Chronic toxicity of fumonisins from Fusarium moniliforme culture material (M-1325) to mink

Adult female mink (Mustela vison) were fed a diet that contained Fusarium moniliforme culture material that provided dietary concentrations of 89 ppm fumonisin B₁, 21 ppm fumonisin B₂, and 8 ppm fumonisin B₃ for 87 days. During the trial, there was mild lethargy in the mink fed fumonisins, but no other clinical signs or differences in feed consumption (measured during the first two weeks), body weights, or survivability were observed between the fumonisin-treated and control mink. Several hematologic parameters (mean corpuscular hemoglobin concentration, plasma total solids, and lymphocyte concentration) and serum chemical concentrations (globulin, phosphorus, potassium, blood urea nitrogen, creatinine, bilirubin, and cholesterol) and activities (alkaline phosphatase, alanine aminotransferase, amylase, and aspartate aminotransferase) were greater in the mink fed fumonisins than in the controls. Serum albumin/globulin and sodium/potassium ratios and chloride concentrations were lower in the fumonisin-fed mink than in the controls. The concentrations of free sphinganine and the ratio of free sphinganine to free sphingosine in the liver and kidneys of the fumonisin-treated mink were greater than in the control mink. No histopathologic alterations were associated with fumonisin treatment. These results indicate that long-term dietary exposure to F. moniliforme culture material containing 118 ppm total fumonisins is not lethal to adult mink, but can produce adverse physiological effects in the animals.     

Effects of chronic dietary hexachlorobenzene exposure on the reproductive performance and survivability of mink and European ferrets

Feeding adult mink and European ferrets diets that contained 1, 5, or 25 mg/kg added hexachlorobenzene (HCB) resulted in reduced reproductive performance as indicated by decreased litter size, increased percentage of stillbirths, increased kit mortality, and decreased early kit growth. Diets treated with 125 or 625 mg/kg HCB were lethal to the adults of both species. In general, the mink were more sensitive to the toxic effects of HCB than were ferrets.In a second experiment, the cross-fostering of mink kits whelped by untreated dams to females fed 2.5 mg/kg HCB, andvice versa, resulted in increased kit mortality when compared to untreated controls. Thein utero exposure to HCB, however, resulted in higher kit mortality than exposure via the dam's milk.Published with the approval of the Michigan Agricultural Experiment Station as Journal Article No.10923     

The reproductive effects of dietary heptachlor in mink (Mustela vison)

Adult female mink were fed diets containing 0 (control), 6.25, 12.5, and 25 ppm (g/g) technical grade heptachlor prior to and throughout the reproductive period (181 days) to evaluate the effects of heptachlor consumption on reproduction and offspring viability and to assess the extent of placental and mammary transfer of heptachlor epoxide to mink offspring. Feeding 12.5 and 25 ppm resulted in significant reductions in feed consumption and body weights of female mink. Mortality was 0, 8, 67, and 100% for the control, 6.25, 12.5, and 25 ppm groups, respectively. All females in the 25 ppm group died within 88 days. Mink fed the two higher heptachlor diets displayed clinical signs indicative of central nervous system involvement just prior to death. Females were mated with males on the same dietary treatments. Whelping success rates were 67, 83, 27, and 0% for the control, 6.25, 12.5, and 25 ppm groups, respectively. High mortality in the 12.5 and 25 ppm groups accounted for the lack of reproductive success. Gestation length, litter size and birth weight of kits were not significantly affected by adult female consumption of 6.25 ppm heptachlor while kits whelped by females on the 12.5 ppm diet weighed significantly less than control kits at birth. Survival of kits in the 12.5 ppm group from birth to three weeks of age was also adversely affected. At three and six weeks of age, kit body weights in both the 6.25 and 12.5 ppm groups were significantly less than body weights in control kits. Examination of heptachlor epoxide concentrations in newborn and developing kits indicated both placental and mammary transfer of the chemical from the dams to the kits. The LC50 for the 181-day exposure period for female mink was 10.5 ppm heptachlor and the LOAEL, based on reduced kit growth, was 6.25 ppm.     

Subacute toxicity of dietary heptachlor to mink (Mustela Vison)

Mink were fed diets that contained 0, 12.5, 25, 50, or 100 mg/kg active ingredient heptachlor (as technical grade formulation) for 28 days followed by a 7-day observation period to determine the toxicity of this insecticide to mink. Diets that contained 25 mg/kg, or more, heptachlor resulted in a significant decrease in feed consumption, while 50 mg/kg, or more, heptachlor caused a significant reduction in body weights. Mortality (37.5%) occurred only in the group fed 100 mg/kg heptachlor. The dead mink showed neurological signs of toxicity prior to death. Animals fed 100 mg/kg heptachlor also had reduced relative weights of the spleen and kidney and increased relative weight of the adrenal glands when necropsied at the time of death or at the termination of the study.This research was supported by Grant No. HHHERP 88-04 of the Hawaii Heptachlor Research and Education Foundation and is published with the approval of the Michigan Agricultural Experiment Station as Journal Article No. 13070.     

