大鼠新生期暴露2,2',4,4',5,5'-六氯联苯对精子发生的影响

目的 探讨新生期SD大鼠暴露持续性有机污染物2,2',4,4',5,5'-六氯联苯(PCB153)对大鼠精子发生的远期效应.方法 大鼠出生当天(postnatal day O,PNDO),将所有雄性大鼠混合后,重新分为12只,窝.在出生1 d(PND1),按窝别随机分成对照组和处理组,每组24只雄性大鼠.自PND1开始连续7 d经口给予PCB153 0.025、0.250、2.500 mg/kg和等量溶剂对照玉米油.在PND8,每组随机选择16只大鼠称重和测肛殖距离后,经乙醚麻醉并处死,分离和称重睾丸后作组织学检查.剩余大鼠在PND21断奶并饲养至PND90,称重和测肛殖距离后经质量分数为10%的水合氯醛麻醉后解剖,分离并称重睾丸和附睾,其中睾丸用作组织学检查和精子头计数,附睾尾作精子计数.结果 从PND3至PND8,2.500 mg/kg剂量组体重与对照组相比明显下降,差异有统计学意义(P<0.05);在光学显微镜和电子显微镜下观察显示,PND8睾丸组织曲精小管结构疏松,精原细胞体积增大、变性并与管内结构相脱离.随着染毒剂量的增加,PND90睾丸每日精子生成量和附睾尾精子计数与染毒剂量呈剂量-反应关系(r值分别为-0.97和-0.99,P<0.05).0.250和2.500mg/kg剂量组的每日精子生成量分别为30x106/g睾丸和18×106/g睾丸,与对照组(36×106/g睾丸)相比,差异有统计学意义(P<0.05);0.250和2.500 mg/kg剂量组附睾尾精子计数分别为42×107/g附睾尾和18x107/g附睾尾,明显低于对照组(51×107/g附睾尾),差异均有统计学意义(P<0.05).结论 SD大鼠新生期暴露PCB153,可引起成年期睾丸生精功能障碍,导致每日精子生成量和附睾尾精子计数下降.新生期化学物暴露可能引起雄性大鼠生殖功能的远期损害.     

13-week subchronic oral toxicity study of ammonium sulfate in rats

A 13-week subchronic oral toxicity study of ammonium sulfate was performed in both sexes of F344 rats by feeding them a CRF-1 powder diet containing concentrations of 0%, 0.38%, 0.75%, 1.5%, and 3.0% of the substance. Rats were randomly divided into 5 groups each consisting of 10 males and 10 females. Male animals in the 3% group exhibited diarrhea during the administration period. No changes indicating obvious ammonium sulfate toxicity were observed in the body weights, organ weights, hematological, serum biochemical, or histopathological examinations. Based on these results, the NOEL (no-observed-effect level) of ammonium sulfate for F344 rats was judged to be 1.5% in males (886 mg/kg/day) and 3% in females (1975 mg/kg/day), and the MTD (maximally tolerated dose) for 2-year carcinogenicity studies in F344 rats was concluded to be 3.0% or more in the diet.     

Subacute toxicity studies of selected organic colorants

The results of subacute toxicity studies on eight selected colorants of low acute oral toxicity (LD₅₀ > 2000 mg/kg) are reported. These eight colorants, selected from widely differing chemical structural types, were administered as 22 daily doses over a period of 30 days (no weekend dosing) at 1000 mg/kg body weight/day by gavage to female and male rats. Animals treated with the vehicle served only as controls. In most cases the treatment period was followed by a 15-day recovery period. Even at this high dose level all products were tolerated without irreversible signs of toxicity. The survey of data available indicated that the substances investigated exhibited a very low cumulative toxicity.     

