home edit2 whole TSD November 2002 PDF format - OEHHA

Ito et al. (1973) exposed groups of 12 mice to 500 ppm Kaneclor 500 (54% chlorine) in the diet for
32 weeks. No liver lesions were seen in 6 untreated controls. The incidence of hepatocellular
carcinoma in the treated mice was 5/12 and the incidence of liver nodules was 7/12.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
Several studies (Kimbrough et al., 1975; Schaeffer et al., 1984; Norback and Weltman, 1985;
Brunner et al., 1996) have demonstrated increased liver tumor incidence in rats exposed to PCB
mixtures. The mixtures found to induce liver tumors range in chlorine content from 60% (Aroclor 1260;
(Norback and Weltman, 1985; Brunner et al., 1996)), through 54% (Brunner et al., 1996), to 41%
(Brunner et al., 1996). Female Sprague-Dawley rat liver tumor incidence data for Aroclor 1260 from
the study by Norback and Weltman (1985) was chosen by US EPA as the basis of a cancer potency
value for "high risk and persistence" PCB exposures. Female Sprague-Dawley rat liver tumor incidence
data for Aroclor 1242 and 1016 from the study by Brunner et al. (1996) were chosen by US EPA as
the basis of cancer potency values for "low risk and persistence" and "lowest risk and persistence" PCB
exposures, respectively.
Methodology
The September 1996 US EPA document "PCBs: Cancer Dose-Response Assessment and Application
to Environmental Mixtures" (US EPA, 1996a) differs from the prior US EPA PCB risk assessment (US
EPA, 1988) which was also used for Proposition 65 purposes in that it includes data from a new study
of rats fed diets containing Aroclors 1260, 1254, 1242, or 1016 which found statistically significant,
dose-related, increased incidences of liver tumors from each mixture (Brunner et al., 1996). Earlier
studies used in the previous US EPA IRIS listing for PCBs found high, statistically significant incidences
of liver tumors in rats ingesting Aroclor 1260 or Clophen A 60 (Kimbrough et al., 1975; Norback and
Weltman, 1985; Schaeffer et al., 1984) in addition to partial lifetime studies which found precancerous
liver lesions in rats and mice ingesting PCB mixtures of high or low chlorine content. However, the
studies used for the previous IRIS listing had no data available indicating that PCBs with chlorine
contents of less than 60% induced frank tumors.
The new US EPA PCB risk assessment document also uses dose scaling to humans using a factor
based on the ¾ power of relative body weight. Cancer potency is described by an ED10 (estimated
dose associated with 10 percent increased incidence) and its lower bound, LED10. These measures
are expressed as equivalent human doses. Formerly, upper-bound slopes were calculated by the
linearized multistage procedure; these were reported as " q1*"s. The LED10 method and the linearized
multistage procedure give similar upper-bound slopes; for example, for female rats fed Aroclor 1254,
the LED10 method and the linearized multistage procedure give upper-bound slopes of 1.5 and 1.6 per
mg/kg-d, respectively. These changes conform to the 1996 draft US EPA cancer risk assessment
guidelines (US EPA, 1996b).
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