Investigations on the cytogenetic and embryotoxic activity of pentachloropyridine

Pentachloropyridine, one of the main components in organic wastes from special plasma etching processes in the semiconductor manufacturing industry, was tested for cytogenetic and embryotoxic activity on mice of different strains. For studying potential mutagenic effects, CFLP‐strain male mice were treated with single oral doses of 11.75 mg kg^‐1 (1/20 of i.p. LD₅₀ in mouse) and 100 mg kg^‐1 of pentachloropyridine followed by bone marrow chromosome analysis 24 and 48 h after treatment. For the prenatal toxicological analysis, single oral doses of 100 mg kg^‐1 of pentachloropyridine were given daily to pregnant Halle:DBA and HallerAB mice at days 6–15 of gestation. Pentachloropyridine proved to be neither mutagenic in CFLP mice nor embryotoxic in Halle:DBA and Halle:AB mice.     

Investigations on the acute toxic, cytogenetic, and embryotoxic activity of phenyl isocyanate and diethoxyphosphoryl isocyanate

Phenyl isocyanate (I) and diethoxyphosphoryl isocyanate (II), used as intermediates in organic chemical syntheses, were tested for their acute toxic, cytogenetic, and embryotoxic activity on mice of different strains. The oral LD50 values for male CFLP mice were determined to be 196 mg/kg for I and 4080 mg/kg for II. Single oral doses of 1/40 and 1/20, respectively, of the LD50 of I (4.9 and 9.8 mg/kg) and II (102 and 204 mg/kg) did not cause any significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice. After oral administration of 9.8 mg/kg I and 204 mg/kg II to pregnant Halle-AB-Jena and Halle-DBA mice at various days of gestation (4, 7, 11, or 15), none of the compounds tested were embryotoxic.     

Cytogenetic, genetic, and embryotoxicity studies with dimethyl 2,2,2-trichloro-1-(2,2,2-trichloro-1-hydroxyethoxy)-ethylphosphonat e, a hypothetical impurity in technical grade trichlorfon

The hemiacetal (CH3O)2P(O)CHOCHOHCCl3)CCl3, a hypothetical contaminant in technical preparations of the organophosphorus pesticide trichlorfon, was tested for cytogenetic, mutagenic, and embryotoxic activity after ip administration to mice of different strains. A single dose of 81 mg/kg (0.2 mmol/kg) caused a significant enhancement in the percentage of chromosome aberrations in bone marrow cells of CFLP mice; a similar effect was induced by an equimolar single dose of chemically pure trichlorfon (51.5 mg/kg). At the same dosage level, the hemiacetal proved to be ineffective in the micronucleus test on fetal blood of DBA and AB Jena/Halle mice. In the dominant lethal mutation assay, a single dose of 81 mg/kg hemiacetal to males resulted in a slight increase in the fetal mortality of DBA mice, whereas AB Jena/Halle mice did not respond under these conditions. Four consecutive doses of 81 mg/kg hemiacetal to pregnant AB Jena/Halle mice at Days 2, 3, 4, and 5 of gestation caused only a very weak embryotoxic effect comparable to that of trichlorfon at equimolar dosage. On the basis of these results the hemiacetal tested may not be considered to represent a potential risk factor in technical grade trichlorfon.     

Cytogenetic studies on chrysotile asbestos

The cytogenetic effects of chrysotile asbestos (chrysotile A) in vivo in Rhesus monkeys and Swiss albino mice, and in vitro in embryonic hamster cells were investigated. Single oral dosages of chrysotile, 100 or 500 mg/kg, failed to induce chromosome aberrations in bone marrow cells of Rhesus monkeys. Similarly, oral or intraperitoneal administration of chrysotile over a dose range from 0.4 to 400 mg/kg, failed to induce micronuclei formation in bone marrow cells of mice. However, chrysotile induced a significant and dose-related increase in chromosome aberrations and a dose-related inhibition of the mitotic index of cultured Syrian hamster embryo cells.     

