Ragan Ha

Toxicity of inhaled chloroprene (2-chloro-1,3-butadiene) in F344 rats and B6C3F1 mice

Chloroprene (2-chloro-1,3-butadiene) is a high production chemical used almost exclusively in the production of polychloroprene (neoprene) elastomer. Because of its structural similarity to isoprene (2-methyl-1,3-butadiene) and to 1,3-butadiene, a potent trans-species carcinogen, inhalation studies were performed on chloroprene to characterize its toxicological potential and to provide a basis for selecting exposure concentrations for chronic toxicity and carcinogenicity studies. Thirteen-week inhalation toxicology studies were conducted in male and female F344 rats and B6C3F(1) mice at exposure concentrations of 0, 5, 12, 32 or 80 ppm (6 h/day; 5 days/week). A 200 ppm exposure group was also included for rats only, because a previous study showed that this concentration of chloroprene is lethal to mice. In mice, exposure to 80 ppm chloroprene caused a marginal decrease in body weight gain in males and epithelial hyperplasia of the forestomach in males and females. This lesion has been observed in mice exposed to isoprene or 1,3-butadiene. In rats, exposure to 80 ppm chloroprene or higher concentrations caused degeneration and metaplasia of the olfactory epithelium and exposure to 200 ppm caused anemia, hepatocellular necrosis and reduced sperm motility. These lesions have not been observed in rats exposed to isoprene or 1,3-butadiene. The profile of toxic effects of chloroprene is considerably different from that of isoprene or 1,3-butadiene; this may be due to differences in exposure concentrations that were used in toxicology studies of these compounds and /or to the influence of the chlorine substitution on the toxicokinetics of these compounds, on their biotransformation, or on the reactivity of metabolic intermediates with tissue macromolecules.

Inhalation toxicity and carcinogenicity of isoprene in rats and mice: comparisons with 1,3-butadiene

As with 1,3-butadiene (BD), inhalation exposure of B6C3F1 mice to isoprene (2-methyl-1,3-butadiene) caused a macrocytic anemia; induced increases in sister chromatid exchanges in bone marrow cells and in levels of micronucleated erythrocytes in peripheral blood; and produced degeneration of the olfactory epithelium, forestomach epithelial hyperplasia, and testicular atrophy. Most notable was the finding that like BD, isoprene induced neoplasms in the liver, lung, Harderian gland, and forestomach of mice. The carcinogenic effects of isoprene were observed after a 26-week exposure (6 h/day, 5 days/week) of male mice to 700 ppm or higher concentrations of isoprene followed by a 26-week recovery period. Unlike BD, isoprene did not induce lymphomas or hemangiosarcomas of the heart in mice under these conditions nor did it induce chromosomal aberrations in mouse bone marrow cells. No toxicological effects were evident in rats exposed for 13 weeks to either isoprene or BD at concentrations up to 7000 ppm or 8000 ppm, respectively. Interstitial cell hyperplasia of the testis was observed in male F344 rats exposed to 7000 ppm isoprene for 26 weeks, and following a 26-week recovery period, there was a marginal increase in benign testicular interstitial cell tumors.

Impaired renal function in owl monkeys (Aotus nancymai) infected with Plasmodium falciparum

Impaired renal function was observed in sixteen Aotus nancymai 25 and 3 months following infection with the Uganda Palo Alto strain of Plasmodium falciparum. Decrease were noted in the clearance of endogenous creatinine, creatinine excretion, and urine volume while increases were observed in serum urea nitrogen, urine protein, urine potassium, fractional excretion of phosphorus and potassium, and activities of urinary enzymes. The results were suggestive of glomerulonephropathy and chronic renal disease.

Serum and urine biochemical diversity among wild-caught and colony-born Aotus nancymae

Serum and urine analytes were compared between adult wild‐caught and adult colony‐born owl monkeys (Aotus nancymae), to determine if normative clinical pathology data were similar. Significant differences (P ≤ 0.05) were noted in serum protein, glucose, sodium, urine calcium, calcium clearance, and fractional clearance of calcium between the two groups. The results suggest that reference data for feral owl monkeys is not completely applicable to colony‐born animals, however, the differences are too small to be of clinical significance.

SERUM AND URINE BIOCHEMICAL DIVERSITY AMONG ADULT WILD-CAUGHT AOTUS NANCYMAE AND SAIMIRI PERUVIENSIS

Serum and urine analytes were compared between adult wild‐caught owl monkeys (Aotus nancymae) and adult wild‐caught squirrel monkeys (Saimiri peruviensis) to determine if normative clinical pathology data were similar. An objective of the study was to confirm that species of neotropical primates are distinct with regard to physiologic parameters, and should not be considered interchangeable in biomedical research. Significant differences (P < 0.05) were noted in many serum and urine analytes between the two groups. The results suggest that reference data for wild‐caught owl monkeys are not applicable to squirrel monkeys, and the differences are sufficiently large to be of clinical significance. These findings illuminate the diversity among species of neotropical primates.