Whole-body inhalation exposure to 2-ethyltoluene for two weeks produced nasal lesions in rats and mice
Madelyn C. Huang, Cynthia J. Willson, Sridhar Jaligama, Gregory L. Baker, Alan W. Singer, Yu Cao, Jessica Pierfelice, Esra Mutlu, Brian Burback, Guanhua Xie, David E. Malarkey, Barney Sparrow, Kristen Ryan, Matthew Stout, and Georgia K. Roberts
Inhalation Toxicology (2021) DOI:
https://doi.org/10.1080/08958378.2021.2002480
DOI:
https://doi.org/10.22427/NTP-DATA-002-03356-0005-0000-4
Publication
Abstract
Objective: 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.
Methods: Time-mated Hsd:Sprague DawleyVR SDVR 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 ¼ 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 ¼ 5/exposure/sex) were exposed to the same concentrations for 2 weeks.
Results and Discussion: 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.
Conclusion: 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.
Short-Term
2-Week Perinatal Study Tables - Rats
- I01 - Animal Removal Summary (99KB)
- I02 - Animal Removals (560KB)
- I03 - Growth Curve (1MB)
- I03C - Growth Curve (1MB)
- I04 - Mean Body Weight Summary (168KB)
- I04G - Mean Body Weight Gain (146KB)
- I05 - Clinical Observation Summary (282KB)
- I05P - Pup Clinical Observations Summary (137KB)
- PA02 - Neoplastic Lesions Summary with Percent Incidence (453KB)
- PA03 - Nonneoplastic Lesion Summary with Percent Incidence (423KB)
- PA05 - Incidence Rates of Neoplastic Lesions with Systemic Lesions Abridged (454KB)
- PA06 - Organ Weights Summary (84KB)
- PA10 - Statistical Analysis of Nonneoplastic Lesions (459KB)
- PA14 - Individual Animal Pathology Data (1MB)
- PA18 - Incidence Rates of Nonneoplastic Lesions by Anatomic Site with Average Severity Grade (423KB)
- PA46 - Summary of Gross Pathology (460KB)
- R01 - Multigeneration Cross Reference (1MB)
- R02 - Reproductive Performance Summary (46KB)
- R03 - Summary of Litter Data (91KB)
- R19 - Pup Mean Body Weight Summary (203KB)
- R19C - Pup Growth Curve (810KB)
- R19G - Pup Mean Body Weight Gain (169KB)
2-Week Perinatal Individual Animal Data - Rats
- Individual Animal Body Weight Data (48KB)
- Individual Animal Clinical Observations Data (88KB)
- Individual Animal Gross Pathology Data (227KB)
- Individual Animal Histopathology Data (34KB)
- Individual Animal Litter Data (62KB)
- Individual Animal Organ Weight Data (11KB)
- Individual Animal Pup Body Weight Data (129KB)
- Individual Animal Pup Clinical Observations Data (186KB)
- Individual Animal Removal Reasons Data (11KB)
- Individual Animal Reproductive Performance Data (8KB)
- Individual Animal Tissue Concentration Data (19KB)
2-Week Study Tables - Mice
- I01 - Animal Removal Summary (50KB)
- I02 - Animal Removals (298KB)
- I03 - Growth Curve (431KB)
- I03C - Growth Curve (441KB)
- I04 - Mean Body Weight Summary (119KB)
- I04G - Mean Body Weight Gain (72KB)
- I05 - Clinical Observations Summary (108KB)
- PA02 - Neoplastic Lesion Summary with Percent Incidence (269KB)
- PA03 - Nonneoplastic Lesion Summary with Percent Incidence (248KB)
- PA05 - Incidence Rates of Neoplastic Lesions with Systemic Lesions Abridged (270KB)
- PA06 - Organ Weights Summary (84KB)
- PA14 - Individual Animal Pathology Data (907KB)
- PA18 - Incidence Rates of Nonneoplastic Lesions by Anatomic Site with Average Severity Grade (248KB)
- PA46 - Summary of Gross Pathology (237KB)
2-Week Individual Animal Data - Mice
- Individual Animal Body Weight Data (14KB)
- Individual Animal Clinical Observations Data (34KB)
- Individual Animal Gross Pathology Data (129KB)
- Individual Animal Histopathology Data (27KB)
- Individual Animal Organ Weight Data (10KB)
- Individual Animal Removal Reasons Data (7KB)
- Individual Animal Tissue Concentration Data (19KB)
Related Publications
Georgia K. Roberts, Cynthia J. Willson, Dorian S. Olivera, David E. Malarkey & Daniel L. Morgan (2017) Comparative inhalation toxicity of ethyltoluene isomers in rats and mice, Inhalation Toxicology, 29:12-14, 577-585, DOI: https://doi.org/10.1080/08958378.2018.1430190