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IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
In the absence of studies in humans useful in evaluating the carcinogenicity of bis(2-chloroethyl)ether, a
single animal study (Innes et al., 1969) has been identified as appropriate for the development of a
cancer potency value. The most sensitive endpoint from this study is the development of hepatomas in
treated male strain X rats. Other studies either do not show development of tumors (Weisburger,
1981) or experimental duration/dosing limited the interpretation of negative data (Van Duuren, 1972;
Theiss, 1977).
Methodology
Lifetime average dose estimates from the Innes et al. study (1969) have been calculated to be 39
mg/kg-day bis(2-chloroethyl)ether (US EPA, 1980). A linearized multistage procedure polynomial was
applied to the tumor incidence data (CDHS, 1985; Anderson, 1983). The upper 95% confidence
bound on the cancer potency estimate is termed q 1 * . Using the data presented in Table 1, the following
cancer potencies were derived from groups showing significant increases in hepatoma incidence:
animal group q * 1 (mg/kg-day) -1
Strain X - males 0.086
Strain X - females 0.013
Strain Y - males 0.031
The selection of the cancer potency value has been based on the q 1 * value from the most sensitive sex
and strain in this case, 0.086 (mg/kg-day) -1 in Strain X males derived from Innes et al.(1969).
Calculation of the cancer potency in animals (q animal ) can be made from the following relationship, where
T is the natural lifespan of the animal (104 weeks) and T e is the experimental duration (80 weeks):
q animal = q 1 * × (T/T e ) 3
The resulting q animal is 0.19 (mg/kg-day) -1 . Conversion to human cancer potency (q human ) is based on
the following relationship, where bw animal is the assumed body weight for the test species (0.03 kg -
mice; US EPA, 1980) and bw human is the assumed human body weight (70 kg):
q human = q animal × (bw h /bw a ) 1/3
The estimate of q human based on this relationship is 2.5 (mg/kg-day) -1 . A unit risk value based upon air
concentrations was derived by OEHHA/ATES assuming a human breathing rate of 20 m 3 /day, 100%
fractional absorption, and average human body weight of 70 kg. The calculated unit risk value is 7.1 E-
4 (µg/m 3 ) -1 .
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