妊娠期邻苯二甲酸二丁酯暴露对雌性子代大鼠生殖发育的影响

目的探讨妊娠期邻苯二甲酸二丁酯(DBP)染毒对雌性子代大鼠生殖发育的影响。方法将50只健康SPF级SD妊娠大鼠按体重随机分为对照组和100、250、500、1 000 mg/kg DBP染毒组,每组10只。采用灌胃方式进行染毒,每天1次,从妊娠第12日至哺乳期第21日(postnatal day 21,PND21)结束。仔鼠出生4 d后,调整每窝仔鼠数量基本一致(12~13只),记录平均窝重,仔鼠出生存活率、仔鼠外观畸形率。断乳后,随机从每笼中抽取2只雌性仔鼠继续饲养至成年(PND63)。检测血清中孕酮和雌二醇的浓度及其合成相关酶[类固醇合成酶基因St AR(Star)、卵巢P450芳香化酶P450arom(Cyp19)、胆固醇侧链裂解酶P450 scc(Cyp11a1)、3β羟甾脱氢酶3βHSD1(Hsd3b1)、17β羟甾脱氢酶17βHSD1(Hsd17b1)、11β羟甾脱氢酶11βHSD1(Hsd11b1)]的m RNA表达水平。结果 1 000 mg/kg DBP染毒组仔鼠出生后不久变得苍白无力,很快便出现死亡现象,仔鼠出生当日存活率为50%(59/117),2 d内全部死亡。其余3个剂量DBP染毒组仔鼠未出现任何中毒症状和死亡现象。与对照相比较,250、500 mg/kg DBP染毒组仔鼠血清中孕酮和雌二醇的浓度较低,而100 mg/kg DBP染毒组仔鼠血清中雌二醇的浓度较高,差异均有统计学意义(P0.05)。与对照组比较,各剂量DBP染毒组雌性仔鼠卵巢中star、cyp19、cyp11α、Hsd3b1、Hsd11b1 m RNA的表达水平均下降,差异均有统计学意义(P0.05);而Hsd17b1 m RNA的表达水平均无明显改变。结论妊娠期DBP染毒对雌性仔鼠成年后的生殖系统有影响,其作用机制可能与雌激素合成相关酶基因表达的降低有关。     

青春期前邻苯二甲酸二(2-乙基)己酯暴露对雌性大鼠生殖发育及过氧化物酶体增殖剂激活受体的影响

目的探讨邻苯二甲酸二(2-乙基)己酯(DEHP)暴露对青春期前雌性大鼠性发育及生殖内分泌功能的影响及其可能机制。方法将40只健康3周龄雌性SD大鼠,随机分成对照组(玉米油)和3个实验组,每组10只。实验组按50、150、500mg/kg DEHP经口灌胃,连续染毒28天。观察阴道开口、乳房发育、第一次发情周期的日龄及体重,于末次染毒24小时后进行阴道涂片,确定动情间期,处死动物。Real-time PCR测定卵巢组织相关基因表达水平;ELISA法检测血清中卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P4)及睾酮(T)水平;通过病理学观察卵巢组织的变化;免疫组织化学法测定卵巢组织中PPARγ的表达。结果 500mg/kg组阴道开口日龄提前,150、500mg/kg组阴道开口时体重增加(P<0.05);150、500mg/kg组芳香化酶(P450Arom)mRNA表达与对照组比较,显著下降;各剂量组与对照组相比,T水平明显下降,150、500mg/kg组FSH、E2水平明显减少,而LH水平明显升高(P<0.05);150、500mg/kg组闭锁卵泡明显增多、黄体数目明显减少;150、500mg/kg组卵泡颗粒细胞和黄体颗粒细胞中PPARγ阳性光密度相对量明显高于对照组及50mg/kg组(P<0.05)。结论青春期前DEHP暴露对雌性大鼠性发育及生殖内分泌功能产生影响,其作用机制可能与激活PPARs有关。     

Effects of dietary trans-fatty acids on reproductive performance of Wistar rats

1. Wistar rats were fed for three successive generations on a semi-purified diet, in which the fat was provided by butter, sunflower oil, rapeseed oil or hydrogenated vegetable fat, differing in the content of cis,cis-18:2 and trans-18:1 fatty acids. Effects of these fats on the composition of adipose tissue and reproductive performance were studied. Fatty acids were analysed using high-performance liquid chromatography. 2. The fatty acid pattern of adipose tissue was closely related to dietary fat composition and, established in the first generation, did not change significantly in successive generations of rats. 3. Hydrogenated fat adversely affected litter size, sperm morphology and regularity of oestrous cycle, and prolonged the period of gestation in experimental animals. Differences observed between the generations were not significant. 4. Hydrogenated fat decreased the level of serum testosterone in males, but the differences observed in levels of serum progesterone in females were not apparently related to the dietary trans-fatty acids.     

