“化学浸出”食用油与大豆蛋白粉含神经毒素正己烷溶剂及其苯残留与内分泌干扰、致生殖毒性、致癌、致畸相关47项科学证据

     Forty-seven scientific evidencesindicating neurotoxin n-hexane solvent and it’s benzene residue contained inchemical extracted food oil and soybean protein powder is linked to endocrinedisruption, carcinogenicity, teratogenicity, and reproduction toxicity

《陈一文顾问博客》


Advisor Chen I-wan Blog:

http://blog.sina.com.cn/s/blog_4bb17e9d0102vt61.html

编译:陈一文,中国灾害防御协会灾害史专业委员会前顾问

ByChen I-wan, Former Advisor, Commission of Disaster History to

ChinaDisaster Prevention Association

2015-08-20

   Thestandards from China, USA, Argentina, India, South Korea and Keyna on n-hexanesolvents used for vegetable cooking oil extraction, all prove that n-hexanesolvents used for vegetable oil extraction, beside n-hexane, also containresidues of benzene and “non volatiles” (crude oil residue) etc..

   中国、美国、阿根廷、印度、韩国与肯尼亚用于植物烹饪油萃取的正己烷溶剂标准,皆证明这样的正己烷溶剂,除了正己烷外,还含苯残留与”不挥发物”(原油残渣)等。

   “Leukemiaand Benzene” (Snyder R., 2012) confirms that a EPA 1998 official documenttruthfully ‘suggests that a specific risk can beassociated with each dose at extremely low doses”.

《白血病与苯》(Snyder R., 2012)确认:美国环保署1998年的一个官方文件如实 “提议每种剂量都可以关联与某种特定的风险”。

This means that the principle of “zero tolerance” mustbe adopted on benzene residues for all and any type of raw materials, foodadditives, extraction materials, process technologies/methods applied inprocessing of food products, including processing of edible vegetable oilproducts.

这意味着,对于应用于食品加工(包括植物食用油产品加工)的所有原材料、食品添加剂、萃取材料、加工工艺/方法,对苯残留必须坚持”零容忍”原则。    

    Upon carefully reviewingall studies we could find in official reports evaluating n-hexane by Dept. of Health And Human Services PublicHealth Service Agency for Toxic Substances and Disease Registry (ATSDR), USA, byEPA, USA, and academic journals, including Chinese journals, 47 scientific evidencesare compiled below:

仔细审视美国卫生与人类服务部(HHS)毒性物质与疾病登记公共卫生服务机构(ATSDR)、美国环保署(EPA)评价正己烷的官方报告中,以及学术刊物,包括中国的刊物中,找到的研究,将47项科学证据汇编如下:

 

 

证据30-3-01:

Scientific Evidence 01(Bus, J.S., 1979)

科学证据01(Bus, J.S., 1979):

   2,5-Hexanedione has also been detected infetal tissue, at a level similar to that in maternal blood, following exposureof F-344 rats to n-hexane (Bus etal., 1979). Bus et al. (1979) exposed pregnant F344 rats to 0 or 1000 ppm onGDs 8–12, 12–16, or 8–16. Progeny of exposed dams had birth weights that wereapproximately 14% lower than controls for up to 3 weeks after birth.

   F-344大鼠暴露于正己烷后,在大鼠胎儿组织中检测到己二酮,水平与怀孕期间母鼠血液中类似(Bus et al., 1979)。Bus et al. (1979)的研究在怀孕后低8-12天、12-16天或8-16天暴露0ppm或1000 ppm正己烷的怀孕F344母鼠。母鼠出生的鼠仔,一直到出生后3周,其体重比对照组低大约14%。

BUS, J.S. & TYL, R.W.(1979) Perinatal toxicity of n-hexane in Fischer 344 rats. Teratology, 19: 22A.

http://www.sciencedirect.com/science/article/pii/0041008X79904721

证据30-3-02:

Scientific Evidence 02 (LittonBionetics, 1979)

科学证据02(Litton bionetics, 1979)

    Groups of 17 – 20 pregnant CD rats wereexposed to 327 or 1436 mg/m3 (93 or 408 ppm) n-hexane (puritynot stated) for 6 h/day on days 6 – 15 of gestation (Litton Bionetics, 1979).There was no embryotoxicity or increase in the incidence of malformations, butsmall, not statistically significant, increases in the incidence ofsubcutaneous haematomas and retarded bone ossification were observed at bothexposure levels.

    17 – 20只怀孕CD大鼠在孕后6-15天期间暴露于327或1436mg/m3(93或408 ppm)正己烷(纯度没有说明)6小时/天(Litton Bionetics, 1979)。没有观察到致胚胎毒性或增加畸形发生率,但是在两个剂量下都观察到非统计显著少量增加皮下血肿与骨头骨化发育不良。

LITTON BIONETICS (1979) Teratology study in rats:  n-hexane, Litton Bionetics (LBI ProjectNo. 20698-9) (Final Report submitted to the American Petroleum Institute).

Quoted from:

引用自:

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY, ENVIRONMENTAL HEALTH CRITERIA 122 n-HEXANE

对于化学安全性国际计划,环境、健康、标准 122 正己烷

http://www.inchem.org/documents/ehc/ehc/ehc122.htm#SubSectionNumber:6.1.1

证据30-3-03:

ScientificEvidence 03 (Katz, G.V.,1980)

科学证据03(Katz, G.V., 1980)

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexane。

   大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

KATZ, G.V.,O’DONOGHUE, J.L., DIVINCENZO, G.D., & TERHAAR, C.J. (1980) Comparativeneurotoxicity and metabolism of ethyl n-butyl ketone and methyl n-butyl ketonein rats.  Toxicol. appl. Pharmacol., 52:153-158.

http://www.researchgate.net/publication/15838408_Comparative_neurotoxicity_and_metabolism_of_ethyl_n-butyl_ketone_and_methyl_n-butyl_ketone_in_rats

证据30-3-04:

ScientificEvidence 04 (Krasavage, W.J.,1980)

科学证据04(Krasavage, W.J.,1980)

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexane。

   大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

KRASAVAGE, W.J., O’DONOGHUE,J.L., DIVINCENZO, G.D., & TERHAAR, C.J. (1980) The relative neurotoxicityof methyl n-butyl ketone, n-hexane and their metabolites. Toxicol. appl. Pharmacol., 52:433-441.

http://www.sciencedirect.com/science/article/pii/0041008X80903385

证据30-3-05:

ScientificEvidence 05 (Cavanagh,J.B. & Bennetts, R.J., 1981)

科学证据05(Cavanagh, J.B. & Bennetts, R.J.,1981)

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexanehas been described

大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

CAVANAGH, J.B.& BENNETTS, R.J. (1981) On the pattern of changes in the nervous systemproduced by 2,5-hexanediol. A topographical study by light microscopy.  Brain, 104: 297-318.

http://brain.oxfordjournals.org/content/104/2/297

证据30-3-06:

ScientificEvidence 06 (Babanov, G.P. & Babanov, A.G., 1981)

科学证据06(Babanov, G.P. & Babanov, A.G., 1981):

The concentration in totalfetal tissue was similar to that in maternal blood

总胎儿组织中正己烷的浓度与其母鼠血液中浓度类似

BABANOV, G.P. & BABANOV,A.G. (1981) [Permeability of tissues to alkanes and their relationship withmolecular weight, parity of carbon atoms and branching of hydrocarbon chains.] Gig.Tr. prof. Zabol., 12: 48-51 (in Russian).

证据30-3-07:

Scientific Evidence 07 (R.A. Kuna, R.W. Kapp Jr., 1981)

科学证据07(R.A. Kuna, R.W. Kapp Jr.,1981)

The purpose of this research was to studythe teratological response of rats to … exposed to benzene vapor for 7 hr/dayfrom Days 6 through 15 of gestation at concentrations of 10, 50, and 500 ppm.An air-exposed control group was also studied. … Skeletal examinationsrevealed developmental abnormalities, not considered to be spontaneous in thisstrain of rat, in offspring of dams exposed to 500 ppm. Benzene vapor, underthe conditions of this test, has been judged to be fetotoxic in the rat atexposure concentrations of 50 and 500 ppm and to manifest a teratogenicpotential at 500 ppm.

