Toxicological Sciences, Vol 48, 14-20, Copyright © 1999 by Society of Toxicology
RS Chhabra, RM Maronpot, JR Bucher, JK Haseman, JD Toft and MR Hejtmancik
Pentachlorophenol (PCP) has been used as an herbicide, algaecide,
defoliant, wood preservative, germicide, fungicide, and molluscicide. A
28-day toxicity study of PCP in F344/N rats of both sexes was conducted to
select dose levels for a carcinogenicity study. Groups of 10 male and 10
female rats were given 0, 200, 400, 800, 1600, or 3200 ppm PCP in feed for
28 days. The incidences of minimal to mild hepatocyte degeneration in males
and females exposed to 400 ppm or greater and the incidences of
centrilobular hepatocyte hypertrophy in the 3200-ppm groups were increased.
For carcinogenicity studies, groups of 50 male and 50 female F344/N rats
were fed diets containing 200, 400, or 600 PCP for 2 years. A stop-exposure
group of 60 male and 60 female rats received 1000 ppm of PCP in feed for 52
weeks and control feed thereafter for the remainder of the 2-year studies;
10 male and 10 female rats were evaluated at 7 months. Survival of 600-ppm
males was significantly greater than that of the controls; survival of all
other exposed groups was similar to that of the control groups. Mean body
weights of the 400- and 600-ppm groups were generally less than those of
the controls throughout the studies. There was no evidence of carcinogenic
activity of PCP in male or female rats fed diets containing 200, 400, or
600 ppm for 2 years. Stop-exposure study males and females regained a
transitory body weight reduction by the end of the 2 year study, and males
had better survival than the controls. At a 7-month interim evaluation, the
incidences of centrilobular hypertrophy in stop-exposure males and females
exceeded those in the controls. At 2 years, malignant mesothelioma
originating from the tunica vaginalis was present in 9 1000-ppm males and 1
control male (p = 0.014). Nasal squamous cell carcinomas were present in
five 1000-ppm males and 1 control male. This incidence was not
significantly increased but exceeded the historical control range (0-4%).
Based on the increased incidences of mesotheliomas and nasal tumors, there
was some evidence of carcinogenic activity of PCP in male rats given a diet
containing 1000 ppm for 1 year followed by control diet for 1 year. There
was no evidence of PCP carcinogenic activity in stop-exposure female rats.
ARTICLES
Toxicology and carcinogenesis studies of pentachlorophenol in rats
National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
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