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IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Human studies do not provide adequate data for the development of a cancer potency value because of
the presence of confounding factors in the studies (multiple compound exposures, no data on smoking
status) and no reporting of exposure levels. The animal study by Lijinsky (1986) showing development
of thyroid tumors in female rats, and forestomach papillomas and carcinomas in male and female mice
provides data from which cancer potency values can be derived.
Methodology
Cancer potency values were derived by US EPA (1989) from the tumor incidence data presented in the
study by Lijinsky (1986). The experimentally administered doses (15 and 30 mg/kg) were converted to
time-weighted dosage based on the dosing schedule (3 times/week) and the experimental duration
(107.5 weeks). The human equivalent dose (HED) was calculated based on an assumed experimental
animal body weight (bw a ) of 0.35 kg and human body weight (bw h ) of 70 kg using the following
relationship:
HED = time-weighted dose × (bw a /bw h ) 1/3
The calculated human equivalent doses in the Lijinsky (1986) study were 1.06 and 2.12 mg/kg-day. A
linearized multistage procedure (CDHS, 1985) was applied to the tumor incidence data for thyroid
tumors in female rats (4/52 controls, 8/51 low-dose, 14/52 high-dose), forestomach tumors in male
mice (0/51 controls, 5/50 low-dose, 32/52 high-dose) and forestomach tumors in female mice (0/52
controls, 5/50 low-dose, 19/51 high-dose). This resulted in estimations of the upper 95% confidence
bound of cancer potency (q 1 * ) of 0.17, 0.056, and 0.12 (mg/kg-day) -1 , respectively. Selection of the
cancer potency value is made in the most sensitive species and site; therefore, the cancer potency value
[0.17 (mg/kg-day) -1 ] derived from the female rat C-cell thyroid tumor data was chosen.
A unit risk value of 4.9 E-5 (µg/m 3 ) -1 was derived by ATES/OEHHA assuming a human breathing rate
of 20 m 3 /day, a human body weight of 70 kg, and 100% fractional absorption after inhalation exposure.
V. REFERENCES
Druckrey H, Kruse H, Preussmann R, Ivankovic S and Landschütz, C. 1970. Cancerogenic alkylating
substances. III. Alkyl-halogenides, -sulfates, -sulfonates and strained heterocyclic compounds. Z
Krebsforsch 74:241-273.
Hazardous Substances Data Bank (HSDB) 1994. National Library of Medicine, Bethesda MD (CD-
ROM Version). Micromedex, Inc., Denver, CO, Edition 22.
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