目的 探讨父亲职业性接触农药与儿童白血病的关系.方法 检索万方、维普、CNKI、Cochrane library和PubMed等国内外数据库中有关父亲职业性接触农药与儿童白血病关系的病例对照试验.按照一定的纳入和排除标准选取文献,采用RevMan5.3软件对文献进行Meta分析.结果 最终选取的10项病例对照试验,Meta分析结果显示:父亲职业接触农药儿童急性白血病患病率的危险性是不接触的1.52倍(OR=1.52,95％CI:1.17～1.96).以对照来源、研究时间、样本量及接触农药种类进行分组,亚组分析结果显示,各亚组父亲职业性接触农药均可增加儿童患急性白血病的风险.结论 父亲职业性接触农药是儿童白血病的危险因素之一.

目的 就戊巴比妥钠与水合氯醛对大鼠的麻醉诱导时间、麻醉持续时间和麻醉死亡率等麻醉效果进行Meta分析.方法 计算机检索万方、维普、CNKI、Cochrane library和PubMed等国内外数据库中有关麻醉剂对大鼠麻醉效果比较的随机对照试验.按照一定的纳入和排除标准选取文献,采用RevMan5.3软件对文献进行统计分析.结果 最终选取的9项随机对照试验,Meta分析结果显示:水合氯醛对大鼠麻醉诱导时间较戊巴比妥钠明显更短(P＜0.01)、麻醉死亡率明显更低(P＜0.05),水合氯醛与戊巴比妥钠对大鼠麻醉持续时间比较,差异无统计学意义(P＞0.05).结论 水合氯醛对大鼠麻醉效果较戊巴比妥钠更好.但由于部分评价指标存在异质性,且多个文献的动物样本数较少,所以需要更大样本、更高质量的研究进一步评价这两种麻醉剂对大鼠的麻醉效果.

目的 探讨添加富硒酵母的油菜花粉对小鼠免疫功能的影响,以期为制定提高缺硒地区人群免疫功能的措施提供参考.方法 经口灌胃给予昆明小鼠250 mg/kg,500 mg/kg,1500 mg/kg 3个剂量的油菜花粉富硒酵母混合物(低、中、高剂量组),以蒸馏水为对照(阴性对照组),30 d后测定小鼠体质量、胸腺质量、脾脏质量、细胞免疫功能、体液免疫功能、巨噬细胞吞噬功能及NK细胞活性.结果 低、中、高剂量组小鼠脾脏质量/体质量比值和胸腺质量/体质量比值与阴性对照组比较,差异均无统计学意义(P>0.05).刀豆蛋白A诱导的小鼠脾淋巴细胞转化实验结果显示:低、中剂量组光密度差值分别为0.116±0.042及0.123±0.049,明显高于阴性对照组的0.075±0.031(P<0.05).小鼠腹腔巨噬细胞吞噬鸡红细胞实验结果显示:低、中、高剂量组小鼠巨噬细胞吞噬鸡红细胞的吞噬指数分别为0.377±0.150,0.539±0.261及0.403±0.113,均高于阴性对照组的0.203±0.072(P<0.05);低、中、高剂量组小鼠巨噬细胞吞噬鸡红细胞的吞噬率分别为(24.0±6.8)％,(28.6±8.1)％及(22.6±4.4)％,均高于阴性对照组的(15.2±4.2)％(P<0.05);低、中、高剂量组小鼠巨噬细胞吞噬鸡红细胞的吞噬率平方根反正旋转换值分别为32.4±4.8,35.7±5.7及31.4±3.4,均高于阴性对照组的25.4±3.6(P<0.05).低、中、高剂量组小鼠NK细胞活性及其数据转换值与阴性对照组比较,差异均无统计学意义(P>0.05).结论 油菜花粉富硒酵母混合物对小鼠细胞免疫功能和巨噬细胞的吞噬功能均有增强作用,可提高小鼠的免疫功能,因此可以尝试用于免疫功能低下人群尤其是缺硒地区的免疫功能低下人群.

