人源THP - 1细胞系活化试验在化妆品皮肤致敏性评价中的应用研究

目的 建立基于人源THP - 1细胞系的皮肤致敏性体外替代测试方法（h - CLAT）,探讨其应用于化妆品体外皮肤致敏性评价的可行性。方法 参考OECD 442E测试指南,通过对10种标准化学品的致敏性预测建立h - CLAT试验方法,验证其准确性及灵敏度,再对10种特殊类化妆品产品进行皮肤致敏性评价,并与体内皮肤变态反应判定结果进行比较分析。结果 使用h - CLAT方法准确判定了10种标准化学品的皮肤致敏性,10种化妆品产品中,9种产品的预测结果与体内皮肤变态反应的判定结果具有一致性,均为无致敏性,1种产品被判定为具有潜在致敏性,与动物试验结果不一致。结论 基于有害结局路径（AOP）AOP理论,体外人源细胞系活化试验可作为化妆品皮肤致敏性评价的一种筛查方法,但针对体外替代试验的局限性,仍需整合其他测试方法进行皮肤致敏性预测。     

蟑螂细小病毒杀虫剂安全性毒理学实验研究

目的　为对蟑螂细小病毒杀虫剂 (简称ssDNA)进行毒理学评价。方法　进行大鼠急性经口LD50 、经皮LD50 、5周致病性试验 ,豚鼠皮肤致敏、小鼠骨髓微核以及兔眼刺激试验。结果　ssDNA对大鼠急性经口LD50 大于 5 0 0 0mg/kg ,经皮LD50 大于40 0 0mg/kg ,均属低毒。经 5周致病性观察 ,个别指标在个别时间与对照组有差异 ,但无明显特异性和剂量 -反应关系 ,无明显致病性依据。 3 0h给药法经腹腔注射的小鼠骨髓微核为阴性。对豚鼠致敏率为 0。对兔眼无刺激性。结论　ssDNA不失为无毒性、无致病性、无诱变性、无致敏反应的安全天然生物杀虫剂     

83—1除草剂对豚鼠皮肤致敏作用的实验研究

作者采用豚鼠耐受试验对83—1除草剂进行皮肤致敏性检测,结果显示,实际喷洒浓度(0.16%)及最大溶解浓度(0.35%)对豚鼠致敏率均为0%,受试皮肤未发现致敏征象及组织病理改变,细胞免疫功能(Ea、Et试验)也未见增强,可以认为83—1除草剂无致敏作用,推论到人是安全的。     

三氯乙烯致敏豚鼠皮肤组织中白细胞介素-1、-6和-8表达的研究

目的研究白细胞介素(IL)-1、IL-6和IL-8在三氯乙烯(TCE)致敏豚鼠皮肤组织中的表达情况,探讨TCE药疹样皮炎发病机制。方法将白色雌性豚鼠随机分成空白对照组、溶剂对照组、TCE实验组、2,4-二硝基氯苯(DNCB)阳性对照组,根据豚鼠最大值试验(GPMT)方法处理豚鼠,在终末激发后(依据致敏结果以及取材时点的不同,将TCE实验组以及DNCB阳性对照组分为TCE致敏组24 h、TCE致敏组72 h、TCE未致敏组24 h和TCE未致敏组72 h;DNCB组24 h和DNCB组72 h)进行皮肤反应评分,并采取皮肤组织,制成蜡块,采用Elivison二步法免疫组织化学法检测各组皮肤组织中IL-1、IL-6和IL-8的表达情况。结果根据皮肤反应评分≥1判断为致敏阳性,TCE实验组致敏率为62.1%;TCE致敏组24 h和TCE致敏组72 h的IL-1水平要显著高于溶剂对照组,且差异有统计学意义(P<0.05);同时TCE致敏组24 h与TCE未致敏组24 h比较、TCE致敏组72 h与TCE未致敏组72 h比较差异也有统计学意义(P<0.05),但IL-6和IL-8水平在各个组别和不同时间点之间差异无统计...     