该项研究的目的时研究怀孕后低6天到15天每天7小时暴露于浓度10、50与500 ppm苯气体大鼠的畸形响应。同时对空气-暴露对照组进行研究。…对暴露于500 ppm苯气体母鼠生的鼠仔骨骼检查揭示发育性异常,被考虑在这种品种大鼠中非自然发生。苯气体,在该项试验条件下,暴露于浓度50 ppm与500 ppm浓度情况下,被判断对大鼠致胎儿毒性,在500 ppm条件下构成致畸形潜力。

R.A. Kuna , R.W.Kapp Jr. †, 1. The embryotoxic/teratogenic potential of benzene vapor in rats.Toxicology and Applied Pharmacology, Volume 57, Issue 1, January 1981, Pages1-7

http://www.sciencedirect.com/science/article/pii/0041008X81900181

证据30-3-08:

Scientific Evidence 08 (HazeltonLaboratories, 1981)

科学证据08(Hazelton Laboratories, 1981)

   In CD rats exposed to 528, 1056, or 1805mg/m3 (150, 300, or 600 ppm) n-hexane (ultraviolet grade)vapour (6 h/day for 5 consecutive days), there was an increase in the incidenceof bone marrow cells with chromatid breaks at 528 and 1056 mg/m3 (HazeltonLaboratories, 1981).  Severe chromosomaldamage with fragments and dicentrics was reported at 2112 mg/m3 (600ppm).  In a preliminary study using adifferent batch of n-hexane, anincrease in the number of aberrations per cell was reported following exposureto 352 and 1408 mg/m3 (100 and 400 ppm).

   在暴露于528、1056或1805mg/m3(150, 300或600 ppm)正己烷(紫外线级)气体(6小时/天持续5天)的研究中,骨髓细胞染色单体断裂发生率在528与1056mg/m3(150与300 ppm)剂量下增加(Hazelton Laboratories, 1981)。在2112mg/m3(600 ppm)剂量下报告发生严重具片段与双着丝的染色体损伤。暴露于352与1408mg/m3(100与400 ppm)另外一批正己烷的初步研究报告每个细胞中畸变数量增加。

HAZELTON LABORATORIES (1981) Invivo and in vitro mutagenicity studies n-hexane (hexane UV), Vienna,Virginia, Hazelton Laboratories (Project No. 596-114 and 596-115) (Prepared forthe American Petroleum Institute).

Quoted from:

引用自:

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY, ENVIRONMENTAL HEALTH CRITERIA 122n-HEXANE

对于化学安全性国际计划,环境、健康、标准 122 正己烷

http://www.inchem.org/documents/ehc/ehc/ehc122.htm#SubSectionNumber:6.1.1

证据30-3-09:

Scientific Evidence 09 (Chapin,R.E. et al., 1982)

科学证据09(Chapin, R.E. et al., 1982)

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexanehas been described

大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

CHAPIN,R.E., NORTON, R.M., POPP, J.A., & BUS, J.S. (1982) The

effects of2,5-hexanedione on reproductive hormones and testicular

enzymeactivities in the F-344 rat.  Toxicol.appl. Pharmacol., 62:

262-272.

http://www.sciencedirect.com/science/article/pii/0041008X82901247

证据30-3-10:

Scientific Evidence 10 (Anthony,D.C.,1983)

科学证据10(Anthony, D.C.,1983)

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexanehas been described

   大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

ANTHONY,D.C., BOEKELHEIDE, K., & GRAHAM, D.G. (1983) The effect of 3,4-dimethylsubstitution on the neurotoxicity of 2,5-hexanedione. I. Accelerated clinicalneuropathy is accompanied by more proximal axonal swellings.  Toxicol. appl. Pharmacol., 71: 362-371.

http://www.sciencedirect.com/science/article/pii/0041008X83900248

证据30-3-11:

Scientific Evidence 11 (Lungarella,G. et al., 1984)

科学证据11(Lungarella, G. et al.,1984):

   NewZealand male rabbits were exposed in an inhalation chamber to 3,000 ppm ofn-hexane 8 h/day, 5 days/week for 24 weeks, resulting in a total of 120 exposures.After a further 120 days in clean air, morphologic examination of lungs bylight and transmission electron microscopy (TEM) revealed three importantexposure-related lesions. These consisted of air space enlargement centered onrespiratory bronchioles and alveolar ducts (centriacinar emphysema), scatteredfoci of pulmonary fibrosis, and papillary tumors of non-ciliated bronchiolarepithelial cells. At TEM examination these tumors were rather homogeneous andwere found to consist of cells showing both small and large electron denseovoid granules in their cytoplasmic matrix, a feature that has been describedfor Clara cells.

   持续24周每周五天每天8小时暴露于3,000ppm正己烷的一组12只新西兰雄性家兔,此后在清洁空气中进一步喂养120天后,用光学与透射电子显微镜(TEM)对肺部形态学检查揭示三种重要的与暴露关联的病变。这包括集中在呼吸细支气管和肺泡导管的空气空间扩大(腺泡中央型肺气肿)、散灶肺纤维化,与无纤毛的细支气管上皮细胞乳头状肿瘤。在透射电子显微镜检查中,这些肿瘤较均匀,而且发现由细胞质基质中含大大小小的电子致密卵圆形颗粒的细胞,与对克拉拉细胞的描述的特征一样。

   A n-hexane safety assessment reportpublished by WHO in 1991 confirmed :Papillary tumors, apparently derived fromClara cells, in the bronchiolar epithelium have been reported in a group of 12New Zealand rabbits exposed to 3,000 ppm n-hexane for 8 hours a day, 5 days aweek for 24 weeks, but the incidence was not reported.

   世界卫生组织1991年发表的对正己烷安全评估报告确认:持续24周每周五天每天8小时暴露于3,000 ppm正己烷的一组12只新西兰家兔研究中出现了显然来自细支气管上皮克拉拉细胞中的乳头状肿瘤,但是该事件没有报告。

LUNGARELLA, G.,BARNI-COMPARINI, I., & FONZI, L. (1984) Pulmonary changes induced inrabbits by long-term exposure to n-hexane. Arch. Toxicol., 55:224-228.

http://www.researchgate.net/publication/16678005_Pulmonary_changes_induced_in_rabbits_by_long-term_exposure_to_n-hexane

证据30-3-12:

Scientific Evidence 12 (Sayre,L.M. et al., 1984)

科学证据12(Sayre, L.M. et al.,1984)

   In pregnant rats the same levels ofn-hexane are found in the fetal tissue as in the maternal blood…

   在怀孕老鼠中,在胎儿组织中发现与母体血液同样水平的正己烷。”;

Mutti A, Falzoi M, Lucertini S, et al. n-Hexane metabolism inoccupationally exposed workers.Br J Ind Med.1984;41:533–8.

   The production of testicular lesions inrats following exposure to 2,5-hexanedione and other metabolites of n-hexanehas been described

   大鼠暴露于2,5-己二酮与正己烷的代谢物后产生了睾丸损伤。

SAYRE, L.M., SHEARSON, C.M.,WONGMONGKOLRIT, T., MEDORI, R., & GAMBETTI, P. (1986) Structural basis ofc-diketone neurotoxicity: non-neurotoxicity of 3,3-dimethyl-2,5-hexanedione, ac-diketone incapable of pyrolle formation. Toxicol. appl. Pharmacol., 84: 36-44.

http://www.researchgate.net/publication/19445803_Structural_basis_of_-diketone_neurotoxicity_Non-neurotoxicity_of_33-dimethyl-25-hexanedione_a_-diketone_incapable_of_pyrrole_formation

证据30-3-13:

Scientific Evidence 13 (Gomez-Arroyo,S. et al., 1986)

科学证据13(Gomez-Arroyo, S. et al.,1986)

   In a study on the frequency of chromosomal alterationsinduced in Vicia faba root tipcells exposed to n-hexane solutions in water at concentrations of 0.10,0.30, 0.50, 0.75, and 1%, an increase in chromosomal aberrations occurred atthe concentration of 0.75% but not at the other concentrations tested(Gomez-Arroyo et al., 1986).

   对暴露于水中正己烷浓度0.10%、0.30%、0.50%、0.75%与1%对蚕豆根尖细胞诱发的染色体改变的频率进行的研究,观察到在0.75%浓度下染色体畸变增加,但是在其他浓度下没有观察到(Gomez-Arroyo et al., 1986)

GOMEZ-ARROYO, S.,CASTILLO-RUIZ, P., & VILLALOBOS-PIETRINI, R. (1986) Chromosomal alterationsinduced in Vicia faba by different industrial solvents: thinner,toluene, benyene, n-hexane, n-heptane and ethyl acetate. Cytologia, 51: 133-142.

https://eurekamag.com/research/004/950/004950813.php

证据30-3-14:

ScientificEvidence 14 (C. De Martino et al., 1987)

科学证据14(C. De Martino et al., 1987):

   Testicular damage was induced in rats byrespiratory treatment withn-hexane… after interruption of the treatment, the testicular lesions becameincreasingly severe, up to complete atrophy of the seminiferous tubules,suggesting an irreversible sterility of the treated animals. The authors could not determinewhether the primary effect was on the Sertoli cell, the germinal cells, orboth.  Signs of testicular damage wereclear before neuropathic symptoms developed in the rats.

   “正己烷诱发睾丸损伤。…干扰处理后,睾丸损伤变得越来越严重,直到细精管完全萎缩,提议处理动物发生了无法逆转绝育。 … 作者们不能确定主要的影响是对于塞尔托利氏细胞,对胚细胞,还是对两者皆影响的结果。大鼠中发展神经性症状前就出现了睾丸已经收到损伤的清楚迹象。”!

