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10,000 ppm 2,4,6-trichlorophenol in feed for 106-107 weeks, plus a control group of 20 rats/sex given
only standard feed. Tumor incidence data are presented in Table 2. Significant increases in
hematopoietic tumor (malignant lymphoma and monocytic leukemia) incidence was observed among
males of both the low-dose (p = 0.013) and high-dose (p = 0.002) groups.
In the same study (NCI, 1979), B6C3F 1 mice were treated with 2,4,6-trichlorophenol in feed for 105
weeks. Male mice (50/group) were treated with 5,000 or 10,000 ppm 2,4,6-trichlorophenol. Female
mice (50/group) were initially treated with diets containing 10,000 and 20,000 ppm 2,4,6-
trichlorophenol; however, indications of reduced growth rate at 38 weeks led the investigators to reduce
the level of compound to 2,500 and 5,000 ppm 2,4,6-trichlorophenol for the balance of the experiment,
leading to time-weighted average concentrations of 5,214 and 10,428 ppm. The control group
consisted of mice (20/sex) given the standard diet. Tumor incidence data are presented in Table 3. A
significant increase in hepatoma incidence was observed among male mice in both treatment groups and
among female mice in the high dose group (p < 0.001, Fisher’s exact test).
In an effort to establish whether 2,4,6-trichlorophenol may be acting as a tumor initiator, Bull et al.
(1986) treated female SENCAR mice (30/group) with 200 mg/kg 2,4,6-trichlorophenol by several
routes of exposure, including gavage, intraperitoneal injection, subcutaneous injection, and dermal
application, followed by dermal application of 1.0 µg 12-o-tetradecanoylphorbol-13-acetate three time
per week for 20 weeks. No skin tumors were found when survivors were examined 52 weeks after
first exposure.
Table 1.
Survival and tumor incidence in male and female B6AKF 1 and B6C3F 1 mice treated with
2,4,6-trichlorophenol (Innes et al., 1969).
tumor incidence
B6C3F 1 B6AKF 1
tumor type treatment 1 total male female male female
total tumors treated 16/36 9/18 2 7/18 3 3/17 2/17
control 30/166 22/79 8/87 16/90 7/82
hepatomas treated 5/36 4 3/18 2/18 5 1/18 1/18
control 17/166 17/79 0/87
reticulum cell treated 6/36 6 4/18 7 2/18 0/18 1/18
sarcomas control 5/166 3/79 2/87
1 B6C3F 1 and B6AKF 1 mice were treated with 100 mg/kg body weight 2,4,6-trichlorophenol by oral gavage from day 7
to 28 of life, then fed diet containing 260 ppm 2,4,6-trichlorophenol for 74 weeks, at which time surviving animals were
sacrificed.
2 p = 0.064, Fisher’s exact test.
3 p = 0.004, Fisher’s exact test.
4 p = 0.059, Fisher’s exact test.
5 p = 0.028, pairwise comparison of summary incidence data.
6 p = 0.005, Fisher’s exact test.
7 p = 0.021, pairwise comparison of summary incidence data.
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