2,2′,4,4′,6,6′-六硝基二苯基乙烯的急性毒性评价

目的研究不敏感含能材料2,2′,4,4′,6,6′-六硝基二苯基乙烯(HNS)的急性经口毒性、急性眼刺激性、皮肤刺激性、皮肤致敏毒性,为HNS的职业健康防护提供理论指导。方法根据《化学品毒性鉴定技术规范》,采用SD大鼠、豚鼠、日本大耳白兔进行急性经口毒性、皮肤致敏毒性、急性眼刺激性和皮肤刺激性试验。结果急性经口毒性采用最大限量法一次性染毒,14 d观察期内大鼠无死亡,大体解剖无异常;急性眼刺激性试验,兔染毒0.1 g HNS后,眼刺激性总积分平均值为0分,未发现损伤作用;皮肤刺激性试验,兔染毒0.5 g HNS后,皮肤刺激性总积分平均值为0分,未观察到腐蚀性和刺激性;皮肤致敏试验,20只豚鼠染毒0.4 ml HNS,诱导浓度为1 000 mg/ml,激发浓度为500 mg/ml,激发接触24 h后共有5只豚鼠皮肤出现轻微红斑或水肿,48 h后染毒组皮肤反应恢复正常。染毒组阳性致敏率与阴性对照组比较,差异有统计学意义(P<0.05)。结论根据毒性分级标准进行判定,HNS低毒,无眼刺激性和皮肤刺激性,具有轻度致敏性。     

组织蛋白酶L激活在三氯乙烯致小鼠皮肤过敏中的作用机制

目的 观察三氯乙烯(TCE)致敏小鼠皮肤中组织蛋白酶L(CTSL)的表达情况,探讨CTSL在TCE所致免疫性皮肤损伤中的作用机制。方法 无特定病原体级雌性BALB/c小鼠随机分为空白对照组(5只)、溶剂对照组(5只)、TCE组(15只)和抑制剂组(15只)。按照豚鼠最大反应实验法进行TCE皮肤致敏实验。TCE组、抑制剂组小鼠根据皮肤致敏结果分为致敏亚组和未致敏亚组。于末次激发后72 h处死小鼠,取其实验部位皮肤,检测表皮厚度,以实时荧光定量聚合酶链式反应检测皮肤中Ctsl mRNA的表达,免疫组化法检测皮肤中CTSL、白细胞介素(IL)-6和IL-17的表达。结果 TCE组与抑制剂组小鼠的致敏率分别为40.0%(6/15)和33.3%(5/15),2组小鼠致敏率比较,差异无统计学意义(P0.05)。TCE致敏亚组、抑制剂致敏亚组小鼠表皮厚度和皮肤中Ctsl mRNA、CTSL、IL-6和IL-17的相对表达水平均高于空白对照组、溶剂对照组、TCE未致敏亚组和抑制剂组未致敏亚组(P0.05),TCE致敏亚组小鼠上述指标均高于抑制剂致敏亚组(P0.05)。TCE致敏亚组小鼠皮肤中Ctsl mRNA、CTSL、IL-6和IL-17的相对表达水平在两两之间均存在正相关(P0.05)。结论 CTSL激活可能在TCE致敏小鼠免疫性皮肤损伤中发挥重要作用,其可能与促进IL-6和IL-17的释放有关。     

三氯乙烯致敏豚鼠体内转化生长因子-β、白细胞介素-10表达水平

目的研究抗炎性细胞因子转化生长因子-β(TGF-β)、白细胞介素(IL-10)在三氯乙烯(TCE)致敏豚鼠血清和皮肤中的水平,探讨TCE接触过敏性皮炎的发病机制。方法选用雌性豚鼠74只,随机分成空白对照组、溶剂对照组、TCE处理组,用豚鼠最大值实验方法建立动物致敏模型,并在终末激发后把致敏豚鼠和未致敏豚鼠分别分为24 h、72h、1周、2周组并在相应时间点采集血样。采用酶联免疫吸附法检测各组血清中TGF-β、IL-10水平,免疫组织化学法检测皮肤组织中TGF-β、IL-10的表达。结果 TCE处理组致敏率为68.8%。血清TGF-β水平检测,致敏72 h和1周组比致敏24 h组明显升高(P<0.05),致敏72 h、1周组高于未致敏同时点组(P<0.05);血清IL-10水平检测,致敏72 h组比致敏24 h组明显升高(P<0.05),致敏2周组显著下降(P<0.05),致敏72 h组高于未致敏72 h组(P<0.05)。皮肤组织中TGF-β、IL-10的表达,致敏72 h组高于致敏24 h组、致敏1周组显著高于致敏72 h组(P<0.05),致敏2周组降至最低,致敏72 h、1周组高于未致敏同时点组(P<0.05)。结论 TCE对豚鼠皮肤具有强致敏作用,TGF-β、IL-10在TCE接触过敏性皮炎发生过程中可能具有重要意义。     