Cytogenetic effects of an agricultural antibiotic, captan, on mouse bone marrow and testicular cells

This paper deals with the cytogenetic effects of Captan on mouse bone marrow and testis. We used (a) the assays of micronuclei (MN) in polychromatic erythrocytes (PCE), (b) the mouse chromosomal aberration test on bone marrow and testis, and (c) the assay of sperm morphology. The tested doses in these assays were 1000, 800, 400, 100, and 50 mg/kg. The results showed that Captan was remarkably mutagenic to bone marrow, the lowest dose inducing MN being 100 mg/kg, and to chromosome breakage, 400 mg/kg. It was also demonstrated that captan was mutagenic to cells of the mouse testis; there was a certain relationship between dosage and response. The lowest doses inducing mutagenicity of spermatocyte and primary spermatogonia and sperm-head abnormality were 50, 800, and 200 mg/kg, respectively.     

In Vivo Genotoxic Evaluation of D-003, a Mixture of Very Long Chain Aliphatic Acids

D-003 is a mixture of very long chain aliphatic acids purified from sugar cane wax with cholesterol-lowering effects. The present study was undertaken to investigate the in vivo cytotoxic and genotoxic potential of D-003 using three established assays: bone marrow micronucleus, sperm morphology, and single cell gel electrophoresis (Comet) assay. In a first experimental series, CEN/NMRI mice (6-8 animals per sex per group) were administered D-003 by gastric gavage at 5, 50, or 500 mg/kg for 90 days, then sacrificed 24 hours after the last administration. The effects on bone marrow micronucleus were evaluated only in female mice. D-003 (5-500 mg/kg) did not increase the frequency of micronucleated polychromatic erythrocytes, nor the ratio of polychromatic to normochromatic erythrocytes, compared with the controls. The assessment of the effects on sperm morphology showed that D-003 did not change the sperm count or the frequency of all types of abnormal head shapes, compared with the controls. In a second series, the micronucleus assay was performed in mice of both sexes given 2,000 mg/kg for 6 days. Likewise, in this series, neither cytotoxic nor genotoxic effects were found. Finally, five male Sprague-Dawley rats were treated with D-003 (1,250 mg/kg) by oral gavage for 90 days, and Comet assay on liver cells was performed. No single-strand breaks or alkali-labile site induction on DNA was observed. These results indicate that D-003 does not show evidence of cytotoxic or genotoxic activity on either somatic or germ cells in rodents.     

溴氰菊酯毒性和致突变性的研究

目的　了解溴氰菊酯的毒性、刺激性、蓄积毒性、致敏性和致突变性。方法　按标准方法分别作大小鼠急性经口毒性 ;大鼠经皮、吸入毒性 ;皮肤、眼刺激性 ;大鼠蓄积毒性和亚慢性经口毒性试验 ;豚鼠致敏试验 ;致突变试验包括Ames、小鼠骨髓微核和睾丸精母细胞染色体畸变试验。结果　大小鼠急性LD50 分别为 2 78mg/kg和 5 6 2mg/kg ;大鼠经皮LD50 >2 0 0 0mg/kg ;急性吸入LC50 >3 0 0 0mg/m3 ;无皮肤刺激性 ,轻度眼刺激性 ;蓄积系数 2 3 ;致敏率为 0 ;Ames试验结果阴性 ;微核和染色体在高剂量组 ( 11 2 4mg/kg)与阴性对照组相比有高度显著性差异 (P <0 0 1) ;大鼠 90天亚慢性经口的最大无作用剂量为 2 82 5mg/kg。结论　溴氰菊酯有明显的蓄积作用 ,为弱致敏物 ,一定剂量下可引起骨髓微核和睾丸精母细胞染色体畸变率增加 ,提示它是一种可能致突变物     