C. De Martinoet al., Effects ofrespiratory treatment with N-hexaneon rat testis morphology: I. A light microscopic study,Experimental and Molecular Pathology,Volume 46, Issue 2, April 1987, Pages199–216

C. De Martinoet al.,吸入正己烷对老鼠睾丸形态学的影响:I.光学显微研究,实验性与分子病理学,第46卷第2期,1987年4月,第199-216页

http://www.sciencedirect.com/science/article/pii/0014480087900669

证据30-3-15:

ScientificEvidence 15 (Goel et al., 1987)

科学证据15(Goel et al., 1987)

   The potential for n-hexane to affectthe haemopoietic system was indicated by the significant inhibition of uptakeof iron by the bone marrow in rats that had received 1 ml n-hexane/kg(ip) on two successive days (Goel et al., 1987).

    连续两天接受1ml正己烷/kg的大鼠中对造血系统的影响:显著抑制骨髓对铁的摄取(Goel et al., 1987)。

GOEL, S.K., RAO, G.S., &KRISHNAMURTI, C.R. (1987) Toxicity of n-hexane and 2,5-hexanediol to thehaemopoietic system: a preliminary report. Xenobiotica, 17: 217-222.

https://www.ncbi.nlm.nih.gov/pubmed/3564536

证据30-3-16:

ScientificEvidence 16 (Mast, T.,1987)

科学证据16(Mast, T., 1987)

   Prenatalexposure to pure n-hexane-induced skeletal anomalies, decreased fetal bodyweight, and increased resorptions, suggesting that the fetus may be affected byn-hexane inhalation exposure. The increase in mean percent incidence per litter ofreduced ossification of sternebrae 1- 4 was statistically significant for thehighest exposure concentration, and the increase was positively correlated withincreasing exposure concentration.

   产前暴露于纯正己烷诱发骨骼异常、胎儿体重下降,并增加吸收,表明正己烷吸入暴露可能会影响到胎儿。暴露浓度最高母鼠的每窝鼠仔平均百分比的胸骨节1 – 4骨化降低发病率增加统计学意义显著,这样的增加度与增加接触浓度呈正相关。

Mast, T. (1987)Inhalation developmental toxicology studies: Teratology study of n-hexane inrats [final report]. Public Health Service, U.S. Department of Health and HumanServices; TER90082. Prepared by the Pacific Northwest Laboratory, Richland, WA,for the National Toxicology Program, National Institute for EnvironmentalHealth Services, Research Triangle Park, NC; PNL-6453.

Complete text:http://www.osti.gov/scitech/servlets/purl/5440289

全文:http://www.osti.gov/scitech/servlets/purl/5440289

证据30-3-17:

ScientificEvidence 17 (Mast et al., 1988)

科学证据17(Mast et al., 1988)

   A companion study in CD-1 mice (Mast etal., 1988a) observed signs of maternal toxicity, such as reduced body weightgain and relative uterus weight in high-dose dams. Fetal resorptions wereevident in all exposure groups.

   CDC-1小鼠中进行的配合研究中(Mast et al., 1988a) 观察到母体致胎儿毒性的迹象,包括高剂量组中鼠仔体重降低与相关的子宫重量。所有暴露组中都有胎儿吸收的证据。

Mast,T; Decker, J; Stoney, K; et al. (1988a) Inhalation developmental toxicologystudies: Teratology study of n-hexane in mice [final report]. Public HealthService, U.S. Department of Health and Human Services; NTP TER90083. Preparedby the Pacific Northwest Laboratory, Richland, WA, for the National ToxicologyProgram, National Institute for Environmental Health Services, ResearchTriangle Park, NC; PNL-6590.

http://www.researchgate.net/publication/255134295_Inhalation_developmental_toxicology_studies_Teratology_study_of_n-hexane_in_mice_Final_report

证据30-3-18:

ScientificEvidence 18 (Boekelheide K., K.1988)

科学证据18(Boekelheide K., K.1988)

   Under identical conditions of treatment andrecovery, pyrrole reactivity of testis proteins increased to maximal levelswithin 2 weeks of treatment and nucleation time for microtubule assembly frompurified testis tubulin was decreased at 2 weeks.  This was associated with the presence ofcross-linked tubulin, which was suggested to lead to germ cell loss(Boekelheide, 1988b).

   类似的处理条例与恢复条件下,睾丸蛋白的吡咯反应性,在处理2周内增加到最高水平,而自纯化睾丸微管蛋白的微管组合成核时间在2周减少了。这与微管蛋白交联的存在关联,提议导致生殖细胞的损失

BOEKELHEIDE, K. (1988) Rattestis during 2,5-hexanedione intoxication and recovery. II. Dynamics ofpyrrole reactivity, tubulin content and microtubule assembly. Toxicol. appl.Pharmacol., 92: 28-33.

http://www.sciencedirect.com/science/article/pii/0041008X88902244

This work was supported by Grant R01 OH02191 from the National Institute forOccupational Safety and Health of the Centers for Disease Control and aPharmaceutical Manufacturers Association Foundation Faculty Development Awardin Toxicologic Pathology.

证据30-3-19:

ScientificEvidence 19 (Boekelheide, K. & Eveleth, J. 1988)

科学证据19(Boekelheide, K. & Eveleth, J. 1988):

   Charles River CD rats were treated with atotal dose of 131 (± 2) mmol 2,5-hexanedione/kg at dose rates ranging from 1.9to 6.1 mmol/kg per day, and testicular damage was assessed 4 weeks after thecessation of treatment.  Reduced testisweight and germ cell depletion were dependent on the rate of intoxicationrather than the total dose.  The rate ofintoxication also determined the extent of testis pyrrole formation.

   在Boekelheide & Eveleth1988年的研究中,查尔斯河CD大鼠被处理总剂量131 (± 2) mmol的2,5-己二酮,每天剂量范围1.9 to 6.1 mmol/kg,处理停止后4周对睾丸损伤进行评估。减少的睾丸重量与生殖细胞的耗竭取决于中毒率而非总剂量。中毒率还决定睾丸吡咯形成的程度。

BOEKELHEIDE, K. & EVELETH,J. (1988) The rate of 2,5-hexanedione intoxication, not total dose, determinesthe extent of testicular injury and altered microtubule assembly in the rat. Toxicol. appl. Pharmacol., 94:76-83.

http://www.cdc.gov/niosh/nioshtic-2/00180949.html

证据30-3-20:

ScientificEvidence 20 (Nylén P et al., 1989)

科学证据20(Nylén P et al., 1989)

   Testicular and germcell line morphology in rats were studied 2 weeks, 10 months and 14 monthsafter cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgenbiosynthetic capacity of testis, testosterone blood concentration, vas deferensmorphology and noradrenaline (NA) concentration, epididymal sperm morphology,and fertility were also studied. Severe testicular atrophy involving theseminiferous tubules with loss of the nerve growth factor (NGF) immunoreactivegerm cell line was found. Total loss of the germ cell line was found in afraction of animals up to 14 months post-exposure, indicating permanenttesticular damage.No impairment ofandrogen synthesis or androgen dependent accessory organs was observed. …

   吸入暴露于1000mmp正己烷后,对老鼠中的睾丸与生殖细胞形态研究了2周、10个月与14个月暴露于1000mmp正己烷后停止吸入61天后。对睾丸的雄性激素生物合成能力、睾丸激素血液浓度、输精管形态与去甲肾上腺素(NA)浓度、附睾的精子形态,,以及生育能力进行了研究。发现涉及细精管的严重的严重的睾丸萎缩与丧失神经生长因子(NGF)免疫反应性的生殖细胞线。暴露于正己烷之后14个月后,在少部分试验动物中依然发现生殖细胞线完全丧失。没有观察到雄性激素合成或依赖于雄性激素的附属器官受损。…

Nylén P et al., Testicular atrophy andloss of nerve growth factor- immunoreactive germ cell line in rats exposed ton-hexane and a protective effect of simultaneous exposure to toluene or xylene.Arch Toxicol.1989;63(4):296-307.

Nylén Pet al.,接触正己烷老鼠发生睾丸萎缩和损失的神经生长因子免疫反应性的生殖细胞线以及同时接触甲苯或二甲苯的保护作用,毒理学档案。1989;63(4):296-307.

http://www.ncbi.nlm.nih.gov/pubmed/2764718

Department of Neuromedicine, NationalInstitute of Occupational Health, Solna, Sweden.

瑞典国家职业健康研究院,神经医学部

证据30-3-21:

Scientific Evidence 21 (BRRC, 1989)

科学证据21(BRRC, 1989)

   In addition, pregnant CD-1 mice (30/group)were exposed to the same regimen as that described for the Sprague-Dawley rats(BRRC, 1989b). … However, there were treatment-related increased incidencesof two individual skeletal variations in high-dose pups. Comparing theincidences of these effects between controls and high-dose groups by litter,the numbers were 0/26 versus 6/26 for bilateral bone islands at the firstlumbar arch and 20/26 versus 26/26 for all unossified intermediate phalanges(statistically significant at p<0.05, Fisher’s Exact test as calculated bythe authors).