二硝酰胺铵的急性毒性和亚慢性毒性研究

目的 对新型含能材料二硝酰胺铵(ADN)的急性毒性、亚急性毒性和亚慢性毒性进行研究,确定ADN的急性毒性分级、毒作用性质及靶器官.方法 根据《化学品毒性鉴定技术规范》,采用大鼠和小鼠急性经口毒性试验、亚急性经口(28d)毒性试验和亚慢性经口(90d)毒性试验.结果 (1)急性经口毒性试验结果表明,ADN对小鼠的经口半数致死剂量LD50为568.9 mg/kg,大鼠为616.6 mg/kg,急性毒性分级属低毒级化学物.(2)亚急性经口(28d)毒性试验结果表明,雌、雄鼠123 mg/kg剂量组体重增长明显低于对照组;61.6、123 mg/kg剂量组血清中总胆红素、天冬氨酸氨基转移酶活力明显高于对照组,肝/体比值明显低于对照组.(3)亚慢性经口(90d)毒性试验结果表明,从染毒第5周开始,123 mg/kg剂量组雌性大鼠体重增长幅度明显降低,与对照组相比,差异有统计学意义(P＜0.05);61.6、123mg/kg剂量组血清中总胆红素、天冬氨酸氨基转移酶活力高于对照组,肝/体比值明显低于对照组,肝脏病变检出例数明显高于对照组,差异均有统计学意义(P＜0.05).结论 ADN急性毒性分级属低毒级,其无可见有害作用水平(NOAEL)为30.8 mg/kg,毒作用的靶器官主要为肝脏.     

R,S及R/S型3-氯-1,2-丙二醇的急性毒性研究

目的探讨R,S和R/S型3-氯-1,2-丙二醇(3-MCPD)对ICR小鼠的急性毒性。方法选用健康性成熟ICR小鼠,对R,S及R/S型3-MCPD染毒剂量依次为176.78、198.43、222.73、250、280.61、314.98和353.55、396.84、445.44和499.99mg/kg,89.09,100,112.25,125.99,141.42,158.74和178.18mg/kg及130.25、150、172.75、198.95、229.13、263.88和303.91mg/kg。经口一次灌胃染毒观察14天,以改良寇式法计算LD50,计算脏体比并进行肝肾病理学检查。结果R,S及R/S型3-MCPD的LD50及95%可信区间(95%CI)分别为290.54mg/kg(280.74~300.68),117.57mg/kg(113.82,121.45),190.73mg/kg(177.76~204.59)。R型异构体在250mg/kg及以上剂量组动物肾体比显著增加(P<0.05),脑体比在353.55mg/kg、445.44mg/kg及最高剂量组亦显著增大(P<0.05);S型3-MCPD染毒组动物各脏体比与对照组比均无显著差异;R/S型3-MCPD,在198.95mg/kg及以上剂量组动物肾体比明显增加,在229.13mg/kg及以上剂量动物脑体比亦明显增加,与对照组比有差异显著(P<0.05)。在353.55mg/kg及以上剂量R型异构体引起肝细胞肿胀、肝窦扩张和明显充血,在229.13mg/kg及以上剂量(R/S)型3-MCPD也引起肝细胞肿胀和肝窦充血,S型则未引起。R、S及(R,S)型均未引起肾脏明显的病理改变。结论三种3-MCPD急性毒性大小依次为S型>R/S型>R型,R、S型异构体均显示出神经毒性。     

Dose-related effects following oral exposure of 2,4-dinitrotoluene on the Western fence lizard, Sceloporus occidentalis

2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species.     

二氧化氯消毒液的致畸性和亚急性毒性研究

目的研究二氧化氯消毒液的致畸性和亚急性毒性。方法设0.1、0.3和1.0g/kg体重三剂量组,进行致畸研究;设0.04、0.2和1.0g/kg体重三个剂量组,进行亚急性毒性试验,观察二氧化氯消毒液对妊娠大鼠的致畸胎性和对大鼠的蓄积毒性作用。结果三个剂量组各项指标均未见有明显的母体毒性和胚胎毒性、致畸性和亚急性毒性。结论在本实验条件下,二氧化氯消毒液无致畸性和亚急性毒性。     

