Pentachlorobenzene
J Liu, Oklahoma State University, Stillwater, OK, USA
Ó 2014 Elsevier Inc. All rights reserved.
l Trade Names: 1,2,3,4,5-Pentachlorobenzene; Benzene,
pentachloro-; Quintochlorobenzene.
l Name: Pentachlorobenzene
l Molecular Formula: C6HCl5
l Chemical Structure:
Cl Cl
Cl Cl
Cl
Background
Pentachlorobenzene (608-93-5) has historically been used as
an intermediate in the synthesis of several pesticides, in
particular the fungicide pentachloronitrobenzene. It can be
found as a contaminant in pentachloronitrobenzene formula-
tions. At one time, pentachlorobenzene was used as a fire
retardant. Today, it is primarily introduced into the environ-
ment through combustion of wastes.
Uses
Pentachlorobenzene is no longer used in the synthesis of
pentachloronitrobenzene and is no longer used in any form
as a biocide. It is being listed by the Persistent Organic
Pollutants Review Committee of the Stockholm Convention
as a persistent organic pollutant that should be eliminated
from any future uses. Unfortunately, pentachlorobenzene
can be produced unintentionally through waste
combustion.
Environmental Fate and Behavior
The half-life in water ranges from about 200 to 1250 days. The
estimated half-life for anaerobic degradation in deep water
ranged from about 800 to 1400 days. In sediment, the half-life
was estimated to be several years and in soil half-lives of
194–345 days were noted. Thus, pentachlorobenzene is highly
persistent in the environment. It should be noted that penta-
chlorobenzene can be and is produced unintentionally via
combustion.
Exposure and Exposure Monitoring
Inhalation and ingestion through contaminated food and
water are the primary routes of human exposures.
Encyclopedia of Toxicology, Volume 3 http://dx.doi.org/10.1016/B978-0-12-386454-3.00177-9
Toxicokinetics
Pentachlorobenzene can be absorbed readily through gastro-
intestinal and respiratory tracts in humans and experimental
animals. Chlorobenzenes accumulate primarily in fatty tissues
and have been shown to cross the placenta. Penta-
chlorobenzene is metabolized via cytochrome P450-dependent
processes to its major metabolites pentachlorophenol and
2,3,4,6-tetrachlorophenol. Food restriction was reported to
increase its metabolism. Metabolites are excreted in the urine as
mercapturic acids, or as glucuronic acid or sulfate conjugates.
Some proportion of the chemical is eliminated unchanged in
the feces.
Mechanism of Toxicity
There is little information available that describes the exact
mechanism of toxicity.
Acute and Short-Term Toxicity
Animal
Acute oral LD50 values for pentachlorobenzene were around
1 g kg 1 for adult male, adult female, and weanling female
rats. In mice, oral LD50 values were slightly higher (about
1.2–1.4 g kg 1 for males and for females). Clinical signs
included tremors and narcosis. Dermal dosages up to
2.5 g kg 1 did not elicit clinical signs in rats.
Human
The limited information regarding effects of chlorobenzenes on
human health is restricted to case reports and to mono- and di-
chloro congeners. Clinical signs and symptoms of excessive
exposure include central nervous system effects, irritation of the
eyes and upper respiratory tract, hardening of the skin, and
hematological disorders. No report is available specifically
regarding pentachlorobenzene in humans.
Chronic Toxicity
Animal
Weanling male rats fed 0, 125, or 1000 ppm penta-
chlorobenzene for 100 days and weanling females fed 0, 125,
250, 500, or 1000 ppm for 180 days exhibited no clinical signs
or body weight changes throughout the study. Suckling pups of
pentachlorobenzene-treated dams fed 250 ppm or higher
developed tremors and lethality was noted at 1000 ppm. Some
increases in adrenal and kidney weights were noted in adults
fed 1000 ppm. With 250 ppm or higher exposures, liver/body
weight ratios were increased in both adults and weanling
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774 Pentachlorobenzene
offspring, with hepatocellular enlargement most prominent
with the 500 and 1000 ppm groups. Changes in kidney were
also most prominent in the 1000 ppm group. Another
study reported that suckling pups from dams fed penta-
chlorobenzene at an exposure level of 12.5 mg kg 1 body
weight exhibited tremors on postnatal days 4–14. Thus,
tremors appear to be elicited in pups following lactational
exposure through the dams.