   此外,怀孕CDC-1小鼠(30只/组)暴露于SD大鼠同样的方案(BRRC, 1989b)。…然而,在高剂量鼠仔中两只出现了与处理相关的骨骼异常发生率增加。在对照与与高剂量组之间对这些影响进行比较,对第一腰椎弓双侧骨岛其数字为0/26对6/26;对所有未骨化的中间指骨其数字为20/26对26/26(统计学意义为p<0.05,依据作者们计算的确切概率法)。

BRRC. (1989b) Draft results ofthe developmental toxicity exposure range-finding studies of commercial hexanevapor in mice and rats with cover letter dated 033089. EPA Document No.FYI-AX-0489-0459; NTIS No. OTS0000459-2.

Quoted from: EPA ToxicologicalReview of n-Hexane, Nov. 2005

摘录自:美国环保署《正己烷毒理学审视》2005年11月

http://www.epa.gov/iris/toxreviews/0486tr.pdf

证据30-3-22:

Scientific Evidence 22 (Gisela,S-D et al., 1990)

科学证据22(Gisela, S-D et al.,1990)

   Inthese cases, a delay in the maturation of cerebellar cortex was also observed.In cases of pre- and postnatal solvent exposure, the effects of malnutritionwere added to the solvent-induced retardation. This resulted in an extremedelay in tissue maturation accompanied by a retarded cell maturation. …

   怀孕老鼠接触正己烷及其混合气体导致后代”小脑皮层延迟成熟。在出生以及出生后接触中,除了溶剂诱发的生长延迟外,还发生营养不良。这导致极为严重的组织成熟延迟与延迟的细胞成熟”!

Gisela Stoltenburg-Didinger at el.,Neurotoxicity of organic solvent mixtures: Embryotoxicity and fetotoxicity, Neurotoxicologyand Teratology, Volume 12, Issue 6, November–December1990, Pages 585–589

Gisela Stoltenburg-Didinger atel.,有机溶剂混合的神经毒性:胚胎毒性与胎仔毒性,神经毒性与畸形学,第12卷第6期,1990年12月,pp585-589

http://www.sciencedirect.com/science/article/pii/089203629090066L

证据30-3-23:

ScientificEvidence 23 (Yu, D.X., Liu R.H., 1991)

科学证据23(于冬雪、刘瑞华,1991)

苯对女工的生殖机能及其子代的智力发育可能有影响。

Benzinemight have effects on the reproduction function of female workers and intelligencedevelopment of their offsprings.

于冬雪、刘瑞华,苯系混合物对女工生殖机能及其子代的影响,工业卫生与职业病,1991(6)

Yu Dong-xue, LiuRui-hua, Effects of benzene compounds in female reproductive function and theiroffspring, Industrial Health & Professional Disease, 1991(6) [Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-GYWZ199106010.htm

就职机构:鞍钢劳动卫生研究所

Organization:Angang Steel Works Labor Hygiene Research Institute

【摘要】:本文对150名苯作业女工、102名非苯作业女工及100名作业男工的妻子进行了调查。结果发现,苯作业女工月经异常发生率显著高于非苯作业女工(P〈0.01),苯作业女工妊娠中毒症的发生率显著高于非苯作业女工(P0.05),苯作业女工的妊娠中毒症、智力低下儿的发生率显著高于苯作业男工的妻于(P0.05)。提示,苯对女工的生殖机能及其子代的智力发育可能有影响。

Abstract: The study investigated 150 females workers exposed to benzene,  102 female workers and 100 wives of male workers with no exposure to benzene.  The result found, the incidence of abnormal menstruation among female workers  exposed to benzene were significantly higher than female workers with no  exposure to benzene (P0.05); the incidence of pregnancy poisoning and mental  retardation of offsprings of the female workers exposed to benzene was also  significantly higher than wives of male workers with no exposure to benzene  (P0.05). Suggests Benzine  might have effects on the reproduction function of female workers and intelligence  development of their offsprings.  

证据30-3-24:

ScientificEvidence 24 (Hazleton Laboratories, 1992)

科学证据24(Hazleton Laboratories, 1992)

   Hazleton Laboratories (1992) recorded aslight, but significant, increase in the number of chromosomal mutationsinduced by n-hexane in albino rat bone marrow cells. Moreover, an in vivo bonemarrow cytogenetic assay found that male albino rats exposed to 150, 300, and600 ppm of n-hexane for 5 days experienced a significant increase in CA(chromatid breaks and markers) at all treatment levels compared with controls(Hazleton Laboratories, 1992).

   Hazleton实验室(1992)的研究记录了正己烷在白鼠骨髓细胞中诱发的轻微但是显著增加的染色体突变。此外,在雄性白鼠持续5天暴露150 ppm、300ppm与600 ppm正己烷的骨髓细胞遗传学分析研究中,发现雄性白鼠在所有剂量处理组中都经历了与对照比较的显著CA(染色单体断裂和标记)增加(Hazleton Laboratories, 1992)。

HazletonLaboratories. (1992) Initial submission: in vivo and in vitro mutagenicity studiesn-hexane (hexane UV) (final report) with attachments and cover letter dated020592. Submitted under Section 8ECP of TSCA. EPA Document No. 88-920000955;NTIS No. OTS0535721.

Quotedfrom EPA TOXICOLOGICAL REVIEW OF n-HEXANE (CAS No. 110-54-3),November 2005

摘引自美国环保署文件《正己烷毒理学审视》(CAS No. 110-54-3),2005年11月。

http://www.epa.gov/iris/toxreviews/0486tr.pdf

证据30-3-25:

ScientificEvidence 25 (Sallmén M., 1995)

科学证据25(Sallmén M., 1995)

   A retrospective time-to-pregnancy study wasperformed among women biologically monitored for exposure to organic solvents.The women were participants in a previous study on spontaneous abortion. … Theresults of the study support the hypothesis that daily or high exposure toorganic solvents is associated with reduced fertility.

   对接触有机溶剂生物学监督的妇女进行了时间相对于怀孕的回顾性研究。这些妇女为以前一项对于自然流产研究的参加者。…该项研究的结果支持日常或者高接触有机溶剂与减少生育相关的假说。依然使用有机溶剂的产业中,更为安全的工作方法确有必要。

SallménM., Reduced fertility among women exposed to organic solvents. AmJ Ind Med.1995May;27(5):699-713.

SallménM.,接触有机溶剂的妇女减少生育。美国工业医学杂志,1995年5月;27(5):699-713.

http://www.ncbi.nlm.nih.gov/pubmed/7611306

Department of Epidemiology andBiostatistics, Institute of Occupational Health, Helsinki, Finland.

就职机构:分类职业健康研究所流行病学与生物统计部门

证据30-3-26:

ScientificEvidence 26 (Bio/Dynamics. 1995)

科学证据26(Bio/Dynamics.1995)

   In a chronic-duration study in B6C3F1 mice(50/sex/group) where exposure to commercial hexane (51.5% n-hexane) was for 6hours/day, 5 days a week for 2 years, a statistically significanttreatment-related increase in hepatocellular neoplasms (adenoma and carcinoma)was observed among females exposed at 9,018 ppm (Bio/Dynamics 1995b).Incidences of adenoma were: 4/50, 6/50,4/50, and 10/50 at 0, 900, 3,000, and9,018 ppm, respectively. Incidences of carcinoma at these exposures were 3/50,2/50, 5/50, and 6/50 and total neoplasms 7/50, 8/50, 9/50, and 16/50.

   在一项慢性–期限研究中,B6C3F1小鼠(50只/组)持续2年每周5天每天6小时暴露于商业性己烷(51.5%正己烷),在暴露于9,018 ppm浓度的雌鼠中观察到处理–相关肝细胞肿瘤(腺瘤和癌)统计性显著增加(Bio/Dynamics 1995b)。腺瘤发生率在0、900、3,000与9,018 ppm浓度下分别为4/50、6/50、4/50与10/50。这些浓度暴露下的癌发生率分别为3/50、2/50、5/50与6/50,总肿瘤发生率分别为7/50、8/50、9/50与16/50。

Bio/Dynamics.1995b. An inhalationoncogenicity study of commercial hexane in rats and mice–2. Mice, abridgedfinal report. American Petroleum Institute Publication TR 405 41-33232.

http://www.freestd.us/soft2/701916.htm

证据30-3-27:

ScientificEvidence 27 (AgnesiR., 1997)

科学证据27(Agnesi R., 1997)

  A high risk of spontaneous abortion was observed in women exposed toorganic solvents during pregnancy. Since this risk was not found in the shoeindustry, where these solvents are widely used, we carried out a case-controlstudy on the risk of spontaneous abortion in a health district (Veneto,Northern Italy) where about 8,000 people work in shoe manufacturing. … Ourresults support the hypothesis that spontaneous abortion may be an adverseeffect of exposure to high levels of organic aliphatic solvents in womenemployed in shoe manufacture.

