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anging from 0.01-1.82 ppm had been in use for more than 45 years (Tseng et al., 1968, 1977).
40,421 inhabitants of 37 villages of the regions were examined for skin lesions, peripheral vascular
disorders and cancers. The study identified 7,418 cases of hyperpigmentation, 2,868 of keratosis
(Type A/benign), 428 of skin cancer (squamous cell carcinoma, basal cell carcinoma, in situ squamous
cell carcinoma, and Type B keratoses/intraepidermal carcinomas) and 360 cases of Blackfoot disease.
The incidence rates for keratosis and skin cancer were 183.5 and 10.6/1000, respectively. A control
population of 7,500 people did not exhibit any of the above disorders.
The above exposed population was divided into “low”, “mid” and “high” exposure groups based upon
the well-water arsenic concentration in each village (0.6 ppm, respectively). A
dose-response relationship was identified for the prevalence of skin cancer and Blackfoot disease (no
dose-response data was presented for hyperpigmentation and keratosis). The prevalence of both
disease was also found to increase with age. Males were found to have higher prevalence rates than
females (male to female ratios for skin cancer and Blackfoot disease were 2.9 and 1.3, respectively).
Additional studies of chronic human arsenic exposure resulting in increased skin cancer or internal organ
cancer incidence have been identified and reviewed (Fierz, 1965; Borgono and Greiber, 1972; Cebrian
et al., 1983; Yue-Zhen et al., 1985; Chen et al., 1985, 1986; reviewed by US EPA, 1988).
Animal Studies
There were two animal inhalation studies on the carcinogenicity of arsenic available at the time the
document Report to the Air Resources Board on Inorganic Arsenic. Part B. Health Effects of
Inorganic Arsenic Compounds was written (CDHS, 1990). Berteau et al. (1977, 1978) exposed
mice to a respirable aerosol of arsenic(III) (containing approximately 27 mg arsenic(III)/m 3 ) for 40
minutes/day for 26 days and 20 minutes/day thereafter. Inhaled doses were approximately 1.3 mg
arsenic/kg/day and 0.69 mg arsenic/kg/day. No evidence of neoplasia was observed grossly in
exposed animals.
In an inhalation study of arsenic trioxide, Glaser et al. (1986) exposed 20 rats for 18 months, at
approximately 60 µg arsenic/kg/day and 40 rats at approximately 20 µg arsenic/kg/day. No tumors
were observed in exposed animals. The report lacked important methodological details, including
sampling to verify exposure levels. Also, the study tested fewer animals than required by standard
cancer bioassay protocols.
In an arsenic (III) trioxide-treated group of 47 male hamsters, Pershagen et al. (1984) found three
carcinomas: two of bronchi or lungs (an adenocarcinoma, and an anaplastic carcinoma) and one of
larynx or trachea (a squamous cell carcinoma). These carcinomas were not statistically significant when
considered in relation to the concurrently treated controls but were statistically significant when
considering additional controls from the same colony (p = 0.01, one-tailed test). In female hamsters,
benign lung tumors (adenomas) were induced by intratracheal instillation of a suspension of solid arsenic
trioxide in a phosphate buffer (Ishinishi et al., 1983; Ishinishi and Yamamoto, 1983), but Ohyama et
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