丙烯腈对大鼠外周血淋巴细胞DNA损伤的研究

［目的］ 探讨丙烯腈对大鼠外周血淋巴细胞ＤＮＡ的损伤作用。［方法］ 在急性和亚急性经口染毒试验中,采用单细胞凝胶电泳技术检测不同染毒剂量（１０ｍ ｇ／ｋｇ、３０ｍ ｇ／ｋｇ 和５０ｍ ｇ／ｋｇ）丙烯腈（ＡＣＮ）及不同染毒时段（２ｈ、１４ｄ、２８ｄ、和４２ｄ）对大鼠淋巴细胞ＤＮＡ 的损伤情况。［结果］ 在急性和亚急性染毒试验中,大鼠淋巴细胞ＤＮＡ损伤程度均随ＡＣＮ 染毒剂量增大或染毒时间延长而逐渐加重,并显著高于对照组或染毒１４ｄ 组（Ｐ＜０．０１）,且存在较好的剂量－反应和时间－反应关系（Ｐ＜ ０．０１）。亚急性染毒试验中,随着染毒剂量的升高和染毒时间的延长,淋巴细胞ＤＮＡ 的损伤程度可达到饱和。染毒组细胞ＤＮＡ 损伤反应模式明显不同于对照组,单个细胞间的差异较大,且这种差异随染毒剂量增大和染毒时间延长也逐渐增大。［结论］ ＡＣＮ对大鼠外周血淋巴细胞ＤＮＡ具有明显的损伤作用,且损伤程度和模式受ＡＣＮ 染毒剂量和染毒时间的共同影响。     

4-hydroxy-2',4',6'-trichlorobiphenyl and 4-hydroxy-2',3',4',5'-tetrachlorobiphenyl are estrogenic in rainbow trout

Many natural and synthetic xenobiotics are known to interact with endocrine systems of animals. Various hydroxylated metabolites of persistent polychlorinated biphenyl contaminants (hydroxy-polychlorinated biphenyls [OH-PCBs]) have been shown to have agonist or antagonist interactions with estrogen receptors (ERs). In this study, 4-hydroxy-2',4',6'-trichlorobiphenyl (OH-PCB 30) and 4-hydroxy-2',3',4',5'-tetrachlorobiphenyl (OH-PCB 61), and the natural estrogen 17 beta-estradiol (E2) and estrone (E1), were incorporated into diet and fed to juvenile rainbow trout. The production of vitellogenin (VTG), an egg yolk protein precursor in oviparous animals, was used as a marker of hepatic ER binding. All compounds induced plasma VTG in a dose-dependent manner, with maximal levels of approximately 5 mg VTG/ml plasma induced by E2, E1, and OH-PCB 30. Maximum plasma VTG of 0.048 mg/ml in the highest dose (50 mg/kg) of OH-PCB 61 was approximately 100-fold lower than natural estrogens and OH-PCB 30. At doses that induced submaximal VTG, E1 was two- to threefold less potent, and OH-PCBs were up to 500-fold less potent, than E2. Sex differences in VTG synthesis were apparent at weakly estrogenic doses, but not at maximal VTG-inducing doses. Predictions from previous receptor-binding studies underestimated the maximum estrogenic response of OH-PCB 30 in trout, which was achieved with a dose 10 times higher than E2. Differences in plasma VTG induction by OH-PCB 30 and OH-PCB 61 support in vitro predictions that the degree and position of chlorination are important for ER activation. Neither mixtures of estrogens nor OH-PCBs resulted in synergistic VTG induction.     

Subchronic toxicity and reproduction effects of tri-n-butyltin oxide in Japanese quail