Subacute and Reproductive Effects in Mink from Exposure to Fusarium fujikuroi Culture Material (M-1214) Containing Known Concentrations of Moniliformin

This study was conducted to ascertain the subacute and reproductive effects in mink (Mustela vison) resulting from exposure to moniliformin, a toxic mycotoxin produced by Fusarium fungi. In a preliminary trial, adult mink were presented diets that contained targeted concentrations of 10, 20, 40, 80, 160, or 240 ppm moniliformin provided by F. fujikuroi culture material (M-1214). The mink fed diets that contained more than 40 ppm moniliformin refused to eat significant quantities of feed. Feeding adult mink diets that contained 8.1 or 17.0 ppm (wet weight) moniliformin, provided by F. fujikuroi culture material, in a 30-day subacute trial produced no significant adverse effects on feed consumption, body weights, hematologic parameters, or serum chemical values, and notable histologic changes in tissues that were examined. In the reproduction trial, female mink were exposed to the same dietary concentrations of moniliformin provided by F. fujikuroi culture material as in the subacute test from 2 weeks prior to the breeding season until their offspring (kits) were 8 weeks old. Consumption of the high-dose (17 ppm) diet resulted in significant neonatal mortality and reduced kit body weights at birth and at 8 weeks of age. Necropsy of 8-week-old kits from the control and high-dose groups revealed no gross or histologic lesions or alterations in liver, lung, or heart tissues that could account for the mortality observed in the kits exposed to the culture material. These results indicate that long-term (105–135 days) dietary exposure to F. fujikuroi culture material containing 17 ppm moniliformin is not lethal to adult female mink, but can have adverse effects on neonatal mink. Received: 18 April 1997/Accepted: 7 April 1998     

杀虫剂对女性生殖系统激素功能的影响

女性生殖系统受多种因素的影响,其中激素是影响女性生殖系统(尤其对卵巢)的一个重要因素,如果激素功能受到影响,患低生殖力的危险将增加.杀虫剂被广泛应用于农业及公共卫生来控制蚊虫等带菌媒介,这对人类是有益的,但某些杀虫剂可通过多种机制干扰女性的激素功能,进而对生殖系统产生负面影响.杀虫剂对女性生殖系统的危害,包括月经周期紊乱、不孕、自然流产/死胎、TTP延长及发育缺陷等,这些已经从流行病学角度得到证实.     

低剂量毒死蜱和氯氰菊酯联合染毒对雌性大鼠生殖发育的影响

目的 观察低剂量毒死蜱(氯吡硫磷)和氯氰菊酯联合染毒对雌性大鼠生育功能的影响。 方法 健康Wistar大鼠雌雄按2∶1合笼,将孕鼠分为对照组、毒死蜱组、氯氰菊酯组和联合染毒组等4组,每组8只。按照1 ml/kg量灌胃,毒死蜱组剂量为1.6 mg/kg,氯氰菊酯组剂量为2.5 mg/kg,联合染毒组给药毒死蜱1.6 mg/kg+氯氰菊酯2.5 mg/kg。从孕1~孕8 d染毒,孕19 d,处死孕鼠,记录黄体数和总着床数,活胎的体重和身长,并观察活胎外观是否有畸形。分离胎盘并记录胎盘重量,测定大鼠全血的乙酰胆碱酯酶(AchE)的活力,免疫组织化学检测P450aromA。 结果 孕第19 d,联合染毒组孕鼠体质量与对照组比较明显降低(P<0.05);各组孕鼠黄体数、总着床数、死胎率、胎仔性别比例和胎仔身长与对照组比较差异无统计学意义(P>0.05)。联合染毒组胎盘质量较对照组显著降低(P<0.05)。染毒各组活胎仔体质量较对照组明显降低(P<0.05)。联合染毒组孕鼠全血中AChE活力较对照组显著降低(P<0.05)。单独染毒组胎盘P450aromA蛋白表达与对照组相似,联合染毒组胎盘P450aromA蛋白表达显著高于对照组(P<0.05)。 结论 低剂量毒死蜱和氯氰菊酯联合染毒产生一定的胚胎毒性,造成仔鼠发育迟缓,并引起了孕鼠AchE的下降和胎盘P450aromA蛋白表达的增强。     

