impaired DNA repair | Arsenic increases chromosomal abnormalities, sister chromatid exchange, oxidative DNA damage, and genomic instability. It inhibits DNA mismatch repair and broader DNA repair responses; cmQTL work highlighted DNA repair candidate Xrcc2. Chronic exposure is linked to 8-oxo-dG elevation and repair gene dysregulation. | XRCC2, MLH1, MSH2, p53-related pathways | GO:0006281 DNA repair; GO:0006974 cellular response to DNA damage stimulus; GO:0036297 interstrand cross-link repair; GO:0006302 double-strand break repair | fibroblast; keratinocyte; urothelial cell | skin (UBERON:0002097); urinary bladder (UBERON:0001255); lung (UBERON:0002048) | inorganic arsenic; arsenite(3+); MMAIII | (pereira2025arsenomearsenobolomeand pages 19-20, pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, ganie2024arsenictoxicitysources pages 2-3) |
| Epigenetic dysregulation and methyl-donor depletion | Arsenic perturbs epigenetic control through SAM depletion, global hypomethylation, locus-specific hypermethylation (e.g., MLH1, MSH2), altered DNMT expression, mitochondrial D-loop hypomethylation, miRNA changes, and m6A-related signaling. Nutritional methyl-donor status (folate, choline, methionine, betaine, B vitamins) modifies toxicity. | DNMT1, DNMT3A, DNMT3B, MLH1, MSH2, METTL3, YTHDF2, JAK2, STAT3, AS3MT | GO:0006306 DNA methylation; GO:0016573 histone acetylation; GO:0032776 DNA methylation on cytosine; GO:0010608 post-transcriptional regulation of gene expression | keratinocyte; hepatocyte; stem/progenitor-like epithelial cell | skin (UBERON:0002097); liver (UBERON:0002107); urinary bladder (UBERON:0001255) | inorganic arsenic; arsenite(3+); methylated arsenicals | (pereira2025arsenomearsenobolomeand pages 20-22, pereira2025arsenomearsenobolomeand pages 19-20, pullella2024elucidatingtherelationship pages 37-41, abuawad2023thefolicacid pages 6-7, abuawad2023thefolicacid pages 7-8, abuawad2023thefolicacid pages 1-2) |
| Mitochondrial dysfunction and apoptosis | Arsenic disrupts mitochondrial respiration and oxidative phosphorylation, lowers ATP production, activates JNK/ERK and GRP78/CHOP stress pathways, and promotes apoptosis/cell death trajectories. These events link upstream redox injury to organ dysfunction and neuro/cardiotoxicity. | JNK, ERK, GRP78, CHOP, pyruvate dehydrogenase complex | GO:0007005 mitochondrion organization; GO:0008635 activation of apoptotic process; GO:1902600 proton transmembrane transport; GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | neuron; cardiomyocyte; hepatocyte | brain (UBERON:0000955); heart (UBERON:0000948); liver (UBERON:0002107) | MMAIII; arsenite(3+); inorganic arsenic | (pereira2025arsenomearsenobolomeand pages 19-20, ganie2024arsenictoxicitysources pages 2-3, chakif2026heavymetaltoxicity pages 12-13) |
| Inflammation, angiogenesis, and malignant transformation | Chronic exposure activates inflammatory signaling (including NF-kB-related and CD14-linked profiles), VEGF/angiogenesis, EMT-like programs, and altered signal transduction, helping connect long-term exposure to skin, bladder, lung, kidney, and liver cancers. | NFkB, VEGF, EGFR, CD14, p38 MAPK pathway components | GO:0006954 inflammatory response; GO:0001525 angiogenesis; GO:0001837 epithelial to mesenchymal transition; GO:0008284 positive regulation of cell population proliferation | endothelial cell; macrophage/monocyte; keratinocyte; urothelial cell | skin (UBERON:0002097); lung (UBERON:0002048); urinary bladder (UBERON:0001255); kidney (UBERON:0002113) | inorganic arsenic; arsenite(3+); methylated arsenicals | (pereira2025arsenomearsenobolomeand pages 20-22, pullella2024elucidatingtherelationship pages 37-41, chakif2026heavymetaltoxicity pages 12-13, ganie2024arsenictoxicitysources pages 1-2) |
