Oligomerisation products of 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane with acrylic acid and lauric acid

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

900 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The study on tthe read-across substance was conducted in accordance with GLP and OECD guideline 422, three groups each comprising five male and five female rats for the toxicity subgroup and five male and ten female rats for the reproductive subgroup received 4,4’-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid at doses of 100, 300 or 900 mg/kg bw/day. Toxicity subgroup males and females and reproductive subgroup males were treated daily for five consecutive weeks. Reproductive subgroup females were treated daily for two weeks before pairing, throughout pairing, gestation, and lactation until the day prior to termination on Day 7 of lactation. A similarly constituted control group received the vehicle, propylene glycol, at the same volume-dose. During the study, data was recorded on clinical condition, performance under detailed physical and arena examination, sensory reactivity, grip strength, motor activity, bodyweight, food consumption, water consumption (visual), haematology, blood chemistry, oestrous cycles, mating performance, and fertility and gestation length. Organ weight, macroscopic, and microscopic pathology investigations were undertaken in the adults. The clinical condition of offspring, litter size and survival, sex ratio, and offspring bodyweight were assessed and macroscopic pathology investigations were undertaken. There was only one mortality during the course of the study, therefore considered unrelated to treatment. There were no signs observed among treated males and females at the routine physical examination or during the arena observations that were considered to be related to treatment. There was no effect of treatment on the food consumption, sensory reactivity findings, grip strength values, and motor activity in males and females throughout the study. At 900 mg/kg bw/day, the mean bodyweight gain of males was slightly lower than control during the first week of treatment. During the second week, weight gain for these males remained slightly (but not significantly) lower than control, but thereafter, mean weight gain was essentially similar to control in all treated groups, and the bodyweight gain of females during gestation and lactation was unaffected by treatment at all dose levels investigated. Haematological assessment revealed slightly prolonged prothrombin time among males and females receiving 900 or 300 mg/kg bw/day. Biochemical changes in the blood plasma comprised high total bilirubin and total bile acid concentrations in males receiving 900 or 300 mg/kg bw/day and females receiving 900 mg/kg bw/day, and high cholesterol concentrations in males and females in all treated groups. A dose-related trend was evident for all of these haematological and biochemical parameters. There was no clear evidence of an adverse effect of treatment on mean organ weights among all animals at scheduled termination. There were no macroscopic abnormalities and no test substance-related lesions at microscopic examination. Oestrous cycle length, pre-coital interval, mating performance, and fertility and gestation length of the reproductive subgroup females were unaffected by treatment. There were no clinical signs observed for F1 offspring that were considered to be related to parental treatment and offspring survival and growth from birth to Day 7 of age were unaffected by treatment. There were no macroscopic abnormalities detected among the offspring that died during the early post-natal period, or at scheduled termination on Day 7 of age that were attributable to parental treatment.

Under the study conditions, the NOAEL for systemic toxicity in the CD rats was determined to be 900 mg/kg bw/day. The NOAEL for the reproductive/developmental toxicity was also concluded to be 900 mg/kg bw/day (Stannard, 2010).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the combined repeated dose and reproductive-developmental toxicity study with the read-across substance, no classification is warranted for this endpoint according to EU CLP Regulation (EC) 1272/2008 criteria.