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Necessity to measure PCBs and organochlorine pesticide concentrations in human umbilical cords for fetal exposure assessment.


Three types of tissue samples--umbilical cord (UC), umbilical cord umbilical cord (ŭmbĭl`ĭkəl), cordlike structure about 22 in. (56 cm) long in the pregnant human female, extending from the abdominal wall of the fetus to the placenta.  serum (CS), and maternal serum (MS)--have often been used to assess fetal fetal /fe·tal/ (fe´tal) of or pertaining to a fetus or the period of its development.

fe·tal
adj.
Of, relating to, or being a fetus.
 exposure to chemicals. In order to know the relationship of contamination between mothers and fetuses, we measured persistent chemicals in comparable sets of the three tissue samples. Also, we analyzed an·a·lyze  
tr.v. an·a·lyzed, an·a·lyz·ing, an·a·lyz·es
1. To examine methodically by separating into parts and studying their interrelations.

2. Chemistry To make a chemical analysis of.

3.
 the association between the chemicals in maternal and fetal tissues to know which tissue is the best sample for fetal exposure assessment. On a wet basis, the chemical concentrations were of the order MS > CS > UC, except for some chemicals such as cis-chlordane and endosulfan endosulfan

an organochlorine insecticide. See chlorinated hydrocarbons.
. On a lipid lipid

Any of a diverse class of organic compounds, found in all living things, that are greasy and insoluble in water. One of the three large classes of substances in foods and living cells, lipids contain more than twice as much energy (calories) per unit of weight as the
 basis, the concentrations in UC were nearly equal or often higher than in MS, but the concentrations in CS were usually lower than in others. Hexachlorocyclohexanes and penta-, hexa-, and heptachlorinated biphenyls showed an association between the concentrations in UC versus MS, and UC versus CS. These chemicals also showed high correlation coefficients Correlation Coefficient

A measure that determines the degree to which two variable's movements are associated.

The correlation coefficient is calculated as:
 between the chemical concentrations in UC of first babies and maternal age maternal age,
n the age of the mother at the period of conception.
. These chemicals were dosely related to each other when grouped on the basis of their concentrations using cluster analysis Cluster analysis

A statistical technique that identifies clusters of stocks whose returns are highly correlated within each cluster and relatively uncorrelated across clusters. Cluster analysis has identified groupings such as growth, cyclical, stable, and energy stocks.
. In conclusion, we insist that UC is the best sample to assess fetal contamination status of persistent chemicals. There is a possibility that the assessment based on the contamination levels in CS result in an underestimation. Key words: cord blood cord blood
n.
Blood present in the umbilical vessels at the time of delivery.
, maternal blood, organochlorine or·gan·o·chlo·rine
n.
Any of various hydrocarbon pesticides, such as DDT, that contain chlorine.
 pesticides, polychlorinated biphenyls polychlorinated biphenyls, (pol´ēklôr´nā´tid bīfē´n  (PCBs), umbilical cord. doi:10.1289/ehp.7330 available via http://dx.doLorg/[Online 14 December 2004]

**********

It is believed that humans are exposed to multiple chemicals from food, air, water, and so forth, including natural products; industrial products, such as polychlorinated biphenyls (PCBs), pesticides, and pharmaceuticals; and nonintentional products, such as dioxins. Human fetuses are exposed to multiple chemicals through placenta placenta (pləsĕn`tə) or afterbirth, organ that develops in the uterus during pregnancy. It is a unique characteristic of the higher (or placental) mammals. In humans it is a thick mass, about 7 in.  in Japan (Mori 2001; Mori et al. 2003; Todaka and Mori 2002), and infants are exposed to these chemicals through milk (Borgert et al. 2003). A number of persistent organochlorine pollutants pollutants

see environmental pollution.
 have been detected in human follicular fluid Follicular fluid is a liquid which fills the follicular antrum and surrounds the ovum in an ovarian follicle. This fluid is rich in hyaluronic acid. External links
  • UIUC Histology Subject 1083
  • MeSH Follicular+fluid
  • Diagram at med.mun.
 (De Felip et al. 2004) and amniotic fluid amniotic fluid
n.
The fluid within the amnion that surrounds the fetus and protects it from injury.