  孕期接触有机溶剂的女性观察到很高自然流产风险。由于该风险不是在广泛使用有机溶剂的制鞋业中发现的,我们在大约8000人在制鞋业中工作的意大利北部Veneto地区进行了该项案例—对照研究。… 该项研究的结果,支持这样的假说,即,自然流产可能是制鞋业妇女接触高水平有机脂肪族溶剂的有害影响。

Agnesi R.,Risk of spontaneous abortion and maternal exposure to organic solvents in theshoe industry. Int Arch Occup Environ Health 1997;69(5):311-6.

Agnesi R., 暴露于制鞋业有机溶剂妇女自然流产的风险,国际职业环境健康档案,1997;69 (5):311-6.

http://pubmed.cn/9192214

就职机构:意大利Dolo预防医学部

证据30-3-28:

ScientificEvidence 28 (Jiang, Q.D. et al., 1997)

科学证据28(姜其德et al.,1997)

  接触超过最高容许浓度和低于最高容许浓度苯及其同系物对女工月经及妊娠均有一定影响。

     Exposure to more than the highestallowable concentration and lower than the highest allowable concentration ofbenzene and its homologue has certain effect on female menstruation andpregnancy.

姜其德etal.,接触不同浓度苯对女工月经及妊娠结局的影响,工业卫生与职业病,1997(2)

JiangQi-de et al., The effect of exposure to different concentration of benzene onthe female menstruation and pregnancy outcome, Industrial Health &Professional Disease, 1997(2) [Chinese]

http://www.cnki.com.cn/Article/CJFDTOTAL-GYWZ199702024.htm

就职机构:淄博第二卫生学校淄博市职业病院

Organization: Zibo No.2 MedicalSchool, Zibo City Occupation Illness Hospital

【摘要】:本文对接触不同浓度苯及同系物甲苯、二甲苯的女工进行了调查,结果表明,接触超过最高容许浓度和低于最高容许浓度苯及其同系物对女工月经及妊娠均有一定影响。提示,对接触低浓度苯及同系物的女工,也应加强劳动保护措施和妇科健康监护,切不能忽视。

Abstract:  The study investigated female workers exposed to different levels of benzene,  and to toluene, xylene. Result indicates, Exposure to more  than the highest allowable concentration and lower than the highest allowable  concentration of benzene and its homologue has certain effect on female  menstruation and pregnancy.

证据30-3-29:

Scientific Evidence 29 (Zhao G.H.et al., 1997)

科学证据29(赵国华 at el.,1997)

   混合苯对作业工人遗传物质具有损害作用。其损害程度随着接触时间呈递增趋势”。

    Benzene mixture causes harm to geneticmaterial of workers. The degree of harm indicates a trend increases withduration of exposure.

赵国华at el.,接触低浓度苯系混合物作业工人细胞微核率及染色体断裂率的观察,现代预防医学,1997(4)

Zhao Guo-hua et al.,Observation of exposure to low concentration benzene  compounds in workers cell micronucleus rateand chromosome fracture rate, Modern Preventive Medicine, 1997(4) [Chinese]

http://www.cnki.com.cn/Article/CJFDTOTAL-XDYF704.004.htm

就职机构:大庆职工医学院优生遗传研究所

Organization: Institute of Prepotency,Daqing Staff Medical College

【摘要】:

Abstract:

目的:探讨混合苯对作业工人遗传物质是否有损害。

Abstract:  Objective: Explore if the mixed benzene compounds causes harm to genetic material  of operation workers.

方法:采用微核技术对混合苯作业工人41人进行微核及染色体断裂率观察。

Method:  Micro nuclear technology is adopted to observe fracture rate of micronucleus  and chromosome caused to 41 workers exposed to mixed benzene compounds operation.


结果:工人的微核率、微核细胞率及染色体断裂三项指标分别为14.49‰、12.97‰、1.75%均明显高于对照组(P<0.01)。在岗年限6年以上组三项指标均高于在岗年限5年以下组(P<0.01)。

Result:  The parameters of micronucleus rate, the rate of micronucleus cells and  chromosome fracture of the workers respectively were 14.49‰, 12.97‰ and 1.75%, all significantly higher than controls (P<0.01).  The rates of the above parameters of workers working at their posts above 6  years, were all higher than those working at their posts less than 5 years (P<0.01).

结论:混合苯对作业工人遗传物质具有损害作用。其损害程度随着接触时间呈递增趋势。

Conclusion: Mixed benzene  compounds causes harm to genetic material of workers. The degree of harm  indicates a trend increases with duration of exposure.

证据30-3-30:

Scientific Evidence 30 (Chen D.F.et al., 1997)

科学证据30(陈大方et al.,1997)

  孕妇混苯化合物暴露是影响新生儿出生体重及身长的主要因素。

  Pregnant woman’s exposure to benzene mixtureis the main factor effecting weight and length of newborns.

陈大方etal.,孕妇混苯化合物暴露对胎儿生长发育的影响,疾病控制杂志,1997(4)

Chen Da-fang, et al., Theeffect of pregnant women exposed to benzene mixture compounds on fetal growthand development, Disease Control Journal, 1997(4) [Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-JBKZ199704008.htm

就职机构:北京医科大学生态遗传与生殖卫生研究中心、北京燕山石化总公司职工医院

Organization:Ecological Genetics & Reproductive Health Research Center, Beijing MedicalUniversity; Beijing Yanshan Petrochemical Company Staff Hospital.

【摘要】:

Abstract:

通过对某石化企业572名孕妇进行回顾性流行病学调查,结果:

Retrospective epidemiological  investigation of 572 pregnant woman working at a petrochemical company,  result:

   (1)暴露于混苯化合物的孕妇与对照组比较,孕周,出生体重,身长,经单因素t检验,差别具有显著性。

    (1) Comparing pregnant women exposed to  mixed benzene compounds with control group, gestational age, birth weight,  body length, the single factor t test, the difference is significant.

   (2)引入多个混杂变量,经多元逐步回归进一步分析结果提示:孕妇混苯化合物暴露是影响新生儿出生体重及身长的主要因素,而孕妇上举或搬运重物,在家被动吸烟,摄入蔬菜,饮用奶类和家务劳动对新生儿出生体重及身长也产生一定的影响。

    (2) Introducing multiple confounding  variables, the result of multiple stepwise regression analysis suggests: Pregnant  woman’s exposure to benzene mixture is the main factor effecting weight and  length of newborns; pregnant woman lifting heavy objects, passive smoking at  home, intake of vegetables, drinking milk and household labor work also have  a certain degree of effect on weight and length of newborns.  

   (3)经Logistic逐步回归分析,孕妇混苯化合物暴露对新生儿早产及出生低体重的影响,可使其相对危险度增加,与对照组比较差别具有显著性。

     (3) Logistic stepwise regression analysis, indicates that pregnant  woman exposure to mixed benzene compounds have  effects on preterm birth and low birth weight of newborns, increases its  related risk, has significant difference with controls.

证据30-3-31:

Scientific Evidence 31 (Sallmén M., 1998)

科学证据31(Sallmén M., 1998)

   To assess whether paternal exposure toorganic solvents is associated with decreased fertility. A retrospective timeto pregnancy study was conducted among men biologically monitored for organicsolvents. … The findings of the study provide limited support for thehypothesis that paternal exposure to organic solvents might be associated withdecreased fertility. Further studies with careful design are warranted.

   评估父母接触有机溶剂是否与减少生育关联。对接触有机溶剂生物学监督的男性进行了怀孕的回顾性研究。该项研究的发现,对父辈接触有机溶剂可能与减少生育有关的假说提供有限的支持。有必要进行仔细设计的进一步研究。

Sallmén M.,Time to pregnancy among the wives of men exposed to organic solvents. Occup Environ Med 1998 Jan;55 (1): 24-30

Sallmén M.,接触有机溶剂男性的妻子怀孕的时间,职业环境医学,1998年1月;55 (1): 24-30

http://pubmed.cn/9536159

就职机构:分类职业健康研究所流行病学与生物统计部门

FinnishInstitute of Occupational Health, Department of Epidemiology and Biostatistics,Helsinki, Finland.

证据30-3-32:

ScientificEvidence 32 (Daughtrey et al., 1999)

科学证据32(Daughtrey et al., 1999)

   The carcinogenicand chronic toxicity potential of commercial hexane solvent was evaluated inF-344 rats and B6C3F1 mice (50/sex/concentration/species) exposed by inhalationfor 6 h/day, 5 days/week for 2 years. Target hexane vapor concentrations were0, 900, 3000, and 9000 ppm. … An increase in the combined incidence ofhepatocellular adenomas and carcinomas was observed in high-exposure femalemice. The incidence of liver tumors was not increased in the mid- orlow-exposure female mice or in male mice exposed to hexane. An increasedincidence of pituitary adenomas was observed in female, but not male mice. Thisfinding was not believed to have been treatment-related because the incidencein the control group was unusually low, and the incidence in exposed groups wasnot dose-related and was within the historical control range…. In conclusion,chronic exposure to commercial hexane solvent at concentrations up to 9000 ppmwas not carcinogenic to F-344 rats or to male B6C3F1 mice, but did result in anincreased incidence of liver tumors in female mice.