目的 检测70％异硫氰酸烯丙酯原药的致突变作用.方法 应用小鼠骨髓多染红细胞微核试验、鼠伤寒沙门菌回复突变试验(Ames试验)、哺乳动物细胞基因(TK位点)突变试验和哺乳动物细胞染色体畸变试验对70％异硫氰酸烯丙酯原药的致突变作用进行研究.结果 70％异硫氰酸烯丙酯原药各剂量组对小鼠骨髓多染红细胞微核率无增加作用.在Ames试验中,70％异硫氰酸烯丙酯原药各剂量组回变菌落数均未超过溶剂对照组的2倍,实验结果为阴性.对哺乳动物细胞基因(TK位点)无致突变效应,对哺乳动物细胞染色体无畸变作用,其差异均无统计学意义(P>0.05).结论 在本实验条件下,70％异硫氰酸烯丙酯原药无明显致突变作用.

急性经口毒性试验是农药安全性评价的第一阶段,其试验结果对亚慢性、慢性及其他多种试验项目的剂量设计和观察指标均具有重要的参考作用,特别是准确的LD50数值及毒性分级.传统试验方法Horn's法虽然能得到较为准确的LD50数值及毒性分级,但需要使用大量的实验动物,不符合动物保护原则.上下增减剂量法(Up-and-Down Procedure,UDP)是经济合作与发展组织(Organization for Economic Cooperation and Development,OECD)于2001年发布的急性经口毒性试验替代方法,我国也在2008年将上述方法纳入了化学品毒性检验国家标准[1-2].但该方法在农药安全性评价中的应用少见报道.本实验室对30个农药样品用UDP检测急性经口毒性,并与传统方法Horn's法进行对比研究,进一步了解UDP的优缺点以及其评价农药急性经口毒性的可靠性,以推动该方法在农药安全性评价中的应用.

目的 评价灵芝刺梨颗粒对小鼠免疫功能的影响.方法 按卫生部《保健食品检验与评价技术规范》(2003年版)规定方法进行实验,以0.083、0.167、0.500 g/kg的剂量经口给予小鼠灵芝刺梨颗粒30天,测定细胞免疫、体液免疫、单核-巨噬细胞吞噬功能指标,以及NK细胞活性.结果 与对照组相比,0.083 g/kg剂量组胸腺/体重比值增高(P<0.05);0.500 g/kg剂量组抗体生成细胞数增高(P<0.01).0.167 g/kg剂量组小鼠单核-巨噬细胞碳廓清能力增强,0.167,0.500 g/kg两个剂量组小鼠巨噬细胞吞噬鸡红细胞吞噬率(转换值)及吞噬系数均增高(P<0.01);0.083 g/kg剂量组小鼠NK细胞活性(转换值)增高(P<0.05).各剂量受试物对小鼠体重增长、脾脏/体重比值、迟发型变态反应能力、ConA诱导的小鼠淋巴细胞转化能力、血清溶素水平均无明显影响(P>0.05).结论 灵芝刺梨颗粒具有增强小鼠免疫功能的作用.

目的 探讨吡蚜酮原药的急性、亚慢性及突变性毒性. 方法 按照GB15670-1995《农药登记毒理学试验方法》进行. 结果 ①急性毒性属低毒;②致突变性的试验结果与对照组比较差异无统计学意义(P＞0.05);③亚慢性毒性试验中:6 000 ppm浓度水平,雌鼠出现体重增长缓慢,心/体、肝/体、脾/体、肾/体和脑/体的比值增高,雄鼠出现血液红细胞计数减低,肝/体比值明显增高;1 500 ppm及以上浓度水平,雄鼠出现体重增长缓慢,脾重量减低,肾/体、脑/体比值明显增高. 结论 本试验提示吡蚜酮对动物的急性毒性低,无明显致突变作用.一定剂量的吡蚜酮可导致动物体重增长缓慢,肝/体、肾/体、脾/体比值增高,血液红细胞数目下降等.最大无作用剂量雌、雄分别为1 500 ppm(150.5 mg·kg-1bw-1 ·d-1)和375 ppm(29.6 mg·kg-1bw-1·d-1).

