Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: Toxicokinetics assessment based on the physico-chemical properties of the substance and on toxicological data. Experimental toxicokinetic studies were not performed.
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Toxicokinetics assessment based on the physico-chemical properties of the substance, on toxicological data and on read across. Experimental toxicokinetic studies were not performed.

Data source

Reference
Reference Type:
other: Toxicokinetics Assessment
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Principles of method if other than guideline:
statement on toxicokinetics

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
test material for read-across

Results and discussion

Any other information on results incl. tables

The following remarks on toxicokinetics are based on the physico-chemical properties of the substance and on toxicological data. Experimental toxicokinetic studies were not performed.

The registered UVCB substance 2 -acetone, condensation product with phenol, in the following referred to as UVCB substance, mainly consists of 4,4'-isopropylidenediphenol (Bisphenol A, CAS-No. 80 -05 -7) that accounts for approximately 40% (typical concentration) of the UVCB substance and can thus be regarded as the leading compound with regard to human health toxicity.

For the assessment of toxicokinetic properties of the UVCB substance data for the UVCB substance itself and read-across based on data for Bisphenol A are taken into consideration.

The UVCB substance is a brown solid with a low water solubility of <1000 mg/L (Currenta, 1989). Its log Pow of >= 3.24 (Currenta, 1990) and its solubility in organic solvents suggest intestinal absorption subsequent to oral ingestion and dermal absorption. In acute oral and dermal toxicity studies a single dose of 2000 mg/kg bw was well tolerated by rats (Bomhard, 1990; Gillissen, 2010). The only clinical sign was slight piloerection within the first 4 hours of treatment after oral administration and skin irritation after dermal application. The NOAEL in a 90 -day repeated oral dose toxicity study in rats was determined with 50 mg/kg bw/day for the UVCB substance.

The major component of the product, Bisphenol A, is known to be well absorbed in the gastrointestinal tract and is also non-toxic in acute oral and dermal toxicity studies (EU Risk Assessment Report 4,4´-Isopropylidenediphenol (Bisphenol A) 2008). The NOAEL for repeated oral dose toxicity in rats and mice was determined with about 50 mg/kg bw/day.

Toxicokinetics and metabolism of Bisphenol A are well examined. Dermal absorption of Bisphenol A was determined in an in vitro study with about 10% of the applied dose (EU Risk Assessment Report 2008 for 4,4´-Isopropylidenediphenol (Bisphenol A) and EFSA 2015. For further information see REACH Registration data of the registrant published on the ECHA homepage (last update of Dossier in December 2015).

Based on the results of several in vitro genotoxicity tests performed with and without metabolic activation (OECD TG 471: Herbold, 2009a; OECD TG 476: Wollny, 2010; OECD TG 473: Hall, 2010) it can be concluded that DNA-reactive metabolites of the UVCB substance will not be generated in mammals in the course of hepatic biotransformation. Also Bisphenol A can be considered as not of concern with regard to mutagenicity (EFSA, 2015).

Applicant's summary and conclusion