Mutagenic evaluations of two rubber accelerators

Because of evidence of mutagenic activity in certain short-term in vitro assays (unpublished data) N-oxydiethylene thiocarbamyl- N-oxydiethylene sulfenamide (OTOS) and N-oxydiethylene-2-benzothiazole sulfenamide (OBTS) were studied to determine their potential to induce dominant lethal mutations. For 56 consecutive days OTOS (0, 6.25, 12.5, or 25 mg/kg) or OBTS (0, 125, 250, or 500 mg/kg) was administered by gavage to groups of male Sprague-Dawley rats, while the negative control received corn oil. Each male then was mated with two virgin females in each of two successive 1-week periods. A positive control group was given triethylenemelamine (TEM, 0.25 mg/kg) in a single ip dose 1 day prior to mating. A significant depression in body weight gain (24.8%) was observed at the highest dose for OTOS (25 mg/kg). No effect on body weight was noted for OBTS at doses as high as 500 mg/kg. Although sequalae were observed in the OBTS top-dose animals during the test period, none were ascribed clearly to the test material. Similar pregnancy rates (70 to 100%) were observed for the concurrent negative and positive controls and for all test groups of both chemicals. In the TEM controls for both compounds, the number of implantation sites and preimplantation losses were significantly decreased, and the number of early fetal deaths per pregnant female were significantly elevated. However, both OTOS and OBTS failed to produce dominant lethal mutations. The absence of a response emphasized the difficulty in using in vitro and in vivo mutagenic assays as predictors of mutagenesis in man.