Hind limb paralysis

Rabbit (New Zealand) 52-163 d 34 102 (hind limb paralysis in 3/3 rabbits) Siegel etal. 1965 TAP1... 

Mice exposed continuously to 100 ppm or intermittently to 400 ppm for 11 days had histopathologic evidence of brain lesions characterized by degeneration and atrophy of the granular layer of the cerebellum. Daily exposure of mice to 1000 ppm for 2 years induced a functional limb muscle impairment and atrophy of the spleen. At 2400ppm administered daily, there were renal and hematopoietic effects and the mice were moribund by day 9. For rats exposed to 3 500 ppm 6 hours/day for up to 12 days, clinical signs included severe diarrhea, incoordination of the forelimbs, and, in a few animals, hind limb paralysis and convulsions. ... 

Findings in rats exposed at 750 or 1500 ppm for 13 weeks included hind limb paralysis, anemia, olfactory epithelial degeneration, and minimal to mild degeneration of the sciatic nerve and the lumbar spinal cord. ... 

There are no studies of musculoskeletal effects following oral exposure to maneb in animals or to mancozeb in humans. Hind limb paralysis has been observed in adult male rats administered a dose as low as 375 mg/kg/day mancozeb for 90-360 days (Kackar et al. 1997a, 1997b Trivedi et al. 1993). Because there is little other evidence for an adverse effect of manganese on the musculoskeletal system, this is likely related to a neurologic effect with effects on the musculature being secondary. 

The rabbit has also been used as a model for manganese toxicity in a few studies (Chandra 1972 Szakm y et al. 1995). The only available neurotoxicity study using the rabbit (Chandra 1972) reported that the species, when dosed intratracheally with 253 mg manganese/kg body weight (inferred as a 1-time dose), developed hind-limb paralysis after an observation period of 18 months. The animals also exhibited widespread neuronal degeneration in the brain. This study suggests that rabbits and humans may be qualitatively similar in the manifestation of neurobehavioral effects. However, further studies are needed to determine if the two species manifest comparable symptoms within the same dose range. 

Mouse P caribaeorum 0.72 (0.64-0.80) Abnormal gait, splaying of hind limbs, paralysis, dyspnea, deafii. No diarrhea No peritonitis or ascites. No other macroscopic changes [20]... 

Mouse L pictor, crude extract — Hind limb paralysis, cyanosis, convulsions, respiratory collapse, exophfiialmus, deafii wifiiin 2 h — [47]... 

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