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It has been considered that cortical malformation in the brain of the reeler mutant mouse is due to a defect in the process of neuroblast migration during development. We examined the process of Purkinje cell migration in the cerebellar primordium of the reeler mutant immunohistochemically and electron-microscopically, employing a specific marker for Purkinje cells and markers for radial glia. To facilitate the recognition of the homozygote of the reeler mutation (r1) at the embryonic stage, we introduced the chromosome carrying the autosomal semi-dominant mutation, hammer-toe (Hm), by crossbreeding and backcross into the heterozygote of the reeler mutation, which is an autosomal recessive and located on the homologous chromosome. Using this double heterozygous strain (+/rl-Hm/+), the homozygote of rl can be selected from littermates by the normal appearance of the feet. Both the heterozygous rl embryos and non-carriers harbor the Hm locus and show the Hm phenotype as a deformity of the feet that can be recognized from the 15th day of gestation. In the cerebellar primordium of control mice, Purkinje cells migrated radially from the ventricular zone towards the cortex. In contrast, most of the migratory Purkinje cells remained in the intermediate zone, and their migration towards the cortex was obstructed in the cerebellum of the reeler mutant. A disorganized arrangement of both the processes and cell bodies of the radial glia was demonstrated in the cerebellar primordium of the reeler by labeling them with the antibody against tenascin, a neuron-glial adhesion molecule, and the monoclonal antibody 1D11, a marker for immature astroglia. Electron-microscopic observations revealed apposition of the migratory cells to the radially oriented glial processes in the intermediate zone of the control cerebellum. In contrast, the apposition of leading processes of the migratory neuroblasts to disorganized processes of the radial glia was observed in the intermediate zone of the reeler cerebellum. These findings suggest that the obstructed migration and disordered cortical alignment of Purkinje cells in the reeler cerebellum is due to dysgenesis and abnormal development of radial glia, resulting in disturbance of contact guidance in the process of Purkinje cell migration.

1-Bromopropane has been newly introduced as an alternative to ozone layer-depleting solvents. We aimed to clarify the dose-dependent effects of 1-bromopropane on the nervous system. Forty-four Wistar male rats were randomly divided into 4 groups of 11 each. The groups were exposed to 200, 400, or 800 ppm of 1-bromopropane or only fresh air 8 h per day for 12 weeks. Grip strength of forelimbs and hind limbs, maximum motor nerve conduction velocity (MCV), and distal latency (DL) of the tail nerve were measured in 9 rats of each group every 4 weeks. The other 2 rats of each group were perfused at the end of the experiment for morphological examinations. The rats of the 800-ppm group showed poor kicking and were not able to stand still on the slope. After a 12-week exposure, forelimb grip strength decreased significantly at 800 ppm and hind limb grip strength decreased significantly at both 400 and 800 ppm or after a 12-week exposure. MCV and DL of the tail nerve deteriorated significantly at 800 ppm. Ovoid or bubble-like debris of myelin sheaths was prominent in the unraveled muscular branch of the posterior tibial nerve in the 800-ppm group. Swelling of preterminal axons in the gracile nucleus increased in a dose-dependent manner. Plasma creatine phosphokinase (CPK) decreased dose-dependently with significant changes at 400 and 800 ppm. 1-Bromopropane induced weakness in the muscle strength of rat limbs and deterioration of MCV and DL in a dose-dependent manner, with morphological changes in peripheral nerve and preterminal axon in the gracile nucleus. 1-Bromopropane may be seriously neurotoxic to humans and should thus be used carefully in the workplace.

