Moch R W
Office of Toxicological Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Washington, D.C. 20204.
Toxicol Pathol. 1988;16(2):172-83. doi: 10.1177/019262338801600210.
Selected pathology lesions from 9 studies, 5 with butylated hydroxyanisole (BHA) and 4 with ethylene dibromide (EDB) are reviewed and their relative importance in regulatory evaluation is discussed. When Fischer 344 (F344) rats were fed BHA at 0.5% and 2.0% of the diet for 2 years, an increased number of rats of both sexes had epithelial hyperplasia of the forestomach at both treatment levels, compared to controls. At the 2.0% level, an increased number of rats had forestomach papilloma or forestomach squamous cell carcinoma. In a second study, in which F344 rats were fed BHA at 1.0% and 2.0% of the diet for 2 years, increased numbers of rats in both treatment groups were reported to have hyperplasia or papilloma of the forestomach. At the 2.0% level, increased numbers of rats developed squamous cell carcinoma of the forestomach. More Syrian golden hamsters fed BHA at 1.0% and 2.0% of the diet for 2 years reportedly had hyperplasia, papilloma or squamous cell carcinoma of the forestomach than did nontreated animals. Ingestion of BHA at 0.5% and 1.0% of the diet by B6C3F1 mice for 2 years was reported to produce an increase of animals with hyperplasia or papilloma of the forestomach at both dosage levels, compared to nontreated mice. When beagle dogs were fed BHA at 1.0% and 1.3% of the diet for 180 days, no lesions/tumors of the distal esophagus or stomach were identified at gross necropsy or by light or electron microscopy. When EDB was administered by gavage to Osborne-Mendel rats and B6C3F1 mice under conditions of the National Toxicology Bioassay Program, more rats and mice, both male and female, developed squamous cell carcinoma of the forestomach than did nontreated groups. EDB administered via inhalation to F344 rats and B6C3F1 mice did not cause squamous cell carcinoma of the forestomach; however, other neoplasms occurred which were considered to be treatment-related. Information gleaned from the BHA and EDB studies with multiple animal species facilitated regulatory decision-making regarding the potential toxicity/carcinogenicity of these compounds to man.
对9项研究中选定的病理损伤进行了回顾，其中5项研究涉及丁基羟基茴香醚（BHA），4项研究涉及二溴乙烷（EDB），并讨论了它们在监管评估中的相对重要性。当在饲料中添加0.5%和2.0%的BHA喂养Fischer 344（F344）大鼠2年时，与对照组相比，两个处理组的雌雄大鼠前胃上皮增生的数量均增加。在2.0%的添加水平下，前胃乳头状瘤或前胃鳞状细胞癌的大鼠数量增加。在第二项研究中，给F344大鼠喂食饲料中添加1.0%和2.0%的BHA，为期2年，据报道两个处理组中前胃增生或乳头状瘤的大鼠数量均增加。在2.0%的添加水平下，前胃鳞状细胞癌的大鼠数量增加。据报道，在饲料中添加1.0%和2.0%的BHA喂养叙利亚金黄地鼠2年，与未处理动物相比，前胃增生、乳头状瘤或鳞状细胞癌的地鼠数量更多。据报道，B6C3F1小鼠在饲料中摄入0.5%和1.0%的BHA，为期2年，与未处理小鼠相比，两个剂量水平下前胃增生或乳头状瘤的动物数量均增加。当给比格犬喂食饲料中添加1.0%和1.3%的BHA，为期180天时，在大体尸检或光镜或电镜检查中均未发现远端食管或胃部的病变/肿瘤。在国家毒理学生物测定计划的条件下，通过灌胃给奥斯本-孟德尔大鼠和B6C3F1小鼠施用EDB，与未处理组相比，更多的雌雄大鼠发生了前胃鳞状细胞癌。通过吸入给F344大鼠和B6C3F1小鼠施用EDB不会导致前胃鳞状细胞癌；然而，出现了其他被认为与处理有关的肿瘤。从对多种动物物种进行的BHA和EDB研究中收集到的信息有助于就这些化合物对人类的潜在毒性/致癌性做出监管决策。
