N,N'-ethylenebis(3,4,5,6-tetrabromophthalimide)

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was performed prior to international guidelines and GLPs. The parameters investigated largely conform to current methodologies. The lack of adverse effects is consistent with the lack of toxicity observed in modern prenatal developmental studies in 2 species.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-ethylenebis(3,4,5,6-tetrabromophthalimide)

EC Number:

251-118-6

EC Name:

N,N'-ethylenebis(3,4,5,6-tetrabromophthalimide)

Cas Number:

32588-76-4

Molecular formula:

C18H4Br8N2O4

IUPAC Name:

N,N'-ethylenebis(3,4,5,6-tetrabromophthalimide)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Duration of treatment / exposure:

daily for 90 days followed by 46 d recovery period

Frequency of treatment:

daily in the feed for 90 days followed by 46 d recovery period

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.01, 0.1, 1% of the diet
Basis:
nominal in diet

No. of animals per sex per dose:

15/sex/group

Control animals:

yes, concurrent no treatment

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

1 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

body weight and weight gain

clinical biochemistry

clinical signs

dermal irritation

food consumption and compound intake

food efficiency

gross pathology

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

neuropathology

organ weights and organ / body weight ratios

urinalysis

water consumption and compound intake

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Key result

Critical effects observed:

no

Lowest effective dose / conc.:

1 ppm

Treatment related:

no

Dose response relationship:

no

Relevant for humans:

no

Any other information on results incl. tables

See attached background material for Tables of Results.

Applicant's summary and conclusion

Conclusions:

The 90-day NOEL was 1% of the diet or approximately 1000 mg/kg bw.

Executive summary:

EBTBP was administered to four groups of Sprague Dawley rats (n=15/sex/group) at 0, 0.01, 0.1 and 1.0% of the diet for 90 days followed by 46 days during which the rats were fed control diet. No changes in hematology or serum chemistry values related to treatment were detected on study days 0, 45, 92. No effect of treatment was found on urinalysis (d 0, 45 and 90). The mean relative and absolute organ weights of the liver, kidney, heart, and thyroids from the control and 1.0% groups were statistically comparable. Several animals died on test from non-test article related causes (most deaths were related to collection of blood for hematology and serum chemistry evaluations).  Gross necropsy from animals dieing on test and sacrificed on days 92, 134, 135 and 136 revealed no test article-related gross lesions. No test article related lesions were detected on histopathology. The 90-day NOEL was 1% of the diet. This is estimated to be ~ 1,000 mg/kg/d using the assumption of consumption of 25 g diet per 250 g rat per day. This study was performed prior to the adoption of Good Laboratory Practices or EPA/OECD guidelines.