Abstract
In this study, we considered whether acute oral toxicity hazard classifications for pesticide formulations and active ingredients (AIs) could be used to assign acute dermal toxicity hazard classifications using U.S. Environmental Protection Agency (EPA) and the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) hazard categories. This retrospective analysis used highly curated acute toxicity data for 503 formulations and 297 AIs. Hazard classifications based on rat oral LD50 values were compared to hazard classifications based on rat dermal LD50 values for the same substance. The concordance of oral and dermal hazard classification was 62% for formulations and 64% for AIs using the EPA system and 71% for formulations and 55% for AIs using the GHS. Overprediction of dermal hazard was 38% for formulations and 32% for AIs using the EPA system and 28% for formulations and 41% for AIs using the GHS. Underprediction of dermal hazard was 1% for formulations and 3% for AIs using the EPA system and 1% for formulations and 3% for AIs using the GHS. While concordance overall was modest, the very low underprediction rates show that acute oral hazard categories are sufficiently protective for acute dermal hazard classification. Use of oral hazard data to also classify dermal hazard would obviate the need to perform acute dermal toxicity tests for classification and labeling and thereby reduce the number of animals used for acute systemic toxicity testing of pesticides.
Highlights
Dermal exposure to chemicals can occur during routine handling of chemicals or during accidental spills
23% (54/233) of the active ingredients (AIs) were classified by the Environmental Protection Agency (EPA) system as Category IV for dermal hazard, but only 12% (29/233) of these substances were classified as Category IV for oral hazard (Fig. 3b)
A higher proportion of formulations were classified by the EPA system as Category IV for oral hazard compared to the AIs (36% [173/476] vs. 12% [29/233]), and more formulations than AIs were classified as EPA Category IV for dermal hazard (70% [331/476] vs. 23% [54/233])
Summary
Dermal exposure to chemicals can occur during routine handling of chemicals or during accidental spills. Dermal exposure can contribute considerably to the internal dose of users exposed to hazardous substances [4], and in particular is an important source of internal dose for occupational chemical exposures [1, 15, 26]. For some types of chemicals, such as pesticides, the dermal route can be the most important route of exposure [12]. The industrial hygiene community develops specific notations for substances expected to present a toxic hazard via dermal absorption [5]. Regulatory agencies use data from acute oral and dermal toxicity tests to determine the potential systemic toxicity of chemicals and chemical products following oral ingestion and topical exposure to the skin, respectively. LD50 values from such tests, representing the dose expected to produce lethality in 50% of the animals tested, are used to assign substances to oral and dermal hazard categories. The hazard categories are used to assign product packaging labels to caution workers and consumers about poisoning potential
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