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Sorahan et al. (1983) studied cancer mortality among British workers occupationally exposed to a
number of compounds including toluene, benzotrichloride, benzoyl chloride, benzyl chloride, and benzal
chloride during the course of producing chlorinated toluenes. Five digestive system cancers and 5
respiratory system cancers were reported among 163 male workers employed more than 6 months
between 1961 and 1970. Expected mortality rates from these tumors in England and Wales were 1.24
and 1.78, respectively, and the mortality ratio was significantly elevated. Smoking rates were not
reported among the workers. Cumulative exposure and death from any cancer among workers
employed before 1951 was shown to be significantly correlated by survival analysis using the Cox
Proportional Hazard Model, although this was not the case when entry cohorts were combined.
Wong and Morgan (1984) studied cancer mortality among a cohort of 697 workers employed from 1
to more than 35 years in a chlorination plant in Tennessee. Workers were exposed to benzyl chloride,
benzoyl chloride, and benzotrichloride. Deaths from respiratory cancers were reported for 7 workers,
5 of whom were exposed for more than 15 years. Expected mortality for U.S. males in a group of this
size was 2.84 deaths (1.32 deaths for the subgroup exposed > 15 years). No data on smoking was
reported.
Animal Studies
Lijinsky (1986) treated F344 rats (52/sex/dose) and B6C3F 1 mice (52/sex/dose) with benzyl chloride
in corn oil by gavage. The rats were dosed with 0, 15, and 30 mg/kg/day benzyl chloride and mice with
0, 50 and 100 mg/kg/day benzyl chloride, with treatments 3 days/week for 2 years. Animals were
histopathologically examined 3-4 weeks after the end of the treatment using the NCI bioassay protocol.
Survival in both species was not significantly affected by treatment. The incidence of C-cell
adenoma/carcinoma of the thyroid was significantly increased in female rats in the high-dose group
compared to control animals (14/52 treated vs. 4/52 control; p < 0.01 by Fisher’s exact test). In male
mice in the high-dose group, significantly increased incidences were found for
hemangioma/hemangiocarcinoma (5/52 treated vs. 0/52 control), forestomach carcinoma (8/52 treated
vs. 0/51 control) and forestomach carcinoma/papilloma (32/52 treated vs. 0/51 control). In male mice
in the low-dose group only, an increased incidence of hepatic carcinoma/adenoma (28/52 treated vs.
17/52 control) was reported. In female mice in the low- and high-dose groups, an increased incidence
of forestomach carcinoma/papilloma (5/50 low-dose, 19/51 high-dose vs. 0/52 control) was reported.
Injection-site sarcomas developed in 3 of 14 BD-strain rats administered benzyl chloride in peanut oil
subcutaneously weekly for 51 weeks at 40 mg/kg-week and 6 of 8 rats administered 80 mg/kg-week
(Druckrey et al., 1970). Mean induction time was 500 days.
Poirier et al. (1975) treated A/H mice (20/dose) 3 times weekly over 24 weeks intraperitoneally with a
total dose of 0.6, 1.5 or 2 g benzyl chloride/kg body weight in tricaprylin. Surviving animals were
sacrificed at 24 weeks. Among the survivors, lung tumors were found in 4/15, 7/16, and 2/8 animals,
respectively. Animals treated with tricaprylin alone had an average of 0.22 lung tumors/mouse and
animals receiving no treatment had 0.21 lung tumors/mouse. The incidence of lung tumors in treated
animals was not found to be statistically significant from control animals.
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