Toxicol Ind Health. 2019 Mar;35(3):189-195. doi: 10.1177/0748233719825531. Epub 2019 Feb 13.
1,1,1,3,3,3-Hexamethyldisilazane (HMDZ) is used industrially to treat the surface of silica, as an intermediate adhesion promoter or silylating agent in the semiconductor industry, as a chemical modifier of inorganic fillers, and as a water scavenger silicone sealant. In animal studies, HMDZ is considered to be slightly to at most moderately toxic following acute administration via oral, dermal, and inhalation routes of exposure. HMDZ is neither an eye irritant nor was it dermally irritating under semiocclusive conditions; however, it caused dermal necrosis in two studies under occlusive conditions. HDMZ is not genotoxic or mutagenic in in vitro assays and was not reproductively or developmentally toxic in an inhalation screening study in rats. Short-term and subacute, high-dose inhalation exposure to HMDZ produced respiratory tract irritation, reduced feed consumption, changes in clinical chemistry parameters, and reversible central nervous system depression in rats. In a 90-day inhalation exposure study in rats, HMDZ exposure-related effects were observed in the kidneys of male rats but were determined to be alpha-2µ-nephropathy, thus, not relevant to humans. Based on the results of the 90-day (subchronic) inhalation study, 75 ppm was determined to be the no-observed adverse effect level (NOAEL) and was selected as the point of departure for the derivation of the 8-h time-weighted average (TWA), health-based workplace environmental exposure level (WEEL) value. This subchronic inhalation NOAEL was adjusted to account for duration of exposure, interindividual variability, and intraindividual variability. The resulting 8-h TWA WEEL value of 10 ppm is fully expected to provide a significant margin of safety against any potential adverse health effects in workers following long-term inhalation exposure to HMDZ vapor. A 15-min short-term exposure limit of 50 ppm was also established to protect workers from reversible effects produced by acute, high-dose inhalation of HMDZ vapor. A skin notation (Skin) is warranted because of the potential for the dermal route to significantly contribute to the overall exposure to HMDZ.
1,1,1,3,3,3-六甲基二硅氮烷（HMDZ）在工业上用于处理二氧化硅表面，在半导体行业用作中间附着力促进剂或硅烷化剂，用作无机填料的化学改性剂，以及用作清除水分的有机硅密封剂。在动物研究中，经口、经皮和吸入途径急性给药后，HMDZ被认为具有轻微至至多中等毒性。HMDZ既不是眼部刺激物，在半封闭条件下也不会引起皮肤刺激；然而，在两项封闭条件下的研究中，它导致了皮肤坏死。在体外试验中，HDMZ没有遗传毒性或致突变性，在大鼠吸入筛选研究中也没有生殖毒性或发育毒性。大鼠短期和亚急性高剂量吸入HMDZ会产生呼吸道刺激、采食量减少、临床化学参数变化以及可逆的中枢神经系统抑制。在一项对大鼠进行的90天吸入暴露研究中，在雄性大鼠的肾脏中观察到了与HMDZ暴露相关的影响，但确定为α-2µ肾病，因此与人类无关。根据90天（亚慢性）吸入研究的结果，确定75 ppm为未观察到有害作用水平（NOAEL），并将其选作推导8小时时间加权平均（TWA）基于健康的工作场所环境暴露水平（WEEL）值的起始点。对该亚慢性吸入NOAEL进行了调整，以考虑暴露持续时间、个体间变异性和个体内变异性。由此得出的8小时TWA WEEL值为10 ppm，完全有望为工人长期吸入HMDZ蒸气后的任何潜在不良健康影响提供显著的安全边际。还确定了15分钟短期暴露限值为50 ppm，以保护工人免受急性高剂量吸入HMDZ蒸气产生的可逆影响。由于经皮途径有可能对HMDZ的总体暴露产生显著影响，因此有必要标注皮肤接触（Skin）。
