PRINCIPLES OF TOXICOLOGY

376 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS
has been suggested by some researchers on the basis of results from genotoxicity assays, animal
experiments, and sporadic reports of excess human leukemias and lymphomas. These reports have
been difficult to substantiate.
Several chlorinated solvents (e.g., carbon tetrachloride, chloroform, tetrachloroethene, trichloroethene,
vinyl chloride) exhibit varying degrees of carcinogenic potential, notably hepatic tumors in
animals. The carcinogenic potential associated with trichloroethene (TCE) exposure has been of
interest since the mid-1970s, when the National Cancer Institute reported increases in liver cancer in
male mice that received TCE by gastric intubation. TCE, like some other chlorinated hydrocarbons,
exhibits limited and controversial mutagenic activity in bacterial test systems after microsomal
activation, so the mutagenic effect is probably dependent on the products of metabolism of this
compound. This has influenced recent concern about actual TCE potency. A similar conclusion applies
to the carcinogenic potential of tetrachloroethene, or perchloroethene (PERC). Although USEPA still
is reviewing the classification of TCE, other groups such as the American Conference of Governmental
Industrial Hygienists (ACGIH) no longer consider the substance to be a significant human carcinogenic
risk under occupational circumstances. A third group of agencies, including the Occupational Safety
and Health Administration (OSHA), and the International Agency for Research on Cancer (IARC),
have not released final positions with respect to carcinogenic potential of TCE.
Except for leukemogenic effects from extreme benzene exposure and hepatic angiosarcoma in vinyl
chloride workers, no unequivocal human reports are available that document cancer hazards from
exposure to the organic solvents. However, there are a number of epidemiologic observations that have
been published regarding cancer and exposure to chlorinated solvents. For example, both Hodgkin’s
and non-Hodgkin’s lymphomas have been linked to occupational exposure to some organic solvents
of the aliphatic, aromatic, and chlorinated types. In a cohort of laundry and dry-cleaning workers (with
putative TCE and PERC exposure), there was a slight excess of liver cancers (approximately 2.5-fold),
and in a case-referent study, a similar elevated incidence was reported for laundering, cleaning, and
other garment service workers. Additional data have suggested an association between exposure to a
variety of solvents and liver cancer, one of them showing an association for females only, whereas the
other study was restricted to males and found about a twofold risk. In a study of nearly 1700 dry-cleaner
workers with potential exposure to PERC, an increased incidence of urinary tract cancer was reported.
The conclusions from this and other studies are complicated by the fact that exposure to petroleum
solvents was likely as well. Another study of over 5300 dry-cleaner workers reported a slight excess
of cancer, with an overall ratio of only 1.2.
Recently, a cohort of nearly 15,000 aircraft maintenance workers with exposure to trichloroethene
and other solvents reportedly showed a decreased overall cancer mortality, but a calculated excess in
non-Hodgkin’s lymphoma, multiple myeloma, and bile duct cancers.
In addition to benzene and vinyl chloride, both of which are classified as Group A (Known Human
Carcinogen), several of the chlorinated solvents or their relatives still are classified by USEPA in the
B2 (Probable Human Carcinogen) or C (Possible Human Carcinogen) categories, based on historical
information. That information presently is under review by that agency. This approach generally is
consistent with both ACGIH and OSHA, as discussed elsewhere in this chapter.
Other Selected Acute Toxic Properties
As noted previously, the CNS-depressant and irritant properties are common to the chemicals usually
referred to as “solvents.” These two properties, as well as carcinogenic potential, are the focus of this
chapter because one or more of the properties are consistently observed in each chemical class
discussed. These classes of chemicals also may produce a number of other acute toxic effects upon
prolonged or high intensity exposure. After systemic absorption, acute effects may include hepatotoxicity,
nephrotoxicity, and cardiac arrhythmias that have been reported as a result of sensitization of
the heart to catecholamines (i.e., adrenaline). Although these effects are seldom reported in occupational
circumstances, they may occur for certain classes such as halogenated hydrocarbons, particularly
in chronic, high-level exposure. As noted previously, many of these substances were historically found