Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented publication which meets basic scientific principles. The justification for the Read Across approach has been attached to the Section 13.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
2,2’,6,6’-tetrabromo-4,4’-isopropylidenediphenol (tetrabromobisphenol-A or TBBP-A) Part II – human health 4th Priority List, Vol. 63.
Author:
ECB - European Chemical Bureau
Year:
2006
Bibliographic source:
Institute for Health and Consumer Protection, European Chemicals Bureau, European Commission Joint Research Centre, Luxembourg
Reference Type:
other: Secondary Source
Title:
Safety evaluation of chemicals for use in household products (VII) teratological studies on tetrabromobisphenol-A in rats.
Author:
Noda et al.
Year:
1985
Bibliographic source:
Annual report of the Osaka Institute of Public Health and Environmental Sciences 48, 106-112.

Materials and methods

Principles of method if other than guideline:
No available information on method used.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
No available data

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
olive oil
Details on exposure:
No available data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No available data
Details on mating procedure:
No available data
Duration of treatment / exposure:
For the gestation period (animals sacrified 20 days)
Frequency of treatment:
Daily
Duration of test:
Animals sacrified during gestation: 20 days for
Animal not sacrified during gestation: Gestation period
Offspring: 21 days post-natal
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
280 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
830 mg/kg bw/day
Basis:
no data
Remarks:
Doses / Concentrations:
2500 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
22 to 24
Control animals:
yes, concurrent vehicle
Details on study design:
No available data

Examinations

Maternal examinations:
ANIMAL SACRIFIED
Gross pathology

ANIMAL NOT SACRIFIED
N. of live and dead offspring
Sex of offspring
Presence of any abnormalities
After sacrifice: Gross pathology
Ovaries and uterine content:
N. of corpora lutea, implants, surviving foetus, early fetal deaths, late fetal deaths

Fetal examinations:
Body weights of surviving foetus
Sex of fetuses
Presence or absence of external abnormalities in foetus
Skeletal abnormalities
Visceral abnormalities

OFFSPRING
During post natal 21-days: Bodyweight, state of growth and general state.
After sacrifice: Skeletal abnormalities and n. of implants.
Statistics:
No available data
Indices:
No available data
Historical control data:
No available data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No toxicologically significant effects in the treated maternal animals throughout gestation. In the early stages of pregnancy in the treated dams there was a slight increase in body weight gain above that of the control animals; by day eight onwards the increase in body weight gain was similar in all groups. In early pregnancy food consumption was significantly reduced in all of the TBBP-A dosed groups, but from mid pregnancy food consumption was increased in the 2500 mg/kg group.
No other differences were evident during the dosing period. With the exception of kidney stones and the resultant deformation of one kidney in one animal in the 830 mg/kg group (clearly not treatment-related), no abnormalities were observed in the dams on gross pathological examination.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
> 2 500 mg/kg bw/day
Based on:
no data
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No effect on the length of the gestation period and no toxicologically significant effects on fetal development. In the fetuses examined on gestational day 20, on external observation, examination of the internal organs and skeletal observations, there were no findings of toxicological significance. In the offspring that were delivered normally and reared to day 21, no difference in development was observed between the treated and control groups.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL > 2500 mg/kg bw/day
Executive summary:

Method

The effects on development were evaluated in Pregnant Wistar rats (Noda et al., 1985[1]). The substance was orally administered in olive oil throughout gestation, from day 0 once a day (280, 830 and 2500 mg/kg bw/day). The doses were established from the results of a preliminary study in which no toxicologically significant effects were observed at the top dose of 2500 mg/kg.

Observations

On gestational day 20, approximately two thirds of the animals were sacrificed and examined.

For the animals that were allowed to deliver their offspring naturally, the gestation period was calculated. Offspring were kept up until weaning on post-natal day 21 and then killed and examined for the presence of any abnormalities. The dams were also killed on day 21 post-partum and then examined.

Results

The substance did not produce adverse effects on development in the rat at dose levels up to 2500 mg/kg. Although this dose did not produce maternal toxicity, it is considered sufficiently high to adequately assess developmental toxicity effects by the oral route.

[1]Noda T, Morita S, Ohgaki S and Shimizu M (1985) Safety evaluation of chemicals for use in household products (VII) teratological studies on tetrabromobisphenol-A in rats. Annual report of the Osaka Institute of Public Health and Environmental Sciences 48, 106-112.