   商业正己烷溶剂的致癌性与慢性毒性潜力在持续两年6小时/天、5天/周、5天/吸入暴露的F-344大鼠与B6C3F1小鼠(50只/性别/剂量/品种)进行评价。目标正己烷其他浓度为0、900、3000,与9000 ppm。… 在高剂量暴露雌性小鼠中观察的结合在一起的肝细胞腺瘤和癌发生率增加。在暴露于中浓度或者低浓度正己烷的雌性小鼠或者暴露于正己烷的雄性小鼠中没有观察到肝肿瘤增加。然而在雌性而非雄性小鼠中还观察到垂体腺瘤发生率增加。这样的发现被认为不是处理相关的,因为对照组中的这样发生率非常低,而且暴露组中的发生率并非剂量相关而且在历史性对照范围内。… 作为结论,慢性暴露于一直到高达9000 ppm商业正己烷溶剂对F-344大鼠或B6C3F1小鼠不致癌,但是确实在雌性小鼠中造成肝肿瘤发生率增加的结果。

Daughtrey,W; Newton, P; Rhoden, R; et al. (1999) Chronic inhalation carcinogenicity studyof commercial hexane solvent in F344 rats and B6C3F1 mice. Toxicol Sci48:21-29.

http://www.ncbi.nlm.nih.gov/pubmed/10330680

证据30-3-33:

ScientificEvidence 33 (Wang, S.L., Du,B., 2000)

科学证据33(王守林、杜冰,2000)

   低浓度混苯暴露可能与职业人群精液质量下降及早早孕丢失有关,,尿液反,反-粘糠酸和人绒毛膜促性腺激素可分别作为接触性和效应性生物标志物

   Exposure to lowconcentration of mixed benzene maybe correlated with the declined quality ofsemen and VEFL in occupational workers, and urinary t, t-MA and beta-hCG can beused as biomarkers of exposure and effect, respectively.

王守林、杜冰,低浓度混苯暴露与精液质量下降及早早孕丢失的关系,中华预防医学杂志,2000(5)

[Wang S, Chen H, Wang X. Studies on relationship betweenexposure to low concentration of mixed benzene and lower quality of semen andvery early fetal loss]. Zhonghua Yu Fang Yi Xue Za Zhi. 2000 Sep;34(5):271-3.

http://www.cnki.com.cn/Article/CJFDTOTAL-ZHYF200005007.htm

英译文:http://www.ncbi.nlm.nih.gov/pubmed/11372393

就职机构:南京医科大学应用毒理研究所

School of Public Health, Nanjing Medical University, Nanjing210029, China.

摘要:

Abstract

目的:研究低浓度混苯暴露对职业人群精液质量和早早孕丢的伯影响。

OBJECTIVE: To study the effects of exposure to low  concentration of mixed benzene on their semen quality and very early fetal  loss (VEFL) in the occupational population.

方法:选择混苯作业工人126人、无混苯作业对照者60人,进行生产环境监测和生物学监测;按混苯接地情况,选择暴露组男工70人,内对照组男工90人,外对照组男工132人,进行精液质量分析;选择暴露组女工42人,内对照组女工49人,外对照组女工118人,进行尿液人绒毛膜促性腺激素的检测。

METHODS: Environmental monitoring and biological monitoring  were conducted in 126 employees exposed to mixed benzene and 60 unexposed  ones selected from a large petrochemical corporation and a large chemical  fiber corporation. Quality of semen in 70 male workers in the exposed group  and 90 male internal controls and 132 male external controls were analyzed,  and urinary beta-human chorionic gonadotropin (beta-hCG) was determined for  42 female exposed workers and 49 female internal controls and 118 external  controls.

 

结果:石化企业混苯暴露以低浓度苯(0.7-27.0mg/m3)为主。工人尿液反,反-粘糠酸与空气苯浓度呈高度相关性;暴露组和内对照组精子的活动度(1.97+/-0.61和1.97+/-0.69)与活动精子百分率(0.55+/-0.16和0.55+/-0.17)均显著低于对外照组(2.56+/-0.61和0.60+/-0.13),但其异常率显著高于对照组、且暴露组精液综合异常率(85.71%)显著高于内对照组(70.00%)和外对照组(76,51%);暴露组和内对照组女工早早孕丢失发生率及其周期发生率均高于外对照组、且二组女工周期发生率(10.42%、9.60%)显著高于对对照组女工(5.09%)。

RESULTS:

  1. Exposure to  mixed benzene mainly existed in low concentrations (0.7-27.0 mg/m3) in the  petrochemical corporation, and urine concentration of t, t-MA in the workers  correlated significantly to benzene concentration in ambient air of the  workshops (r = 0.64, P = 0.03).

  2. The sperm  progression and motility in the exposed (1.97 +/- 0.63 and 0.55 +/- 0.16) and  the internal control (1.97 +/- 0.69 and 0.55 +/- 0.17) groups were  significantly (P < 0.05) lower than those in the external control group  (2.56 +/- 0.61 and 0.60 +/- 0.13), however, the sperm abnormality rates in  the exposed and internal control groups were significantly (P < 0.01)  higher than those in the external control group, and the summary abnormality  rate of sperm in the exposed group (85.71%) was higher than that in the  internal (70.00%) and external control (76.51%) groups (P < 0.05).

   3. The incidence  rates of the VEFL in female workers and the cyclic occurrence of VEFL both in  the exposed and internal control groups (10.42% and 9.60%) were higher than  those in the external control group (5.09%), with statistical significance (P  < 0.05).

结论:低浓度混苯暴露可能与职业人群精液质量下降及早早孕丢失有关,尿液反,反-粘糠酸和人绒毛膜促性腺激素可分别作为接触性和效应性生物标志物。

CONCLUSIONS: Exposure to low concentration of mixed benzene  maybe correlated with the declined quality of semen and VEFL in occupational  workers, and urinary t, t-MA and beta-hCG can be used as biomarkers of  exposure and effect, respectively.

证据30-3-34:

ScientificEvidence 34 (Liang, W.H. et al., 2000)

科学证据34(梁伟辉et al.,2000)

   正己烷对中毒患者染色体损伤的诱导作用。

   N-hexane induces chromosome damage on poisoned patients.

梁伟辉et al.,职业性正己烷中毒患者外周血微核检查,中国科学院上海冶金研究所; 材料物理与化学(专业) 博士论文,2000

Liang Wei-hui et al., Peripheral bloodmicronucleus tests of occupational n-hexane poisoned patients, China Academy ofScience Shanghai Metallurgical Research Institute; Material physics andchemistry PhD thesis, 2000 [Chinese]

http://www.chemyq.com/health/ep109/1083892_A7928.htm

就职机构:广东省职业病防治院; 本溪市卫生局.

Organization: Guangdong Provincial Occupation IllnessPreventative Hospital; Benxi City Health Bureau.

证据30-3-35:

ScientificEvidence 35 (Chen, H.Y. et al., 2001)

科学证据35(陈海燕 et al.,2001)

   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。

   Exposure to lowlevel of mixed benzene in workspaces could interrupt the function ofhypothalamic-pituitary-ovarian axis and affect their normal levels of FSH, PdGand E1C.

陈海燕et al.,低浓度混苯对女工生殖激素分泌的影响,中华预防医学杂志,2001(2)

Chen Hai-yan et al., Effects of lowconcentration mixed benzene on female reproductive hormones, China PreventativeMedicine Journal, 2001(2) [Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-ZHYF200102003.htm

全文/Completetext:http://www.docin.com/p-638556972.html

英译文/English:http://www.ncbi.nlm.nih.gov/pubmed/11413688

就职机构:江苏省南京医科大学公共卫生学院应用毒理研究所、徐州医学院卫生学教研室

Organization: Application Toxicology Research Institute, Public Health College,Nanjing Medical University; Health Teaching Section, Xuzhou Medical College.

【摘要】:

Abstract:

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。

OBJECTIVE: To study the  effects of exposure to low level of mixed benzene on reproductive hormone  secretion during menstrual cycle in female workers.

方法:对 5 0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 ,对暴露组女工及外对照组和内对照组女工各 35名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)。

METHODS: Concentrations of  benzene, toluene and xylene in the expiratory air of 50 exposed female  workers from their breathing zone were determined with gas chromatography.  Their menstrual cycles of 50 exposed workers and 35 internal control and 35  external control workers were studied prospectively. Urine  pregnandiol-3-glucuronide (PdG), follicle stimulating hormone (FSH) and  estrone conjugate (E1C) were measured by enzyme immunoassay.