| Electrophysiologic cardiotoxicity | Arsenic blocks repolarizing potassium currents (IKr, IKs), prolonging QT and predisposing to torsades/arrhythmias; this is a key downstream mechanism in acute severe poisoning. | IKr channel, IKs channel | GO:0086001 cardiac muscle cell action potential; GO:1903779 regulation of cardiac conduction; GO:0006813 potassium ion transport | cardiomyocyte | heart (UBERON:0000948) | arsenite(3+); inorganic arsenic | (pereira2025arsenomearsenobolomeand pages 19-20, balalimood2025recentadvancesin pages 12-13, chakif2026heavymetaltoxicity pages 12-13) |
| Population genetic susceptibility and gene-by-environment interaction | Toxic response varies with arsenic methylation phenotype and genetic background. Human and model-system evidence implicates AS3MT genotype in methylation/toxicity variability, while cell-based QTL mapping identified response loci including Abcc4, Txnrd1, and Xrcc2 under MMAIII exposure. | AS3MT, ABCC4, TXNRD1, XRCC2 | GO:0006805 xenobiotic metabolic process; GO:0042221 response to chemical; GO:0006974 cellular response to DNA damage stimulus | fibroblast; hepatocyte | liver (UBERON:0002107); skin (UBERON:0002097); kidney (UBERON:0002113) | MMAIII; inorganic arsenic; arsenite(3+) | (ganie2024arsenictoxicitysources pages 2-3, pullella2024elucidatingtherelationship pages 37-41, abuawad2023thefolicacid pages 8-9, abuawad2023thefolicacid pages 1-2) |
Table: This table summarizes major molecular and cellular mechanisms of arsenic poisoning and links them to suggested ontology terms for knowledge-base curation. It integrates toxicokinetics, oxidative stress, DNA damage, epigenetic dysregulation, mitochondrial injury, carcinogenic signaling, and genetic susceptibility.
References
(balalimood2025recentadvancesin pages 12-13): Mahdi Balali-Mood, Nastaran Eizadi-Mood, Hossein Hassanian-Moghaddam, Leila Etemad, Mohammad Moshiri, Maryam Vahabzadeh, and Mahmood Sadeghi. Recent advances in the clinical management of intoxication by five heavy metals: mercury, lead, chromium, cadmium and arsenic. Heliyon, 11:e42696, Feb 2025. URL: https://doi.org/10.1016/j.heliyon.2025.e42696, doi:10.1016/j.heliyon.2025.e42696. This article has 65 citations.
(ganie2024arsenictoxicitysources pages 2-3): Shahid Yousuf Ganie, Darakhshan Javaid, Younis Ahmad Hajam, and Mohd Salim Reshi. Arsenic toxicity: sources, pathophysiology and mechanism. Toxicology research, 13 1:tfad111, Dec 2024. URL: https://doi.org/10.1093/toxres/tfad111, doi:10.1093/toxres/tfad111. This article has 170 citations.
(chakif2026heavymetaltoxicity pages 12-13): Dib Chakif and Julien Furrer. Heavy metal toxicity in clinical and environmental health: sources, mechanisms, diagnostics, and evidence-based management of mercury, lead, cadmium, and arsenic. International Journal of Molecular Sciences, 27:3513, Apr 2026. URL: https://doi.org/10.3390/ijms27083513, doi:10.3390/ijms27083513. This article has 0 citations.
(visciano2025arsenicinwater pages 10-12): Pierina Visciano. Arsenic in water and food: toxicity and human exposure. Foods, 14:2229, Jun 2025. URL: https://doi.org/10.3390/foods14132229, doi:10.3390/foods14132229. This article has 11 citations.
