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Subchronic inhalation toxicity of dimethylformamide in rats and mice
Abstract:
Fisher F344 rats and B6C3F1 mice were exposed to concentrations of 0, 150, 300, 600 and 1200 ppm of dimethylformamide (DMF) for 6 hours a day, 5 days a week for 12 weeks. Detailed clinical observations were obtained weekly and body weights biweekly on all animals. Clinical chemistry and hematology evaluations were made on all rats and approximately half the mice at terminal sacrifice. Gross necropsy examinations were made on all animals. Histopathologic evaluations were conducted on selected tissues of animals of both species at all dose levels. Few overt signs of toxicity were seen in either rats or mice. There was a dose related depression in body weight gain in rats that was significant at the 1200 ppm level from the second week of study onwards. A total of 11 mice died or were sacrificed moribund during the study, 8 from the high dose and 2 from the 600 ppm dose level. Both clinical chemistry (in rats only) and gross necropsy observations, and histopathology of tissues indicate the possibility that liver may be the target in specific organ toxicity. The no-effect DMF dose was below the 150 ppm level for both rats and mice and the maximum tolerated dose was below the 600 ppm level.
Insights
Dimethylformamide (DMF) exposure in rats and mice showed minimal toxicity, with liver as a potential target organ. The no-effect dose was below 150 ppm, and the maximum tolerated dose was below 600 ppm.
Area of Science:
- Toxicology
- Environmental Health
- Occupational Safety
Background:
- Dimethylformamide (DMF) is a widely used industrial solvent with potential health risks.
- Understanding the toxicological profile of DMF is crucial for establishing safe exposure limits.
Purpose of the Study:
- To assess the subchronic toxicity of dimethylformamide (DMF) in Fisher F344 rats and B6C3F1 mice.
- To determine the no-effect level (NOEL) and maximum tolerated dose (MTD) of DMF.
Main Methods:
- Animals were exposed to 0, 150, 300, 600, or 1200 ppm DMF for 6 hours/day, 5 days/week for 12 weeks.
- Clinical observations, body weight, clinical chemistry, hematology, gross necropsy, and histopathology were evaluated.
Main Results:
- A dose-related decrease in body weight gain was observed in rats at 1200 ppm.
- Liver was identified as a potential target organ for DMF toxicity based on clinical chemistry, necropsy, and histopathology findings.
- Mortality was observed in mice at higher DMF concentrations (600 and 1200 ppm).
Conclusions:
- The no-effect DMF dose was below 150 ppm for both rats and mice.
- The maximum tolerated dose of DMF was below 600 ppm.
- DMF exhibits potential target organ toxicity, primarily affecting the liver, at higher exposure levels.