Bioassay of 5-nitroacenaphthene for possible carcinogenicity (CAS No. 602-87-9).

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Abstract

A bioassay of 5-nitroacenaphthene for possible carcinogenicity was conducted using Fischer 344 rats and B6C3F1 mice. 5-Nitroacenaphthene was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. For male and female rats, the high and low dietary concentrations of 5-nitroacenaphthene were 0.24 and 0.12 percent, respectively. The high and low time-weighted average concentrations for mice were 0.12 and 0.06 percent, respectively, for males and 0.12 and 0.05 percent, respectively, for females. After a 78-week dosing period, observation of surviving rats continued for up to 22 weeks and observation of the mice continued for 18 weeks. For the chronic rat bioassay, 49 male and 50 female rats were placed on test as high dose controls, and 50 rats of each sex served as low dose controls. For the mice, 50 males and 50 females were placed on test as controls. Accelerated mortality was observed in all dosed groups except the low dose female mice. There was a positive association between mortality and dietary concentration of 5-nitroacenaphthene for both sexes of both species. Early deaths were most apparent among high dose male mice; half of the animals in this group were dead by week 20 and insufficient male mice survived to be at risk from late-developing tumors. Among rats, the incidence of malignant tumors of the ear canal (incidences of ceruminous carcinomas and squamous-cell carcinomas were combined) was significant at each dose level in each sex. Among both dosed groups of female rats, the incidence of clitoral gland carcinoma and the incidence of mammary adenocarcinoma were significant. A significant incidence of alveolar/bronchiolar carcinoma was observed in low dose rat groups of each sex. Among female mice, the incidence of hepatocellular carcinoma was significant at each dose level. The combined incidence of granulosa-cell tumors, luteomas, and tubular-cell adenomas of the ovary was significant in the high dose female mouse group. Under the conditions of this bioassay, 5-nitroacenaphthene was carcinogenic to Fischer 344 rats, causing increased incidences of malignant tumors of the ear canal and lung in both sexes, and of the clitoral gland and mammary gland in females. 5-Nitroacenaphthene was also carcinogenic to female but not male B6C3F1, mice, causing carcinomas of the liver and ovarian tumors.

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5-硝基苊可能致癌性的生物测定(CAS No. 602-87-9)。
采用Fischer 344大鼠和B6C3F1小鼠对5-硝基苊的致癌性进行了生物测定。将5-硝基苊以两种浓度中的任意一种添加到饲料中,每组50只雄性和50只雌性动物。对雄性和雌性大鼠,5-硝基苊的高、低饲粮浓度分别为0.24%和0.12%。雄性小鼠的高、低时间加权平均浓度分别为0.12%和0.06%,雌性小鼠的高、低时间加权平均浓度分别为0.12%和0.05%。78周给药期后,对存活大鼠的观察持续22周,对小鼠的观察持续18周。慢性大鼠生物实验采用雄性大鼠49只,雌性大鼠50只作为高剂量对照,雌雄各50只作为低剂量对照。将50只雄性和50只雌性小鼠作为对照进行试验。除低剂量雌性小鼠外,所有给药组均观察到死亡加速。两种动物的死亡率与饲粮中5-硝基苊的浓度呈正相关。高剂量雄性小鼠的早期死亡最为明显;这一组中有一半的动物在第20周死亡,存活下来的雄性老鼠数量不足,无法承受晚期肿瘤的风险。大鼠耳道恶性肿瘤的发生率(耵聍癌和鳞状细胞癌的发生率合并)在各剂量水平下均有显著性差异。两剂量组雌性大鼠阴蒂腺癌和乳腺腺癌的发生率均有显著性差异。低剂量各组大鼠肺泡/细支气管癌发生率均显著升高。在雌性小鼠中,在每个剂量水平下,肝细胞癌的发生率都很显著。高剂量雌性小鼠卵巢颗粒细胞瘤、黄体瘤和管状细胞腺瘤的合并发生率显著高于雌性小鼠。在本实验条件下,5-硝基萘对Fischer 344大鼠具有致癌性,使雌雄大鼠耳道和肺恶性肿瘤的发生率增加,雌性大鼠阴蒂腺和乳腺恶性肿瘤的发生率增加。5-硝基苊对雌性B6C3F1小鼠也有致癌性,但对雄性B6C3F1小鼠无致癌性,可引起肝癌和卵巢肿瘤。
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