(issanov2023arsenicindrinking pages 1-2): Alpamys Issanov, Betty Adewusi, Trevor J. B. Dummer, and Nathalie Saint-Jacques. Arsenic in drinking water and urinary tract cancers: a systematic review update. Water, Jun 2023. URL: https://doi.org/10.3390/w15122185, doi:10.3390/w15122185. This article has 17 citations.
(ganie2024arsenictoxicitysources pages 1-2): Shahid Yousuf Ganie, Darakhshan Javaid, Younis Ahmad Hajam, and Mohd Salim Reshi. Arsenic toxicity: sources, pathophysiology and mechanism. Toxicology research, 13 1:tfad111, Dec 2024. URL: https://doi.org/10.1093/toxres/tfad111, doi:10.1093/toxres/tfad111. This article has 170 citations.
(bhat2024arseniccontaminationneeds pages 1-2): Abhijnan Bhat, Kamna Ravi, Furong Tian, and Baljit Singh. Arsenic contamination needs serious attention: an opinion and global scenario. Pollutants, 4:196-211, Apr 2024. URL: https://doi.org/10.3390/pollutants4020013, doi:10.3390/pollutants4020013. This article has 76 citations.
(pullella2024elucidatingtherelationship pages 37-41): K Pullella. Elucidating the relationship between arsenic exposure and cancer risk in canada. Unknown journal, 2024.
(pereira2025arsenomearsenobolomeand pages 20-22): Fernando J. Pereira, Roberto López, and A. Javier Aller. Arsenome, arsenobolome, and arsenobiolome. International Journal of Molecular Sciences, 26:10761, Nov 2025. URL: https://doi.org/10.3390/ijms262110761, doi:10.3390/ijms262110761. This article has 0 citations.
(abuawad2023thefolicacid pages 7-8): Ahlam K. Abuawad, Anne K. Bozack, Ana Navas-Acien, Jeff Goldsmith, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Angela M. Lomax-Luu, Faruque Parvez, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, and Mary V. Gamble. The folic acid and creatine trial: treatment effects of supplementation on arsenic methylation indices and metabolite concentrations in blood in a bangladeshi population. Environmental Health Perspectives, Mar 2023. URL: https://doi.org/10.1289/ehp11270, doi:10.1289/ehp11270. This article has 16 citations and is from a highest quality peer-reviewed journal.
(abuawad2023thefolicacid pages 1-2): Ahlam K. Abuawad, Anne K. Bozack, Ana Navas-Acien, Jeff Goldsmith, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Angela M. Lomax-Luu, Faruque Parvez, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, and Mary V. Gamble. The folic acid and creatine trial: treatment effects of supplementation on arsenic methylation indices and metabolite concentrations in blood in a bangladeshi population. Environmental Health Perspectives, Mar 2023. URL: https://doi.org/10.1289/ehp11270, doi:10.1289/ehp11270. This article has 16 citations and is from a highest quality peer-reviewed journal.
(o’connor2024unravelingthegenetics pages 1-2): Callan O’Connor, Gregory R. Keele, Whitney Martin, Timothy Stodola, Daniel Gatti, Brian R. Hoffman, Ron Korstanje, Gary A. Churchill, and Laura G. Reinholdt. Unraveling the genetics of arsenic toxicity with cellular morphology qtl. PLOS Genetics, 20:e1011248, Apr 2024. URL: https://doi.org/10.1371/journal.pgen.1011248, doi:10.1371/journal.pgen.1011248. This article has 6 citations and is from a domain leading peer-reviewed journal.
(balalimood2025recentadvancesin pages 13-14): Mahdi Balali-Mood, Nastaran Eizadi-Mood, Hossein Hassanian-Moghaddam, Leila Etemad, Mohammad Moshiri, Maryam Vahabzadeh, and Mahmood Sadeghi. Recent advances in the clinical management of intoxication by five heavy metals: mercury, lead, chromium, cadmium and arsenic. Heliyon, 11:e42696, Feb 2025. URL: https://doi.org/10.1016/j.heliyon.2025.e42696, doi:10.1016/j.heliyon.2025.e42696. This article has 65 citations.
