Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
800 mg/kg bw/day
Additional information

The toxicity of trimethylolpropane (TMP) was determined in combined repeated dose toxicity study with reproduction/developmental toxicity screening test; OECD guideline 422 (MHLW, 1994). TMP was administered by gavage to male and female Slc:SD rats at doses of 0, 12.5, 50, 200 and 800 mg/kg bw/d. Male rats were dosed daily for 45 days, female rats were dosed daily for 14 days prior to mating until day 3 of lactation. There were no effects of the test substance on copulation, fertility or oestrus cycle of the rats. The NOAEL was therefore considered to be 800 mg/kg bw/d.

No evidence of any effects on reproduction were seen in the screening study with the component TMP at a dose level of 800 mg/kg bw/d. The absence of histopathological changes in reproductive organs in repeated dose toxicity studies with TMP and the absence of specific reproductive effects in a screening study indicate that the substance will not have any adverse effects on fertility. By read-across, no effects are predicted for the component DMP. There are currently no data on the repeated dose toxicity of the component CTF, however a testing proposal for a 90-day study is included in this dossier. This study will include full assesssment of relevant reproductive system tissues, and the need for specific testing for reproductive toxicity will be reconsidered in light of the findings in this study. Based on these considerations, no further testing is considered to be required for assessment of reproductive toxicity of Polyol TD at present.


Short description of key information:
No relevant effects were seen in a screening study performed with the component TMP at dose levels of up to and including the highest dose level of 800 mg/kg bw/d. No additional testing is proposed.

Effects on developmental toxicity

Description of key information
The results of a screening study performed with the component TMP do not indicate any potential for developmental toxicity at dose levels of up to and including the highest dose level investigated of 800 mg/kg bw/d.  Testing proposals are included for full developmental toxicity studies with TMP and CTF.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
800 mg/kg bw/day
Additional information

The toxicity of trimethylolpropane (TMP) was determined in combined repeated dose toxicity study with reproduction/developmental toxicity screening test; OECD guideline 422 (MHLW, 1994). TMP was administered by gavage to male and female Slc:SD rats at doses of 0, 12.5, 50, 200 and 800 mg/kg/day. Male rats were dosed daily for 45 days, female rats were dosed daily for 14 days prior to mating until day 3 of lactation. There were no effects on delivery or on the dams during the lactation period. External examination of the pups revealed no increase in the incidence of abnormalities. Body weight gain of pups was normal up to day 4 of the lactation period. Stillborn, dead pups and pups killed on day 4 of lactation showed no abnormal gross lesions attributable to treatment with the test substance. The NOAEL for developmental/reproductive toxicity was 800 mg/kg bw/d.

Testing proposals are included for developmental toxicity studies with the components TMP and CTF; the study with TMP is also intended to cover (by read-across) the developmental toxicity of the other component, DMP.

Justification for classification or non-classification

The results of a screening study with the component TMP do not indicate any potential for developmental or reproductive toxicity. No additional data are available at present. No classification for reproductive or developmental toxicity is therefore proposed under Directive 67/548/EEC or Regulation 1272/2008/EC.