Human
Epidemiological information on potential chronic effects in
humans is not available. Little other information is available
on the potential for pentachlorobenzene to cause chronic
toxicity in humans.
Immunotoxicity
Very little information is available regarding penta-
chlorobenzene’s immunotoxic potential. One study reported
that IL-6 levels were reduced in cell cultures.
Reproductive Toxicity
Using an in vitro model, pentachlorobenzene was found to
accumulate in the porcine ovarian follicles and elicit a stimu-
latory effect on testosterone and estradiol secretion. Fertility
and fecundity were not affected in either sex of rats that were
pair-bred with untreated partners after 67 days of feeding with
pentachlorobenzene (up to 1000 ppm).
Genotoxicity
Pentachlorobenzene was negative in a number of in vitro gen-
otoxicity tests, including Ames mutagenicity tests with and
without metabolic activation, chromosomal alterations in
Chinese Hamster ovary cells, and micronuclei assays in
peripheral blood smears.
Carcinogenicity
Due to lack of human and animal data, pentachlorobenzene is
not classifiable as to human carcinogenicity.
Clinical Management
First aid should be provided based on the route of exposure.
Clinical treatment is symptomatic.
Ecotoxicology
Pentachlorobenzene is considered very toxic to aquatic organ-
isms. There is concern for long-term adverse effects in the
aquatic environment with pentachlorobenzene contamination.
Marine and freshwater organisms appear relatively similar in
sensitivity.
Exposure Standards and Guidelines
The most recent oral reference dose estimate was
0.8 mg kg 1 day 1.
Further Reading
Bailey, R.E., van Wijk, D., Thomas, P.C., 2009. Sources and prevalence of penta-
chlorobenzene in the environment. Chemosphere 75, 555–564.
den Besten, C., Peters, M.M., van Bladeren, P.J., 1989. The metabolism of pen-
tachlorobenzene by rat liver microsomes: the nature of the reactive intermediates
formed. Biochem. Biophys. Res. Commun. 163 (3), 1275–1281.
den Besten, C., Vet, J.J., Besselink, H.T., Kiel, G.S., van Berkel, B.J., Beems, R., van
Bladeren, P.J., 1991. The liver, kidney, and thyroid toxicity of chlorinated
benzenes. Toxicol. Appl. Pharmacol. 111 (1), 69–81.
Devos, S., Van Den Heuvel, R., Hooghe, R., Hooghe-Peters, E.L., 2004. Limited effect
of selected organic pollutants on cytokine production by peripheral blood leuko-
cytes. Eur. Cytokine Netw. 15 (2), 145–151.
Gregoraszczuka, E., Ptaka, A., Rak-Mardy1aa, A., Falandyszb, J., 2011. Differential
accumulation of HCBz and PeCBz in porcine ovarian follicles and their opposing
actions on steroid secretion and CYP11, CYP17, 17b-HSD and CYP19 protein
expression. A tissue culture approach. Reprod. Toxicol. 31 (4), 494–499.
Linder, R., Scotti, T., Goldstein, J., McElroy, K., Walsh, D., 1980. Acute and subchronic
toxicity of pentachlorobenzene. J. Environ. Pathol. Toxicol. 4 (5–6), 183–196.
Umegaki, K., Ikegami, S., Ichikawa, T., 1993. Effects of restricted feeding on the
absorption, metabolism, and accumulation of pentachlorobenzene in rats. J. Nutr.
Sci. Vitaminol. 39 (1), 11–22.
Relevant Websites
http://www.epa.gov/iris/subst/0085.htm – Environmental Protection Agency.
http://www.pops.int/documents/meetings/poprc/submissions/Comments_2008/
Canada_comments_PeCB.pdf – Persistent Organic Pollutants.
http://www.popstoolkit.com/about/chemical/pecb.aspx – Persistent Organic Pollutants
Toolkit.