Amniotic fluid
The liquid that surrounds the baby within the amniotic sac.
 (Foster et al. 2000). Because human fetuses and infants are considered significantly more sensitive to a variety of environmental toxicants compared with adults (Branum et al. 2003; Charnley and Putzrath 2001; Needham and Sexton sex·ton  
n.
An employee or officer of a church who is responsible for the care and upkeep of church property and sometimes for ringing bells and digging graves.
 2000), the adverse effects of chemicals on these fetuses and infants are of concern.

Three types of tissue samples--umbilical cord (UC), umbilical cord serum (CS), and maternal serum (MS)--have often been used to assess fetal exposure to chemicals. There are several reports indicating that the chemical concentrations were higher in maternal blood than in cord blood (Sarcinelli et al. 2003; Waliszewski et al. 2000; Walker et al. 2003). The assessments using cord blood have suggested fetal contamination. However, the chemical concentrations in fetal tissues are still unclear. There are only a few reports using fetal tissues such as UC (Covaci et al. 2002; Grandjean et al. 2001).

In order to know the relationship of contamination between mothers and fetuses, we measured persistent chemicals in comparable sets of the three tissue samples (UC, CS, and MS). Also, we analyzed the association between the chemicals in maternal and fetal tissues to know which tissue is the best sample for fetal exposure assessment.

Materials and Methods

Sample. Thirty-two pregnant women who were general citizens and lived in the cities of Chiba and Yamanashi, near Tokyo, Japan, were surveyed in 2002 and 2003. UC (- 20 cm), maternal blood (10 mL), and cord blood (10 mL) were collected from the cases delivered by cesarean section cesarean section (sĭzâr`ēən), delivery of an infant by surgical removal from the uterus through an abdominal incision. The operation is of ancient origin: indeed, the name derives from the legend that Julius Caesar was born in this . The deliveries were conducted at least 12 hr after the last meal. UC without cord blood and MS and CS were stored at -20[degrees]C until use in glassware that had been checked to be without contamination. In the whole-study subjects, 20 mothers had complete samples (MS, CS, and UC), and their average age at delivery was 32.8 [+ or -] 4.0 years. There were 12 mothers without CS samples, and their average age was 31.9 [+ or -] 4.9 years. In total, 32 cases were used for the analysis of correlation between maternal age and chemical concentrations. This study has been approved by the Congress of Medical Bioethics bioethics, in philosophy, a branch of ethics concerned with issues surrounding health care and the biological sciences. These issues include the morality of abortion, euthanasia, in vitro fertilization, and organ transplants (see transplantation, medical).  of Chiba University Chiba University (千葉大学 Chiba Daigaku  and the University of Yamanashi The University of Yamanashi is a university with campuses in Kofu and Tamaho, Japan. It was founded in 1949 by a merger between Yamanashi University and Yamanashi Medical University, as is formally referred to as the National university corporation, University of Yamanashi. , and all the samples were obtained after receipt of written informed consent.

Chemicals measured. We measured 19 organochlorine pesticides: dichlorodiphenyltrichloroethane di·chlo·ro·di·phen·yl·tri·chlo·ro·eth·ane
n.
DDT.
 (DDT DDT or 2,2-bis(p-chlorophenyl)-1,1,1,-trichloroethane, chlorinated hydrocarbon compound used as an insecticide. First introduced during the 1940s, it killed insects that spread disease and feed on crops. ) and its metabolites Metabolites
Substances produced by metabolism or by a metabolic process.

Mentioned in: Interactions
 [dichlorodiphenyldichloroethylene (DDE (Dynamic Data Exchange) A message protocol in Windows that allows application programs to request and exchange data between them automatically.