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/m3 、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 ,低浓度混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。

RESULTS: Mixed benzene  existed mainly in the form of low-level benzene in the air of workplaces,  with a detection rate of 29.10% at an average level of 8.88 (0.90-876.47)  mg/m3, and 21% of measurements exceeded the national maximum allowable  concentration with the highest one as 20.91 folds high as that of the  national hygienic standard. Length of luteal phase in the exposed group (13.7  +/- 1.5) days was significantly shorter than that in the internal and  external control groups (14.5 +/- 1.2) days and (15.2 +/- 1.1) days (P <  0.05 or P < 0.01). Urine level of E1C before ovulation, that of FSH at  early follicular phase and that of PdG in luteal phase after ovulation in the  exposed group were significantly lower than those in the internal control group  (P < 0.05 or P < 0.01)

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。

CONCLUSION: Exposure to low level of mixed benzene in  workspaces could interrupt the function of hypothalamic-pituitary-ovarian  axis and affect their normal levels of FSH, PdG and E1C.

证据30-3-36:

ScientificEvidence 36 (Xu, X.C., 2004)

科学证据36(许雪春,2004)

女性, 年龄 17 ~ 22 岁, 平均18 岁。既往均身体健康…监测显示, 所用树脂胶中挥发性气体主要成分为正己烷…本组 11例均出现停经或月经失调”。

   Female, agebetween 17 to 22, average 18. Past history all indicate healthy … monitoringshows, the main composition of the evaporated fume from the resins is hexane …11 girls among this group all appeared with no periods or out of order.

许雪春,慢性正己烷中毒临床观察分析,工业卫生与职业病,2004(3)

Xu Xue-chun, Clinical observation analysis of chronicn-hexane poisoning, Industrial Health & Occupational Disease, 2004(3)[Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-GYWZ200403019.htm

就职机构:河南省职业病防治研究所

Organization:Henan Provincial Occupation Illness Preventative Research Institute

证据30-3-37:

ScientificEvidence 37 (Huo, Z.L., Pu, X.Y., 2004)

科学证据37(火忠礼 卜晓岩,2004)

   苯职业接触可引起女工月经及生殖机能障碍。

  Professional exposure to benzene could cause problems with periods orreproduction functions.

火忠礼卜晓岩,苯及其同系物对职业女工生殖机能的影响,中国妇幼保健,2004(4),39-40

Huo Zhong-li, Pu Xiao-yan, Influence of benzeneand its homologue on reproductive function of occupational female, China’s Maternity& Child Care, 2004(4),39-40

http://www.chemdrug.com/databases/7_41_akjrtegreeveuyow.html

就职机构:包头医学院预防医学系

Organization:Preventative Medical Dept., Baotou Medical Collegue

证据30-3-38:

ScientificEvidence 38 (Chevrier C. et al., 2006)

科学证据38(Chevrier C.et al.,2006)

   To examine the association between maternaloccupational exposure to mixtures of organic solvents during pregnancy and therisk of non-syndromic oral clefts. … Results suggest that maternaloccupational exposure to organic solvents during pregnancy may play a role inthe aetiology of oral clefts. The limited number of subjects and the problem ofmultiple exposures require that these results be interpreted cautiously.

   审查孕期中职业接触有机溶剂混合物与 非综合征型唇腭裂风险之间相关性。…该项研究的结果提议孕期接触有机溶剂可能在唇腭裂病因中发挥作用。有限数量的研究对象以及多重接触问题要求对这些结果谨慎解释。

Chevrier C. et al.,孕期职业接触有机溶剂混合物与非综合征型唇腭裂风险。职业环境医学,2006年9月;63 (9):617-23.

Chevrier C. et al., Occupational exposure to organic solvent mixtures duringpregnancy and the risk of non-syndromic oral clefts. Occup Environ Med 2006 Sep;63(9):617-23.

http://pubmed.cn/16644895

证据30-3-39:

ScientificEvidence 39 (Sallmén M et al., 2007)

科学证据39(Sallmén M et al., 2007)

The findings provide further evidencethat exposure to organic solvents is hazardous for female reproduction. Theobserved association may be related to any of the following solvents commonlyused in shoe manufacturing: n-hexane and hexane isomers, toluene, acetone,ethyl acetate and dichloromethane.

   该研究的发现提供进一步证明证实接触有机溶剂对女性繁殖造成危险。…正己烷及其异构体、丙酮、丁酮与二氯甲”。

SallménM et al., Reduced fertility among shoe manufacturing workers. Occup EnvironMed.2008 Aug;65(8):518-24. Epub 2007Nov 7.

SallménM et al.制鞋业工人中的减少生育。职业环境医学,2008年8月;65(8):518-24.上线发表:2007年11月7日。

http://www.ncbi.nlm.nih.gov/pubmed/17989205

芬兰赫尔辛基,芬兰职业健康研究所,健康与工作能力专长中心

Centre of Expertise for Health and WorkAbility, Finnish Institute of Occupational Health, Topeliuksenkatu 41 aA,FI-00250 Helsinki, Finland.

证据30-3-40:

ScientificEvidence 40 (Cao, J.T., 2007)

科学证据40(曹静婷 et al., 2007)

  显示正己烷染毒所致的不同程度的脂质过氧化损伤.镜下观察7 d组生殖腺及发育中生殖细胞的微细结构出现明显异常。结论正己烷吸入染毒对大鼠生殖腺及发育中的生殖细胞有肯定的损伤作用,脂质过氧化损伤可能是毒性作用的机制之一。”

Shows thatn-hexane caused different levels of lipid peroxidation damage. The microscopicobservation  7 d group micro-structure ofgerm cells shows apparent anomalies in the development of gonad. Conclusion: N-hexanesuction cause certain damage to gonad and developing germ cells of rat, lipidperoxidation damage may be one of the mechanism of such toxic effects.

曹静婷 et al., 正己烷静式染毒致SD大鼠生殖腺损伤,中华劳动卫生职业病杂志,2007(5)

CaoJing-ting et al., N-hexane static type causes gonad damage to SD rats, ChinaLabor Health Occupational Disease Journal, 2007(5) [Chinese]

http://d.wanfangdata.com.cn/Periodical_zhldwszyb200705005.aspx

就职机构:暨南大学医学院、广州市第十二人民医院

Organization:Jinan University Medical College, Guangzhou City No.12 People’s Hospital

证据30-3-41:

ScientificEvidence 41 (Xing, L.H., Deng, X.M., 2007)

科学证据41(邢良红、邓小梅,2007)

  苯、甲苯可导致月经异常改变,患病率和工龄呈正相关关系;观察组的自然流产率、低体重儿出生率均高于对照组。

   Benzine, ….. causes abnormal changes toperiods, incidence shows positive relevance with the number of years ofprofessional exposure; incidence of natural miscarriage, newborn low weight areboth higher than control group.

邢良红、邓小梅,日照市某皮鞋厂苯作业女工月经及其生育情况的调查,预防医学论坛,2007(10)

XingLiang-hong, Deng Xiao-mei, Survey of female menstruation and fertility workingwith benzene exposure in leather shoe manufacturer at Shandong Rizhao city,Preventative Medicine Forum, 2007(10) [Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-YXWX200710034.htm

就职机构:山东省日照市东港区卫生防疫站山东省日照市卫生局卫生监督所

Organization:Shandong Rizhao City Donggang District Health Epidemic Prevention Station,Shandong Rizhao City Health Bureau Health Supervision Dept.

证据30-3-42:

ScientificEvidence 42 (Pang, F., 2009)

科学证据42(厐芬,2009)

  1、正己烷具有明显的雌(女)性性腺毒性,主要表现为卵巢湿重及其脏器系数明显降低、动情后期明显缩短及动情周期异常发生率明显上升、各级卵泡发育紊乱。2、正己烷可明显降低血清激素P1水平,卵巢切碎组织培养液中E2和P4水平明显下降。正己烷对卵巢性激素分泌功能的直接抑制作用可能是其内分泌干扰作用的重要机制。…4、正己烷暴露后,卵巢对超量促性腺激素反应机能(超数排卵)明显下降…5、正己烷导致卵巢细胞凋亡,诱导卵巢颗粒细胞凋亡可能是正己烷对卵巢损伤的重要机制之一。

    1. N-hexane has obvious female gonads toxicity, N-hexane can decreasethe organ weights and organ coefficients of ovaries, the period of estrousstages in rats decreased significantly, the constituent rate of primordialfollice, atrestic folicle, mature follicle and corpus uterum/albiacans numberwere in disorder. N-hexane can decrease the level of serum P4, N-hexane caninhibit P4 and E2 release in the ovaries, having the direct adverse effects,which might be the important mechanism in endocrine disruption …4. N-hexane candecrease the reaction of super gonadotrophic hormones, but it not sure of thereaction of normal gonadotrophic hormones. 4. N-hexane can decrease thereaction of super gonadotrophic hormones, but it not sure of the reaction ofnormal gonadotrophic hormones.

