Enomoto A, Harada T, Maita K, Shirasu Y
Mitsukaido Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.
Toxicology. 1989 Jan;54(1):45-58. doi: 10.1016/0300-483x(89)90077-2.
A 24-month chronic feeding toxicity study with zinc dimethyldithiocarbamate (ziram) was performed on Fischer 344 rats of both sexes (80 animals/sex per group) at dietary levels of 0, 20, 200, or 2000 ppm. Eight animals of either sex from each group were sacrificed after 26, 52 and 78 weeks, and all surviving animals were killed after 104 weeks. Epiphyseal abnormalities in the long bones of the hind legs were observed in both sexes at 2000 ppm. Clinically, 3 male rats showed partial paralysis of the hind legs. At necropsy, marked curvature of the proximal end of the crus which could cause a restricted extension of the tibio-femoral joint was seen in 11 of 34 males killed at terminal sacrifice. While females had neither clinical signs nor gross abnormalities during the study, histopathological examination revealed retarded epiphyseal closure of the proximal end of the tibia in both sexes. Females also showed the epiphyseal lesion at the distal end of the femur. In severely affected rats marked proliferation of epiphyseal cartilaginous tissue was also noted together with the irregular arrangement of chondrocytes. These changes were evident only in aged animals. The incidence of the lesions in all males and females examined in this group was 22/77 (29%) and 13/73 (18%), respectively. The occurrence of the lesions appeared to be caused by impaired regulation of epiphyseal closure which might be related to the treatment with ziram.
