3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate

Endpoint summary

Description of key information

In the key 28-day oral study, conducted according to a protocol similar to OECD TG 407, and in compliance with GLP, the reported NOAEL value for 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate was 80 mg/kg bw/day in rats (TNO, 1989).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

80 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In the key 28-day oral study, conducted according to a protocol similar to OECD TG 407, and in compliance with GLP, the reported NOAEL value for 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate was 80 mg/kg bw/day in rats (TNO, 1989).

80, 400 and 2000 mg/kg bw/day of test substance in corn oil were administered daily to 5 male and 5 female rats per dose for 28 days. Negative control group of animals was also included. Control rats and high-dose rats (2000 mg/kg bw/day) were selected for further examination of reversibility of effects for 14-day after administration of final dose. Cage side observations for mortality and clinical signs of toxicity were performed twice daily during the week days and one daily during the weekends. Body weights were recorded on days 4, 7, 11, 14, 18, 21, 25 and 28. During the recovery period the rats were weighed on days 35 and 42. Blood was collected from all the animals for haematological and clinical chemistry examinations on days 24 or 26, respectively. At the end of the treatment period (day 28), animals treated with 80 and 400 mg/kg bw/day were sacrificed, while control and high-dose animals (2000 mg/kg bw/day) were sacrificed 14 days later. All the animals were subject to gross necropsy, organs were collected and examined for macroscopic changes. Some of the organs were weighed and used for tissue preparation for histopathology.

1/5 male treated with 2000 mg/kg bw/day showed emaciation, weakness, ataxia, pallor and a low body temperature. 1/5 control females showed emaciation, cyanosis, encrustrations around the nose and porphyrin accumulation along the eye lids. 1/5 males of the mid-dose group was found death on day 21 of the study. No statistically-significant differences in body weight gain was observed in any of the animals. At haemathology prothrombin time was decreased in the high-dose rats of both sexes and in males of mid-dose. At the end of the recovery period high-dose rats still exhibited decreased prothrombin time, but statistical significance was reached only in males. Increased number of lymphocytes, resulting in an increased total white blood cell count, in high-dose males was noted towards the end of the treatment period. The same trend was observed in 1 male from low-dose group, which was not considered treatment-related.

At clinical chemistry examinations increased alanine aminotransferase and aspartate aminotransferase activities in top-dose rats of both sexes was observed. Decreased gamma glutamyl transferase activity in all dose levels in both sexes, decreased albumin concentrations at all dose levels in males, decreased total protein concentration in low-dose males and increased potassium concentration in low and top-dose males were also observed. Changes in aspartate aminotransferase and gamma glutamyl transferase activities were statistically significant in males only. At the end of the recovery period alanine aminotransferase and aspartate aminotransferase activities were still increased in most of top-dose males and 2/5 females. Other changes observed after recovery were: decreased albumin concentration and albumin to globulin ratio in both sexes, increased gamma glutamyl transferase activity in females and decreased plasma sodium concentration in males. No treatment-related change to urinary volume or density were noted at urinalysis. Relative organ weights revealed an increased liver weight in the mid and top-dose animals from both sexes. This change persisted till the end of the recovery period. Relative testes weight in males and relative brain weight in females were significantly increased at termination of recovery period. At histopathology clear fluid and fat droplets were observed in the thoracic cavity of the mid-dose male found dead on day 21. The cause of death was probably trauma due to the gavage treatment. At the end of the 14-day recovery period, treatment-related changes of liver such as yellow discolouration and yellow spots were observed. Treatment-related hepatic changes characterised by multifocal aggregates of RES cells and necrotic hepatocytes were observed in mid and high-dose males. Adrenals, heart, kidneys and spleen did not show any treatment-related changes. At the end of the 14-day recovery period, liver lesions related to hepatotoxicity were observed. Liver damage was more severe after the recovery period than after the 28-day treatment period.

Justification for classification or non-classification

Based on the available data for 3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate, no classification for repeated dose toxicity is required according to Regulation (EC) No. 1272/2008. The main effects seen in low dose animals that reached statistical significance in males only included decreased gamma glutamyl transferase activity, decreased albumin concentration, decreased total protein and increased potassium. As these effects were seen in males only they were not considered to be adverse. Liver effects were seen in middle and high dose animals showing clear toxic effect. Therefore, the LOAEL was established at 400 mg/kg bw/day. This value does not fall in the classification criteria for target organ toxicity following 28-day oral exposure (300 mg/kg bw/day). Therefore, no classification applies for this substance.