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13-week inhalation toxicity study of dimethylformamide (DMF) in cynomolgus monkeys
M E Hurtt1, M E Placke, J M Killinger
1Du Pont, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware 19714.
Abstract:
This study was conducted to assess the subchronic inhalation toxicity of dimethylformamide (DMF) in the cynomolgus monkey. Particular attention was paid to the liver since DMF has been shown to produce liver damage in rodents, dogs, and humans. Groups of three cynomolgus monkeys/sex/group received whole-body exposures for 6 hr/day, 5 days/week for 13 weeks to 0, 30, 100, or 500 ppm DMF. Evaluations for toxicity included body and organ weights, clinical observations, hematology, serum chemistry, urinalysis, and gross and microscopic examinations. Clinical laboratory evaluations were conducted twice prior to the start of the study at exposure weeks 2, 4, 8, and 12 and at necropsy. Semen, collected from male monkeys three times prior to the start of the study and weekly during the course of the study, was analyzed for sample volume, sperm count, motility, and morphology. In addition, daily vaginal swabs were obtained from all females prior to exposure to determine mean menses cycle length. Although there was a slight trend toward increased cycle length, this trend could not be definitely attributed to compound exposure. Based on extensive monitoring of the monkeys' clinical condition, semen quantity and quality, and clinical and pathological evaluations, no exposure-related adverse health effects were detected following exposure to concentrations of DMF ranging from 30 to 500 ppm for 13 weeks.
Insights
Dimethylformamide (DMF) inhalation toxicity was assessed in cynomolgus monkeys over 13 weeks. No adverse health effects were observed in monkeys exposed to DMF up to 500 ppm, indicating a low toxicity profile.
Area of Science:
- Toxicology
- Primate Studies
- Inhalation Exposure
Background:
- Dimethylformamide (DMF) is known to cause liver damage in various species, including humans.
- Assessing DMF toxicity in non-human primates is crucial for understanding potential human health risks.
- Cynomolgus monkeys are a relevant model for subchronic inhalation toxicity studies.
Purpose of the Study:
- To evaluate the subchronic inhalation toxicity of dimethylformamide (DMF) in cynomolgus monkeys.
- To identify potential target organs and adverse effects, with a focus on the liver.
- To establish a safe exposure level for DMF in this primate model.
Main Methods:
- Groups of cynomolgus monkeys (3/sex/group) underwent whole-body exposure to 0, 30, 100, or 500 ppm DMF for 6 hours/day, 5 days/week, over 13 weeks.
- Comprehensive toxicity assessments included clinical observations, body/organ weights, hematology, serum chemistry, urinalysis, and gross/microscopic examinations.
- Reproductive parameters in males (semen analysis) and females (menstrual cycle length) were monitored throughout the study.
Main Results:
- No exposure-related adverse health effects were detected across all measured parameters.
- No significant changes in clinical condition, hematology, serum chemistry, or urinalysis were observed.
- Semen analysis and menstrual cycle length showed no compound-related alterations, despite a slight, non-attributable trend in cycle length.
Conclusions:
- Subchronic inhalation exposure to dimethylformamide (DMF) up to 500 ppm for 13 weeks did not result in adverse health effects in cynomolgus monkeys.
- The liver, a known target organ in other species, did not show any DMF-induced damage in this study.
- Cynomolgus monkeys demonstrate a low susceptibility to the toxic effects of inhaled DMF under these experimental conditions.