A subchronic toxicity/reproduction study was performed in Japanese quails that were fed a diet containing 0, 24, 60, and 150 mg tri-n-butyltin oxide (TBTO) per kg basal diet for 6 weeks. Eggs produced during the 6 weeks of treatment were incubated and hatched, and chicks hatched from eggs collected in weeks 5 and 6 of exposure were reared for 2 weeks. In parent quail, neither diminished food consumption nor any overt toxic or histopathologic signs were observed following exposure to TBTO. A statistically significant decrease in hatchability and increase in percent of chicks found dead in the shell were observed following TBTO exposure at concentrations of 60 and 150 mg/kg food. However, no significant, adverse effects were recorded on total egg production, eggshell thickness and cracked eggs. Blood chemistry parameters of birds measured at the last day of TBTO treatment revealed a statistically significant decrease in serum aspartate aminotransferase (ASAT) enzyme activity among both sexes in all treatment groups. In addition, a statistically significant dose-related decrease in serum calcium level was observed in females only, while serum follicle stimulating hormone (FSH) levels were statistically significantly reduced in male birds in all treatment groups (approximately 50% of the controls).Moreover, a significant decrease in hepatic microsomal 7-ethoxyresorufin (EROD) activity was recorded in females fed 24 and 60 mg TBTO/kg diet and males fed 60 and 150 mg TBTO/kg diet, whereas pentoxyresorufin-o-deetylase (PROD) activity was only significantly decreased in males fed 150 mg TBTO/kg diet. No TBTO related effects were found on serum alanine aminotransferase (ALAT), serum total thyroxine (TT₄), luteinizing hormone (LH) or retinol levels in both sexes. In summary, TBTO affected mainly reproduction in Japanese quail at a dose where no overt toxicity is observed.     

Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.

We studied the effect of polychlorinated biphenyls (PCBs) on hepatic porphyrin accumulation in female Sprague-Dawley rats by feeding them diets containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or combinations of the single PCB congeners with TCDD for 13 weeks. A dose-dependent increase in hepatic porphyrin accumulation occurred after TCDD, PCB 126, or PCB 156 administration, reaching maximal levels of about twice control values. The lowest dose levels for which a significant increase in hepatic porphyrin accumulation was found were 0.7 microgram TCDD/kg diet, 50 micrograms PCB 126/kg diet, or 6 mg PCB 156/kg diet. These doses are equivalent to 47 ng TCDD/kg/day, 3.2 micrograms PCB 126/kg/day, and 365 micrograms PCB 156/kg/day. Relative potencies for hepatic porphyrin accumulation, using TCDD as a reference, ranged from 0.015 to 0.06 for PCB 126 and from 0.0001 to 0.0003 for PCB 156. CYP1A2 activities significantly correlated with hepatic porphyrin levels, with coefficients of 0.629, 0.483, or 0.808 for TCDD, PCB 126, or PCB 156, respectively. Administration of PCB 153 alone did not result in hepatic porphyrin accumulation. Co-administration of PCB 153 and TCDD revealed a strong synergistic effect on porphyrin accumulation (about 800 times control levels). This synergistic effect was significant in rats fed diets containing any combination of PCB 153 with TCDD. Uroporphyrin III and heptacarboxylic porphyrin were accumulated in porphyrinogenic livers. These results suggest that TCDD induction of CYP1A2 may be involved, leading to oxidation of uroporphyrinogen III to uroporphyrin III, in combination with an increase in delta-aminolevulinic acid synthetase induced by PCB 153. Under porphyrinogenic conditions, an inhibitor of CYP1A2 activity may also be formed. The interactive effects on porphyrin accumulation after co-administration of dioxinlike and non-dioxinlike compounds may have significant implications for the risk assessment of these chemicals.     

Toxicological analysis and antihyperalgesic,antidepressant, and anti-inflammatory effects of Campomanesia adamantium fruit barks

Objective: This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant.

Methods: The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats.

Results: No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3–15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI.

Discussion: The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity.     

Evaluation of Developmental Toxicity of Amitraz in Sprague-Dawley Rats

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo–fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.     

Developmental toxicity of Clarified Slurry Oil applied dermally to rats

Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg/day. All groups received the test material on gestation days 0-19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions/deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.     

