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Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: In this guideline study according to OECD TG 407 and GLP reproductive organs of male and female rats were examined for adverse effects.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Principles of method if other than guideline:
Bis(2-ethylhexyl) tetrabromophthalate was administered via the diet to three groups of ten male and ten female CD rats at concentrations of 200, 2 000 or 20 000 ppm (= ca. 21.97, 223.4 or 2331 mg/kg/day) for four weeks. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. epididymides, mammary glands - caudal, ovaries, prostate, testes, and uterus (with cervix).
GLP compliance:
yes
Type of method:
in vivo

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) tetrabromophthalate
EC Number:
247-426-5
EC Name:
Bis(2-ethylhexyl) tetrabromophthalate
Cas Number:
26040-51-7
Molecular formula:
C24H34Br4O4
IUPAC Name:
bis(2-ethylhexyl) tetrabromophthalate

Test animals

Species:
rat
Strain:
other: CD rats
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
21.97 mg/kg bw/day
Dose / conc.:
223.4 mg/kg bw/day
Dose / conc.:
2 331 mg/kg bw/day
No. of animals per sex per dose:
Three groups of ten male and ten female CD rats per dose
Control animals:
other: A positive control group of five male and five female CD rats received di-2-ethyl hexyl phthalate (DEHP) via the diet at a concentration of 15 000 ppm for four weeks.

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
ca. 2 331 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: non-neoplastic

Any other information on results incl. tables

Bis(2-ethylhexyl) tetrabromophthalate:

There were no signs of reaction to treatment with FR-45B. Slightly low overall bodyweight gain was recorded for females receiving the highest dietary concentration of FR-458. Males treated with FR-458 were unaffected. Marginally low alanine amino-transferase activities were seen in females receiving the highest dietary concentration of FR-458, and marginally low phosphorus concentrations were seen in all females and males receiving the highest dietary concentration of FR-458. Urinary composition was unaffected by treatment with FR-458.

There were no organ weight changes and no treatment-related histopathological changes in rats that received FR-458.

Di-2 -ethylhexylphthalate (DEHP) - positive control substance:

Hairloss from the dorsal surface of rats receiving DEHP was recorded from the second week of treatment. Markedly low food consumption and bodyweight gain, and high food conversion ratio, were recorded for rats receiving DEHP. Rats receiving DEHP had higher platelet numbers than controls. Changes in rats receiving DEHP were minor and comprised high alkaline phosphatase activities, urea and albumin concentrations and albumin to globulin ratios in males, and low alanine and aspartate amino-transferase activities in females.

Organ weight analysis indicated markedly high liver and markedly low testes weights in rats receiving DEHP. At necropsy males receiving DEHP were found to have small, flaccid testes. Histopathological changes in animals that received DEHP comprised panacinar hepatocytic granular eosinophilic extensive cytoplasm in males and females, a lack of centriacinar hepatocytic glycogen in males, and a lack of germinal epithelium in the testes.

Applicant's summary and conclusion

Conclusions:
No clinical signs and no organ weight changes and histopathological changes in reproductive organs were found in male and female rats treated with 200, 2 000 or 20 000 ppm (= ca. 21.97, 223.4 or 2331 mg/kg/day) bis(2-ethylhexyl) tetrabromophthalate.
Therefore, the NOAEL for fertility is 20 000 ppm (ca. 2331 mg/kg bw).
Executive summary:

Bis(2-ethylhexyl) tetrabromophthalate was administered via the diet to three groups of ten male and ten female CD rats at concentrations of 200, 2 000 or 20 000 ppm (= ca. 21.97, 223.4 or 2331 mg/kg/day) for four weeks. At the end of the treatment period all animals were killed and necropsied. The pathologic evaluation consisted of organ weight, gross and microscopic examination of reproductive organs, incl. epididymides, mammary glands - caudal, ovaries, prostate, testes, and uterus (with cervix).

No clinical signs and no organ weight changes and histopathological changes in reproductive organs were found in male and female rats treated with 200, 2 000 or 20 000 ppm (= ca. 21.97, 223.4 or 2331 mg/kg/day) bis(2-ethylhexyl) tetrabromophthalate.

Therefore, the NOAEL for fertility is 20 000 ppm (ca. 2331 mg/kg bw).