Bruce A. Burgess

1-methyl-2-pyrrolidone (nmp): reproductive and developmental toxicity study by inhalation in the rat

A two-generation reproduction study with a developmental toxicity component was conducted. For the reproduction phase, male and female rats inhaled 0, 10, 51, or 116 ppm NMP daily for 6 hr/day, 7 days/week from 34 days of age to the end of the mating period for the males (100 exposure days) and till weaning for the females (about 143 exposure days, but interrupted from Day 20 of gestation to Day 4 Postpartum). On Day 70 postpartum, one male and one female selected from each litter later mated with newly obtained, nonexposed adults of the opposite sex to produce an F2 generation. For the developmental phase, rats of both sexes inhaled 0 or 116 ppm NMP as outlined above, but euthanization of the females occurred on Day 21 of gestation followed by fetal examination for structural alterations. The indices of reproductive performance for the NMP-exposed rats did not differ significantly from those obtained for the control rats. Rats exposed to 116 ppm had a detectable decrease in response to sound. No other signs of NMP-related toxicity were detected among the parental rats. An exposure-related but slight decrease in fetal weight was detected only among the F1 offspring whose parents both inhaled NMP at 116 ppm. This slight effect also appeared at birth among the pups of the reproductive phase where it persisted till 21 days after birth when NMP inhalation by the mother ceased. Thereafter, the body weight of the offspring was comparable to the control values. No detectable or developmental effects appeared in the 10 or 51 ppm groups.

The embryo-fetal toxicity and teratogenic potential of ammonium perfluorooctanoate (APFO) in the rat.

Ammonium perfluorooctanoate (APFO, greater than 95% pure) was administered to Sprague-Dawley rats from Days 6 through 15 of gestation by inhalation as a dust (whole body exposure) for 6 hr/day at 0, 0.1, 1, 10, and 25 mg/m3, or by gavage at 100 mg/kg body wt/day in corn oil. Maternal deaths occurred in the groups given the highest level of APFO by each route and overt toxicity was evident among the surviving dams of these groups and among those of the 10-mg/m3 group. The fetuses were examined for external, visceral, and skeletal alterations and for APFO-related macroscopic and microscopic alterations of the eyes. In the postpartum period, pups from additional control and experimental dams were examined externally and ophthalmoscopically, and the usual fertility and viability indices were calculated. A teratogenic response was not demonstrated. Toxic effects on the conceptus were noted only in the groups given the highest level of APFO by each route. Hence, APFO was not demonstrated to represent a unique hazard to the conceptus of the rat.

Inhalation studies in rats exposed to dimethylacetamide (DMAc) from 3 to 12 hours per day

Male rats were exposed by inhalation from 10 to 300 ppm Dimethylacetamide (DMAc) for either 3, 6, or 12 hrs/day for a total of 10 exposures (5 exposures, 2 rest days, 5 exposures). Rats were observed daily for signs of DMAc-related effects, growth was monitored by body weights, clinical laboratory tests and microscopic examination of the liver, testes epididymides, and nasal passages were conducted. One half of the rats in each group was allowed a 14-day post-exposure period to evaluate the reversibility of DMAc-induced changes. No clinical signs of toxicity or DMAc-related gross changes at necropsy were seen in any of the rats although 1 rat exposed to 300 ppm for 12 hours per day died following the seventh exposure. Slight (< 5%) decreases in body weight gain were seen in rats exposed to 300 ppm for 6 or 12 hrs/day. Serum cholesterol levels were elevated in rats exposed to either 100 or 300 ppm (all exposure durations) and in rats exposed to 30 ppm for 12 hours. Total serum protein concentrations were increased in rats exposed for 12 hours/day to either 30, 100, or 300 ppm. Hepatocellular hypertrophy together with margination of hepatocellular cytoplasmic contents and lipid-like cytoplasmic vacuolation in hepatocytes were seen microscopically only in rats exposed for 12 hours/day to 300 ppm. Recovery from these liver changes was not complete after 14-day post-exposure period. No evidence of either testicular damage or irritation to the upper respiratory tract was seen.

