[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
