Registration Dossier

Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
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:
review article or handbook
Title:
Unnamed
Year:
2014
Reference Type:
other: Secondary Source
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

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:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No available data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
F0 generation

Exposition premating period: 10 weeks
Exposition mating period: 2 weeks


Exposition premating period: 10 weeks
Exposition mating period: 2 weeks
Exposition during gestation and lactation: Yes

F1 generation

Exposition premating period: 10 weeks
Exposition mating period: 2 weeks


Exposition premating period: 10 weeks
Exposition mating period: 2 weeks
Exposition during gestation and lactation: Yes
Details on mating procedure:
The F0 generation was sacrificed after the pups were weaned
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No available data
Duration of treatment / exposure:
Premating period: 10 weeks
Mating period: 2 weeks
For female exposition to the test substance during gestation and lactation.
Frequency of treatment:
Daily
Details on study schedule:
No available data
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
No available data
Control animals:
yes, concurrent vehicle
Details on study design:
No available data
Positive control:
No available data

Examinations

Parental animals: Observations and examinations:
No available data
Oestrous cyclicity (parental animals):
No available data
Sperm parameters (parental animals):
No available data
Litter observations:
No available data
Postmortem examinations (parental animals):
No available data
Postmortem examinations (offspring):
No available data
Statistics:
No available data
Reproductive indices:
No available data
Offspring viability indices:
No available data

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
1000 mg/kg bw/day group: T4 lower (F0 ♂ ♀); T3 lower (F0 ♂);
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
1000 mg/kg bw/day group: T4 lower (F1 ♂ ♀); 100 mg/kg bw/day group: T4 lower (F1 ♂ ♀)
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
no effects observed

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
ca. 1 000 mg/kg bw/day
Based on:
not specified
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The F0 generation was sacrificed after the pups were weaned, and decreases in T4 levels were found at the high dose in males and females. In the F1 generation, lower serum T4 concentrations were observed in both sexes at 100 and 1000 mg/kg. T3 serum levels were significantly lower only in F0 males of the 1000 mg/kg group. No changes in serum TSH levels, compared to vehicle control animals, were observed in any of the treated groups.

Applicant's summary and conclusion

Conclusions:
NOAEL = 1000 mg/kg bw/day
Executive summary:

Method

The effects on reproductive performance and fertility were evaluated in a 2 generation study. The substance was administered daily by oral gavage. Sprague Dawley rats were exposed to 10, 100, or 1000 mg/kg bw/day in the F0 generation during 10 weeks premating and during a 2-week mating period. Females were treated also during gestation and lactation. The same treatment regime as in F0 animals was also applied in F1 animals.

Observations

The F0 generation was sacrificed after the pups were weaned, and decreases in T4 levels were found at the high dose in males and females. In the F1 generation, lower serum T4 concentrations were observed in both sexes at 100 and 1000 mg/kg. T3 serum levels were significantly lower only in F0 males of the 1000 mg/kg group. No changes in serum TSH levels, compared to vehicle control animals, were observed in any of the treated groups.

Results

No treatment-related histopathologic changes were observed. The substance has no toxicologically significant effects in fertility or reproductive performance at doses of up to 1000 mg/kg bw/day.