Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was performed by an experienced laboratory using the former lower purity DecaBDE commercial product (~77% BDE 209, ~22% NonaBDEs, 0.8% OctaBDEs).

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Toxicology of octabromobiphenyl and decabromodiphenyl oxide.
Author:
Norris et al.
Year:
1975
Bibliographic source:
Environ Health Perspect 11:153–161.
Reference Type:
publication
Title:
Toxicology and human health assessment of decabromodiphenyl ether
Author:
Hardy et al.
Year:
2009
Bibliographic source:
Critical Reviews in Toxicology 39(S3):1-44.
Reference Type:
publication
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Principles of method if other than guideline:
see below
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Former commercial product FR-300-BA composed of 77% BDE209, 22% NonaBDEs and 0.8% OctaBDEs.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 3, 30, 100 mg/kg/d
Basis:
actual ingested
No. of animals per sex per dose:
see belwo
Control animals:
yes, concurrent no treatment

Results and discussion

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
> 100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: lack of toxicity in all endpoints

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Using the low purity former DecaBDE commerc ial product, e.g. FR-BA-300, 77% BDE 209, 22% NonaBDEs, and 0.8% OctaBDEs, no effects on reproduction were observed in a one-generation study in rats at 100 mg/kg/d, the higherst dose tested.
Executive summary:

A one-generation reproduction test was conducted on male and female Sprague-Dawley rats (Norris et al., 1975). No adverse effects in either parent or F1 offspring were noted. Groups of male and female rats were maintained on diets containing sufficient FR-300-BA to provide dose levels of 0, 3, 30, or 100 mg/kg-day for 60 days prior to mating, 15 days during mating, and subsequently throughout gestation and lactation. There were 10 males and 20 females at the 2 lower dose levels, and 15 and 30 males and females, respectively, at the high-dose level. Twenty male and 40 female rats served as controls. The additional males and females were included with the controls and the group receiving the high dose level for tissue analysis for bromine content. After 60 days on the test diet, each male was placed with 2 females from the same treatment regimen for 15 days (3 estrus cycles). After the 15-day mating period, the males and females were separated and maintained on the appropriate treatment diets. The females continued to receive the test diets throughout gestation and for 21 days following parturition. After 21 days of lactation, the females and their young were killed and necropsied. The brain, heart, liver, and kidneys of 10 adult males (including testes) and females in each group were removed and weighed. Microscopic examination of approximately 30 tissues was performed on 5 animals/sex in the control and high-dose groups. Serum chemistries (blood urea nitrogen, ALP, and GPT) and urinalysis were performed on the control and highdose animals at termination (~day 120). Sections of brain, liver, kidney, pancreas, spleen, heart, lung, testes/ ovaries, adrenal gland, small intestine, large intestine, urinary bladder, and uterus were preserved from 1 male and 1 female of each litter for microscopic examination. After gross examination, the remaining weanlings of each litter were prepared for skeletal examination. Bone marrow was preserved from 5 male and 5 female adults and weanling animals/dose level at termination of the study for cytogenic evaluation. The results indicate that incorporation of the FR-300-BA in the diet of rats for 60 days prior to mating, and subsequently throughout mating, gestation and lactation had no effect

reproductive parameters or development. No signs of toxicity were observed in the adult rats or the neonates during the study or at necropsy. Unaffected parameters included body weight gain and food consumption by adults, reproductive parameters (the percent pregnant and neonatal growth, survival, and development), preterminal urinalyses and clinical chemistry measures in adult rats, gross and microscopic examination of selected tissues of all adult males, females, and weanling animals. Cytogenic aberrations were not detected in bone marrow collected from the femurs of adults or weanlings. Thus, no toxicological manifestations were associated with ingestion of the FR-300-BA at the highest dose level tested, 100 mg/kg-day.