DDE - Dynamic Data Exchange
) and dichlorodiphenyldichloroethane (DDD DDD Direct Distance Dialing
DDD Digital/Digital/Digital (audio CD format, recording/mixing/mastering)
DDD Degenerative Disc Disease
DDD Domain Driven Design
DDD Data Display Debugger (GNU Project) 
): p,p'-DDT, o,p'-DDT, p,p'-DDE, o,p'-DDE, p,p'-DDD, o,p'-DDD], chlordane chlordane (klōr`dān): see insecticide.  and its metabolites (cis-chlordane, trans-chlordane, trans-nonachlor, oxychlordane), heptachlor heptachlor: see insecticides.  and its metabolites (heptachlor, heptachlor epoxide epoxide /epox·ide/ (e-pok´sid) an organic compound containing a reactive group resulting from the union of an oxygen atom with two other atoms, usually carbon, that are themselves joined together. ), methoxychlor methoxychlor

one of the group of chlorinated hydrocarbon insecticides which cause typical signs of that poisoning.
, "drins" (dieldrin dieldrin: see insecticides. , aldrin aldrin (ôl`drĭn): see insecticides. , endrin endrin (ĕn`drĭn): see insecticides. ), endosulfan isomers isomers (ī´sōmurz),
n.pl 1. organic compounds having the same empirical formula–i.e.
 (mixture of [alpha]- and [beta]-endosulfan), hexachlorobenzene (HCB HCB

hexachlorobenzene.
), and hexachlorocyclohexane (HCH HCH Hexachlorocyclohexane
HCH Health Care for the Homeless
HCH National Health Care for the Homeless Council
HCH Holy Cross Hospital
HCH Hypochondroplasia
HCH Highline Community Hospital
HCH Huntsman Cancer Hospital (Salt Lake City, UT) 
) isomers (mixture of [alpha]-, [beta]-, [gamma]-, and [delta]-HCH). We also measured 10 groups of PCB PCB: see polychlorinated biphenyl.
PCB
 in full polychlorinated biphenyl

Any of a class of highly stable organic compounds prepared by the reaction of chlorine with biphenyl, a two-ring compound.
 congeners grouped by their number of chlorines from 1 to 10.

Pretreatment pretreatment,
n the protocols required before beginning therapy, usually of a diagnostic nature; before treatment.

pretreatment estimate,
n See predetermination.
. MS (4-5 mL), CS (3-4 mL), and UC (17-27 g) were used for the preparation of samples for gas chromatography-mass spectrometry spectrometry /spec·trom·e·try/ (spek-trom´e-tre) determination of the wavelengths or frequencies of the lines in a spectrum.

spec·trom·e·try
n.
. The details were revealed to the public through the homepage of the Ministry of Environment of the Government of Japan (2002). Briefly, the UC samples were homogenized ho·mog·e·nize  
v. ho·mog·e·nized, ho·mog·e·niz·ing, ho·mog·e·niz·es

v.tr.
1. To make homogeneous.

2.
a. To reduce to particles and disperse throughout a fluid.

b.
 with ethanol/hexane (1:3) and sodium sulfuric sul·fu·ric  
adj.
Of, relating to, or containing sulfur, especially with valence 6.



sulfuric  

Containing sulfur, especially sulfur with a valence of 6. Compare sulfurous.

Adj. 1.
 anhydride anhydride (ănhī`drīd, –drĭd) [Gr.,=without water], chemical compound formed by removing water, H2O, from another compound; the anhydride can also react with water to form the original compound.  by a Polytron PT3100 (Kinematica AG, Littau-Lucerne, Switzerland) after 13C12-labeled PCB, [sup.13][C.sub.6]-labeled [beta]-HCH, [sup.13][C.sub.6]-labeled HCB, 13C9-1abeled endosulfan-I, [sup.13][C.sub.12]-labeled pentaCB, and [sup.13][C.sub.12]-1abeled p,p'-DDT had been added as quantitative standards. After filtration, the filtrate filtrate /fil·trate/ (fil´trat) a liquid or gas that has passed through a filter.

