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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug 10, 1990 - Sept 21, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to international guidelines and Good Laboratory Practise standards by an experienced testing laboratory.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1991
Reference Type:
publication
Title:
Unnamed
Year:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
96.3% Decabromodiphenyl ethane
3.6 % Dodecabromodiphenyl ethane

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Per guidelines.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Once daily for 28 consecutive days for all groups followed by a 14 day withdrawal in subsets of the control and high dose groups only.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
gravimetric
Duration of treatment / exposure:
28 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (vehicle), 125 , 400 and 1,250 mg/kg
Basis:

No. of animals per sex per dose:
12/sex/dose in the control and high dose groups.
6/sex/dose in the low and mid dose groups.
Control animals:
yes, concurrent vehicle
Details on study design:
Animals were acclimated to the laboratory conditions prior to the start of the study. Animals, of the age specified in the guidelines, were randomly assigned to treatment groups such that mean body weights were similar at study initiation.
Positive control:
no

Examinations

Observations and examinations performed and frequency:
see below
Sacrifice and pathology:
see below
Other examinations:
see below
Statistics:
ANOVA with Dunnet's post test or nonparametric statistics as appropriate for the particular endpoint.

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:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
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
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
see below

Effect levels

Dose descriptor:
NOEL
Effect level:
>= 1 250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see results

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No adverse effects were seen in rats treated orally at doses up to 1,250 mg/kg/day for 28 days. No rats died prior to scheduled sacrifice. Clinical signs were non-specific, low in incidence, non-dose-related and not related to test article administration. No test-article-related ocular lesions were detected on ophthalmic exam. No statistically significant differences were observed at any time point in mean body weight, body weight gain or food consumption between the control and low, mid and high dose groups. No treatment related effects were found on hematology, serum chemistry or urinalysis values. No gross lesions attributable to the test article were detected at either sacrifice. No biologically or toxicologically significant differences in absolute organ weight, organ to body weight or organ to brain weight were found at either sacrifice between treated and control groups. No treatment-related microscopic changes were found in any of the tissues evaluated from rats in the high dose group (adrenals, heart, kidneys, liver, mesenteric lymph node, parathyroids, spleen, and thyroid). The no-observed-effect-level (NOEL) was >= 1,250 mg/kg/d. The NOEL was based on the absence of toxicity at this dose as measured by: body weight, food consumption, body weight gain, hematology and serum chemistry values, urinalysis, ocular exam, gross necropsy results, organ weight, and light microscopic exam of selected tissues. This study was conducted according to OECD Guideline 407 and Good Laboratory Practices, and was reviewed as a part of the substance's registration in Japan.

Applicant's summary and conclusion

Conclusions:
The 28-d NOEL was >= 1250 mg/kgd, the highest dose tested.
Executive summary:

No adverse effects were seen in rats treated orally at doses up to 1,250 mg/kg/day for 28 days. No rats died prior to scheduled sacrifice. Clinical signs were non-specific, low in incidence, non-dose-related and not related to test article administration. No test-article-related ocular lesions were detected on ophthalmic exam. No statistically significant differences were observed at any time point in mean body weight, body weight gain or food consumption between the control and low, mid and high dose groups. No treatment related effects were found on hematology, serum chemistry or urinalysis values. No gross lesions attributable to the test article were detected at either sacrifice. No biologically or toxicologically significant differences in absolute organ weight, organ to body weight or organ to brain weight were found at either sacrifice between treated and control groups. No treatment-related microscopic changes were found in any of the tissues evaluated from rats in the high dose group (adrenals, heart, kidneys, liver, mesenteric lymph node, parathyroids, spleen, and thyroid). The no-observed-effect-level (NOEL) was >= 1,250 mg/kg/d. The NOEL was based on the absence of toxicity at this dose as measured by: body weight, food consumption, body weight gain, hematology and serum chemistry values, urinalysis, ocular exam, gross necropsy results, organ weight, and light microscopic exam of selected tissues.