饮用水中2,6-二氯-1,4-苯醌的体内急性毒性和遗传毒性研究

目的研究饮用水中2,6-二氯-1,4-苯醌(2,6-DCBQ)对小鼠的急性毒性和遗传毒性作用。方法选择健康6~8周龄SPF级昆明小鼠进行试验。将50只小鼠随机分为5组,分别为阴性对照(玉米油)组和215、464、1 000、2 150 mg/kg 2,6-DCBQ染毒组,每组10只,雌雄各半。采用一次性经口灌胃方式进行染毒,染毒容量为20 ml/kg。染毒后观察14 d,记录动物死亡数,计算其半数致死剂量(median lethal dose,LD50)。将50只小鼠随机分为5组,分别为溶剂对照(玉米油)组和62.5、125和250 mg/kg 2,6-DCBQ染毒组及阳性对照组(40 mg/kg环磷酰胺),每组10只,雌雄各半。采用灌胃方式进行染毒,染毒容量为20 ml/kg,两次灌胃间隔24 h;第二次灌胃后6 h,进行骨髓细胞微核试验。将50只雄性小鼠随机分为5组,分别为溶剂对照(玉米油)组和62.5、125和250 mg/kg 2,6-DCBQ染毒组及阳性对照组(40 mg/kg环磷酰胺),每组10只。采用经口灌胃方式进行染毒,染毒容量为20 ml/kg,连续灌胃5 d。染毒后第35天,进行精子畸形试验。结果 2,6-DCBQ对雄性、雌性小鼠经口急性毒性的LD50分别为501 mg/kg(95%CI:344~730 mg/kg)和584 mg/kg(95%CI:430~794mg/kg)。不同剂量2,6-DCBQ染毒组小鼠的骨髓细胞微核率及精子畸形率与溶剂对照组比较,差异均无统计学意义(P0.05)。各组PCE/NCE值均在正常范围内。结论 2,6-DCBQ对小鼠经口急性毒性属于低毒级,且未发现其具有遗传毒性。     

氟化钠对小鼠的急性毒性和致染色体突变作用研究

目的:研究氟化钠对小鼠的急性毒性及致染色体突变作用。方法:采用急性毒性试验和小鼠骨髓微核试验。设35.0 mg/kg、55.56 mg/kg8、8.18 mg/kg1、39.97 mg/kg2、22.18 mg/kg3、52.67 mg/kg5、59.79 mg/kg 7个剂量组NaF,观察氟化钠的急性毒性,计算经口半数致死量(LD50);另设高(34 mg/kg)、中(17 mg/kg)、低(8.5 mg/kg)3个剂量组NaF及环磷酰胺阳性对照组(50 mg/kg)、生理盐水空白对照组,观察小鼠骨髓细胞微核率的变化。结果:急性毒性实验各剂量组中毒小鼠均出现不同程度的抽搐、中枢神经系统先兴奋后抑制等表现,氟化钠经口LD50为168.34 mg/kg;氟化钠能诱变小鼠骨髓细胞微核率增高,中、高剂量组微核率均明显高于空白对照组(P<0.01),低剂量组微核率与空白对照组相比,差别无统计学意义(P>0.05)。结论:氟化钠属中等毒性,高浓度氟有致突变作用,能引起染色体损伤,具有潜在的遗传毒性效应。     

锌化物的毒性研究

本文对锌化物(ZnS0_4·7H_2O)的毒性进行了一系列试验。结果表明,经口灌胃急性毒性试验,锌对大白鼠属低毒物质。对小白鼠属中等毒物质。蓄积毒性试验,锌对大白鼠仅有弱的蓄积毒性作用。骨髓细胞和睾丸细胞染色体畸变试验,剂量为58.25mg/kg,畸变率增高。亚慢性毒性试验,最大无作用剂量为195ppm。     

对二氯苯染毒雄性小鼠体细胞与生殖细胞染色体畸变分析

[目的 ]研究对二氯苯的遗传毒性作用。 [方法 ] 40只雄性昆明种小鼠随机分成 5组 ,每组 8只。实验组小鼠连续 5d分别以 180 0、90 0、45 0mg/kg剂量对二氯苯经口灌胃 ,阴性对照组小鼠以等量花生油灌胃 ,阳性对照组小鼠以40mg/kg剂量环磷酰胺腹腔注射。末次染毒 2 4h后处死动物 ,分析骨髓细胞以及精原细胞与初级精母细胞染色体畸变率。 [结果 ]对二氯苯各剂量染毒组雄性小鼠骨髓细胞以及精原细胞和初级精母细胞染色体畸变率与阴性对照组比较均无统计学显著性增高 (P >0 0 5 ) ,各剂量染毒组初级精母细胞常染色体早熟分离发生率与阴性对照组比较也均无统计学显著性差异 (P >0 0 5 ) ,但高剂量染毒组初级精母细胞性染色体早熟分离发生率非常显著高于阴性对照组 (P <0 0 1)。[结论 ]在本实验剂量下未观察到对二氯苯对骨髓细胞染色体结构畸变的诱发作用 ,但一定剂量对二氯苯可能对初级精母细胞性染色体早熟分离有一定的影响     