Inhalation Toxicology of Trimethylamine

AbstractTrimethylamine (TMA) is a pungent gas that occurs in nature and has many industrial applications, including use as an intermediate in the manufacture of many chemicals. The lowest lethal concentration following a single 4-h inhalation exposure was determined to be 3500 ppm. Croups of 70 male rats each were then exposed by nose-only inhalation 6 h/d, 5 d/wk for 2 wk to either 0 (control), 75, 250, or 750 ppm TMA. Rats were sacrificed either immediately following exposure or following a 14-d recovery period. Parameters investigated included in-life observations and body weights, clinical pathology, and histopathology with organ weights. Exposure to 750 ppm produced a decreased rate of weight gain in rats. Evidence of mild, reversible, polycytnemia was also seen in these rats. Effects of TMA were present in the nose, trachea, and lungs. Degenerative changes in the nose were reversible at 75 ppm, but not at 250 or 750 ppm. Mild emphysematous alveoli were seen in lungs of rats exposed to 750 ppm immedi...

Inhalation Toxicology of 1,4-Butanediol

Abstract1,4-Butanediol is a clear, slightly viscous liquid with a low vapor pressure used in manufacturing polyester glycols and polyurethanes. The material has a low order of acute inhalation toxicity with a 4-h ALC of 15 mg/l in male rats. In the repeated dose study, groups of 10 male Crl:CD rats were exposed nose-only, 6 h/day, 5 days/wk for 2 wk to aerosol concentrations of either 0, 0.20, 1.7, or 5.2 mg/l. Rats were given pathological, urinalysis, and clinical chemical examinations after the last (tenth) exposure and after a 2-wk recovery period. No adverse effects were observed in rats exposed to either 0.20 or 1.1 mg/l. Rats exposed to 5.2 mg/l had depressed body weight evident after the third exposure. After 10 exposures, these rats had increased erythrocyte count and hematocrits and decreased serum cholesterol concentrations. Pathological examination showed slight atrophy of lymphoid cells in the thymus and depressed mean heart weights in these rats. No adverse effects were observed after 2 wk of...

2-week inhalation study of N-monomethylformamide in rats.

N-Monomethylformamide (MMF) is a chemical intermediate with potential for inhalation exposure in humans. Human exposures to MMF have occurred in cancer chemotherapy but have been limited due to liver damage. To assess the toxicity of MMF, groups of 15 male rats each were exposed by nose-only inhalation, 6 hr/day, 5 days/week, for 2 weeks to either 0 (control), 50, 130, or 400 ppm MMF. Five rats per group were killed following the 10th exposure, five were killed after a 14-day postexposure recovery period, and five rats were used to determine urinary MMF excretion. Parameters investigated were clinical observations and body weights, clinical pathology, and gross and microscopic pathology including organ weights. Liver damage occurred in rats exposed to either 130 or 400 ppm. This was detected both by increases in serum enzyme activity indicative of liver injury and by microscopic changes in the liver. The changes were more severe in the 400-ppm rats and were partially reversible. Other organs were not adversely affected by inhalation of MMF. The amount of MMF excreted in the urine was dependent on the exposure concentration and MMF was present 14 days postexposure at the higher exposure levels. The no-observed-effect level under the conditions of this experiment was 50 ppm.

Inhalation Toxicity of Methyl Difluoromalonyl Fluoride in Rats

Methyl 2,2-difluoromalonyl fluoride (MMF) is highly toxic by inhalation producing mortality in rats exposed for 4 hours to 0.55 mg/L. Repeated inhalation exposures of rats to 0.009 mg/L produced irritation but no other signs of a toxic response. Mortality was encountered following repeated exposures to 0.066 mg/L.

Inhalation Toxicology of ρ-Nitrobenzylchloride

Abstractρ-Nitrobenzylchloride (p-NBC, G4S no. 700–74–7) was tested for its inhalation toxicity to rats following both single and repeated exposures. One of 6 rats exposed a single time to 280 mg/m3 died, as did 4 of 6 exposed to 7300 mg/m3. The material is considered moderately toxic following acute inhalation. The only adverse response in rats exposed to 6 mg/m3, 6 h/day, 5 days/wk for 2 wk was irritation to the nasal epithelium. Rats exposed to 20 mg/m3 showed decreased rate of weight gain, altered liver enzyme activity without anatomic pathology, and irritation of the nasal cavity. Rats exposed to 60 mg/m3 did not tolerate the exposure regimen, with 2 of 10 rats dying. The number of exposures in this group was reduced from 70 to 7. These rats showed evidence of distress (weight loss, lethargy, breathing difficulties) as exposures continued. The target tissues at this concentration were the nasal and tracheal epithelium, with the lesions being more pronounced than seen at the lower concentrations tested...