Repeated dose inhalation developmental toxicity study in rats exposed to cellulose insulation with boric acid additive

Cellulose insulation (CI), a common building material, is a mixture of cellulose fibers and borates. Borates are approximately 20% of the product weight and act as a flame retardant. Given possible exposure to workers and consumers, an inhalation toxicity study was conducted following Organization for Economic Co-operation and Development (OECD) 414 for Prenatal Development Toxicity to evaluate if CI is a developmental toxicant. Pregnant female rats were exposed by nose-only inhalation to CI aerosols containing 20% boric acid for six h/day, from gestational day (GD) 6–19, and fetuses were evaluated for developmental parameters. Respirable CI was produced by grinding to produce respirable particles (MMAD 2.7–2.9 µm, geometric standard deviations (GSD) 1.9–2.6), which were then aerosolized. Target air concentrations were 15, 90, and 270 mg CI/m³. Controls were exposed to air only. Slight body weight reductions (average decrease &lt;7% vs. control) were observed in male and female GD 20 fetuses in the mid and high dose groups. No embryo/fetal developmental toxicity or alterations in any other measured variable were reported at any dose. The no observed adverse effect level (NOAEL) for developmental outcomes was 270 mg/m³.纤维素隔热材料（Cellulose Insulation, CI）是一类常见建筑材料，由纤维素纤维与硼酸盐复配而成。硼酸盐约占产品总重量的20%，可作为阻燃剂发挥作用。鉴于工人与消费者均可能存在CI暴露风险，本研究参照经济合作与发展组织（Organization for Economic Co-operation and Development, OECD）414号《产前发育毒性试验指南》开展吸入毒性研究，以评估CI是否具备发育毒性。实验选用妊娠雌性大鼠，自妊娠第6天至第19天（GD 6–19）每日以鼻吸入方式暴露于含20%硼酸的CI气溶胶，单次暴露时长为6小时，随后对胎鼠的各项发育参数进行检测评估。可吸入级CI通过研磨工艺制备为可吸入颗粒物（质量中值空气动力学直径（Mass Median Aerodynamic Diameter, MMAD）2.7–2.9 µm，几何标准差（Geometric Standard Deviation, GSD）1.9–2.6），随后将其气雾化形成受试气溶胶。本研究设定的目标空气暴露浓度分别为15、90及270 mg CI/m³，对照组大鼠仅暴露于洁净空气。中、高剂量组的妊娠第20天（GD 20）雌雄胎鼠均出现轻微体重降低，平均降幅较对照组<7%。各剂量组均未观察到胚胎/胎儿发育毒性，其余各项检测指标亦未出现异常改变。本研究中，与发育毒性相关指标的未观察到有害作用水平（NOAEL）为270 mg/m³。