氧氯化铜的毒性研究

氧氯化铜急性经口ＬＤ＿（５０）在雄性大鼠为２７５６ｍｇ／ｋｇ，雌性大鼠为４３１７ｍｇ／ｋｇ，雌雄有显著性差异；小鼠的急性经口ＬＤ＿（５０）为１１３０ｍｇ／ｋｇ，雌雄无显著性差异。Ａｍｅｓ试验、小鼠骨髓细胞微核试验和小鼠精子畸形试验均未发现其诱变性；氧氯化铜对皮肤无刺激性。结果表明氧氯化铜属低毒类农药，其使用是较为安全的。     

锰对小鼠骨髓细胞微核率的影响

为研究锰对小鼠骨髓微核率的影响 ,给小鼠腹腔注射二价锰 (Mn2 + ,MnCl2 ) ,剂量分别为 0、2 5、5 0和 10 0mg kgBW ,然后计数胸骨骨髓 10 0 0个嗜多染红细胞中的微核细胞数。结果表明 ,在中、高浓度组 ,小鼠骨髓微核率分别为 1 2 0 %和 1 6 4% ,明显高于阴性对照组 (P <0 0 1)。低浓度组与阴性对照组比无显著性差异 ,但有增高趋势 ,提示Mn2 + 浓度越高 ,对小鼠骨髓嗜多染红细胞毒性作用越强 ,可以认为MnCl2 具有致染色体突变性及潜在的遗传毒性。     

含银复合空气消毒剂的毒性试验研究

目的含银复合空气消毒剂使用的安全性。方法用昆明种小鼠对含银复合空气消毒剂进行了急性经口毒性、急性吸入毒性、骨髓细胞微核试验;用家兔进行了急性眼刺激等毒性试验。结果该含银复合空气消毒剂小鼠急性经口毒性LD50大于5000 mg/kg,属实际无毒;小鼠急性吸入毒性LC50大于10 000 mg/m3,属实际无毒;小鼠骨髓细胞微核试验为阴性;对家兔眼刺激的刺激指数为0,属无刺激性。结论提示含银复合空气消毒剂在使用浓度下是安全的。     

杀虫净的毒性研究—人的日容许摄入量建议值

本文对杀虫净进行了大鼠急性经口毒性、小鼠骨髓微核试验和大鼠９０天喂饲试验。杀虫净经口ＬＤ５０为９６．３１ｍｇ／ｋｇ，属中等毒农药，对小鼠骨髓嗜多染红细胞微核无明显影响。大鼠９０天喂饲试验结果表明，杀虫净剂量为０．１ｍｇ／ｋｇ时，大鼠的生长发育、血液生化及病理组织学指标均未见不良改变，大鼠最大无作用剂量为０．１ｍｇ／ｋｇ，人的日容许摄入量建议植为０．００１ｍｇ／ｋｇ。     

The influence of DDT analogues (nuarimol and fenarimol) on the frequency of occurrence of micronuclei in erythrocytes of bone marrow and spleen in mice]

The clastogenic potential of the two DDT analogues: fenarimol and nuarimol was investigated, and the usefulness of the mouse spleen cells for this purpose was evaluated. Nuarimol and fenarimol were administered per o to 8-10 weeks old male mice (Swiss) according to the following protocol: nuarimol 100 and 200 mg/kg b.w. and fenarimol 50 and 100 mg/kg b.w. twice during 24 hours. Mitomycin C (2 and 4 mg/kg b.w.) and cyclophosphamide (25 and 75 mg/kg b.w.) were administered to the positive control mice. After 30, 48, 72 hours following the first administration the animals were killed and the number of micronuclei were calculated in spleen and bone marrow polychromatic and normochromatic erythrocytes. The results show that the spleen could be regarded as an appropriate tissue for the evaluation of micronuclei induction. Fenarimol and nuarimol did not cause micronuclei induction in the bone marrow and spleen erythrocytes.     

