Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Study duration:
subacute
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

In a repeated dose oral toxicity study in rats (Wistar, OECD TG 407), the substance was adimistered via gavage to 5 rats/sex/dose at 0, 10, 30, 90 mg/kg bw (male) or 0, 5, 15, 45 mg/kg bw (female) in corn oil for 4 weeks. No adverse effects on reproductive organs or tissue were observed at 45 mg/kg bw (females) and 90 mg/kg bw (males).

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study planned
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
A prenatal developmental toxicity study (EU B.31, OECD TG 414), conducted in one species, is a standard data requirement at REACH Annex IX level. No information, which fulfill this requirement, is available for the UVCB substance.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out:
2,2',6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies
No GLP study is available for the registered substance to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- Available non-GLP studies
No non-GLP study is available for the registered substance to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- Historical human data
No human data is available for the registered substance to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- (Q)SAR
Currently available Q(SAR) methods are not considered adequate to be used on their own for regulatory decision making with respect to risk assessment and C&L for repeated dose toxicity. There is thus no information obtained in (Q)SAR models available for the registered substance to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- In vitro methods
Currently available in vitro methods are not considered adequate to be used on their own for regulatory decision making with respect to risk assessment and C&L for repeated dose toxicity. There is thus no data obtained in in vitro methods available for the registered substance to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- Weight of evidence
No information is available for the registered substance that would allow drawing a Weight of Evidence conclusion to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- Grouping and read-across
No information is available for the registered substance that would allow Grouping and/or a read-across conclusion to cover the endpoint ‘prenatal developmental toxicity in rats (OECD 414)’.
- Substance-tailored exposure driven testing [if applicable]
Not applicable
- Approaches in addition to above [if applicable]
Not applicable
- Other reasons [if applicable]
Not applicable

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- The substance is registered as UVCB in the tonnage band 100-1000 t/a. Thus, according to REACH Regulation 1907/2006 Annex IX a prenatal developmental toxicity in one species (OECD 414) is a standard data requirement for the registered substance. The specific rules for adaption (Annex IX, 8.7. Reproductive toxicity, column 2) are not adequate:
- The registered substance is not known to be a genotoxic carcinogen.
- The registered substance is not known to be a germ cell mutagen.
- The registered substance is not of low toxicological activity, i.e. evidence of toxicity were seen in acute and short-term repeated (28-day) oral toxicity studies.
- The registered substance is not known to cause developmental toxicity, meeting the criteria for classification as Repr Cat 1 or 2. No developmental toxicity studies are available for the registered substance.
Therefore, the testing proposal for a prenatal developmental toxicity in rats (OECD 414) is for formal and scientific reasons appropriate to fulfill the standard information requirement as laid down in ANNEX IX, Section 8.7.2 of REACH Regulation.


FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed
A prenatal developmental toxicity in rats following OECD TG 414 (EU B.31) should be performed in rats.
The results of the subacute repeated dose toxicity study demonstrate that dosing is limited by local effects in the intestine for which the female rat is the most sensitive sex. Therefore a step-wise approach should be considered. Firstly conduct the subchronic toxicity study (OECD TG 408) in rats (see testing proposal) by oral route to better understand the potential interaction of the test item with physiological matrices of the digestive tract and potential subsequent effects. Secondly, based on the outcome of this study, consider the added value and design of a prenatal developmental toxicity study (OECD TG 414), oral route in one species.
The substance to be tested is a solid which is only used/marketed in solution. According to CLP Article 6 (3) the classification for CMR hazards of the solution (= mixture) will therefore decisively depend on the classification of all individual ingredients in the mixture. Having this in mind a prenatal developmental toxicity study with 2,2’,6,6'-Tetrabromo-4,4'-isopropylidenediphenol, oligomeric reaction products with Propylene oxide and n-butyl glycidyl ether should not be conducted before outstanding results from testing on developmental toxicity of an ingredient is available (submission deadline 29 March 2018) which may have impact on the C & L of the solution.
Qualifier:
according to
Guideline:
EU Method B.31 (Prenatal Developmental Toxicity Study)
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Species:
rat
Route of administration:
oral: gavage
Abnormalities:
not specified
Developmental effects observed:
not specified
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 all available data a classification according to Regulation (EC) No 1272/2008, Annex I is not warranted.