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

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 LD₅₀ 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.