重组人乳铁蛋白皮肤变态反应和皮肤光变态反应试验研究

目的确定和评价重组表达的人乳铁蛋白作为化妆品原料对哺乳动物引起变态反应或者光变态反应的程度。方法通过豚鼠皮肤变态反应试验和弗氏完全佐剂试验法考察重组人乳铁蛋白的致敏性和光敏性。结果皮肤变态反应试验中,受试物重组人乳铁蛋白未见引起皮肤红斑、水肿等过敏症状反应,且未见其他中毒指标(受试物组中皮肤反应积分≥2的动物数为0例,致敏率为0%);皮肤光变态反应试验中,豚鼠皮肤局部涂抹受试物重组人乳铁蛋白后进行UVA照射,未引起皮肤刺激和过敏等光变态反应(受试物组中皮肤反应积分≥2的动物数为0例,致敏率为0%)。结论重组人乳铁蛋白无皮肤致敏性和光致敏性。     

局部淋巴结改良法在化妆品皮肤刺激性和致敏性检测中的应用

目的 探讨小鼠局部淋巴结三磷酸腺苷检测法(LLNA:DA)检测化妆品原料及产品的皮肤刺激性和致敏性.方法 选取已知特性的4种化妆品原料(邻苯二甲酸酐、丁香酚、硫酸和水杨酸甲酯)以及未知特性的6种化妆品产品(编号1-6),选耳厚差、耳重为刺激指标,淋巴结重量、淋巴细胞数和ATP发光值为致敏指标进行以下实验:Balb/c小鼠4次重复染毒后分离耳后淋巴结并制成单细胞悬液,经ATP试剂盒处理后于多功能酶标仪上测定ATP发光值,根据刺激指标值分别计算刺激指数(SI1、SI2和SI3),根据SI3计算有效浓度(EC1.8)值.结果 2.5％以上的硫酸和4号化妆品可引起耳厚差和耳重的增加,与对照组相比差异有统计学意义(P＜0.01),可能判为刺激物,其余均无刺激性.邻苯二甲酸酐、丁香酚和1号化妆品致敏检测阳性,其余无致敏性.两个刺激指标中耳重敏感度较高,三个致敏指标中ATP发光值和淋巴细胞计数敏感度较高.结论 刺激指标和致敏指标结合可对化妆品刺激性和致敏性做出较好评价,有望成为化妆品刺激性和致敏性安全性评价的动物替代方法.     

10％联苯菊酯水乳剂的急性毒性研究

目的研究10%联苯菊酯水乳剂的急性毒性,为其毒理安全性评价和农药的登记提供依据。方法按《农药登记毒理学试验方法(》GB15670-1995)及《农药登记资料规定(农业部2007)》进行急性经口、经皮、吸入毒性、皮肤及眼刺激试验、皮肤致敏试验。结果 10%联苯菊酯水乳剂对雌雄性SD的大鼠急性经口LD50雌、雄性均为271mg/kg b.wt.属中等毒类;对雌雄性SD大鼠急性经皮的LD50雌、雄性均为4 300mg/kg b.wt.,属低等毒类;对雌雄性SD大鼠的急性吸入LC50(2h)雌、雄性均大于5 000mg/m3,属微毒类;对雌雄性家兔的急性眼刺激性,未冲洗时急性眼刺激积分指数为6.0,平均指数为2.5,属轻度刺激性。对雌雄性家兔的急性皮肤刺激性,积分为0.0,属无刺激性。受试物原药致豚鼠致敏率为0.0%,属弱致敏物。结论 10%联苯菊酯水乳剂经口、经皮、吸入毒性分别为中低、微毒类,轻度眼刺激性、无皮肤刺激性、弱致敏性的农药。     

甲基丙烯酸环氧丙酯(GMA)亚急性毒性、致突变性和致畸性的研究

本文报道了甲基丙烯酸环氧丙酯的蓄积毒性、皮肤刺激性、致敏性、亚急性毒性以及致突变和致畸性。实验结果表明,大鼠蓄积系数8.36,属弱蓄积;0.1ml原液反复涂抹家兔皮肤可引起一系列皮肤的局部病变,迟发和速发性致敏反应,结果属强致敏物,家兔50mg/kg经口染毒15天,可引起心电图、血压、脑电图、血液学指标和肝功能的改变;Ames试验TA_(100)呈阳性,微核试验呈阳性,大鼠致畸试验(5.38～108mg/kg经口染毒)未见明显异常。     

Endocrine disrupting, mutagenic, and teratogenic effects of upper Danube River sediments using effect-directed analysis

