A Read‐Across Approach to Oral Acute Toxicity of Corrosive Acids and Bases: What Salts Can Tell Us, When, and Why

ABSTRACT Evaluating the oral acute toxicity (AT) of corrosive acids and bases remains a challenge in chemical safety assessment. In current regulatory practice, waiving experimental testing often results in assignment to the highest hazard category. This may overestimate systemic toxicity and influence the treatment prioritization in poisoning cases, where local corrosive injury is the dominant driver of clinical outcome. This study proposes a mechanistically grounded hypothesis that the systemic AT of corrosive acids and bases is primarily determined by their counterions. Based on this premise, a read‐across framework is developed in which noncorrosive, soluble sodium or potassium salts for acids and chlorides or sulfates for bases are used as source substances to approximate the systemic toxicity of the parent compounds. The approach integrates physicochemical, physiological, and toxicokinetic considerations and is formalized as a stepwise decision algorithm with criteria for solubility, noncorrosivity of the salts, and interpretation of LD 50 thresholds within a regulatory context. Its applicability domain and testable implications are also discussed. Illustrative examples across inorganic and organic acids and bases indicate internal consistency of the framework. If further experimentally supported, the proposed framework could improve differentiation between local and systemic toxicity and support more accurate hazard classification in regulatory practice.

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Publication Details

Journal
Journal of Applied Toxicology
Published
2026-09-06
DOI
https://doi.org/10.1002/jat.70427
Primary Topic
Corrosion Behavior and Inhibition
Type
article
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article

A Read‐Across Approach to Oral Acute Toxicity of Corrosive Acids and Bases: What Salts Can Tell Us, When, and Why

Dzmitry S. Valuyeu
Journal of Applied Toxicology
Corrosion Behavior and Inhibition
article

A Read‐Across Approach to Oral Acute Toxicity of Corrosive Acids and Bases: What Salts Can Tell Us, When, and Why

Dzmitry S. Valuyeu
article en

Abstract

ABSTRACT Evaluating the oral acute toxicity (AT) of corrosive acids and bases remains a challenge in chemical safety assessment. In current regulatory practice, waiving experimental testing often results in assignment to the highest hazard category. This may overestimate systemic toxicity and influence the treatment prioritization in poisoning cases, where local corrosive injury is the dominant driver of clinical outcome. This study proposes a mechanistically grounded hypothesis that the systemic AT of corrosive acids and bases is primarily determined by their counterions. Based on this premise, a read‐across framework is developed in which noncorrosive, soluble sodium or potassium salts for acids and chlorides or sulfates for bases are used as source substances to approximate the systemic toxicity of the parent compounds. The approach integrates physicochemical, physiological, and toxicokinetic considerations and is formalized as a stepwise decision algorithm with criteria for solubility, noncorrosivity of the salts, and interpretation of LD 50 thresholds within a regulatory context. Its applicability domain and testable implications are also discussed. Illustrative examples across inorganic and organic acids and bases indicate internal consistency of the framework. If further experimentally supported, the proposed framework could improve differentiation between local and systemic toxicity and support more accurate hazard classification in regulatory practice.

Journal of Applied Toxicology
KazMunayGas (Kazakhstan) (KZ)
Openalex Percentile: Top 23%
Corrosion Behavior and Inhibition
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