(pereira2025arsenomearsenobolomeand pages 19-20): Fernando J. Pereira, Roberto López, and A. Javier Aller. Arsenome, arsenobolome, and arsenobiolome. International Journal of Molecular Sciences, 26:10761, Nov 2025. URL: https://doi.org/10.3390/ijms262110761, doi:10.3390/ijms262110761. This article has 0 citations.
(singh2024arsenicexposurein pages 1-5): N Singh. Arsenic exposure in c57bl/6 mice carrying human as3mt elevates fasting glycemia and impairs beta cell function according to sex and developmental window …. Unknown journal, 2024.
(abuawad2023thefolicacid pages 6-7): Ahlam K. Abuawad, Anne K. Bozack, Ana Navas-Acien, Jeff Goldsmith, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Angela M. Lomax-Luu, Faruque Parvez, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, and Mary V. Gamble. The folic acid and creatine trial: treatment effects of supplementation on arsenic methylation indices and metabolite concentrations in blood in a bangladeshi population. Environmental Health Perspectives, Mar 2023. URL: https://doi.org/10.1289/ehp11270, doi:10.1289/ehp11270. This article has 16 citations and is from a highest quality peer-reviewed journal.
(abuawad2023thefolicacid pages 8-9): Ahlam K. Abuawad, Anne K. Bozack, Ana Navas-Acien, Jeff Goldsmith, Xinhua Liu, Megan N. Hall, Vesna Ilievski, Angela M. Lomax-Luu, Faruque Parvez, Hasan Shahriar, Mohammad N. Uddin, Tariqul Islam, Joseph H. Graziano, and Mary V. Gamble. The folic acid and creatine trial: treatment effects of supplementation on arsenic methylation indices and metabolite concentrations in blood in a bangladeshi population. Environmental Health Perspectives, Mar 2023. URL: https://doi.org/10.1289/ehp11270, doi:10.1289/ehp11270. This article has 16 citations and is from a highest quality peer-reviewed journal.
(mitchell2023acomprehensivesurvey pages 6-8): Erika J. Mitchell and Seth H. Frisbie. A comprehensive survey and analysis of international drinking water regulations for inorganic chemicals with comparisons to the world health organization’s drinking-water guidelines. PLOS ONE, 18:e0287937, Nov 2023. URL: https://doi.org/10.1371/journal.pone.0287937, doi:10.1371/journal.pone.0287937. This article has 33 citations and is from a peer-reviewed journal.
(mitchell2023acomprehensivesurvey pages 2-4): Erika J. Mitchell and Seth H. Frisbie. A comprehensive survey and analysis of international drinking water regulations for inorganic chemicals with comparisons to the world health organization’s drinking-water guidelines. PLOS ONE, 18:e0287937, Nov 2023. URL: https://doi.org/10.1371/journal.pone.0287937, doi:10.1371/journal.pone.0287937. This article has 33 citations and is from a peer-reviewed journal.
(pullella2024elucidatingtherelationship pages 41-44): K Pullella. Elucidating the relationship between arsenic exposure and cancer risk in canada. Unknown journal, 2024.
(o’connor2024unravelingthegenetics pages 2-3): Callan O’Connor, Gregory R. Keele, Whitney Martin, Timothy Stodola, Daniel Gatti, Brian R. Hoffman, Ron Korstanje, Gary A. Churchill, and Laura G. Reinholdt. Unraveling the genetics of arsenic toxicity with cellular morphology qtl. PLOS Genetics, 20:e1011248, Apr 2024. URL: https://doi.org/10.1371/journal.pgen.1011248, doi:10.1371/journal.pgen.1011248. This article has 6 citations and is from a domain leading peer-reviewed journal.