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exposed more than 16 years before the time of the study. No bladder tumors were reported among the
study subjects.
Animal Studies
Stula et al. (1975) conducted a study on ChR-CD rats (50/sex/group), exposing animals to 1000 ppm
3,3’-dichlorobenzidine in feed for life (mean survival 51 weeks), with an interim exposed group of 6
rats/group sacrificed after 12 months. Control animals receiving no added compound were observed
for up to two years (mean survival 81 weeks (males) and 90 weeks (females)). Male animals showed
statistically significant increases in incidences of granulocytic leukemias (9/44 treated vs. 2/44 control; p
< 0.05 by Fisher’s exact test), mammary adenocarcinomas (7/44 treated vs. 0/44 control; p < 0.01),
and Zymbal gland carcinomas (8/44 treated vs. 0/44 control; p < 0.01). Female animals only showed
increased incidence of mammary adenocarcinomas (26/44 treated vs. 3/44 control; p < 0.01).
Stula et al. (1978) later conducted a study on six female beagle dogs, administering 100 mg 3,3’-
dichlorobenzidine in gelatin capsules 3 times/week for 6 weeks followed by 100 mg, 5 times/week for
up to 7.1 years, plus 6 untreated control animals sacrificed at 8-9 years of age. One animal which died
during the course of the study (3.5 years) showed no sign of tumors, whereas another animal which died
at 6.6 years showed both undifferentiated liver carcinoma and papillary transitional cell carcinoma of the
bladder. Among the animals surviving to the end of the study there was an increased incidence of
hepatocellular carcinoma (3/4 treated vs. 0/6 control; p < 0.05) and papillary transitional cell carcinoma
of the bladder (4/4 treated vs. 0/6 control; p < 0.01). Control animals showed a high incidence of
adenocarcinoma and carcinoma of the mammary gland (4/6).
Pliss (1959) reports on carcinogenesis in Rappolovskii white rats exposed to 3,3’-dichlorobenzidine in
feed for 12 months. The addition of 10-20 mg added to feed in the form of a paste (50% with water) 6
days/week resulted in an estimated total dose of 4.5 g/animal. A group of 130 animals receiving
injections of octadecylamine and methylstearylamine were termed a “historical control”. Twenty-two of
29 animals were examined for tumors at the time of the first tumor’s appearance. Findings included
tumors of Zymbal gland (7/29), mammary gland (7/29), skin (3/29), bladder (3/29), hematopoietic
system (3/29), adenocarcinoma of the ileum (2/29), connective tissue (2/29), salivary gland (2/29), liver
(1/29), and thyroid (1/29). No tumors were reported among “control” animals. Pliss (1959, 1963) also
conducted studies exposing rats to 3,3’-dichlorobenzidine by the subcutaneous route. In the first study
(Pliss, 1959), animals (25 female, 36 male) received 120 mg 3,3’-dichlorobenzidine weekly for 10-11
months. The dose was reduced to 20 mg/rat after the sixth month due to toxicity. The same
“control”animals were used as with the feeding study. The author notes the appearance of tumors of the
Zymbal gland (10/35), mammary gland (6/35), skin (5/35), hematopoietic system (2/35), connective
tissue (2/35), salivary gland (1/35), and local subcutaneous sarcomas (7/35) among animals surviving to
the time of the appearance of the first tumors.
Griswold et al. (1968) dosed 20 female Sprague-Dawley rats with 300 mg 3,3’-dichlorobenzidine in
sesame oil by gavage (10 doses at three day intervals) and observed the animals after 9 months for
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