目的比较国内生产的47种含嘧菌酯农药急性毒性结果，为此类农药的毒理学安全性评价以及安全使用提供参考。方法依据GB 15670-1995《农药登记毒理学试验方法》相关要求进行检测。结果大鼠对含嘧菌酯农药中毒症状以中枢神经系统与躯体感觉和运动系统异常为主。5种农药大鼠急性经口毒性属中毒或低毒类，42种属低毒或微毒类。42种农药大鼠急性经皮毒性属低毒，1种为微毒。复配制剂中毒类比例高于嘧菌酯原药/单一制剂。结论本实验室检测的国内生产的含嘧菌酯农药多为低毒农药，但部分复配制剂因可能存在联合毒性，安全性需进一步研究。

<正>嘧菌酯(Azoxystrobin),化学名称(E)2-[2-[6-(2-氰基苯氧基)嘧啶-4-基氧]苯基]-3-甲氧基丙烯酸甲酯,是由英国某公司研制出的一种甲氧基丙烯酸酯类杀菌剂。由于它具有极好的杀菌效果、极广的杀菌范围,且与目前已有杀菌剂无交互抗性,适用作物广,因而成为当今世界上热门的杀菌剂之一。为了在国内进行登记,本实验室对嘧菌酯原药进行了急性毒性、致突变性及亚慢性经口毒性试验,现将结果报道如下。

Objective To explore the mutagenicity of trifloxystrobin TC, and study its genetic hazard and potential carcinogenesis. Methods The test was conducted in compliance Toxicological Test Methods of Pesticides for Registration(GB15670- 1995), Chemicals- Test Method of in Vitro Mammalian Cell Gene Mutation(GB/ T 21793- 2008), andChemicals- Test Method of in Vitro Mammalian Chromosome Aberration(GB/ T 21794- 2008). Results Mice bone marrow cell micronucleus test, in vitro mammalian cell gene mutation test and in vitro mammalian chromosome aberration test showed that each dosage group showed no statistically significant difference in comparison with the solvent control group(P0.05). Ames test showed that there was no reproducible increase at the three test concentrations in the number of revertant colonies per plate among the test strains. Conclusion Trifloxystrobin TC shows no obvious mutagenicity under this experimental condition.

目的 研究年龄和性别因素对SPF级SD大鼠血液生理生化指标的影响,探讨不同性别SD大鼠在不同年龄阶段的血液生理生化指标正常值. 方法 离乳3周龄SPF级SD大鼠80只,随机分为4、13、26、52周龄四个实验组.大鼠颈静脉采血后用BC-5300Vet兽用全自动血液细胞分析仪以及BACKMANCOULTER全自动生化分析仪测定大鼠血液的生理生化指标. 结果 4周龄与13、26、52周龄大鼠白细胞计数(WBC)、红细胞计数(RBC)、血红蛋白含量(HGB)、红细胞压积(HCT)、白细胞分类、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLB)、碱性磷酸酶(ALP)、尿素氮(BUN)、肌酐(CREA)、葡萄糖(GLU)和Na离子含量比较差异均有统计学意义(P＜0.01或0.05).13、26以及52周龄大鼠血液WBC雌雄差异均有统计学意义(P＜0.01或0.05),13和52周龄大鼠血液ALB、GLB、白球比(A/G)和ALP雌雄差异均有统计学意义(P＜0.01或0.05),26和52周龄大鼠血液RBC、HGB、HCT和平均红细胞血红蛋白含量(MCH)雌雄差异均有统计学意义(P＜0.01或0.05).4周龄大鼠血液ALP雌雄差异有统计学意义(P＜0.01),13周龄大鼠血液谷草转氨酶(AST)、总胆固醇(CHOL)、BUN、CREA和Na离子雌雄差异均有统计学意义(P＜0.01或0.05),52周龄大鼠血液GLU和K离子含量雌雄差异均有统计学意义(P＜0.01或0.05). 结论 不同年龄SD大鼠血液生理生化指标差异有统计学意义,同一年龄阶段SD大鼠雌雄之间也存在一定差异.

Objective To study the mutagenicity and subchronic toxicity of fluazifop-P-butyl TC in rats.Methods The test was conducted in compliance with the National Standard of PRC,Toxicological Test Methods of Pesticides for Registration(GB15670-1995).Results Fluazifop-P-butyl TC was negative for mutagenicity in Ames test,mice bone marrow cell micronucleus test and mice testicle cell chromosome aberration test.Subchronic toxicity test indicated that compared with the control group,the alkaline phosphatase(ALP)levels in the female rats in the middle and high dose groups were significantly elevated(P0.05).The body weights were statistically decreased(P0.05) and the relative weights of liver and brain were markedly elevated in the male rats in the middle and high dose groups(P0.05 or P0.01).The relative weights of kidney in the males in the high dose group were elevated(P0.01).Conclusions Fluazifop-P-butyl TC does not show mutagenicity.It may have some cumulative toxicity and the main target organs are brain,liver and kidney.Under the experimental conditions of this study,the no-observable-adverse-effect levels(NOVELs) of fluazifop-P-butyl TC in the subchronic oral toxicity test for the female and male rats are 6.8 mg/kg·d and 8.4 mg/kg·d,respectively.

