[Federal Register Volume 59, Number 10 (Friday, January 14, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-912]


[[Page Unknown]]

[Federal Register: January 14, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

National Toxicology Program; Availability of Technical Report on 
Toxicology and Carcinogenesis Studies of Pentachloroanisole

    The HHS' National Toxicology Program announces the availability of 
the NTP Technical Report on the toxicology and carcinogenesis studies 
of pentachloroanisole, a chlorinated aromatic compound which is widely 
distributed at low levels in the environment and in food products. 
Formation of pentachloroanisole in the environment may result from the 
degradation of structurally related, commercially important, ubiquitous 
chlorinated aromatic compounds such as pentachlorophenol and 
pentachloronitrobenzene which are known rodent toxins or carcinogens.
    Two year toxicology and carcinogenesis studies were conducted by 
administering pentachloroanisole in corn oil by gavage 5 days per week 
for up to 2 years to groups of 70 male and 70 female rats and mice of 
each sex. Male rats received doses of 0, 10, 20, and 40 mg/kg of 
pentachloroanisole; female rats and mice received doses of 0, 20, and 
40 mg/kg pentachloroanisole.
    Under the conditions of these 2-year gavage studies, there was some 
evidence of carcinogenic activity\1\ of pentachloroanisole in male 
F344/N rats based on increased incidences of benign pheochromocytomas 
of the adrenal medulla. There was equivocal evidence of carcinogenic 
activity of pentachloroanisole in female F344/N rats based on 
marginally increased incidences of benign pheochromocytomas of the 
adrenal medulla. There was some evidence of carcinogenic activity of 
pentachloroanisole in male B6C3F1 mice based on increased incidence of 
benign pheochromocytomas of the adrenal medulla and hemangiosarcomas of 
the liver. There was no evidence of carcinogenic activity of 
pentachloroanisole in female B6C3F1 mice given doses of 20 or 40 mg/kg.
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    \1\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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    Pentachloroanisole administration was associated with increased 
incidences of adrenal medulla hyperplasia in female rats and increased 
incidences of pigmentation in the renal tubule epithelium, olfactory 
epithelium, and hepatocytes of male and female rats. In addition, 
decreased incidences of pancreatic adenomas and focal hyperplasia in 
male rats and decreased incidences of mammary gland fibroadenomas and 
uterine stromal polyps and sarcomas (combined) in female rats were 
observed. Hyperthermia-related lesions in male rats receiving 20 or 40 
mg/kg were considered indirectly related to pentachloroanisole 
administration.
    Pentachloroanisole administration was associated with increased 
incidences of adrenal medulla hyperplasia and hypertrophy and 
hepatocellular mixed cell foci in male mice. In male and female mice, 
nonneoplastic liver lesions associated with pentachloranisole 
administration included hepatocellular cytologic alteration, Kupffer 
cell pigmentation, biliary tract hyperplasia, and subacute 
inflammation.
    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 
Pentachloroanisole (CAS No. 1825-21-4) in F344/N Rats and B6C3F1 Mice 
(Gavage Studies) (TR-414) are available without charge from Central 
Data Management, NIEHS, MD AO-01, P.O. Box 12233, Research Triangle 
Park, NC 27709; telephone (919) 541-3419.

    Dated: January 7, 1994.
Kenneth Olden,
Director, National Toxicology Program.
[FR Doc. 94-912 Filed 1-13-94; 8:45 am]
BILLING CODE 4140-01-M