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al. (1968) found no tumors in lifetime benzidine feeding study, but poor survival also limits the study’s
value.
Zabezhinski (1970) exposed 48 albino rats (male and female numbers not specified) to 10-20 mg/m 3
benzidine aerosol for 4 hours/day, 5 days/week for 20 months. Among animals surviving at 13 months,
5/28 developed leukemia (0/21 untreated; p =0.052)
Tumors have also been observed in animals injected subcutaneously with benzidine. They include
hepatocellular carcinomas, Zymbal gland tumors and injection-site tumors (Spitz et al., 1950; Bonser et
al, 1956; Pliss, 1964; Prokofjeva, 1971). Intraperitoneal injection of benzidine resulted in the induction
of mammary tumors in a single study (Morton et al, 1981).
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
The data presented by Zavon et al. (1973) are the only human cancer data appropriate for the
development of a cancer potency value for benzidine. The US EPA (1986, 1987, 1988), Allen et al.
(1987), and CDHS (1988) have each provided estimates of cancer potency based on human data.
However, different assumptions made in the calculation of exposure levels has resulted in different
estimates of the cancer potency. Potencies derived in these studies assume that cancer risk is
proportional to cumulative exposure. Previously, IARC (1982) had suggested that benzidine cancer
risk be based on the assumption that the empirical distribution of cumulative incidence rate is a function
of the duration of continual exposure. Derivations of cancer potencies from the human data using these
different methodologies and exposure assessments are described in the Methodology section below.
Cancer potency values have also been derived from animal studies, in particular those of Griswold et al.
(1968), Miakawa and Yoshida (1975), Saffioti et al (1967), and Littlefield et al. (1984). Resulting
potency estimates were well below those derived from the human data, suggesting humans may be more
sensitive to the carcinogenic effects of benzidine, and therefore animal data are not appropriate for use
in the establishing a cancer potency value. CDHS has based its benzidine cancer potency value on the
human data of Zavon et al. (1973) using exposure level assessment modifications of Allen et al. (1987)
and the methodology of US EPA (1986, 1987, 1988).
Methodology
US EPA (1986, 1987, 1988) made exposure estimates from the Zavon et al. study (1973) based upon
reported mean urinary concentrations of 0.04 mg/l. Assuming that average body weight is 70 kg,
average urinary output is 1.2 l/day, and 1.45% of absorbed benzidine is excreted in the urine, US EPA
calculated the average daily dose to be 0.047 mg/kg-day. Adjusting this value for work time exposure,
with 11.46 years the average time exposed, 56.5 years the average age of the cohort, and 240 work
days per year, final lifetime exposure levels were calculated to be 0.0063 mg/kg-day.
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