Whole-body inhalation exposure to 2-ethyltoluene for two weeks produced nasal lesions in rats and mice

Ethyltoluenes are isolated during crude oil refinement for use in gasoline and commercial products and are ubiquitous in the environment. However, minimal toxicity data are available. Previously, we identified 2-ethyltoluene (2-ET) as the most potent isomer via nose-only inhalation exposure in roden...

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Published in:Inhalation toxicology 2021-12, Vol.33 (9-14), p.334-346
Main Authors: Huang, Madelyn C., Willson, Cynthia J., Jaligama, Sridhar, Baker, Gregory L., Singer, Alan W., Cao, Yu, Pierfelice, Jessica, Mutlu, Esra, Burback, Brian, Xie, Guanhua, Malarkey, David E., Sparrow, Barney, Ryan, Kristen, Stout, Matthew, Roberts, Georgia K.
Format: Article
Language:English
Subjects:
Administration, Inhalation
Alkylbenzene
Animals
Female
inhalation
Inhalation Exposure - adverse effects
Male
Mice
Mice, Inbred Strains
occupational exposure
Pregnancy
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
rodent
toxicity
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Summary:Ethyltoluenes are isolated during crude oil refinement for use in gasoline and commercial products and are ubiquitous in the environment. However, minimal toxicity data are available. Previously, we identified 2-ethyltoluene (2-ET) as the most potent isomer via nose-only inhalation exposure in rodents. Here, we expanded the hazard characterization of 2-ET in two rodent models using whole-body inhalation exposure and evaluated the role of prenatal exposure. Time-mated Hsd:Sprague Dawley ® SD ® rats were exposed to 0, 150, 300, 600, 900, or 1200 ppm 2-ET via inhalation starting on gestation day 6 until parturition. Rat offspring (n = 8/exposure/sex) were exposed to the same concentrations as the respective dams for 2 weeks after weaning. Adult male and female B6C3F1/N mice (n = 5/exposure/sex) were exposed to the same concentrations for 2 weeks. Exposure to ≥600 ppm 2-ET produced acute toxicity in rats and mice characterized by large decreases in survival, body weight, adverse clinical observations, and diffuse nasal olfactory epithelium degeneration (rats) or necrosis (mice). Due to the early removal of groups ≥600 ppm, most endpoint evaluations focused on lower exposure groups. In 150 and 300 ppm exposure groups, reproductive performance and littering were not significantly changed and body weights in exposed rats and mice were 9-18% lower than controls. Atrophy of the olfactory epithelium and nerves was observed in all animals exposed to 150 and 300 ppm. These lesions were more severe in mice than in rats. Nasal lesions were observed in all animals after whole-body exposure up to 600 ppm 2-ET for 2 weeks. Future studies should focus on 2-ET metabolism and distribution to better understand species differences and refine hazard characterization of this understudied environmental contaminant.
ISSN:0895-8378
1091-7691
DOI:10.1080/08958378.2021.2002480