A tiered approach to life stages testing for agricultural chemical safety assessment.

A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Life Stages Task Force proposes a tiered approach to toxicity testing that assesses a compound's potential to cause adverse effects on reproduction, and that assesses the nature and severity of effects during development and adolescence, with consideration of the sensitivity of the elderly. While incorporating many features from current guideline studies, the proposed approach includes a novel rat reproduction and developmental study with enhanced endpoints and a rabbit development study. All available data, including toxicokinetics, ADME data, and systemic toxicity information, are considered in the design and interpretation of studies. Compared to existing testing strategies, the proposed approach uses fewer animals, provides information on the young animal, and includes an estimation of human exposure potential for making decisions about the extent of testing required.

Relevance of the developmental toxicity of ethanol in the occupational setting: a review.

Numerous studies have been conducted investigating the reproductive toxicology of ethanol, the overwhelming majority concerning the adverse effects of consuming alcohol in beverages during pregnancy. Because many of the in vivo studies were designed to model alcoholism, they used comparatively high doses and assessed relatively few endpoints. Outcomes may have been affected by disturbances of metabolism at such high exposures, giving rise to secondary effects on development. The available data on ethanol from "conventional" developmental toxicity study test methods of the type used for regulatory hazard assessment of chemicals are limited. It is in this context, however, i.e. the use of ethanol as an industrial chemical rather than as a component of beverages, that this review is based. Using the usual criteria applied for the purpose of hazard assessment of industrial chemicals, it is concluded that there is no evidence that industrial exposure to ethanol is a developmental toxicity hazard. Developmental toxicity may result from drinking alcoholic beverages, the threshold level for all aspects of which has yet to be de fi ned. This is not, however, considered relevant to the low blood alcohol concentrations resulting from any conceivable inhalation or dermal exposure in the workplace or through the directed use of any consumer product containing ethanol.