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Description of key information

In the key 90-day repeated dose oral toxicity study with tri(isopropyl)silyl acrylate (CAS 157859-20-6), conducted according to OECD Test Guideline 408 and in compliance with GLP, the reported NOAEL for specific target organ toxicity was greater than 100 mg/kg bw/day based on no test item related effect observed on mortality, clinical signs, body weight development, food consumption, functional observation battery, weekly detailed clinical observations, haematology and blood coagulations, clinical biochemistry, urinalysis, gross pathological findings, organ weight and histopathology ( Eurofins / BSL Bioservice, 2018).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subchronic
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

The key 90-day repeated dose oral toxicity study with tri(isopropyl)silyl acrylate (CAS 157859-20-6) was conducted according to OECD Test Guideline 408 and in compliance with GLP (Eurofins / BSL Bioservice, 2018). In this study 10, 50, and 100 mg/kg body weight day of test material in dried corn oil was administered to male and female rats for 90 days orally (gavage).

During the period of administration, the animals were observed precisely each day for signs of toxicity. At the conclusion of the test, all animals were sacrificed and observed macroscopically. To detect possible delayed occurrence or persistence of, or recovery from toxic effects, animals in the recovery group were observed for an additional period of 28 days following the last administration.

Body weight and food consumption were measured weekly. Multiple detailed behavioural observations were made outside the home cage using a battery of functional observational tests.

Haematological, coagulation and clinical biochemical parameters were determined with blood samples obtained from overnight fasted animals at their terminal sacrifice. Urinalysis was performed on samples collected from all animals prior to or as part of their terminal sacrifice. At the conclusion of the test, all surviving animals were sacrificed and observed macroscopically.

The wet weight of a subset of tissues was taken and a set of organs/tissues was preserved for histopathological examination.

No mortality occurred in any of the dose or control groups during the treatment or recovery periods of this study. There were no observed clinical findings related to a systemic effect of the test item. During the weekly detailed clinical observation, no treatment related changes or differences between the dose and control groups were found. No relevant and test item related effects were observed in any of the parameters of the functional observation battery both at the end of the treatment period and at the end of the recovery period. No ophthalmologic findings were observed in any of the animals of this study. In both males and females, the mean body weight increased during the progress of the study in the control, LD, MD, HD and recovery groups. The test item had no effect on food consumption in this study. In males and females sacrificed at the end of treatment period and recovery period, no test item-related effect of toxicological relevance was observed for haematological and coagulation parameters. In males and females sacrificed at the end of the treatment period and recovery period, no test item-related effect of toxicological relevance was observed for clinical biochemistry parameters. The test item had no toxicologically relevant effect on urinary parameters analysed at the end of the treatment period or recovery period of this study. Few specific gross pathological changes in uterus were recorded in a few female animals. These findings were not considered to be treatment-related and assumed to be common background findings in this strain. No gross pathological findings were observed in males sacrificed at the end of the treatment period and both males and females sacrificed at the end of the recovery period. The test item had no toxicologically relevant effect on organ weights determined at the end of the treatment period or recovery period of this study. Histopathologically, accumulation of α2-microglobulin in kidneys from several test item-treated males and control animals was observed. The comparison between group 4 (treatment and recovery period) and group 1 animals (control and recovery period control) revealed similar α2-microglobulin accumulation in both groups. The α2-microglobulin accumulation detected by immunohistochemistry using a specific anti-Alpha 2u Globulin antibody corresponded with the presence of hyaline inclusions that was observed in hematoxylin and eosin stained kidney sections. Dose dependency was not observed during the histopathological evaluation. The accumulation of α2-microglobulin comprises a male-rat-specific syndrome without toxicological relevance to humans. In the absence of further renal lesions, this change was considered non-adverse. All remaining findings recorded were considered incidental or were within the range of spontaneous background alterations that can be found in Wistar rats at these ages.

The reported NOAEL for specific target organ toxicity was greater than 100 mg/kg bw/day based on no test item related effect observed on mortality, clinical signs, body weight development, food consumption, functional observation battery, weekly detailed clinical observations, haematology and blood coagulations, clinical biochemistry, urinalysis, gross pathological findings, organ weight and histopathology.

In another study tri(isopropyl)silyl acrylate was tested in a 28-day oral subacute toxicity study conducted according to OECD test guideline 407 and in compliance with GLP (RCC, 2005b). Tri(isopropyl)silyl acrylate was administered at doses of 0, 10, 50 or 250 mg/kg bw/day via gavage, to groups of 5 male and 5 female rats, 7 days/week for 28 days and the animals examined for clinical signs of toxicity, outside cage observations, food consumption, body weight gains, effects on locomotor activity and grip strength, haematological and biochemical analyses, organ weights and gross and microscopic appearance of a range of organs. All treated animals survived the study period and no clinical signs of toxicity were observed. There were no effects on grip strength, locomotor activity, food consumption, body weight gains or macroscopic appearance of the tissues and organs. At the top dose level, haematological effects (possibly indicative of haematopoietic depression), increased relative kidney weight and microscopic changes in the kidney were noted in the males, with clinical biochemical effects being seen in both sexes. Based on these results, the authors of the study reported a LOAEL for tri(isopropyl)silyl acrylate of 250 mg/kg bw/day and NOAEL of 50 mg/kg bw/day. However, considering that similar effects were not observed in a 90-day oral exposure study, it is the reviewer's opinion that the observed effects in the treated rats are adaptive and the no-adverse-effect-level would be the highest dose tested 250 mg/kg bw/day.


Justification for classification or non-classification

Based on the available data, tri(isopropyl)silyl acrylate is not classified for adverse effects following repeated exposures according to Regulation (EC) No 1272/2008.