home edit2 whole TSD November 2002 PDF format - OEHHA

NTP (1982b) also conducted a dermal oncogenicity bioassay on TCDD in male and female
Swiss-Webster mice. TCDD in an acetone suspension was applied to the skin three days per week for
104 weeks. The male rats received 0.001 µg per application and the females received 0.005 µg per
application. Separate groups of male and female mice were treated with one application of 50 µg
7,12-dimethylbenz(a)anthracene (DMBA) one week prior to the start of TCDD treatments. The only
significantly (p = 0.01) increased incidences of tumors observed were among female mice. Both the
TCDD- and DMBA/TCDD-treated groups had a similar incidences of fibrosarcoma in the
integumentary system (8/27 and 8/29, respectively), compared to the vehicle control of 2/41. In NTP's
judgement, the results of this experiment indicated that TCDD was carcinogenic.
HexaCDDs have been tested for carcinogenicity by NTP (1980a) in both Osborne-Mendel rats and
B6C3F l mice. The bioassay tested a mixture of HexaCDDs containing 31 percent
1,2,3,6,7,8-HexaCDD and 67 percent l,2,3,7,8,9-HexaCDD. Lower chlorinated PCDDs made up the
remaining 2% of the mixture, including 0.04 percent TetraCDDs. Male and female rats and male mice
received weekly doses of 1.25, 2.5 or 5 µg/kg, administered by gavage twice a week. The female mice
were administered doses of 2.5, 5.0, or 10 µg/kg/week.
A dose-related "toxic hepatitis", which was noninflammatory and consisted of degenerative changes in
the liver, was observed in treated rats. The treated groups of female rats had significantly increased
incidences of liver neoplastic nodules. Four high-dose animals were diagnosed as having hepatocellular
carcinoma. The mice also had a dose-related incidence of "toxic hepatitis" and the high-dose male and
female mouse groups had statistically significant increased incidences of hepatocellular adenomas and
combined incidences of hepatocellular adenomas and carcinomas. The incidences of these tumors are
given in Table 4.
Table 4: Tumor incidences in female Osborne-Mendel rats and male and female B6C3F l
mice given HexaCDD by gavage for two years (NTP, 1980a)
Sex, species, tumor type
Dose level (µg/kg-week)
0 1.25 2.5 5.0
(2.5) (5.0) (10)
Tumor incidence
female rat
liver, neoplastic nodule or 5/75 10/50 (p = 0.026) 12/50 (p = 0.007) 30/50 (p < 0.001)
hepatocellular carcinoma
male mice
liver, hepatocellular adenoma 7/73 5/50 9/49 15/4 (p = 0.003)
liver, hepatocellular adenoma or carcinoma 15/73 14/50 14/49 24/48 (p = 0.001)
female mice
liver, hepatocellular adenoma 2/73 4/48 4/47 9/47 (p = 0.003)
liver, hepatocellular adenoma or carcinoma 3/73 4/48 6/47 10/47 (p = 0.004)
P values determined using Fisher’s exact test.
a Dose administered to male mice; dose administered to female mice in parentheses.
b Number of animals with tumor over number of animals examined.
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