fil·trate
v.
To put or go through a filter.

n.
 and an additional filtrate of the rehomogenate of the residue residue n. in a will, the assets of the estate of a person who has died with a will (died testate) which are left after all specific gifts have been made. Typical language: "I leave the rest, residue and remainder [or just residue] of my estate to my grandchildren.  were washed with water twice. The resulting hexane hexane /hex·ane/ (hek´san) a saturated hydrogen obtained by distillation from petroleum.

hex·ane
n.
 extract was dehydrated de·hy·drate  
v. de·hy·drat·ed, de·hy·drat·ing, de·hy·drates

v.tr.
1. To remove water from; make anhydrous.

2. To preserve by removing water from (vegetables, for example).
 using sodium sulfuric anhydride and concentrated by evaporation evaporation, change of a liquid into vapor at any temperature below its boiling point. For example, water, when placed in a shallow open container exposed to air, gradually disappears, evaporating at a rate that depends on the amount of surface exposed, the humidity . One-sixth of the concentrated extract was used for measurement of PCBs, another sixth for that of organochlorine pesticides, and half for the gravimetric gravimetric /grav·i·met·ric/ (grav?i-me´trik) pertaining to measurement by weight; performed by weight, as a gravimetric method of drug assay.

grav·i·met·ric
adj.
1.
 fat determination.

The MS and CS samples were extracted twice using an ether/hexane (3:1) mixture after addition of the quantitative standards. The resulting ether/hexane extract was dehydrated using sodium sulfuric anhydride and concentrated by evaporation (crude extract). A fourth the crude extract was used for measurement of PCBs, and another fourth for organochlorine pesticides.

Measurement of PCBs. After the crude extract was treated with 1 mol/L KOH/ethanol for 18 hr, it was extracted using hexane three times and was concentrated with nitrogen. The concentrate was then eluted through a silica gel silica gel, chemical compound. It is a colloidal form of silica, and usually resembles coarse white sand. It may be prepared by partial dehydration of metasilicic acid, H2SiO3. Because it has many tiny pores, it has great adsorptive power.  60 column (70-230 ASTM-mesh; Merck, Darmstadt, Germany) with 10 mL hexane, evaporated evaporated

reduced in volume by evaporation; concentrated to a denser form.
 to a final volume of 0.1 mL, and analyzed after the addition of [sup.13][C.sub.12]-labeled PCB.

PCBs were quantitated by gas chromatography-mass spectrometry. Gas chromatography gas chromatography (GC)

Type of chromatography with a gas mixture as the mobile phase. In a packed column, the packing or solid support (held in a tube) serves as the stationary phase (vapour-phase chromatography, or VPC) or is coated with a liquid stationary phase
 was performed using a Hewlett Packard HP6800 series equipped with a Micromass AutoSpec Ultima mass spectrometer spectrometer