Interactions in Developmental Toxicology: Effects of Concurrent Exposure to Lead, Organic Mercury, and Arsenic in Pregnant Mice

The development toxicity of lead nitrate (25 mg/kg, SC), methylmercury chloride (12.5 mg/kg, PO), and sodium arsenite (6 mg/kg, SC) was assessed in CD1 mice following administration on gestation day 10 of these chemicals separately or in their binary and ternary combinations. Cesarean sections were performed on day 18 of gestation, and fetuses were examined for malformations and variations. Three fetuses from each dam were used for whole-body analyses of Pb, Hg, and As. Maternal toxic effects were more remarkable in the group concurrently exposed to Pb, Hg, and As than in those given binary combinations of the elements. In turn, maternal toxicity was more notable in these groups than in those given separately the test compounds. With regard to developmental toxicity, the most relevant effects (decreased fetal weight, cleft palate) corresponded to the Hg-treated groups. It is in agreement with the finding that in all experimental groups the levels of Pb and As in whole fetuses were under their respective detection limits. In general terms, the present data suggests that at the current doses, the interactive effects of Pb and As on Hg-induced developmental toxicity were not greater than additive. In contrast, exposure of pregnant mice to Pb and As at doses that were practically nontoxic to dams, concurrently with organic Hg at a toxic dose, caused supra-additive interactions in maternal toxicity. Received: 26 March 2001/Accepted: 15 July 2001     

乙烯利对小鼠生殖能力的影响

目的研究乙烯利对小鼠生殖能力的影响。方法选用乙烯利作为染毒药物,实验设阴性对照组（0mg／kg）、低剂量组（85mg／kg）、中剂量组（170mg／kg）和高剂量组（340mg／kg）,雄鼠经口染毒14d,于首次给药第15天起以1：1与雌鼠合笼。于合笼后第21天以颈椎脱臼处死雌鼠,剖腹检查确定受孕情况并计算生育仔鼠数。于首次给药第28天后用颈椎脱臼法处死雄鼠,观察乙烯利对雄鼠精子运动率的影响。结果高剂量组雌鼠受孕率与阴性对照组比较明显降低（P〈0．05）;与阴性对照组相比,高剂量组精子计数明显减少（P〈0．05）;各剂量组精子活动率均低于阴性对照组（P〈0．05）。结论乙烯利对雄性小鼠产生了一定的生殖毒作用。     

二氯五氟丙烷的28天吸入毒性试验观察

[目的]研究二氯五氟丙烷(HCFC-225)的毒性及安全性。[方法]通过实验动物急性毒性试验来确定该物质的急性毒性等级，通过大鼠28天吸入毒性试验找出亚急性毒作用浓度闽值及靶器官。急性毒性用霍恩氏法计算；亚急性毒性用不同剂量的该物质对动物染毒，分别对各剂量组的动物进行血液生化测定，称量动物体置、脏器重量并进行组织病理学检查(肺、肝、肾、心)。[结果]小鼠总性LD50雌性为20g／kg，雄性为14．7g/kg；小鼠急性LC50幼为526670mg/m^3；大鼠急性LD50大于21．5g／kg；大鼠28d吸入毒性试验结果提示，AK-225吸入毒作用的主要靶器官为动物的肺脏和肝脏，其次是肾脏。主要的毒性表现有血清中ALT、AST、cR、BUN含量升高；肺组织淤血、出血及炎症细胞浸润；肝组织轻度及水样变病理改变等。最小毒作用浓度(LOEC)为37350mg/m^3，未观察到毒作用浓度(NoEc)为12450mg/m^3。[结论]二氯五氟丙烷(HCFC-25)的急性毒性用于微毒；本次大鼠28d吸入毒性试验结果提示，HCFC—225吸入毒作用的主要靶器官为动物的肺脏和肝脏，其次是肾脏。最小毒作用浓度(LOEC)为37350mg/m^3，未观察到毒作用浓度(NOEC)为12450mg/m^3。     

