Subchronic inhalation toxicity of 1,3,5-trichlorobenzene.

Male and female rats were exposed to 0, 10, 100 or 1000 mg/m3 of 1,3,5-trichlorobenzene vapors for 6 hours daily, 5 days a week, for up to 13 weeks. After 4 and 13 weeks of exposure, animals were sacrificed and examined for changes in blood, clinical chemistry, internal organs, and tissues resulting from the 1,3,5-trichlorobenzene treatment. No treatment-related effects on the blood and clinical chemistry were evident. The only effects that were considered treatment-related were a squamous metaplasia and hyperplasia in the respiratory epithelium in the nasal passages of high-dose rats and the increased incidence of dried red material on the faces of these rats during exposures compared with other groups.

Short-term oral toxicity of 2,4,6-trinitrotoluene in mice, rats, and dogs.

The short-term oral toxicity of 2,4,6-trinitrotoluene (alpha-TNT) was determined in dogs, rats, and mice. Single-dose oral LD50s for alpha-TNT in corn oil were 1320 and 794 mg/kg in male and female rats, respectively, and 660 mg/kg in both male and female mice. For multiple-dose studies, dogs were dosed daily for up to 13 wk with alpha-TNT at 0, 0.2, 2.0, or 20 mg/kg by capsule; rats received 0, 0.002, 0.01, 0.05, or 0.25% and mice received 0, 0.001, 0.005, 0.025, or 0.125% alpha-TNT in their diets over the same period. All species receiving the highest doses exhibited anemia, with reduced erythrocytes, hemoglobin, and hematocrit. Alterations were observed in organ weights, including enlarged spleens (accompanied by hemosiderosis) and livers, and depressed body weight and/or body weight gain (temporary in dogs and mice). Alterations in clinical chemistry values included elevated cholesterol and depressed serum glutamicpyruvic transaminase activity in dogs and rats; no effect on serum glutamic-oxaloacetic transaminase activity was observed. Some effects, such as SGPT depression in rats, appeared after 13 wk, suggesting a cumulative toxicity. Reduced testes size was observed in rats at the highest dose regardless of length of exposure. Most of the toxic effects were reversible, but testicular atrophy was not in rats allowed a 4-wk recovery period after treatment. Signs of anemia were present at intermediate dose levels. "No observable effects" levels for alpha-TNT were: dogs, 0.20; rats, 1.42; and mice, 7.76 mg/kg . d.

Single-dose and repeated-exposure toxicity of a complex wastewater from munitions manufacturing plants.

The single-dose and repeated-exposure toxicity of a synthetic mixture of 30 nitrotoluene analogs, representative of a complex industrial wastewater termed condensate water, was evaluated in dogs, rats, and mice. The single-dose oral LD50s for the synthetic condensate water (CW) were 447 and 295 mg/kg in male and female rats, respectively. In the repeated-exposure studies, dogs were given 0, 0.05, 0.5, or 5 mg of CW per kilogram of body weight by capsule daily for 26 wk. Rats and mice received 0, 0.001, 0.01, or 0.1% of this mixture in their diet for 4 or 13 wk. Groups of each rodent species were set aside for 4 wk to assess recovery. The most notable findings were a compensatory anemia with reticulocytosis (severe in rats), Heinz body formation, and related blood cell abnormalities and hemosiderin in the spleen; pigmentation in the liver cells; atrophy and aspermia in the testes; hyperplasia and inflammation in the female reproductive organs; and neurotoxic signs at the high doses. Rats and mice also experienced food intake and body weight depression and exhibited some alterations in organ weights (spleen, testes, and liver). The findings were referable principally to the two major components 2,4,- and 2,6-dinitrotoluene, but the "no observable effects" levels were lower for the mixture.

Short-term oral toxicity of a 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine mixture in mice, rats, and dogs.