目的:通过大鼠亚慢性毒性试验对吡蚜酮原药进行毒理学研究.方法:按照GB15670-1995《农药登记毒理学试验方法》进行.结果:1.亚慢性毒性试验中:雌鼠出现体重增长缓慢,血液红细胞平均体积、血糖增高,心/体、肝/体、脾/体、肾/体和脑/体的比值增高,雄鼠出现红细胞计数、红细胞比积降低,红细胞平均体积、红细胞平均血红蛋白量增高,血清总胆红素、总胆固醇增高,肝/体、睾/体比值明显增高;在1500 ppm及以上浓度水平,雌鼠出现血液红细胞平均血红蛋白量、红细胞平均血红蛋白浓度增高,雄鼠出现体重增长缓慢,肾/体、脑/体比值明显增高.结论:该药可影响动物的生长发育及免疫功能,部分动物体重增长缓慢,部分血液指标(红细胞计数及血小板)、生化指标(谷丙氨酸转氨酶,葡萄糖,及白蛋白)及部分脏器系数改变.SD大鼠亚慢性(90天)经口毒性的最大无作用剂量分别为34.7 mg /(kg bw·d)(375 ppm)和29.6 mg /(kg bw·d)(375 ppm).

目的探讨特丁津原药致突变性。方法按照GB15670-1995《农药登记毒理学试验方法》[1]进行。结果特丁津原药Ames试验、微核试验、小鼠睾丸初级精母细胞染色体畸变试验结果均为阴性。结论特丁津原药不引起小鼠骨髓嗜多染红细胞染色体断裂或整条染色体丢失,本试验提示特丁津原药无明显致突变作用。

Objective To study the toxicity of bendiocarb by acute oral and dermal toxicity tests in rats(LD50),acute dermal and eye irritation tests in rabbits,dermal sensitization test in guinea pigs,and sub-chronic toxicity test in rats and to provide basic data for setting no observed adverse effect level(NOAEL)and occupational exposure limit(OEL).Methods The tests were conducted in compliance with the Technical Guideline of Chemicals Toxicity Evaluation.Results The oral and dermal LD50 values to both females and males were 31.6 mg/kg and>2150 mg/kg bendiocarb classified as high and low toxicity chemicals respectively.Bendiocarb had no-irritability to rabbits'eyes and skin,and the skin-sensitization rate in guinea pigs was 0%.In the sub-chronic oral toxicity test,the female rats(0.50,2.47 mg/(kg bw·d))showed increased total protein,serum aspartate aminotransferase,creatinine and LDH compared with the control group(P<0.01),and the male rats(0.44,2.18 mg/(kg bw·d))showed increased BUN(P<0.01).In the highest dosage groups(2.47 and 2.18 mg/(kg bw·d)for female and male respectively),globulin and BUN in female rats increased significantly(P<0.01)and A/G decreased(P<0.05),while aspartate aminotransferase,alanine aminotransferase and creatinine in male rats increased significantly(P<0.01)and choline esterase decreased(P<0.05).Conclusions Bendiocarb may damage animal's liver.NOVELs for sub-chronic oral toxicity tests(90 days)in male and female rats of bendiocarb were 0.10 mg/(kg bw·d)and 0.09 mg/(kg bw·d)respectively under the experimental conditions of the study.The evaluated OEL was 0.0045 mg/m3,so we should enhance measures for preventing and controlling occupational poisoning in the work places.

乙草胺(Acetochlor),IUPAC标准命名法为2-甲基-6-乙基-N-乙氧基甲基-α-氯化乙酰替苯胺,1971年由美国Monsanto公司研制生产的一种优秀的选择性芽前酰胺类除草剂.现国内市场上最大吨位的除草剂产品[1].有研究表明,乙草胺为一种环境内分泌干扰物,经皮接触可产生不同程度的皮炎[2-3].皮肤吸收为乙草胺进入体内的主要途径之一,比较缓慢不易引起人们的注意,而更容易发生中毒事故,本研究通过急性经皮和亚急性经皮毒性试验分析乙草胺的经皮毒性.