苯乙烯对大鼠不同脑区多巴胺递质含量及单胺氧化酶活性的影响

目的观察苯乙烯在不同染毒期限和染毒剂量下对大鼠神经系统多巴胺递质含量及单胺氧化酶活性的影响。方法大鼠随机分为5组,每组12只动物,雌雄各半。苯乙烯急性染毒剂量为600mg/kg,亚急性染毒剂量为150~600mg/kg,恢复组在苯乙烯染毒后正常饲养3周,L-dopa组在苯乙烯染毒同时腹腔注射600mg/kgbw的L-dopa。方法监测动物尿中苯乙烯代谢物苯乙醇酸(MA)和苯乙醛酸(PGA)的含量作为苯乙烯染毒的内剂量,测定苯乙烯染毒大鼠不同脑区多巴胺(DA)含量及参与多巴胺代谢的单胺氧化酶(MAO)活性的变化。结果尿中的PGA和MA含量与染毒剂量均呈正相关,由于存在一定的环境本底,MA比PGA在作为苯乙烯染毒内剂量的指标上更有代表性。视网膜、垂体和纹状体中的DA含量在苯乙烯染毒下显著降低,垂体中的MAO活性增加,而纹状体和视网膜中的MAO活性减小。结论苯乙烯可以通过多巴胺通路产生对机体的神经损伤。     

Effect of diplodiatoxin (Stenocarpella maydis) on some enzymatic profiles in male and female rats

Acute and subacute effects of diplodiatoxin were monitored with special reference to biochemical target enzymes like acid phosphatase (AcP), alkaline phosphatase (AkP), and acetylcholinesterase (AChE) in male and female rats. For acute toxicity study the rats were treated with single oral dose of 5.7 mg/kg of diplodiatoxin, whereas for subacute toxicity study the rats were orally treated with 0.27 mg/kg/day for 21 days. Diplodiatoxin caused loss in body weight and feed intake with other clinical symptoms. Due to the acute and subacute treatment of diplodiatoxin significant decreases were observed in serum AcP and AkP and also in liver AkP, whereas liver AcP increased in both male and female treated rats. Further, significant inhibition of brain AChE was observed in acute and subacute treated animals, indicating its effect on nerve synapsis. Sexual dimorphism was recorded when the activity of male rats was compared with female rats. The values were near those of controls on Day 7 (posttreatment), indicating recovery in the altered enzymes once the treatment was ceased. These results suggest that diplodiatoxin is toxic and has potential to affect the normal functioning of individuals and can cause changes in vital tissues such as liver.     

Joint neurodevelopmental and behavioral effects of nonylphenol and estradiol on F1 male rats

The purpose of present study is to examine whether gestational exposure of two major environmental endocrine-disrupting chemicals, nonylphenol (NP) and estradiol (E₂), would affect nervous system development of offspring rats and explore the joint effects of NP and E₂. After impregnation, dams were assigned to seven groups. The first and second groups received gavage with NP at dose levels of 50 mg/kg/day (NP-L) and 100 mg/kg/day (NP-H); the third and fourth groups were gavaged with E₂ at dose levels of 10 μg/kg/day (E₂-L) and 20 μg/kg/day (E₂-H); the fifth and sixth groups were gavaged with joint NP and E₂ [NP 50 mg/kg/day + E₂ 10 μg/kg/day (NP–E₂-L) and NP 100 mg/kg/day+E₂ 20 μg/kg/day (NP–E₂-H)] dissolved in groundnut oil; and the seventh group was orally administered with groundnut oil alone (vehicle control; 2 ml/kg/day), respectively, daily from gestational days 9 to 15 (transplacental exposures). Compared to the control, exclusive NP and E₂ treatment groups, joint exposure to NP–E₂-L and NP–E₂-H has both produced a significant decrease in mean litter size and number of live pups per litter in dams; Offspring rats spent more time to perform cliff-drop aversion reflex, surface righting reflex, air righting reflex, auditory startle, and visual placing; In Morris water maze task, an increased escape latency was presented in offspring rats; In step-down avoidance test, offspring rats jointly exposed to NP and E₂ spent more reaction time. Decrease in acetylcholinesterase activity and increase in choline acetyltransferase activity were observed in the hippocampus of offspring rats. Gestational joint exposure to NP and E₂ might induce nervous development impairment of offspring rats. Moreover, additive toxic effects of NP and E₂ on nervous development have been identified among offspring rats as well.