烟嘧磺隆原药致突变实验研究

目的：探讨烟嘧磺隆原药的致突变性，预测其遗传危害和潜在致癌作用的可能性。方法：用昆明种小鼠经口灌胃染毒（骨髓细胞染色体畸变实验的剂量分别为250、500、1000mg/kg，睾丸细胞染色体畸变实验的剂量分别为300、1500、3000mg/kg），取其股骨或睾丸组织，常规制片，观察分散良好的中期分裂相，鼠伤寒沙门氏菌回复突变(Ames)试验采用平板掺入法（剂量分别为0．032、0．16、0．84、4．0μg/皿）。结果：小鼠骨髓，睾丸细胞染色体畸变实验显示，烟嘧磺隆原药给药组与阴性对照组相比，差异无显著性（P＞0．05）；Ames试验显示各菌株的各测试浓度的回变菌落数均未超过自发回变菌落数的两倍。结论：在本实验范围内，烟嘧磺隆原药无效突变性。     

戊唑醇原药诱变性与亚慢性经口毒性的实验研究

目的探讨戊唑醇原药的诱变性及亚慢性毒性作用。方法按照我国GB15670-1995《农药登记毒理学试验方法》要求进行。结果 62.5~250μg/皿的Ames实验结果为阴性;染毒14.7~294 mg/kg的剂量组微核试验结果为阴性;染毒36.8~147 mg/kg的剂量组的小鼠睾丸精母细胞染色体畸变率未见增加;亚慢性经口毒性试验高剂量组(71.7mg/kg.bw/d)的雄鼠在染毒中后期出现精神不振、少动、被毛蓬松、会阴部污秽等中毒症状。结论戊唑醇原药无明显致突变作用。戊唑醇原药有一定的蓄积毒性作用,可引起潜在的慢性中毒,主要的毒作用部位是肝脏与血液系统。戊唑醇原药SD雌、雄大鼠亚慢性(90 d)经口试验未观察到有害效应的剂量水平分别为16.3、8.0 mg/kg.bw/d。     

氯化锂对小鼠体细胞遗传毒性作用的实验研究

观察氯化锂的遗传毒性特征并对其毒作用机制做一初步探讨。以氯化锂为受试物,昆明种小鼠为受试对象,分低（２２．５ｍｇ／ｋｇ）、中（７５．０ｍｇ／ｋｇ）、高（２２５．０ｍｇ／ｋｇ）３个不同剂量组进行小鼠体细胞遗传毒性试验。氯化锂经口灌胃染毒后,小鼠骨髓细胞染色体畸变率增高（Ｐ〈０．０５）;骨髓细胞微核率、胎肝细胞微核率增高（Ｐ〈０．０５,Ｐ〈０．０１）。结果表明,一定剂量的氯化锂对昆明种小鼠体细胞具有遗     

甲基吡(口恶)磷原药致突变性实验研究

目的探讨甲基吡噁磷原药的致突变性,预测其遗传危害和潜在致癌作用的可能性。方法用昆明种小鼠经口灌胃染毒,骨髓微核实验的剂量分别为320、160、80、40mg/kg,睾丸细胞染色体畸变实验剂量为160、80、40mg/kg,分别取胸骨、睾丸组织,常规制片,镜下观察。鼠伤寒沙门氏菌回复突变(Ames)实验采用平板掺入法,剂量分别为0.50、1.25、2.50、5.00mg/皿。结果小鼠骨髓微核、睾丸细胞染色体畸变实验显示:甲基吡噁磷原药染毒组与阴性对照组相比,差异无统计学意义(P>0.05);Ames实验显示各菌株的各剂量组的回变菌落数均未超过自发回变菌落数的2倍。结论在本实验条件下,未发现甲基吡噁磷原药的致突变性。