Effects of dietary exposure of mink (Mustela vison) to 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran, and 2,3,7,8-tetrachlorodibenzofuran on reproduction and offspring viability and growth

This study assessed the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) on the reproductive performance of female mink (Mustela vison) and the viability and growth of their offspring. Nine adult female mink were randomly assigned to one of 13 dietary treatments (one control and four doses each of TCDD, PeCDF, and TCDF [2.1-8.4, 4.0-15 and 5.2-25 ng TCDD toxic equivalents (TEQ)/kg body wt/d]). Diets were fed from two months prior to breeding through weaning of offspring at six weeks of age. At least nine kits per treatment group were maintained on their diets through 27 weeks of age. There were no effects on litter size or viability of offspring. No consistent effects were observed on body mass or relative organ masses of animals at any age. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and PeCDF accumulated in the liver and adipose tissue, but TCDF cleared rapidly. The lack of significant effects on reproduction and offspring viability contrasts with effects reported for mink exposed to environmentally derived PCB mixtures with equivalent TCDD potencies. This suggests that it may be inappropriate to apply toxicity reference values associated with PCB mixtures to animals also exposed to TCDD, PeCDF, or TCDF, and the World Health Organization TCDD toxic equivalency factors for some congeners may not be appropriate for mink.     

低浓度混苯对女工生殖激素分泌的影响

目的：探讨低浓度混苯作业对女工月经周期生殖激素分泌的影响。方法：对50名暴露组女工采用气相色谱法测定呼吸带空气中的苯、甲苯和二甲苯的浓度,对暴露组女人及外对照组和内对照组女工各35月进行月经 周期特征前瞻性调查,用酶免疫分析法测定尿液中的孕二醇－3－葡糖苷酸（PdG)、雌酮结合物（E1C）和卵泡刺激素（FSH）。结果：空气中混苯以低浓度苯为主,苯检出率29．10％、浓度8．88（0．90－876．47）mg/m^3、超标率21％、最大超标倍数20．91倍;与内对照组和外对照组相比,低浓度浊苯接触组女工黄体期长度缩短,与内对照组相比,暴露组的排卵前E1C水平、卵泡早期FSH水平以及卵泡早期和黄体期PdG水平明显降低,结论：低浓度混苯可以干扰接触女工下丘脑－垂体－卵巢轴中FSH、雌激素和孕激素的正常水平。     

Effects of dietary methylmercury on reproductive behavior of fathead minnows (Pimephales promelas)

We examined the effects of dietary methylmercury on the production of testosterone in and the reproductive behavior of male fish. Juvenile fathead minnows (Pimephales promelas) were fed one of three diets contaminated with methylmercury at concentrations of 0.06 (control), 0.87 (low), and 3.93 (medium) microg Hg/g dry weight. After attaining sexual maturity, fish were paired for mating, and male behaviors were recorded. Carcass mercury and plasma testosterone concentrations also were measured. No significant differences were found in the amount of time spent by male fish in nest preparation or courtship activities, but dietary methylmercury suppressed mating behavior. Fish that were fed control diets spent approximately 5% of their time spawning; fish that were fed methylmercury-contaminated diets spent approximately 0.5% of their time spawning. Total mercury concentration in the carcass was not correlated with any individual reproductive behavior but was correlated with hypoactivity. Fish that were fed the low- and medium-methylmercury diets and with mean carcass concentrations of 0.71 to 4.2 microg Hg/g dry weight spent an average of 19 to 26% of their time being inactive; control fish with an average of 0.07 microg Hg/g dry weight spent only 8% of their time being inactive. No significant difference was found in testosterone concentrations among dietary treatments; however, testosterone was positively correlated with individual nest preparatory, courtship, and spawning behaviors and negatively correlated with the total amount of time spent in all nonreproductive behaviors. The relation between testosterone, reproductive behavior, and spawning success suggests that altered behavior is, in part, responsible for suppression of reproduction in methylmercury-exposed fish. Moreover, reproductive behavior may be more sensitive than steroid hormones to alteration by dietary methylmercury.     

