Environmental Profiles of Chemical Flame-Retardant Alternatives for

Basis for Conclusion:
No repeated-exposure inhalation toxicity studies were located.
• 90-Day Inhalation Toxicity (OPPTS Harmonized Guideline 870.3465; OECD
Guideline 413)
No studies of this type were located.
REPRODUCTIVE TOXICITY
Conclusion:
The available reproductive toxicity data were judged inadequate to meet the endpoint.
Basis for Conclusion:
A fertility assay in male rabbits exposed by oral gavage for 12 weeks prior to mating (Ref. 62)
partially characterizes this endpoint, but is not sufficient to satisfy the reproductive toxicity
endpoint since it was described only in an abstract and females were not tested. Other studies
(Ref. 26, 59) described below under Developmental Toxicity reported that in pregnant female
rats exposed orally to Proprietary A, adverse reproductive effects occurred only at maternally
lethal doses. However, no study evaluated reproductive function in females treated prior to
mating.
The 2-year feeding bioassay in rats by Ref. 24 (Ref. 9, 9a), discussed below under Chronic
Toxicity, provides reproductive histopathology data that are, however, insufficient to satisfy the
reproductive toxicity endpoint. This study provided histopathology results for the testis,
epididymis, seminal vesicle, ovary, and uterus for the control and high-dose groups (0 and 80
mg/kg/day) after 1 year (10 scheduled sacrifices/sex/group) and for survivors in all groups after
2 years; unscheduled sacrifices (rats killed in a moribund state) were also examined. The 2-year
exposure is too long to represent reproductive toxicity, because of the confounding effects of
aging; the results pointed to dose-related effects in male reproductive organs (at $5 mg/kg/day,
atrophy and decreased secretory product of the seminal vesicles; at $20 mg/kg/day, testicular
germinal atrophy with oligospermia, and at 80 mg/kg/day, atrophy and decreased secretory
product of the seminal vesicles and oligospermia and luminal accumulation of degenerated
seminal products in the epididymis). No significant effect was observed in females. The tested
doses, which were considerably lower than the guideline limit dose of 1,000 mg/kg/day, were not
high enough to induce significant reproductive histopathology after one year of exposure; 1/10
high-dose males had oligospermia. Thus, a LOAEL for reproductive effects following
subchronic (90-day) exposure is not available and cannot be extrapolated from the existing data,
but the chronic data indicate a LOAEL of 5 mg/kg/day for atrophy and decreased secretory
product of the seminal vesicles.
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