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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Cited experiment was summarized in the National Toxicology Program-Center for the Evaluation of Risks to Human Reproduction Monograph on the Potential Human Reproductive and Developmental Effects of 2-Bromopropane; original study was not reviewed
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Principles of method if other than guideline:
No details on guideline used were provided. Six rats/dose/age group were injected sc with 0, 200, 600, or 1,800 mg/kg bw 2-bromopropane (99.6% purity), 5 days/week with treatment lasting for 5 and 7 weeks in mature and immature rats, respectively. The authors stated that although exposure through the sc route does not occur in occupational settings, sc injection was chosen to ensure complete and rapid absorption. The basis for dose selection was stated to be previous data and preliminary results. After treatment, reproductive performance was assessed in the mature rats by mating them 1:2 with untreated females for 7 days. Sperm quality and testicular histology (fixed in 10% formalin and stained with hematoxylin-eosin) were examined in both age groups. Mature rats were sacrificed 4 days after mating to allow for restoration of sperm levels. Immature rats were sacrificed immediately after the treatment period. Analysis of data included ANOVA and Dunnett's test for weight effects, the Kruskal-Wallis or Mann-Whitney test for sperm, fetal, and hormonal data, and the chi square test for reproductive function data.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Several effects were noted in both mature and immature rats at the lowest dose (200 mg/kg bw) and included dose-related reductions in sperm count and viability, and increases in deformed sperm and testicular lesions. Testicular lesions increased in severity with dose and included atrophied seminiferous tubules with reductions in germ cell numbers. Serum testosterone levels were first reduced at 200 and 600 mg/kg bw in mature and immature rats, respectively. A dose-related reduction in absolute and relative testicular weight was first noted in mature and immature rats at the 600 mg/kg bw dose. Bodyweight gain was significantly reduced in mature rats exposed to >=600 mg/kg bw and immature rats at all dose levels. Additional effects seen at the highest dose level (1,800 mg/kg bw) in both age groups included reductions in absolute epididymis, prostate seminal vesicle, and pituitary weight and relative epididymis weight. Dose-related adverse effects on the reproductive performance of mature rats were first noted at 600 mg/kg bw and included reduced mating and pregnancies and an increase in the number of days for pregnancy initiation to occur. Effects also noted in dams mated with the high dose group (1,800 mg/kg bw/day) included a reduced number of implantation sites and increased fetal mortality. Expression of B-luteinizing hormone gene was measured in mature rats and was found to be increased in rats treated with 1,800 mg/kg bw. Based on testicular and sperm effects, the authors estimated that the NOAEL for 2-bromopropane was below 200 mg/kg bw/day.

Applicant's summary and conclusion

Conclusions:
In this key study, a NOAEL for 2-bromopropane was determined to be below 200 mg/kg bw/day in the male rat, based on adverse effects to the male reproductive organs and sperm effects.