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Animal Studies
Male and female HaM/ICR mice and male Charles River CD-1 rats (25/sex/species/group) were
exposed to MOCA hydrochloride in the diet for 18 months by Russfield et al. (1975). Mice were fed
diet containing 0, 1000 or 2000 mg/kg diet MOCA hydrochloride; rats were fed diet containing 0, 500
or 1000 mg/kg diet MOCA hydrochloride. Surviving animals were killed after 24 months; about 55%
of the control and treated animals were still alive at 20-22 months. Hemangiomas or hemangiosarcomas
were noted in 0/10 control, 3/13 low dose and 8/20 high dose male mice; hepatomas were noted in
0/20 control, 9/21 low dose and 7/14 high dose female mice (p < 0.01, Fisher exact test), and in 0/22
control, 1/22 low dose and 4/19 high dose rats (p < 0.05, Cochran-Armitage trend test).
Male and female Charles River CD rats (50/sex/group) were fed diet containing 0 or 1000 mg/kg diet
MOCA in a standard diet (23% protein) for life (Stula et al., 1975). Average experiment duration was
80 weeks for treated and control males, 89 weeks for female controls and 78 weeks for treated
females. Six animals from each group were killed for an interim evaluation at one year. Lung
carcinomas were observed in 21/44 treated males (p < 0.05, χ 2 test) and in 27/44 treated females (p <
0.05, χ 2 test); a lung squamous-cell carcinomas was also observed in one treated male and female.
Pleural mesotheliomas occurred in 4/44 treated males and 2/44 treated females. Hepatocellular
adenomas and carcinomas occurred in 3/44 and 3/44 treated males and 2/44 and 3/44 treated females,
respectively. No lung tumors, pleural mesotheliomas or hepatocellular adenomas and carcinomas were
noted in control animals.
Male Charles River CD rats were fed a “protein-adequate” diet containing 0, 250, 500 or 1000 mg/kg
diet MOCA (group sizes 100, 100, 75 and 50, respectively) for 18 months followed by a 32 week
observation period (Kommineni et al., 1979). MOCA exposure was associated with decreased
survival; mean survival time was 89, 87, 80 and 65 weeks for controls, low-dose, mid-dose and highdose
animals, respectively. Dose-related increases in the incidences of lung tumors, mammary
adenocarcinomas, Zymbal gland adenocarcinomas and hepatocellular carcinomas were noted. Tumor
incidence data is listed in Table 1.
Table 1.
4, 4'-methylene bis(2-chloroaniline) (MOCA)-induced tumor incidence in male Charles
River CD rats (Kommineni et al., 1979)
Tumor type
dietary MOCA (mg/kg diet)
0 250 500 1000
lung tumors 1/100 23/100 28/75 35/50
Zymbal gland carcinomas 1/100 8/100 5/75 11/50
mammary adenocarcinomas 1/100 5/100 8/75 14/50
hepatocellular carcinomas 0/100 3/100 3/75 18/50
Stula et al. (1977) exposed a group of 6 female beagle dogs to a daily dose of 100 mg MOCA by
capsule 3 days/week for 6 weeks, then 5 days/week for up to 9 years. A second group of 6 females
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