Effects of chronic dietary exposure to trace elements on banded water snakes (Nerodia fasciata)

Little currently is known about the accumulation or effects of contaminants on reptiles. To date, most studies examining reptile exposure to trace elements report tissue burdens of field-captured animals, but seldom provide insight into the dose, duration, or mode of exposure involved. For two years, we fed juvenile banded water snakes (Nerodia fasciata) prey items collected from a coal ash-contaminated site that contained elevated levels of As, Cd, Cu, Se, Sr, and V. With the exception of Cu, snakes accumulated significant concentrations of elements, usually in a dose-dependent manner. Accumulation varied significantly among liver, kidney, and gonads, and in most cases between sexes. Selenium accumulation was most notable, greatly exceeding established toxicity thresholds for other vertebrates. Despite the high concentrations of pollutants accumulated, snakes exposed to the contaminated diet survived through the study and exhibited normal food consumption, growth, condition factor, overwinter survival and mass loss, metabolic rate, and gonadosomatic index. The results of this study confirm that diet can be a significant route of exposure to trace elements in snakes and indicate that further studies on snakes are warranted to better understand their responses to contaminants.     

性成熟前期染砷对雌性SD大鼠生殖功能影响

目的 探讨性成熟前期亚砷酸钠（NaAsO₂）染毒致雌性SD大鼠子宫、卵巢结构改变及性激素水平变化影响。方法 SD大鼠40只,随机分为4组,即对照组、低、中、高剂量砷组,分别灌胃给予双蒸水、1.25、2.50、5.00 mg/kg NaAsO₂,4周后,断颈处死,双侧卵巢及子宫做苏木素-伊红染色观察卵巢及子宫组织形态学变化;采用放射免疫法测定血清中卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇、孕酮含量;酶联免疫法检测血清中血管内皮生长因子（VEGF）、细胞周期蛋白D₁（cyclin D₁）、孕激素受体（PR）含量。结果 随NaAsO₂剂量增加,染砷组大鼠卵巢内总卵泡数减少、细胞发育不良、成熟卵泡减少及畸形发育;子宫内膜变薄,腺体减少,腺腔变窄,腺上皮细胞由长柱状变成短柱状,间质增宽;与对照组比较,中、高剂量砷组大鼠血清中FSH、LH、雌二醇含量[分别为（3.23±0.20）、（3.21±0.18） IU/L、（2.64±0.27）、（2.62±0.25） ng/mL、（56.69±6.37）、（55.95±7.25） pg/mL]明显下降,差异有统计学意义（P<0.05）;与对照组比较,中、高剂量砷组大鼠血清中VEGF、cyclin D₁、PR蛋白含量[分别为（13.54±1.98）、（12.44±2.06） ng/L、（1.089±0.133）、（1.040±0.136）μg/L、（324.27±19.77）、（320.46±18.01） ng/L]下降,差异有统计学意义（P<0.05）。结论 性成熟前期染毒NaAsO₂可引起SD雌性大鼠卵巢与子宫结构改变,其机制可能与NaAsO₂导致大鼠雌二醇水平下降,下丘脑分泌FSH、LH减少有关。     

Effects of excessive dietary zinc on the intrauterine and postnatal development of mink

Dietary exposure to 1000 ppm of supplemental Zn did not result in grossly observable Zn toxicity or Zn-induced Cu deficiency in adult mink. These same concentrations did, however, produce achromatrichia, alopecia, lymphopenia and a reduced rate of growth in the offspring produced by the Zn-treated females. These mink kits also exhibited profound immunosuppression. The in vitro blastogenic response of peripheral blood lymphocytes to concanavalin A was significantly (P less than 0.001) lower in kits born to Zn-treated dams than the response of those born to control dams. The depressed immunoresponsiveness was not a permanent defect since a normal lymphocyte response was seen approximately 14 weeks after weaning and being placed on an unsupplemented basal diet. The impaired lymphocyte reactivity is believed to be the result of altered DNA synthesis in these cells and/or an inhibition of macrophage functions necessary for normal response to the mitogen concanavalin A.     

Effects of exposure to environmental tobacco smoke on reproductive health

The scientific evidence on the effects of preconceptional and prenatal exposure to environmental tobacco smoke on reproductive health is reviewed in this article. The evidence is the most convincing for the adverse effects of environmental tobacco smoke on birthweight. In meta-analyses, exposure to environmental tobacco smoke has been estimated to reduce mean birthweight by about 25-40 grams. The majority of the studies on low birthweight also show a moderately or slightly increased risk among infants of exposed women. There is also some support for an association between high exposure to environmental tobacco smoke and preterm birth. The evidence on the effects of environmental tobacco smoke on spontaneous abortion and birth defects is weak and inconsistent. Very little is known about the impact of exposure on fertility, menstrual function, reproductive health of men, and childhood cancer. Further studies, paying attention to study design and careful exposure assessment, are therefore needed on these associations.