Toxicol Ind Health. 2017 Jan;33(1):2-15. doi: 10.1177/0748233716670061.
Octamethylcyclotetrasiloxane (D4; CAS No. 556-67-2) is used as a monomer in the manufacture of polymeric materials, which are widely used in various industrial and/or medical applications, such as breast implants. D4 has a relatively low order of toxicity following acute administration via the oral, dermal, and inhalation routes of exposure and is not considered to be a dermal or eye irritant or to be a dermal sensitizer. There is no appreciable dermal absorption of D4 based on results from in vivo and in vitro studies. D4 has not been shown to be genotoxic/mutagenic when tested in a number of short-term in vitro and in vivo assays. Overall, studies have demonstrated adverse effects on specific female reproductive endpoints at higher exposure concentrations; however, no D4 exposure-specific effects were noted with respect to developmental endpoints. Inhalation exposure of rats to 700 ppm D4 for up to 24 months produced effects in the liver, kidney, and uterus (weight changes, hepatocellular hypertrophy, endometrial hyperplasia, and nephropathy). Changes in the nasal epithelium (eosinophilic globules) were also noted at 150 and 700 ppm. Despite 24 months of exposure, only mild to minimal inflammatory responses were found at 150 ppm, and overall, the basic integrity of the respiratory tract was unchanged at this dose. At 700 ppm, there was an increased incidence of endometrial adenomas in female rats. Based on the adverse changes in the respiratory tract, kidney, and female reproductive tract in the chronic inhalation study, 150 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 workplace environmental exposure level (WEEL®) value. The inhalation NOAEL was adjusted to account for interindividual variability and residual uncertainty regarding upper respiratory tract changes still occurring at 150 ppm. An 8-h time-weighted average WEEL value of 10 ppm is expected to provide a significant margin of safety against any potential adverse health effects in workers exposed to airborne D4.
八甲基环四硅氧烷（D4；化学物质登记号：556-67-2）用作制造聚合材料的单体，这些聚合材料广泛应用于各种工业和/或医疗领域，如隆胸植入物。经口、经皮和吸入途径急性给药后，D4的毒性相对较低，不被认为是皮肤或眼睛刺激物，也不是皮肤致敏剂。体内和体外研究结果表明，D4没有明显的经皮吸收。在多项短期体外和体内试验中，D4未显示出遗传毒性/致突变性。总体而言，研究表明在较高暴露浓度下对特定的雌性生殖终点有不良影响；然而，未观察到D4暴露对发育终点有特定影响。大鼠吸入浓度高达700 ppm的D4长达24个月，会对肝脏、肾脏和子宫产生影响（体重变化、肝细胞肥大、子宫内膜增生和肾病）。在150 ppm和700 ppm时，还观察到鼻上皮细胞的变化（嗜酸性小球）。尽管暴露了24个月，但在150 ppm时仅发现轻度至中度炎症反应，总体而言，该剂量下呼吸道的基本完整性未改变。在700 ppm时，雌性大鼠子宫内膜腺瘤的发病率增加。基于慢性吸入研究中呼吸道、肾脏和雌性生殖道的不良变化，确定150 ppm为未观察到不良影响水平（NOAEL），并将其作为推导工作场所环境暴露水平（WEEL®）值的出发点。对吸入NOAEL进行了调整，以考虑个体间差异以及150 ppm时上呼吸道仍发生变化的残留不确定性。预计8小时时间加权平均WEEL值为10 ppm，可为接触空气中D4的工人提供显著的安全边际，以防止任何潜在的不良健康影响。
