Abstract
Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oral-inhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than 98% of cases, which calls into question the value of routine dermal route testing for acute toxicity. Oral classifications were equivalent to or more severe than for the inhalation route for 83% of industrial chemicals and for 48% of pesticides examined.
Highlights
Acute toxicity refers to adverse effects occurring following a single exposure to a substance or following multiple exposures within 24 hours
Pharmaceutical companies have stated that “these studies have limited value in terms of pre-clinical and human safety assessment compared to the substantial adverse effects experienced by some of the animals” (Robinson et al, 2008), and this sector itself has recently moved to discontinue the routine requirement for stand-alone acute toxicity studies (ICH, 2009)
Data for industrial chemicals were obtained from the European Union (EU) New Chemicals Database (NCB), a proprietary repository of toxicity information for all substances notified to European authorities since 1981
Summary
Acute toxicity refers to adverse effects occurring following a single exposure to a substance or following multiple exposures within 24 hours. In the area of regulatory toxicology, acute toxicity studies are the longest standing class of toxicity test, dating back to the “lethal dose 50 percent” method developed by Trevan (1927). Pharmaceutical companies have stated that “these studies have limited value in terms of pre-clinical and human safety assessment compared to the substantial adverse effects experienced by some of the animals” (Robinson et al, 2008), and this sector itself has recently moved to discontinue the routine requirement for stand-alone acute toxicity studies (ICH, 2009). Available statistics indicate that more animals have been used in recent years in assessment of this endpoint than in any other single area of toxicology (EC, 2007)
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