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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study with sufficient data to evaluate methods and results.

Data source

Referenceopen allclose all

Reference Type:
other: secondary source
Title:
Unnamed
Year:
2005
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
other: Addendum to Study Report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
: no data presented on hematology or clinical chemistry.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Bisphenol A Dianhydride (BPA-DA; CAS RN 38103-06-9); Lot UI-82-4 from General Electric Company

Test animals

Species:
rat
Strain:
other: Sprague-Dawley Crl:COBS®, CD®, (SD) Br
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Details on oral exposure:
Groups of 10 rats/sex were fed BPA-DA at concentrations of 0, 1, 2 and 4% in the diet.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
30 days
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1, 2, and 4% of BPA-DA in basal diet (approximately 646 – 765, 1277 – 1490, and 2750 – 3160 mg/kg/day, respectively)
Basis:
nominal in diet
No. of animals per sex per dose:
10/sex/group
Control animals:
yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:
All rats were observed for mortality twice each day. Clinical signs and body weights were recorded at initiation and weekly thereafter. Food consumption was recorded weekly.
Sacrifice and pathology:
After 31 days of treatment, all surviving rats were weighed, killed and a gross necropsy was performed. At necropsy, the liver and kidneys of each animal were weighed and organ to body weight ratios determined. The following tissues were preserved from all animals: brain, pituitary, thoracic spinal cord, eyes, salivary glands, thyroid, parathyroids, thymus, trachea, esophagus, lung, heart, liver, spleen, kidneys, adrenals, stomach, pancreas, duodenum, jejunum, ileum, colon, cecum, mesenteric lymph node, urinary bladder, testes with epididymides and prostate (males), ovaries and uterus (females), femur, costal bone marrow, skeletal muscle, and all gross lesions. Microscopic evaluation was conducted on sections of the lungs, liver, brain and kidneys from rats of all treatment groups. Reproductive organs were not evaluated histologically.
Statistics:
The following statistical tests were utilized to evaluate body weight changes, total food consumption and organ weights: Bartlett’s test for homogeneity of variance and one-way classification analysis of variance (ANOVA). Since the ANOVA proved to be not significant for all of the analyses, no other tests were performed. All analyses were performed at the 5% one-tailed probability level.

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
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
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:
not examined
Details on results:
No deaths occurred during the study. No compound-related clinical observations were noted throughout the study. Body weight and food consumption data of the compound-treated males and females were generally comparable to those of their respective controls. Individual and mean terminal body weights, absolute organ weights and organ weights relative to terminal body weight were not affected by treatment. No compound-related organ or tissue changes were evident macroscopically or microscopically.

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 4 other: %
Sex:
male/female
Basis for effect level:
other: approximately 2750 to 3160 mg/kg/day

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL >= 4% (approximately 2750 to 3160 mg/kg/day)