毒理性
鉴定和使用：4,5-二氯-2-辛基-3-异噻唑啉酮（DCOIT）是一种固体。它被用作海洋防污剂。人类研究：由于杀菌剂DCOIT导致职业接触性皮炎爆发。在日本一家纺织品整理工厂工作的19人中有8人，6名女性，年龄在20至63岁之间，他们的前臂、上臂、面部或颈部出现了水肿性红色皮疹。这些受试者对DCOIT产生了敏感反应，而没有明显的交叉敏感反应。动物研究：在狗身上，1500 ppm剂量下观察到体重减轻和食物消耗减少，血液学和临床化学参数发生变化。在大鼠吸入浓度为0.02、0.63和6.72 mg/立方米，每天6小时，每周5天，持续十三周的情况下，中剂量和高剂量处理的大鼠的鼻、喉和肺观察到治疗相关的显微病变。观察到鼻部的轻微或轻度亚急性炎症增加，以及过渡性呼吸道上皮细胞增生和杯状细胞增生。在中剂量和高剂量的大鼠的会厌上，观察到鳞状上皮和立方上皮的增生，以及会厌的慢性活动性炎症。在高剂量大鼠的肺中，观察到杯状细胞增生和急性炎症的增加。在兔子的发育研究中，没有观察到与治疗相关的外部、内脏或骨骼畸形或变异。在大鼠中，100 mg/kg/天的胎儿数量增加，波浪状肋骨的胎儿数量增加，以及这种效果的总数和严重程度也增加。在沙门氏菌TA1535、TA1537、TA98、TA100菌株有或没有代谢激活的情况下，它不是致突变物。在中国仓鼠卵巢体外细胞遗传学试验中，它诱导了在有或无代谢激活的情况下断裂反应。生态毒性研究：在海洋鱼（Oryzias melastigma）基因转录分析显示，DCOIT在雄性下丘脑-垂体-性腺-肝脏轴上具有正向调节作用，在雌性上的影响较小。刺激的类固醇生成活动导致两种性别中类固醇激素浓度增加，包括雌二醇（E2）、睾酮（T）和11-KT-睾酮（11-KT），导致激素稳态失衡和E2/T比例增加。两种性别的相对雌激素细胞内环境诱导了肝脏合成，并增加了肝脏和血浆中卵黄蛋白原（VTG）或绒毛膜蛋白的含量。此外，亲代暴露于DCOIT跨代损害了后代的生存能力，表现为孵化率和游泳活动的降低。DCOIT在海洋鱼（Oryzias melastigma）的雄性大脑中诱导了26种蛋白质的差异表达，在雌性大脑中诱导了27种蛋白质的差异表达，在环境现实浓度2.55 ug/L下暴露28天后。
IDENTIFICATION AND USE: 4,5-Dichloro-2-octyl-3-isothiazolone (DCOIT) is a solid. It is used as a marine antifoulant. HUMAN STUDIES: An outbreak of occupational contact dermatitis occurred due to the biocide DCOIT. Eight of 19 persons, six females, 20 to 63 years old, employed in a Japanese textile finishing factory developed edematous reddish eruptions on their forearms, upper arms, face, or neck. The subjects have been sensitized to DCOIT without apparent cross sensitization to DCOIT. ANIMAL STUDIES: In dogs decreased body weight and food consumption, hematologic and clinical chemistry parameter changes observed at 1500 ppm. After inhalation in rats at concentrations of 0.02, 0.63, and 6.72 mg/cu m for 6 hours per day, 5 days per week, for thirteen weeks, treatment-related microscopic lesions in the nose, larynx, and lungs were observed in mid- and high-dose treated rats. Minimal or mild subacute inflammation of the nose was observed in increased incidence, as was transitional respiratory epithelial hyperplasia and goblet cell hyperplasia. In the epiglottis, hyperplasia of the squamous and cuboidal epithelium was observed in mid- and high dose rats, as was chronic-active inflammation of the epiglottis. Goblet cell hyperplasia and acute inflammation was observed in increased incidence in the lungs of high dose rats. In the developmental study in rabbits, there were no treatment-related external, visceral, or skeletal malformations or variations. In rats, fetuses at 100 mg/kg/day showed an increase in the number of fetuses with wavy ribs, along with an increase in number of litters with this effect as well as the severity of the effect. It was not mutagenic in Salmonella strains TA1535, TA1537, TA98, TA100 with or without metabolic activation. It induced clastogenic response in Chinese hamster ovary in vitro cytogenetic assays in the presence or absence of metabolic activation. ECOTOXICITY STUDIES: In marine medaka (Oryzias melastigma) gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male of the hypothalamus-pituitary-gonadal-liver axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. DCOIT induced differential expression of 26 proteins in male brains and of 27 proteins in female brains of the marine medaka (Oryzias melastigma) after a 28-day exposure to environmentally-realistic concentration at 2.55 ug/L.
来源:Hazardous Substances Data Bank (HSDB)
