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, 33 (4), 333-342

A 90-Day Inhalation Toxicity Study of Ethyl Formate in Rats

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A 90-Day Inhalation Toxicity Study of Ethyl Formate in Rats

Mi Ju Lee et al. Toxicol Res.

Abstract

Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and is suggested as a potential fumigant for stored crop and fruit. Its primary contact route is through the respiratory tract; however, reliable repeated toxicological studies focusing on the inhalation route have not been published to date. Therefore, the present study was conducted to investigate the safety of a 90-day repeated inhalation exposure in rats. Forty male and 40 female rats were exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330, and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body weights, food consumption, urinalysis, hematologic parameters, serum chemistry measurements, organ weights, necropsy, and histopathological findings were compared between the control and ethyl formate-exposed groups. Locomotor activity decreased during exposure and recovered afterward in male and female rats exposed to 1,320 ppm ethyl formate. Body weight and food consumption continuously decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3 compared with the control values. The increases in adrenal weight and decreases in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm. Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal tissue, or both were noted in the male and female rats at 1,320 ppm and female rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl formate-induced changes were not observed in male and female rats at 330 and 66 ppm, respectively. This indicates that exposure to ethyl formate at concentrations below 66 ppm for 90 days is relatively safe in rats. This is the first report of a full-scale repeated inhalation toxicity assessment in rats and could contribute to controlling occupational environmental hazards related to ethyl formate.

Keywords: 90-day repeated inhalation toxicity; Ethyl formate; Occupational health.

Conflict of interest statement

CONFLICT OF INTEREST The authors declare that there are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Changes in body weight in (A) male and (B) female rats exposed to ethyl formate over time. Body weight was measured weekly for 13 weeks. Black squares, blank squares, triangles, and circles indicated mean values of 0, 66, 330, and 1,320 ppm ethyl formate groups, respectively. *p< 0.05 and **p< 0.01.
Fig. 2
Fig. 2
Changes in food consumption of (A) male and (B) female rats exposed to ethyl formate over time. Food consumption was calculated weekly for 13 weeks. Black squares, blank squares, triangles, and circles indicated the mean values of 0, 66, 330, and 1,320 ppm ethyl formate groups, respectively. *p< 0.05 and **p < 0.01.
Fig. 3
Fig. 3
Histopathological alterations in the nasopharyngeal tissue of rats exposed to (C)-(F) 1320 ethyl formate and (A), (B) control. (A), (B) Olfactory epithelium of rats exposed to fresh air was intact (for line 1) while that of rats exposed to 1,320 ppm ethyl formate showed (B), (C) degeneration characterized by cilia loss (arrow), disarrangement of the cellular organization (line 2), atrophy (line 2), and apoptosis (arrow) and (D), (F) squamous metaplasia (line 3). Magnification: (A), (C), (E) × 200, (B), (D), (F) × 400. Scale Bar (A), (C), (E) 100 μm, (B), (D), (F) 50 μm. Hematoxylin and eosin (H&E) staining.

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