Testicular and Hematopoietic Toxicity of 2‐Bromopropane, a Substitute for Ozone Layer‐Depleting Chlorofluorocarbons: Gaku Ichihara, et al. Department of Hygiene, Nagoya University School of Medicine—In 1995r unexpected amenorrhea, oligozoospermia and anemia were discovered in Korean workers exposed to solvents containing 2‐bromopropane which was a substitute for chlorofluorocarbon. We aimed to determine experimentally the testicular and hematopoietic toxicity of 2‐bromopropane in male rats. Thirty‐six Wistar male rats were divided into four groups of nine each. The rats were exposed to 300r 1,000 and 3,000 ppm 2‐bromopropane or only fresh air, respectively, 8 hr a day, 7 days per week. The 300 ppm and 1,000 ppm groups were exposed for 9 weeks, but the 3,000 ppm group's exposure was discontinued and three rats in this group were dissected after 9‐11 days’ exposure because of serious illness. The others were dissected at the end of the experiment. At 300 ppm or over, the testicular and epididymal weights per body weight, epididymal sperm count, motile sperm percentage and the number of erythrocytes and platelets had decreased compared to the control. Histopathologically, all types of germ cells decreased in the 300 ppm group. Germ cells were absent but Sertoli cells still remained in the 1,000 ppm and 3,000 ppm groups at the end of the experiment. Spermatogonia were absent and the number of spermatocytes decreased in the 3,000 ppm group rats sacrificed after 1 1 days’ exposure. Sertoli cell vacuolations were marked in two of these three rats. Bone marrow was hypocellular in the 1,000 ppm group and in all the rats in the 3,000 ppm group. These results clearly showed that 2‐bromopropane had a testicular and hematopoietic toxicity in male rats.

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ABSlRACT The neurotoxicity of n-pentane, n-hexane, and n-heptane have been studied in Wistar strain male rats after exposure to 3000 ppm of n-pentane, n-hexane, or n-heptane for 12 hours a day for 16 weeks. The nerve conduction velocity and the distal latency were measured before the beginning of the exposure and after exposure for four, eight, 12, and 16 weeks. The experiment showed that n-hexane disturbed the conduction velocity of the motor nerve and the mixed nerve and prolonged the distal latency in the rat's tail, but that n-pentane and n-heptane did not. The light and electron microscopic examination showed that the peripheral nerve, the neuromuscular junction, and the muscle fibre of the rats exposed to n-hexane were severely impaired, but those of the rats exposed to n-pentane or n-heptane showed no particular changes even after 16 weeks of exposure. These results show that n-hexane is far more toxic to the peripheral nerve of the rat than n-pentane or n-heptane. It is necessary to study the neurotoxicity of other petroleum hydrocarbons, since some reports suggest that petroleum solvents might possibly contain neurotoxic hydrocarbons other than n-hexane.For many years petroleum solvents had been considered to be relatively non-toxic, although they were recognised as being fire hazards.' 2 One of the main ingredients in many petroleum solvents, n-hexane, was one of those considered to be non-toxic, but recently many cases have been reported of polyneuropathy caused by commercial hexane or by petroleum solvents containing n-hexane.3-9 Animal experiments have shown that commercial hexane and pure n-hexane could damage the peripheral nerves of mice and rats'0-'3 and also the central nervous system of rats and cats.12 1415 Therefore many cases of polyneuropathy that have occurred in factories where organic solvents were used have been attributed by many researchers to n-hexane. Commercial hexane, however, usually contains not only n-hexane but also its isomers and other hydrocarbons. For example, hexane used in the manufacture of vinyl sandals was found to contain n-hexane, 2-methylpentane, 3-methylpentane, and methylcyclopentane, with n-hexane accounting for about 60 % of the total. caused by a petroleum solvent containing 5 % hexane, 14% heptane, and 80% pentane in a beltmanufacturing shop.7 A petroleum benzine that caused five cases of polyneuropathy in a workshop cleaning silk brocade sash contained C5 to C9 hydrocarbons-that is, n-pentane to n-nonane and their isomers-and n-hexane accounted for only 12-3 % of the total.8 The solvents and glues used in the shoe factories where 20 workers developed polyneuropathy were reported to contain 79 %-95 % of alkanes including n-pentane, n-hexane, n-heptane, and their isomers.

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