The oral toxicity of a mixture of 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine (1:0.62, w/w) compounds typically found in munitions plant effluents, was evaluated in mammalian species. Single-dose oral LD50s of the mixture were 574 and 594 mg/kg in male and female rats and 947 and 1130 mg/kg in male and female mice, respectively. Long dispersion periods during preparation or ultraviolet irradiation of the mixture lowered the LD50s. In repeated-exposure studies, dogs were given 0.50, 5.0 or 50 mg/kg X d by capsule for up to 90 d. Rats and mice were fed the mixture in the diet at 0.005, 0.05, or 0.5% for 90 d; mice were also fed at 0.25%. Mortality resulted at the highest dose level in each species. All three species showed depression of body weight or body weight gain, depressed food intake, moderate to severe anemia, and alterations in the spleen (hemosiderosis), liver (hepatomegaly), and testes (atrophy) at the highest dose levels. Cholesterol was elevated in rats and dogs after 90 d. Several species differences were also noted. Uric acid values were elevated in rats but not in dogs, serum glutamic-pyruvic transaminase (SGPT) activity was low in dogs but unchanged in rats, and rats developed hypoplasia of the uterus but dogs did not. Signs of anemia were present at the intermediate dose levels. The lowest dose level in all three species was designated at a "no observable effects" level, based on the absence of clearly treatment-related effects. In a 4-wk study, the irradiated mixture fed to rats at 0.003, 0.03, or 0.3% in the diet was less toxic than the unirradiated mixture.

Rapid hepatoma induction in rats by dipentylnitrosamine and its modification by other carcinogens.

Dipentylnitrosamine (DPN), administered in the diet at a concentration of 2,000 ppm to Fischer-344 rats, produced hepatomas in 27% of both males and females within 8 weeks. Bile-duct carcinomas were also produced. All animals also showed liver nodular hyperplasia and bile-duct cell proliferation. Feeding DPN at 1,500 ppm produced hepatomas or bile-duct carcinomas in 7% of the males and varying degrees of nodular hyperplasia and duct cell proliferation after 8 weeks of feeding. The total cumulative dose after feeding 2,000 ppm DPN was of the order of 7,700 mg/kg body weight in males and 8,200 mg/kg in females. There was a 28% weight decrement in animals feed 2,000 ppm DPN when compared to controls but no mortality. DPN carcinogenicity was enhanced when DPN was combined with a liver carcinogen, cycasin (fed as cycad not flour, equivalent to 160 ppm cycasin). No effect on DPN carcinogenicity was found in rats fed DPN and lasiocarpine, another known liver carcinogen with antimitotic activity. Neither was there any effect of DPN carcinogenicity in rats fed DPN and N-butyl-N-(4-hydroxybutyl) nitrosamine or N-methyl-N'-nitro-N-nitrosoguanidine. In contrast, the trisodium salt of nitrilotriacetic acid reduced the hepatocarcinogenic action of DPN. The enhancement of DPN carcinogenicity with cycasin is compatible with the hypothesis that DPN-induced liver cell populations (hyperplastic nodules) can resist the cytotoxic effect of cycasin and differentiate rapidly towards hepatomas, while other areas of the liver are suppressed.

Comparison of segmented polyether urethane with polyethylene IUDs in rabbits.

A segmented polyether urethane IUD was compared with a polyethylene IUD in rabbits. The contraceptive efficacy of urethane IUDs was excellent. Moreover, the purulent slippery deposit present with the polyethylene IUDs and observed by Davis et al. (1) was absent. Our studies indicate that the polyether urethane IUDs have a high degree of antifertility activity in rabbits and these IUDs have reduced inflammatory response, based on leucocytic infiltration and tissue debris in the uterine lumen. It is suggested that polyether urethane IUDs not requiring copper or other medication can be designed for high contraceptive efficacy, intrauterine compatibility and with the necessary rigidity for proper uterine retention in humans.

Tumorigenic activity of lead chromate.

Lead chromate was investigated for its carcinogenic potential in both rats and mice. Results show that this compound is a very potent carcinogen in rats when administered i.m. Sixty-four % of the animals treated developed malignant tumors at the injection site. Three renal carcinomas were also found after i.m. treatment with lead chromate. Since lead powder is a comparatively weak carcinogen in rats, whether given p.o. or i.m., it is suggested that the combination of lead and chromium (also weak carcinogen) accounts for the high carcinogenic activity of lead chromate in rats. Swiss albino female mice could not tolerate the same high dose level as did the rats; at the lower dose administered to the mice, no tumors were detected.