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Description of key information

Test substance (Methyl Polyhydroxymethyl Stearate) was evaluated in a repeated oral gavage study according to OECD TG 422. CD rats were administered 100, 500 or 1000 mg/kg/day. Females were dosed once daily for two weeks prior to breeding, through breeding (two weeks), gestation (three weeks), and through postpartum day 4 or 5. Females were necropsied on postpartum day 5 or 6. Males were dosed two weeks prior to breeding and continuing through breeding (two weeks) until necropsy (test day 34). Effects on reproductive and neurological function as well as general toxicity were evaluated.  Based on these results, the no-observed effect level (NOEL) for general toxicity was 500 mg/kg/day, and the no observed-adverse-effect level (NOAED) was 1000 mg/kg/day.  The NOEL for reproductive and neurological effects was 1000 mg/kg/day, the highest dose level tested.  

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day

Additional information

The repeat dose oral toxicity of Natural Oil Monomer (Methyl Polyhydroxymethyl Stearate)was evaluated in male and female rats as part of a combined repeat dose toxicity study and reproductive/ developmental toxicity screening assay conducted in accordance with GLP and following the OECD testing guideline OECD 422.Groups of 12 male and 12 female Crl:CD(SD) rats were administered NOM (methyl polyhydroxymethyl stearate) in corn oil daily, by gavage at dose levels of 0 (control), 100, 500, or 1000 mg/kg/day. Females were dosed once daily for two weeks prior to breeding, through breeding (two weeks), gestation (three weeks), and through postpartum day 4 or 5. Females were necropsied on postpartum day 5 or 6, giving an exposure period of approximately 54 days. Males were dosed two weeks prior to breeding and continuing through breeding (two weeks) until necropsy giving an overall exposure period of 34 days. Parameters used to asswess general toxicity included in life observations, measurement of body weight gain, food consumption, clinical chemistry, haematology, gross athology examination , measurement of selected organ weights and histopathology. The study also included measurements of neurotoxicology including sensory evaluation, rectal temperature, grip performanceand and examination of motor activity.

Of all parameters of general toxicity which were measured during the course of the study the only treatment-related effect was a minor, non-adverse change in the liver. Specifically, male and female rats administered 1000 mg/kg/day had increases in absolute and relative liver weights compared to control animals. The increased liver weights in males was accompanied by mild histopathological changes characterized by an increase in the incidence of very slight hypertrophy of centrilobular and midzonal hepatocytes with altered tinctorial properties (increased eosinophilia of hepatocytes) at this dose level. No histopathological changes were seen in the livers of female rats receiving the highest dose of 1,000 mg/kg/day. The changes in livers were were interpreted as a mild non-adverse adaptive response reflecting the induction of hepatic enzymes to metabolise NOM (methyl polyhydroxymethyl stearate). Based on these results the No Adverse Effect Level (NOAEL) for general toxicity was 1,000 mg/kg/day.

Justification for classification or non-classification

With a NOAEL of 1,000 mg/kg/day, this test substance does not merit classification.