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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 days dosing between gestation days 6 and 15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data review as part of the US National Toxicity Program (NTP) and considered reliable.
Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.
It is concluded that further animal testing cannot be justified

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Treatment during day 6 - 15 by oral gavage at doses from 30 - 10 000 mg/kg
GLP compliance:
not specified
Remarks:
Study performed 1978
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrabromophthalic anhydride
EC Number:
211-185-4
EC Name:
Tetrabromophthalic anhydride
Cas Number:
632-79-1
Molecular formula:
C8Br4O3
IUPAC Name:
Tetrabromophthalic anhydride
Test material form:
solid
Specific details on test material used for the study:
Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.

Test animals

Species:
rat
Strain:
CD-1

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Not described as study comenced on Day 6 of gestation
Duration of treatment / exposure:
From Day 6 - 15 (10 treatment days)
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
30 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
3 000 mg/kg bw/day
Dose / conc.:
10 000 mg/kg bw/day
No. of animals per sex per dose:
Five females per treatment level
Control animals:
not specified

Examinations

Maternal examinations:
Yes
Ovaries and uterine content:
Yes

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Death in four animals at 10000 mg/kg and greatly reduced bodyweight gain with anogenital staining
Parental NOAEL considered to be 3000 mg/kg/day
Mortality:
mortality observed, treatment-related
Description (incidence):
Death in four animals at 10000 mg/kg
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Reduced body weight in surviving animals at 10 000 mg/kg
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Subdued
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
not specified
Details on maternal toxic effects:
NOEAL 3000 mg/kg/day

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
ca. 3 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
mortality

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Noting that maternal mortality was not taken into account
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
Noting that maternal mortality was not taken into account
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
Details on embryotoxic / teratogenic effects:
No changes observed to the number of viable or non-viable foeti were observed. There were no compound related effects to resorptions, implantations or corpus lutea

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 3 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Highest treatment level without significant maternal toxicity

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
In common with this class of substance, thre was no reported teratogenic effects up to the maximum tolerated maternal treatment level.
Executive summary:

Although testing performed on the acid form (the anhydride quickly hydrates to the acid on ingestion), the data is considered reliable with respect to simple salts such as potassium salt.

It is noted that treatment levels were far in excess of those permitted in modern studies in Europe and that in view of the parental toxicity reported, these high treatment levels were inappropriate.