抄録
[2-(2-methoxymethylethoxy)methylethoxy]propanol (tripropylene glycol monomethyl ether, TPGME, CAS No. 25498-49-1) is a type of glycol ether coupling solvent used in diverse industrial applications. TPGME has recently been targeted for screening assessment under the Japanese Chemical Substances Control Law (CSCL); however, public data on its repeated-dose toxicity are limited. Therefore, a combined repeated-dose and reproductive/developmental toxicity study was performed to assess toxicity of TPGME and to fill these data gaps. Male and female Crl:CD(SD) rats were orally administered TPGME at doses of 0, 100, 300, or 1,000 mg/kg/day. No toxicologically significant changes were observed at doses up to 300 mg/kg/day in both sexes. At 1,000 mg/kg/day, females showed clinical signs of neurotoxicity, such as staggering gait, decreased spontaneous locomotor activity, and reduced grip strength, while males exhibited a downward trend in grip strength, decreased serum T4 levels, and α2u-globulin nephropathy. Both sexes showed increased liver weights at this dose. The changes in serum T4 levels were reversible with no corresponding thyroid or liver histopathology. Furthermore, the α2u-globulin nephropathy was rat-specific and deemed irrelevant to human health risk. Given the lack of associated histopathological changes, the increased liver weights were considered adaptive changes. Therefore, these findings of general toxicity were collectively deemed non-adverse. On the other hand, no reproductive or developmental toxicity was observed at any dose tested up to 1,000 mg/kg/day. Based on these findings, the no-observed-adverse-effect level for repeated-dose toxicity was determined at 300 mg/kg/day for both sexes, while that for reproductive and developmental toxicity was at ≥ 1,000 mg/kg/day.