Effect-directed analysis (EDA) can be useful in identifying and evaluating potential toxic chemicals in matrixes. Previous investigations of extracts of sediments from the upper Danube River in Germany revealed acute nonspecific and mechanism-specific toxicity as determined by several bioassays. In the present study, EDA was used to further characterize these sediments and identify groups of potentially toxic chemicals. Four extracts of sediments were subjected to a novel fractionation scheme coupled with identification of chemicals to characterize their ability to disrupt steroidogenesis or cause mutagenic and/or teratogenic effects. All four whole extracts of sediment caused significant alteration of steroidogenesis and were mutagenic as well as teratogenic. The whole extracts of sediments were separated into 18 fractions and these fractions were then subjected to the same bioassays as the whole extracts. Fractions 7 to 15 of all four extracts were consistently more potent in both the Ames fluctuation and H295R assays. Much of this toxicity could be attributed to polycyclic aromatic hydrocarbons, sterols, and in fraction 7-naphthoic acids. Because the fraction containing polychlorinated biphenyls, polychlorodibenzodioxin/furan, dichlorodiphenyltrichloroethane, and several organophosphates did not cause any observable effects on hormone production or a mutagenic response, or were not detected in any of the samples, these compounds could be eliminated as causative agents for the observed effects. These results demonstrate the value of using EDA, which uses multiple bioassays and new fractionation techniques to assess toxicity. Furthermore, to our knowledge this is the first study using the recently developed H295R assay within EDA strategies.     

Safe administration of an inactivated virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy

In order to evaluate whether the virosomal adjuvanted influenza vaccine that has been shown to have the lowest egg protein content (Inflexal V, Berna Biotech) could be administered to children with even severe egg allergy without any risk of allergic reactions, we used epicutaneous skin testing with the undiluted vaccine in 88 asthmatic children (44 with and 44 without egg allergy), none of whom had a positive response. They were then vaccinated with the whole dose of Inflexal V intramuscularly in a one-dose protocol, and the occurrence of any immediate or delayed adverse events were actively monitored for 28 days. The results showed the safety of the administration, and demonstrated that Inflexal V can be safely given without performing a vaccine skin test in children with any kind of egg allergy.     

Assessment of the mutagenic potential of ethanol auto engine exhaust gases by the Salmonella typhimurium microsomal mutagenesis assay, using a direct exposure method.

The mutagenic activity of the new Brazilian fuel, ethanol, was determined by employing the Salmonella typhimurium microsomal mutagenesis assay (TA97, TA98, TA100, TA102, and TA104) and a direct exposure method. This methodology was first used to determine the mutagenic activity of gasoline, revealing mutagenic activity of base-pair substitution without any need for metabolic activation, indicating the presence of direct-action mutagens. Experiments with ethanol suggest an indirect mutagenic activity of the oxidant type. The exposure system was considered suitable for future studies of gaseous mixtures.     

The safety of beta-carotene

Epidemiological studies have associated low dietary and/or plasma level of carotenoids with higher incidences of certain cancers. This evidence has led the National Cancer Institute to initiate more than a dozen prospective clinical trials in which supplements of beta-carotene alone, or in combination with other micronutrients, are being taken. In these trials, the beta-carotene supplements are given in the range of 15-50 mg/day. The safety of this level of intake is well documented. beta-Carotene has been successfully used to treat inherited photosensitivity diseases for more than 15 years at dosages of 180 mg/day or more, without any adverse effects other than hypercarotenemia. Toxicity studies in animals have shown that beta-carotene is not carcinogenic, mutagenic, embryotoxic, or teratogenic and does not cause hypervitaminosis A. In the few isolated reports of carotenoid-related toxicity, the findings are associated with very large intakes of foods containing beta-carotene, among other constituents, and have not been substantiated in individuals who have taken high doses of beta-carotene for several years.     

Evaluation of the effect of drug intake during pregnancy based on the Monitoring Surveillance of the Pathogenesis of Congenital Anomalies]

The data of the Hungarian Case-Control Surveillance of Congenital Anomalies, 1980-1987 were evaluated concerning drug intake during pregnancy in 10,698 index patients, 21,564 negative controls and 828 positive controls. Excluding pregnancy supplements, the proportion of no drug users was about 30% and the mean number of drugs used was 2.0 in negative control group. These figures did not differ significantly from data of study and positive control groups. The analysis of most commonly used drugs indicated an extremely high proportion of hormonal support therapy. The teratogenic effect of several human teratogenic drugs was confirmed. However, their use is relatively rare and their attributable risk within the etiology of congenital anomalies is low, at about 0.3-1.0%. At present the teratogenic risk of drugs in humans is exaggerated and it has several unfortunate con-sequences: negligence of necessary drug use, unnecessary anxiety in pregnant women, termination of planned pregnancies without any reasonable cause.     

