[Federal Register Volume 59, Number 137 (Tuesday, July 19, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-17445]


[[Page Unknown]]

[Federal Register: July 19, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

National Toxicology Program; Availability of Technical Report on 
Toxicology and Carcinogenesis Studies of Polybrominated Biphenyls 
(Firemaster FF-1)

    The HHS' National Toxicology Program announces the availability of 
the NTP Technical Report on the toxicology and carcinogenesis studies 
of Polybrominated biphenyls, synthetic chemicals used as flame 
retardants. The technical product used in these studies, Firemaster FF-
1, is a mixture of brominated biphenyls. Firemaster FF-
1 is a known liver carcinogen in rats and mice and is one of 
three compounds chosen by the National Toxicology Program to 
investigate the potential value of perinatal exposures in assessing 
chemical carcinogenicity.
    Chronic toxicity and carcinogenicity studies were performed by 
administering polybrominated biphenyls (Firemaster FF-1) at 
concentrations of 0, 1, 3, 10, or 30 ppm in feed to groups of 50 F344/N 
rats and B6C3F1 mice of each sex. The studies were designed to 
determine: a) the effects of polybrominated biphenyls in rats and mice 
receiving adult (F1) exposure only (a typical carcinogenicity 
study), b) the toxic and carcinogenic effects of polybrominated 
biphenyls in rats and mice receiving perinatal (F0) exposure only 
(dietary exposure of dams prior to breeding and throughout gestation 
and lactation), and c) the effects of combined perinatal and adult 
exposure to polybrominated biphenyls.
    Adult-Only Exposure: Under the conditions of these 2-year, adult-
only, dietary exposure studies, there was clear evidence of 
carcinogenic activity* for polybrominated biphenyls in male and 
female F344/N rats and male and female B6C3F1 mice based on 
increased incidences of hepatocellular neoplasms.
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    *The NTP uses five categories of evidence of carcinogenic 
activity observed in each animal study: two categories for positive 
results (``clear evidence'' and ``some evidence''), one category for 
uncertain findings (``equivocal evidence''), one category for no 
observable effect (``no evidence''), and one category for studies 
that cannot be evaluated because of major flaws (``inadequate 
study'').
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    Perinatal-Only Exposure: Perinatal exposure alone (through dietary 
administration of 10 ppm polybrominated biphenyls to the dams) had no 
effect on the incidences of neoplasms in female F344/N rats, but in 
male F344/N rats, perinatal exposure was associated with a marginally 
increased incidence of hepatocellular adenomas that may have been 
related to chemical administration. In male and female B6C3F1 
mice, perinatal exposure to 30 ppm polybrominated biphenyls resulted in 
significantly increased incidences of hepatocellular neoplasms. The 
incidences of a number of nonneoplastic lesions in the liver 
(cytomegaly, eosinophilic focus, and clear cell focus) were increased 
in male and female B6C3F1 mice.
    Combined Perinatal and Adult Exposure: Combined perinatal and adult 
dietary exposure to polybrominated biphenyls confirmed findings of the 
adult-only exposures for the increased incidences of hepatocellular 
neoplasms in F344/N rats and B6C3F1 mice. In male F344/N rats, 
there were no enhancing effects of combined perinatal and adult 
exposure. However, perinatal exposure enhanced the susceptibility of 
female F344/N rats receiving adult exposure of 10 or 30 ppm to the 
induction of liver neoplasms.
    For male and female F344/N rats, a combined analysis of the 
incidences of leukemia in the adult-only, perinatal-only, and combined 
perinatal and adult exposure groups revealed an apparent association 
between increasing incidences of mononuclear cell leukemia and exposure 
to polybrominated biphenyls.
    In male and female B6C3F1 mice, it was not possible to 
adequately assess the enhancing effects of combined perinatal and adult 
exposure on hepatocellular neoplasms, because adult-only exposure to 10 
or 30 ppm polybrominated biphenyls resulted in high incidences (84% to 
98%) of liver neoplasms. However, with increased perinatal exposure, 
there were increases in the numbers of B6C3F1 mice with 
hepatocellular carcinomas and in the numbers of B6C3F1 mice with 
multiple hepatocellular adenomas, which suggests an enhancement of 
polybrominated biphenyls-related hepatocellular carcinogenicity 
associated with perinatal exposure.
    Questions or comments about the Technical Report should be directed 
to Central Data Management at P.O. Box 12233, Research Triangle Park, 
NC 27709 or telephone (919) 541-3419.
    Copies of Toxicology and Carcinogenesis Studies of Polybrominated 
Biphenyls (Firemaster FF-1) (CAS No. 67774-32-7) in F344/N 
Rats and B6C3F1 Mice (Feed Studies) (TR-398) are available without 
charge from Central Data Management, NIEHS, MD A0-01, P.O. Box 12233, 
Research Triangle Park, NC 27709; telephone (919) 541-3419.

    Dated: July 12, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-17445 Filed 7-18-94; 8:45 am]
BILLING CODE 4140-01-M