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numbers of mice of each sex were at risk for tumor development for determination of tumor incidence
significance. The percentage of mice surviving to study week 52 was at least 95% for all sexes and
treatment groups. No significant tumor incidence increase was observed in male or female F344 rats as
a result of p-chloro-o-toluidine exposure. Significant treatment-related increases (p < 0.001) were
observed in the incidence of both hemangiosarcomas and hemangiomas and hemangiosarcomas
combined in both male and female mice. Tumor incidence data is listed in Table 1.
Table 1:
Incidence of vascular tumors (hemangiomas and hemangiosarcomas) in male and female
mice treated with p-chloro-o-toluidine hydrochloride by dietary administration
Study Sex/Strain Dietary
concentration
(mg/kg diet)
Weisburger et al.
(1978) 2
male CD-1 0
750
1500
female CD-1 0
2000
Weisburger et al.
(1978) 3
NCI (1979) 2 male B6C3F 1 0
3750
15000
NCI (1979) 3 female B6C3F 1 0
1250
Average Dose 1
(mg/kg-day)
0
90
180
0
260
0
450
1800
0
162
Tumor Incidence
0/14
12/20
13/20
0/15
18/19
0/20
6/50
41/50
1/20
43/50
1. Doses as reported by Gold et al. (1984).
2. Decreased survival according to Gold et al.; a time-to-tumor analysis was performed using
TOX_RISK (Crump et al., 1991; Cal/EPA, 1992).
3. Analysis of the data set using the computer program TOX_RISK (Crump et al., 1991)
indicated that inclusion of the high dose group resulted in a p-value of = 0.05 based on the chisquare
goodness-of-fit test, indicating non-linearity. Following procedures described by US
EPA (Anderson et al., 1983; US EPA, 1986), the high dose group was excluded from the
analysis to correct for the poor fit (Cal/EPA, 1992).
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
On the basis of positive bioassay results, the hydrochloride salt of p-chloro-o-toluidine was classified as
a compound with sufficient evidence of carcinogenicity in animals by IARC (1987). The results of
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