Case-control study of allergic reactions to Japanese encephalitis vaccine

Japanese encephalitis (JE) vaccine is widely used in Asia for childhood immunizations, but the vaccine is also used for travellers to Asia from other parts of the world. In Denmark, more than 400,000 doses have been distributed from Statens Serum Institut since 1982. In 1989, the first allergic mucocutaneous reactions after JE vaccination were registered in Denmark and, although the number of reactions have decreased since 1992, reactions are still observed. No explanation of these reactions have been found. The present case-control study, including 49 travellers with allergic reactions and 148 travellers without similar reactions after JE vaccination was performed in order to clarify any possible risk factors. About one third of the adverse reactions to the vaccine could be attributed to an allergic predisposition in the vaccinees. The main risk factors were young age, female gender and previous allergic skin reactions or hayfever. The study also indicated that cases more often reacted to nickel and more often had severe edema after mosquito or other insect bites. Hormone intake was more often spontaneously reported by females in the case group. Accordingly, information on any history of allergy in young adults should be given before JE vaccination, the vaccination should be carried out more than a week before departure and antihistamine treatment should be available if a reaction occurs.     

除草剂噻磺隆原药的毒性及致突变性研究

目的　了解噻磺隆原药的毒性及致突变性。方法　选择大鼠、豚鼠及家兔 ,采用经口、经皮肤、黏膜染毒途径 ,研究其急性毒性。同时用Ames实验、微核实验、小鼠睾丸精母细胞染色体畸变实验进行致突变性研究。结果　噻磺隆原药的大鼠经口LD50 大于 464 0mg/kg ;家兔皮肤及眼刺激强度为轻度刺激性 ;豚鼠皮肤变态反应实验为弱致敏性 ;Ames实验阴性 ,在 10 0 0～ 5 0 0 0mg/kg剂量范围小鼠骨髓嗜多染红细胞微核率无显著增高 ;噻磺隆原药各剂量组染色体畸变细胞率与阴性对照组比较差异无显著性 (P >0 0 5 )。结论　噻磺隆原药属于低毒、弱致敏性农药 ,在本实验条件下 ,噻磺隆原药无致突变作用     

Water chlorination and birth defects.

Chlorination of drinking water that contains organic compounds leads to the formation of by-products, some of which have been shown to have mutagenic or carcinogenic effects. As yet, too little is known about the possible teratogenic effects on the human fetus. We linked the Norwegian waterwork registry, containing 1994 data on chlorination practice and color (an indicator for natural organic matter), with the Medical Birth Registry for 1993-1995. The proportion of the population exposed to chlorination and a weighted mean color number in drinking water was computed for each municipality. Among 141,077 births, 2,608 (1.8%) had birth defects. In a comparison between exposed (high color; chlorination) and reference groups (low color; no chlorination), the adjusted odds ratio was 1.14 (0.99-1.31) for any malformation, 1.26 (0.61-2.62) for neural tube defects, and 1.99 (1.10-3.57) for urinary tract defects. This study provides further evidence of the role of chlorination of humic water as a potential cause of birth defects, in a country with relatively low levels of chlorination byproducts.     

Association of Food Allergy,Respiratory Allergy,and Skin Allergy with Attention Deficit/Hyperactivity Disorder among Children

Background: Previous studies have predominately examined associations of respiratory allergy and skin allergy with ADHD, but little is known about the association between food allergy and ADHD. Methods: We included 192,573 children aged 4–17 years from the National Health Interview Survey (NHIS), a leading health survey in a nationally representative sample of the US population. Allergy conditions and ADHD were defined based on an affirmative response in the NHIS questionnaire. We used weighted logistic regression to estimate the odds ratio (OR) of ADHD. Results: Among the 192,573 children, 15,376 reported ADHD diagnosis. The prevalence of ADHD was higher among children with allergic conditions: 12.66% vs. 7.99% among children with and without food allergy; 12.16% vs. 7.63% among children with and without respiratory allergy; and 11.46% vs. 7.83% among children with and without skin allergy. After adjusting for covariates, the OR of ADHD was 1.72 (95% CI, 1.55–1.91) comparing children with and without food allergy, 1.50 (95% CI, 1.41–1.59) comparing children with and without respiratory allergy, and 1.65 (95% CI, 1.55–1.75) comparing children with and without skin allergy. The observed associations remained significant after mutual adjustment for other allergic conditions. Conclusions: In a nationally representative sample of US children, we found a significant association of common allergic conditions (food allergy, respiratory allergy, and skin allergy) with ADHD.