Agarwal D K, Eustis S, Lamb J C, Jameson C W, Kluwe W M
Toxicol Appl Pharmacol. 1986 Jun 15;84(1):12-24. doi: 10.1016/0041-008x(86)90412-6.
Groups of 48 adult male F344 rats were maintained on synthetic diets containing 20 ppm (normal), 2 ppm (low), or 200 ppm (high) zinc. After 1 week of acclimation to the various diets, groups of 12 rats from each dietary regimen were gavaged for 13 consecutive days with 0.0 (vehicle), 0.33, 1.0, or 3.0 g/kg di(2-ethylhexyl)phthalate (DEHP). These were selected as relatively nontoxic, mildly toxic, and moderately toxic doses for producing testicular injury in adult male rats. At termination on the 14th day, body weight gain was reduced by 3.0 g/kg DEHP dose in the normal and low-zinc diet groups but not in the high-zinc diet group. The low-zinc diet alone reduced body weight gain, independent of DEHP treatment. DEHP had no perceptible effects on the weights of testis, seminal vesicle, prostate, or epididymis from rats maintained on normal- or high-zinc diets, but reduced the weights of all of these organs from animals on the low-zinc diet in a dose-dependent manner. Lactate dehydrogenase activity, total and free sulfhydryl contents, and zinc concentrations in testes were also reduced, and testicular degeneration was induced by DEHP in the low-zinc diet groups. In contrast, dose-dependent liver enlargement and hypolipidemia (reduction of serum cholesterol and triglyceride concentrations) were produced by equivalent doses of DEHP in all of the three zinc groups. The selectively enhanced susceptibility of adult male F344 rats on a zinc deficient diet to the gonadotoxic effects of DEHP supports the hypothesis that testicular zinc depletion is causally related to the ensuing testicular and accessory sex organ atrophies. Other biological effects of DEHP (e.g., hypolipidemia, hepatomegaly) appear to occur independent of zinc homeostasis.
将48只成年雄性F344大鼠分成几组，分别饲喂含20 ppm（正常）、2 ppm（低）或200 ppm（高）锌的合成饲料。在适应各种饲料1周后，从每个饮食方案中选取12只大鼠组成的组，连续13天灌胃0.0（赋形剂）、0.33、1.0或3.0 g/kg邻苯二甲酸二（2-乙基己基）酯（DEHP）。这些剂量被选为在成年雄性大鼠中产生睾丸损伤的相对无毒、轻度毒性和中度毒性剂量。在第14天处死时，正常和低锌饮食组中，3.0 g/kg DEHP剂量使体重增加减少，但高锌饮食组未出现这种情况。单独的低锌饮食就会降低体重增加，与DEHP处理无关。DEHP对正常或高锌饮食喂养的大鼠的睾丸、精囊、前列腺或附睾重量没有明显影响，但以剂量依赖的方式降低了低锌饮食动物所有这些器官的重量。睾丸中的乳酸脱氢酶活性、总巯基和游离巯基含量以及锌浓度也降低了，低锌饮食组中DEHP诱导了睾丸变性。相比之下，在所有三个锌组中，同等剂量的DEHP都会产生剂量依赖性的肝脏肿大和低脂血症（血清胆固醇和甘油三酯浓度降低）。成年雄性F344大鼠在缺锌饮食时对DEHP的性腺毒性作用选择性增强的易感性支持了这样一种假设，即睾丸锌缺乏与随后的睾丸和附属生殖器官萎缩存在因果关系。DEHP的其他生物学效应（如低脂血症、肝肿大）似乎与锌稳态无关而发生。
