Kluwe W M, Dill G, Persing R, Peters A
J Toxicol Environ Health. 1985;15(6):745-67. doi: 10.1080/15287398509530702.
Acute (single exposure), 14-d repeated exposure, 91-d subchronic, and 103-wk chronic toxicity studies of orally administered (gavage, in corn oil) monochlorobenzene were conducted in male and female Fischer-344 rats and B6C3F1 hybrid mice. A single exposure to 4000 mg/kg was lethal to male and female rats, while a single exposure to a dose as low as 1000 mg/kg was lethal to mice. Fourteen daily exposures to 1000 mg/kg caused death in rats of both sexes, but neither survival nor clinical health were compromised at 500 mg/kg in rats or mice. In the 91-d studies, wherein monochlorobenzene was administered once daily, 5 d/wk, survival was reduced by doses of 500 mg/kg and higher in rats, and by doses of 250 mg/kg and higher in mice. Dose-dependent necrosis of the liver (hepatocytes), degeneration or focal necrosis of the renal proximal tubules, and lymphoid or myeloid depletion of the spleen, bone marrow, and thymus (mild to severe) were produced by doses of 250 mg/kg or greater of monochlorobenzene in both sexes of rats and mice, although the incidences of these lesions varied considerably by sex and species. Consistent changes in the circulating blood components were not observed, but a mild porphyrinuria was detected at the higher doses. No toxic effects were observed at doses of 125 mg/kg or less. In the 2-yr studies, wherein monochlorobenzene was administered once daily, 5 d/wk, doses of 30 or 60 mg/kg in male mice and 60 or 120 mg/kg in female mice and male and female rats did not produce any evidence of toxicity. Doses of 60 or 120 mg/kg caused slight (statistically significant at 120 mg/kg; p less than 0.05) increases in the frequencies of male rats with neoplastic nodules of the liver. Increased tumor frequencies were not observed in female rats or in male or female mice receiving monochlorobenzene.
对雄性和雌性Fischer - 344大鼠以及B6C3F1杂交小鼠进行了经口给予（玉米油灌胃）一氯苯的急性（单次暴露）、14天重复暴露、91天亚慢性和103周慢性毒性研究。单次暴露4000mg/kg对雄性和雌性大鼠具有致死性，而单次暴露低至1000mg/kg对小鼠具有致死性。每天暴露于1000mg/kg，连续14天会导致雌雄大鼠死亡，但在大鼠或小鼠中，500mg/kg剂量下的存活和临床健康均未受到影响。在91天的研究中，一氯苯每天给药一次，每周5天，500mg/kg及以上剂量会降低大鼠的存活率，250mg/kg及以上剂量会降低小鼠的存活率。250mg/kg及以上剂量的一氯苯会导致大鼠和小鼠两性肝脏（肝细胞）出现剂量依赖性坏死、肾近端小管变性或局灶性坏死以及脾脏、骨髓和胸腺的淋巴细胞或髓细胞减少（轻度至重度），尽管这些病变的发生率因性别和物种而异。未观察到循环血液成分的一致变化，但在较高剂量下检测到轻度卟啉尿。在125mg/kg及以下剂量未观察到毒性作用。在为期两年的研究中，一氯苯每天给药一次，每周5天，雄性小鼠30或60mg/kg、雌性小鼠60或120mg/kg以及雄性和雌性大鼠的剂量均未产生任何毒性证据。60或120mg/kg的剂量会使雄性大鼠肝脏肿瘤结节的发生率略有增加（120mg/kg时具有统计学意义；p小于0.05）。接受一氯苯的雌性大鼠或雄性及雌性小鼠未观察到肿瘤发生率增加。
