Methyl salicylate (MS) is used as a fragrance and flavoring agent, but is lethal at sufficient doses, and is teratogenic in rodents. MS was tested to update and expand the reproductive toxicity database, and used, in part, as a known positive: this is the second of two simultaneous studies conducted at different laboratories, using the RACB protocol and Swiss mice. Food and water consumptions, clinical signs,and body weights were used in the Task 1 dose-range-finding study to set doses for the continuous cohabitation phase (Task 2) at 25, 50, and 100 mg/kg/d by gavage in corn oil.
Deaths occurred at a rate of 2, 1, 5, and 3 mice in the control to high dose groups, respectively. Some of these deaths were apparently due to gavage trauma; the cause of death was not determined in the remaining cases.
MS exposure had no effect on parental body weights or clinical signs.
There was no adverse effect of MS exposure on the reproductive endpoints measured in Task 2. Since there were no treatment-related changes, no Task 3 was conducted.
The last litter in Task 2 from the control and high dose groups was reared by the dams until weaning (pnd 21), and then dosed with MS until the Task 4 mating at nearly equal to pnd 74. There were no reductions in pup viability or weight during nursing, and no differences between treated and control mice before and during the week of mating in Task 4.
In the single mating that comprises Task 4, there were no MS-related changes in the number of pups/litter, their viability or sex ratio, or their body weight adjusted for litter size.
After the F2 litters were evaluated, all animals were killed, and the F1 adults necropsied. For males and females, there were no effects on body weights or organ weights. The percent motile, density, and percent morphologically abnormal endpoints were all unchanged for epididymal sperm. No estrous cyclicity evaluation was performed.
At the doses used for this study (which were 20% the dose used in the previous positive study), MS caused no adverse effects on body weight or reproductive indices in either the first or second generation.
NTIS #PB84241140