目的 研究克菌丹对Ames试验菌株的致突变性. 方法取农药克菌丹,按照GB15670-1995《农药登记毒理学试验方法》中的平板掺入法进行试验和结果评价. 结果在不加S-9代谢活化系统条件下,TA97、TA100试验菌株各剂量组(10～50μg/皿)回复突变菌落数随剂量增高而增多,均大于自发回复突变菌落数的2倍,存在剂量-反应关系,且有重复性,为阳性反应;在加S-9代谢活化系统条件下,TA97、TA98、TA100试验菌株中、高剂量组(25～50 μg/皿)回复突变菌落数随剂量增高而增多,均大于自发回复突变菌落数的2倍,存在剂量-反应关系,且有重复性,为阳性反应. 结论在本试验条件下,克菌丹对鼠伤寒沙门氏菌回复突变试验(Ames试验)为阳性.

Objective To explore the mutagenicity and subchronic toxicity of methylaminoemamectin benzoate.Method The Ames assay,mouse bone marrow cell micronucleus test,mouse testicle cell chromosome aberration test and subchronic toxicity test in rats were conducted according to National Standards of Toxicological Methods of Pesticides for Registration (GB15670—1995 of PRC).Result 50～200 μg/plate of emamectin benzoate did not induce positive mutations of strains TA97,TA98,TA100,TA102 in Ames test.Mouse bone marrow cell micronucleus test(6.25～50.00 mg/kg) showed that the micronucleus rate in each dosage group significantly increased compared with control group(P0.05),and it also so did in mouse testicle cell chromosome aberration test(12.5～50.0 mg/kg).Subchronic toxicity test showed that at highest dosage(8.0 mg·kg-1·d-1),part of the administrated rats presented some clinical symptoms such as general fremitus,poor spirit,blowzy fur,slow growth of body weight during 11 to 13 weeks after experiment;at the end of experiment,there were some decrease of lymphocyte proportion,increase of intermediate cells(MID) proportion and obvious rise of liver coefficiente in female rats,but there were some increases of kidney and brain coefficientes in male rats.While in middle and high dosage groups,the decrease of lymphocyte proportion,increase of intermediate cells(MID) proportion and obvious rise of heart coefficiente only could be seen in male rats.There was no drug-related effects in rats at the dose level of 0.89 mg·kg-1·d-1.Conclusion The emamectin benzoate did not show any obvious mutagenicity,but it could induce nervous symptoms,interfere with body-weight growth and immunity function. The maximal non-effect dose of emamectin benzoate under oral administration for 90 days in SD rats should be 0.89 mg·kg-1·d-1 accoding to this experiment.

目的研究烯啶虫胺原药的急性毒性作用,为该药的安全性评价提供毒理学依据。方法参照GB15670-1995《农药登记毒理学试验方法》中规定的试验方法进行试验。结果雌、雄大鼠急性经口LD50分别为2610mg/kg和2150mg/kg。雌、雄大鼠急性经皮LD50均>2150mg/kg。眼刺激积分指数(I.A.O.I.)最高为3.5,眼刺激的平均指数(M.I.O.I.)48h后为0,对实验兔眼睛无刺激性。皮肤刺激平均分值为0.25(1h),对实验兔皮肤无刺激性。皮肤致敏试验致敏率为0%,对豚鼠皮肤有弱致敏作用。结论烯啶虫胺原药急性经口、经皮属于低毒,对皮肤、眼睛无刺激作用,属弱致敏物。

Objective To explore the normal value range variations for hematology indexes and biochemical indexes in serum of male and female SD rats.Methods The data of hematology indexes and biochemical indexes in serum of 586 rats in 3 experiments were collected and statistically analyzed.Results The average value and the 95% normal value range of ?hematology indexes and 10 serum biochemical indexes showed no significant difference between both sexes.No significant difference was found in RBC(P＞0.05).But significant differences were found in WBC and AST in female rats(P＜0.05),and no difference was found in male rats.The ALB and TG of male rats showed significant differences(P＜0.05),but not in fe- male rats.Conclusions The normal value ranges of hematology and serum biochemical indexes in serum of SD rats(be- fore the test)are consistent with those literatures reported,and it is feasible to combine the female and male rat's data during statistical analysis.