Device for detecting and analyzing wavelengths of electromagnetic radiation, commonly used for molecular spectroscopy; more broadly, any of various instruments in which an emission (as of electromagnetic radiation or particles) is spread out according to some
 (Micromass Ltd., Manchester UK). An HT8 fused silica fused silica
n.
See quartz glass.
 capillary capillary (kăp`əlĕr'ē), microscopic blood vessel, smallest unit of the circulatory system. Capillaries form a network of tiny tubes throughout the body, connecting arterioles (smallest arteries) and venules (smallest veins).  column [0.25 mm inner diameter (i.d.) x 25 m with a 0.33-mm film thickness; SGE SGE Sun Grid Engine (cluster computing)
SGE Starport: Galactic Empires (online game)
SGE Siegerland Airport (Airport Code)
SGE Small Group Evaluation
SGE Support Group Europe
 International Pty Ltd PTY LTD Propriety Limited (company structure in Australia) ., Austin, TX, USA] was used to separate each PCB congener congener /con·ge·ner/ (kon´je-ner) something closely related to another thing, as a member of the same genus, a muscle having the same function as another, or a chemical compound closely related to another in composition and exerting . The column temperature was maintained at 100[degrees]C for 2 min, raised to 180[degrees]C at a rate of 5[degrees]C/min, maintained at 180[degrees]C for 0.5 min, raised to 270[degrees]C at a rate of 20[degrees]C/min, then to 300[degrees]C at a rate of 5[degrees]C/min, and finally maintained at 300[degrees]C for 2 rain. The carrier gas (helium helium (hē`lēəm), gaseous chemical element; symbol He; at. no. 2; at. wt. 4.0026; m.p. below −272°C; at 26 atmospheres pressure; b.p. −268.934°C; at 1 atmosphere pressure; density 0. ) flow rate was 1 mL/min. The ionizing current was 600 [micro]A, the ionizing energy was 38 eV, and the accelerating voltage was 8 kV. The resolution of the mass spectrometer was maintained at approximately > 10,000 (10% valley) throughout, and the analysis was carried out according to according to
prep.
1. As stated or indicated by; on the authority of: according to historians.

2. In keeping with: according to instructions.

3.
 selected ion monitoring.

Measurement of organochlorine pesticides. The crude extract was evaporated to a final volume of 0.5 mL and extracted twice with hexane-saturated acetonitrile acetonitrile /ac·e·to·ni·trile/ (as?e-to-ni´tril) a colorless liquid with an etherlike odor used as an extractant, solvent, and intermediate; ingestion or inhalation yields cyanide as a metabolic product. . The resulting acetonitrile extract was added to water and extracted with hexane twice, then dehydrated using sodium sulfuric anhydride, and evaporated with nitrogen. The concentrate was eluted through a Florisil column (1 g/6 cc, Sep-pak Vac Florisil; Waters, Milford, MA, USA) using 10 mL hexane, evaporated to a final volume of 0.1 mL, and analyzed after the addition of fluoranthene-d10.

Organochlorine pesticides were quantitated by gas chromatography-mass spectrometry in the same manner as for PCBs, except that the column was a BPX-25 fused silica capillary column, 0.22 mm i.d. x 30 m with a 0.25-mm film thickness (SGE International Pty Ltd.). The column temperature was maintained at 60[degrees]C for 1 min, raised to 300[degrees]C at a rate of 10[degrees]C/min, and finally maintained at 300[degrees]C for 10 min.

Lipid contents. Lipid contents in the UC samples were determined gravimetrically, and lipid contents in MS and CS were determined enzymatically as the sum of the total cholesterol, triglycerides Triglycerides
Fatty compounds synthesized from carbohydrates during the process of digestion and stored in the body's adipose (fat) tissues. High levels of triglycerides in the blood are associated with insulin resistance.
, and phospholipids.

Statistical analysis. The statistical analysis was performed using Microsoft Excel (tool) Microsoft Excel - A spreadsheet program from Microsoft, part of their Microsoft Office suite of productivity tools for Microsoft Windows and Macintosh. Excel is probably the most widely used spreadsheet in the world.

Latest version: Excel 97, as of 1997-01-14.
 2002 (Microsoft, Redmond, WA, USA). Cluster analysis was performed by the cosine cosine: see trigonometry.


See sine.

COSINE - Cooperation for Open Systems Interconnection Networking in Europe. A EUREKA project.
 correlation method using GeneMaths software (version 1.50; Applied Maths BVBA BVBA Besloten Vennootschap met Beperkte Aansprakelijkheid , Sint-MartensLatem, Belgium).

