Method of establishing exposure limits for inhaled chamecal sustances

为了提高现行接触限值的可靠性或对新化学品提出新的推荐限值，研究了以下几个特殊问题。为了从实验动物到人类进行合理的种属间外推，结果表明两种属之间的代谢和毒代动力学数据差异是根本性的。这一发现是通过使用两种有机溶剂，间二甲苯和氯仿的模型实验得到的.过渡金属的毒性通常根据价态而不同.汞蒸气和无机汞化合物显示出不同的毒性，并建议应考虑到这种差异设置适当的接触限值.当考虑这些化学品的接触限值时，对化学品的超敏反应是一个难题。钴，敏化金属之一，是这类化学品的一个例子。本文以钴作业工人为研究对象，结合生活方式的影响因素，探讨了钴接触限值的确定方法。铅和镉等常见金属元素的接触限值已相当明确，但最近人们更多地认识到利用血液、尿液和其他生物标本进行生物监测的有用性。通过对两种金属接触工人的队列观察，表明生物监测对个体危险性评价的准确性优于环境空气监测，并对有机溶剂的神经毒性进行了研究，明确了胶质细胞标记物作为敏感毒性指标的作用。本文研究了甲苯、二甲苯混合物对作业工人的毒性，提出了混合物接触限值的建议。最后，作为日本职业卫生协会推荐的职业接触限值的补充，编制了致敏化学品清单。

For the purpose of improving the reliability of current exposure limits or to newly recommend limits for novel chemicals, following supecific problems were investigated. To make reasonable inter-species extrapolation from experimental animals to humans, it was shown that the differences of metabolism and toxicokinetic data between the both species are fundamental. This finding was obtained by model experiments using two organic solvents, m-xylene and chloroform.The toxicities of the transient metals generally differ according to the valency states.Mercury vapor and inoganic mercury compounds were shown to have different toxicity, and it was proposed that proper exposure limits should be set considering this difference. The hypersensitivity to chemicals poses a difficult problem when exposure limits for these chemicals ara considered. Cobalt, one of the sensitizing metals, is an example of this type of chemicals. The method of establishing exposure limits for cobalt was studied on cobalt-exposed workers in reference with several life style determinants. The exposure limits for such polular metal elements as lead and cadmium have been fairly well established, but the usefulness of biological monitoring by the use of blood, urine and other biological specimens has been morre recognized recently. Cohort observation on he workers exposed to these two metals clearly indicated that the biological monitoring is super to ambient air monitoring in accuracy of risk evaluation of individual workers.The neurotoxicity of organic solvents were investigated and the usefulness of glia markers as a sensitive toxicity parameter was made clear. The toxicity of the mixture of tolene and xylene was studied on the exposed workers and a proposal was made on the exposure limit for the mixture of these chemicals. Finally, a list of sensitizing chemicals wasmade as the supplement for the list of occupational exposure limits recommended by Japan Association of Occupational Health.