福建医科大学,卫生毒理学专业,厐芬《正己烷雌(女)性性腺生殖毒性与生殖内分泌干扰作用研究》(硕士学位论文,指导教师:张文昌;2009-03-01)

Pang Fen, N-hexane (female) female sexgonad reproductive toxicity and reproductive endocrine disruption studies,(Master degree thesis, 2009-03-01), Health Toxicology, Fujian MedicalUniversity

http://d.wanfangdata.com.cn/Thesis_Y1487285.aspx

【题目】正己烷雌(女)性性腺生殖毒性与生殖内分泌干扰作用研究

【Title】The Effect of N-hexane on the Female gonads  toxicity and reproductive endocrine secretion interference

【目的】研究正己烷的雌(女)性性腺毒性及其生殖内分泌干扰作用,为正己烷性腺生殖毒性作用的预防与控制及其机制的进一步研究提供科学依据。

【Objective】

This  study examined the effects of N-hexane on the female gonadal toxicity and the  female reproductive endocrine disruption, in order to provide further  research on the prevention and control of N-hexane on the effects of gonadal  reproductive toxicity.

【结论】

【Conclusions】

  1、正己烷具有明显的雌(女)性性腺毒性,主要表现为卵巢湿重及其脏器系数明显降低、动情后期明显缩短及动情周期异常发生率明显上升、各级卵泡发育紊乱。

  1. N-hexane has obvious female gonads  toxicity, N-hexane can decrease the organ weights and organ coefficients of  ovaries, the period of estrous stages in rats decreased significantly, the  constituent rate of primordial follice, atrestic folicle, mature follicle and  corpus uterum/albiacans number were in disorder.

  2、正己烷可明显降低血清激素P1水平,卵巢切碎组织培养液中E2和P4水平明显下降。正己烷对卵巢性激素分泌功能的直接抑制作用可能是其内分泌干扰作用的重要机制。

  2. N-hexane can decrease the level of  serum P4, N-hexane can inhibit P4 and E2 release in the ovaries, having the  direct adverse effects, which might be the important mechanism in endocrine  disruption.

  3、正己烷对子宫ER、卵巢PR表达没有明显影响。

  3. Under our experiment, N-hexane did not  have direct disrupting effect on the estradiol and progesterone receptor in  the ovary and uterus, which might be not the mechanism of the endocrine  disruption.

  4、正己烷暴露后,卵巢对超量促性腺激素反应机能(超数排卵)明显下降,但尚不能明确对常量性腺激素的反应机能状况。

  4. N-hexane can decrease the reaction of  super gonadotrophic hormones, but it not sure of the reaction of normal  gonadotrophic hormones.

  5、正己烷导致卵巢细胞凋亡,诱导卵巢颗粒细胞凋亡可能是正己烷对卵巢损伤的重要机制之一。

  5. N-hexane can induce the cell apoptosis  on the ovaries, which might be the important mechanism of ovaries damage.

证据30-3-43:

Scientific Evidence 43 (Ou, Y.J.et al., 2009)

科学证据43(欧阳江 et al.,2009)

  正己烷能引起明显的雌性性腺毒性,卵巢是其毒作用的重要靶器官之一。

  Hexane couldcause obvious femalegonads toxicity, ovaries is one of the main toxicity  organ targets.

欧阳江at el.,正己烷对雌性大鼠性腺毒性作用实验研究,海峡预防医学杂志,2009(4)

Ou Yang-jiang et al., N-hexane gonad toxic effect onfemale rats, Haixia Preventive Medical Journal, 2009(4) [Chinese]

http://www.cnki.com.cn/Article/CJFDTotal-HXYF200904003.htm

就职机构:福建医科大学公共卫生学院

Organization:Fujian Medical University Public Health College

证据30-3-44:

ScientificEvidence 44 (Ou, Y.J., Zhang, W.C.)

科学证据44(欧阳江、张文昌,2010)

正己烷具有明显的雌性生殖内分泌干扰作用,能够引起大鼠动情周期的异常变化、卵巢颗粒细胞性激素合成功能障碍;正己烷可通过影响卵巢颗粒细胞雌、孕激素合成过程中StAR蛋白、P450scc和P450arom的表达进而干扰雌、孕激素的合成。这可能是正己烷的生殖内分泌干扰作用的重要机制之一。

   Hexane demonstrates obvious female reproduction gonads interruption, can cause abnormalchanges in period of estrous stages, cause Ovarian sex hormone synthesisdysfunction of granulosa cells; N-hexane through effect StAR protein, P450sccand P450arom expression in the process offemale, progestational hormone synthesis of ovarian granulosa cells, thusfurther interfere synthesis of both male and female, progestational hormone. Thismay be one of the important mechanisms how n-hexane causes disruption ofreproductive endocrine.

欧阳江、张文昌,正己烷对卵巢雌、孕激素合成干扰及其机制研究,全国生化/工业与卫生毒理学学术会议论文集,2010年

Ou Yang-jiang, Zhang Wen-chang, Studies ofN-hexane’s disruption of ovarian female male, progestational hormone synthesisand mechanism, Biochemical/Industrial & Health Toxicology Academic ConferenceProceedings, 2010.

http://cpfd.cnki.com.cn/Article/CPFDTOTAL-ZGDV201007001088.htm

就职机构:福建医科大学公共卫生学院

Organization:Fujian Medical University Public Health College

证据30-3-45:

ScientificEvidence 45 (Liu, J., Zhang, W.C., 2010)

科学证据45(刘瑾、张文昌,2010)

   正己烷影响了小鼠卵母细胞GVBD率,并能抑制其卵母细胞的核成熟。

   N-hexaneaffected mice oocyte GVBD rate, and inhibit its nuclear mature oocytes.

刘瑾、张文昌,正己烷对卵母细胞成熟的毒作用研究,全国生化/工业与卫生毒理学学术会议论文集,2010年

Liu Jin, Zhang Wen-chang, N-hexane toxiceffect study of oocyte maturation, Biochemical/Industrial & Health ToxicologyAcademic Conference Proceedings, 2010. [Chinese]

http://cpfd.cnki.com.cn/Article/CPFDTOTAL-ZGDV201007001095.htm

就职结构:福建医科大学公共卫生学院

Organization:Fujian Medical University Public Health College

证据30-3-46:

ScientificEvidence 46 (Liu, J., Zhang, W.C., 2010)

科学证据46(刘瑾,张文昌,2010)

   正己烷的生殖内分泌干扰作用(如动情周期紊乱、性激素水平改变等)不是通过对小鼠性激素受体表达的影响而产生的。…其生殖分泌干扰作用有可能是通过影响性激素配体与受体的结合或其他信号途径而产生。

   N-hexane reproductiveendocrine disruption (like estrus cycle disorder, sex hormone level change, etc),is caused not by the influence of sex hormone receptor expression in mice. … Itsreproductive secrete interference effect may be through the influence of thecombination of sex hormone ligand and receptor or other signaling pathways.

刘瑾,张文昌,亚慢性接触正己烷对小鼠子宫、卵巢性激素受体表达的影响,全国生化/工业与卫生毒理学学术会议论文集,2010年

Liu Jin, Zhang Wen-chang, The chronicexposure of n-hexane to uterus, ovarian hormone receptor expression in mice, Biochemical/Industrial& Health Toxicology Academic Conference Proceedings, 2010. [Chinese]

http://cpfd.cnki.com.cn/Article/CPFDTOTAL-ZGDV201007001095.htm

就职结构:福建医科大学公共卫生学院

Organization:Fujian Medical University Public Health College

证据30-3-47:

ScientificEvidence 47 (Liu, J., 2011)

科学证据47(刘瑾,2011)

   1.正己烷可抑制小鼠卵母细胞的发育成熟,包括核成熟与质成熟。2,5-己二酮是正己烷影响卵母细胞核成熟的主要活性代谢产物。2.卵母细胞线粒体的损伤及早期凋亡的出现,可能是正己烷抑制小鼠卵母细胞发育成熟的重要因素之一。3.正己烷可以诱导卵巢颗粒细胞凋亡。

   1. N-hexanecan inhibit mouse oocyte mature, including nuclear maturity and maturity; 2,5-adipicketone is an effect how n-hexane affects the main active metabolite of oocytenucleus maturity. 2. Mitochondrial damage and early apoptosis of oocytes, mightbe one of the important factors of n-hexane inhibition of mouse oocytes mature;3. N-hexane can induce ovarian granulosa cell apoptosis.

刘瑾,正己烷对卵母细胞成熟和颗粒细胞凋亡的影响及其机制研究,福建医科大学,博士论文 2011年

Liu Jin, Studies of N-hexane effect on oocytematuration and granulosa cell apoptosis and its mechanism, PhD thesis, FujianMedical University, 2011

http://cdmd.cnki.com.cn/Article/CDMD-10392-1011154760.htm

就职结构:福建医科大学公共卫生学院

Organization:Fujian Medical University Public Health College

 

 

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