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Description of key information

Key value for chemical safety assessment

Additional information

No data are available that describe the toxicokinetics of Tetramethyl Bisphenol A, therefore relevant substance properties and data from toxicity studies indicating systemic bioavailability were taken together to assess the general toxicokinetics of the substance.

 

Physical-chemical properties

Tetramethyl Bisphenol A is a white to off-white powder with a molecular weight of 284.4 g/mol. The log Pow of the substance is 4.51. Its solubility in water is 3.17 mg/L.

 

Data from acute and repeated dose toxicity studies

Acute oral and dermal toxicity studies

The available acute oral and dermal toxicity studies did not result in mortality and overt signs of toxicity were not observed. In both studies the dose level was 2000 mg/kg bw.

In a combined repeated dose toxicity / reproductive toxicity screening assay, groups of 12 male and 12 female rats were exposed via gavage at doses of 0, 10, 100 and 1000 mg/kg bw/day. No parental animals died during the test. Test substance-related clinical findings of clear and red material around the mouth and/or nose were noted at approximately 1-2 hours following dose administration in the 100 and 1000 mg/kg/day groups. Test substance-related lower mean body weight gains were noted in the 100 and 1000 mg/kg/day group F0 males compared to the control group throughout the entire treatment period (study days 0-27). As a result, mean body weights in the 100 and 1000 mg/kg/day group males were 4.2% and 5.1% lower, respectively, than the control group on study day 27. Correspondingly lower mean food consumption was noted for males in these groups only during the first week of treatment (study days 0-7). During the recovery period, mean body weights, body weight gains, and food consumption in the1000 mg/kg/day group males were comparable to the control group. No test substance-related effects in the following parameters were noted in the F0 males at any dose level: FOB or locomotor activity evaluations, hematology and coagulation, serum chemistry, urinalysis, macroscopic findings at necropsy or organ weights. Test substance-related, minimal to mild vacuolation of the lamina propria in the duodenum and jejunum was noted in the 100 (duodenum only) and 1000 mg/kg/day F0 group males at the primary necropsy. These vacuoles were rarely positive with Oil red O stain and suggested lipid accumulation. Persistence of test substance-related, minimal vacuolation in the duodenum and jejunum at slightly higher incidence was noted in the 1000 mg/kg/day F0 group males at the recovery necropsy. No correlating clinical pathology alterations or effects on organ weight were noted. Therefore, the toxicological significance of vacuolation in the present study is uncertain. Similar changes were not noted in the F1 generation.

 

Absorption figures used for the DNEL derivation

No information on absorption of Tetramethyl Bisphenol A is available. In accordance with Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) is proposed to be used in the case of oral-to-inhalation extrapolation. Based on the water solubility of 3.17 mg/L, the Log Pow of 4.51 and the physical state of the substance (solid), the dermal absorption will be low and the rate of penetration will be limited. Furthermore, no effects were observed in an acute dermal toxicity study. Therefore, a factor 0.1 is proposed for oral-to-dermal extrapolation.