Non-relevance of acute dermal toxicity testing for assessing human health protection in the regulatory decision-making for agrochemical formulated products

• Published in: Regulatory toxicology and pharmacology Vol. 106; pp. 105 - 110
• Main Authors: Latorre, Andreia O., Floresta, Pedro V.M., Boff, Marylia M., Fagundes, Priscila M., Martins, Ana P., Ihlaseh-Catalano, Shadia M., Cazarin, Karen C.C., Romeo, Ligia L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-08-2019
• Subjects: Acute toxicity tests; Administration, Cutaneous; Administration, Oral; Agrochemicals - administration & dosage; Agrochemicals - toxicity; Animal testing reduction; Animals; Brazil; Classification; Crop protection; Decision Making; Dermal toxicity; Dose-Response Relationship, Drug; Humans; LD50; Oral toxicity; Rats; Reduction; Replacement; Risk Assessment; Skin - drug effects; Toxicity Tests, Acute; United States; United States Environmental Protection Agency; Waiver of data; Brazil; United States; LD50; Reduction; Animal testing reduction; Classification; Acute toxicity tests; Oral toxicity; Replacement; Crop protection; Dermal toxicity; Waiver of data; LD
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2019.04.014

Compared to oral toxicity tests, dermal toxicity tests offer little or no additional scientific information or public health protection for agrochemical-formulated products (US EPA, 2016). Based on that, a retrospective analysis of the results of acute oral and dermal LD50 studies of agrochemical products registered in Brazil was carried out by the Technical Group on Toxicological Risk Assessment (GT-ART) of the Brazilian Crop Protection Association (ANDEF). The data were obtained from 6 agrochemical industries that are associated to ANDEF, following these considerations: only rat studies were selected; only paired studies were chosen; only studies performed with top doses ≥2,000 mg/kg were selected; biological products were excluded. The dataset includes 342 formulated products in 21 formulation types. Among these 342 formulated products, 228 have a single active ingredient, 107 have 2 and 7 have 3 or more. The comparison of acute oral to dermal toxicity studies of agrochemical-formulated products registered in Brazil corroborates the United States Environmental Protection Agency (US EPA) conclusion on waiving acute dermal toxicity tests, which will result in avoiding unnecessary use of time and resources, data generation costs and animal testing.
•Compared to the oral toxicity test, the dermal toxicity test offers no further information for the protection of public health.•Acute oral toxicity data can be used to predict the acute dermal hazard.•Waiving dermal toxicity tests avoid unnecessary animal testing.