The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
1-Chloro-2-propanol (1CP), a chemical that is a widely used synthetic intermediate and is also formed in foods following fumigation with propylene oxide, was tested for its effects on reproduction and fertility in Sprague-Dawley rats using the RACB protocol. This was stimulated by preliminary reproductive data that showed a decrease in epididymal weight, an increase in sperm abnormalities, and a change in estrous cycle in rats dose for 90 days with 1CP. Data from a two week dose-range-finding study (Task 1) were used to set exposure concentrations for the Task 2 continuous cohabitation study at 0.0, 0.03, 0.065, and 0.13% in drinking water. These concentrations produced estimated exposures of nearly equal to 30, 65, and 100 mg/kg/d.
In the F0 animals in Task 2, one control, 1 low dose, and 1 high dose female died; two from kidney problems, and the remaining cause of death was undetermined. There was no change in the number of litters/pair, or the number or weight of live pups/litter. The high dose females took 2 days longer than controls to deliver their last litter; the biological significance of 116 days (control) vs. 118 days is questionable. Post-partum dam weights were reduced for the middle dose (by nearly equal to 7%) and high dose females (by nearly equal to 15%); low dose females were reduced, but not significantly so. Sire weights were reduced only at the high dose (by nearly equal to 7%). This is consistent with the 10% and 30% reduction in water consumption measured for the middle and high dose animals, respectively.
The last litter from all groups was reared by the dams until weaning at pnd 21. While pup viability was unaffected by 1CP consumption, pup weight was reduced by nearly equal to 9% and nearly equal to 20% at the middle and high dose levels, respectively.
No F0 crossover test was conducted since no reproductive changes were observed for the first generation rats.
Task 4 was conducted with the control and high dose rats. At the time of mating, body weights were reduced by 14% for males and 11% for females. Despite this difference, there were no differences between the 2 groups in reproductive parameters: both groups delivered equivalent number of litters, numbers of live pups/litter, and the viability and weight of those pups was unchanged by 1CP exposure.
After the F2 pups were evaluated and removed, the F1 control and high dose adults were killed and necropsied. For males, body weight was reduced (see above), relative kidney weights increased by 7% in males. Absolute testis weight was 8% lower in 1CP-treated males while relative epididymis weight was increased by 8%. The proportion of abnormal sperm in control rats was 0.78% and the exposed value was 2.4%, a significant increase, but within the historical range. Female body weight was reduced by nearly equal to 11%, relative kidney weight was increased by nearly equal to 8%, and estrous cycle length was unchanged.
These data show that even in the presence of 1CP sufficient to limit water consumption by approximately 30% and to produce significant differences in body weight, 1CP caused no adverse effects on fertility in either generation. The statistically significant effects on testis weights and sperm abnormalities may indicate very slight reproductive toxicity. No effects were observed in females.
NTIS # PB91158469