Neurotoxicity and behavioral effects of thiram in rats.

Abstract

Eight of 24 female rats fed 66.9 mg/kg-day of thiram developed neurotoxicity. The neurotoxic effects were characterized by ataxia and paralysis of the hind legs. There were demyelination, degeneration of the axis cylinders, and presence of macrophages in the nerve bundle of the sciatic nerve. Degeneration in the ventral horn of the lower lumbar region of the spinal cord was evidenced by chromatolysis of motorneurons, pyknosis, and satellitosis. During a second experiment, 4 of 24 females fed 65.8 mg/kgday also developed ataxia and paralysis. An additional 9 females showed clasping of the hind feet when picked up by the tail. Nerve conduction could not be measured for one severely ataxic rat and the electromyogram indicated a loss of motor unit function. Histopathology of this rat, along with the others, suggests the peripheral nerve as the primary site of the lesion. Thiram also caused behavioral changes in apparently normal rats. The walking pattern of the hind legs was altered with decreases in stride width and the angle between contralateral steps. These rats required significantly more shockmotivations and cleared a lower height in a jump/climb ability test. An open-field study indicated that thiram caused hyperactivity in the nonataxic rats of both sexes. Three of 24 rats fed 95.8 mg/kg-day of ferbam also developed ataxia or paralysis.

High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes

“…The most potent hypoactive chemicals at 24 hpf (LEL ≤ 0.064 μL) were emamectin benzoate (Carmichael et al 2013 ), rotenone (Swarnkar et al 2011 ), triphenyltin hydroxide (Zsombok et al 1997 ), thiram (Lee and Peters 1976 ), mercuric chloride (Yasutake et al 2010 ), dapsone (Waldinger et al 1984 ), and fluconazole (van Schie et al 2011 ). Although all of these compounds have been implicated in nervous system perturbations related to neuromuscular dysfunction, this behavioral assay detected diverse mechanisms of action.…”

High-Throughput Cell-Based Screening of 4910 Known Drugs and Drug-like Small Molecules Identifies Disulfiram as an Inhibitor of Prostate Cancer Cell Growth

“…Thiram has been shown to block tumor angiogenesis in C6 glioma xenograft model, and to reduce metastases and spontaneous leukemia in rodents (33,34). However, large doses of thiram have also been reported to cause toxic effects such as neurotoxicity and muscle dysfunction in rats (35). Studies in cultured cells indicate that DSF inhibits myeloma, leukemia, lymphoma, small cell lung cancer, cervical adenocarcinoma, melanoma, neuroblastoma, and colorectal cancer cell survival as well as osteosarcoma invasion (36,37).…”

Proliferative and Nonproliferative Lesions of the Rat and Mouse Central and Peripheral Nervous Systems

“…In general, the term satellitosis should only be used after a critical comparison to the degree of satellite cells located near neurons in site-matched structures from control animals. The lesion has been described following such insults as lead acetate (Ozsoy et al 2010) and thiram (dimethylcarbamothioylsulfanyl N, Ndimethylcarbamodithioate, a fungicidee; Lee and Peters 1976).…”