Results

Detection rate. Tables 1-4 show the concentration of organochlorine pesticides (Tables 1 and 2) and PCBs (Tables 3 and 4) in the three types of tissues (MS, CS, and UC). It became clear that human fetuses were contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object.
 with multiple chemicals in Japan. However, o,p'-DDE, o,p'-DDD, aldrin, endrin, and methoxychlor were not detected in any of the tissues in this study. Other chemicals were detected in MS and/or UC, but the detection rate was very low in the CS (Tables 1 and 2). In particular, cis-chlordane, endosulfan, p,p'-DDT, dieldrin, p,p'-DDD, and heptachlor were not detected in CS; however, both were detected in MS (detection rate > 70%) and UC. PCB congeners with five to seven chlorines were detected in all samples, whereas other congeners showed a relatively low detection rate in CS (Tables 3 and 4).

Contamination levels. The highest concentrations found were p,p'-DDE, HCHs, and HCB in all three tissues both on a lipid basis (Table 1) and wet basis (Table 2). Generally, the chemical concentrations on a wet basis were of the order MS > CS > UC. This is due to the difference in lipid content. Lipid content in MS, CS, and UC (20 complete samples) was 0.76 [+ or -] 0.13%, 0.23 [+ or -] 0.04%, and 0.11 [+ or -] 0.02%, respectively. Remarkably, the concentrations of some chemicals in UC on a wet basis, such as cis-chlordane and endosulfan, were almost equal to those in MS (Table 2). On the other hand, on a lipid basis, the concentrations of the following chemicals in UC were nearly equal or often higher than in MS: HCHs, p,p'-DDT, cis-chlordane, trans-chlordane, endosulfan, and heptachlor epoxide (p < 0.001, paired t-test; Table 1). The chemical concentrations in CS were usually lower than in other tissues.

PCB congeners grouped on the basis of their number of chlorines showed different patterns of distribution depending on the number of chlorines. TetraCB and pentaCB concentrations were higher in MS than in UC (p < 0.05, paired t-test), whereas hexaCB and heptaCB concentrations were higher in UC than in MS (p < 0.001, paired t-test) on a lipid basis (Table 3); particularly, heptaCBs and octaCBs showed a high UC:MS ratio. The UC:MS ratio varied according to the number of chlorines in the range of 3-8: UC < MS for congeners with 3-5 chlorines, and UC > MS for congeners with 6-8 chlorines (Table 3). The detection rates of congeners with 1 or 2 chlorines were higher in UC than in MS, whereas those with of 9 or 10 chlorines were higher in MS than in UC. The concentrations (average and median, on a lipid basis) of congeners with 9 or 10 chlorines were higher than those with 1 or 2 chlorines in MS, whereas concentrations of congeners with 1 or 2 chlorines were higher than those with 9 or 10 chlorines in UC. These facts suggest that the accumulation of PCBs in UC is different depending on the number of chlorines; PCB congeners with 1, 2, 6, 7 and 8 chlorines easily accumulate in UC compared with other congeners.

Association between the chemical concentrations among chemicals. We reported that correlation existed between total PCBs and other persistent chemicals, such as p,p'-DDE, HCB, and HCHs, in human UC (Mori et al. 2003). To confirm our previous findings, we applied a cluster analysis technique in the present study. We used the cluster analysis to discover "natural" groupings of objects that reflect evolutionary or functional relationships among the objects; some of the cluster analyses often done in toxicogenomics research have this objective (Immermann and Huang 2003). The cluster analysis was performed using cosine correlation matrix Noun 1. correlation matrix - a matrix giving the correlations between all pairs of data sets
statistics - a branch of applied mathematics concerned with the collection and interpretation of quantitative data and the use of probability theory to estimate population
 for chemical concentrations in UC for UC, and the clustering results were represented in the dendrogram A dendrogram is a tree diagram frequently used to illustrate the arrangement of the clusters produced by a clustering algorithm (see cluster analysis). Dendrograms are often used in computational biology to illustrate the clustering of genes.  (Figure 1). Consequently, we found that PCBs with 5-8 chlorines and some organochlorines organochlorines

see chlorinated hydrocarbons.


organochlorines poisoning
cause excitement and irritability, tremor, ataxia, weakness, paralysis, convulsions.
, such as p,p'-DDE, HCB, and HCHs, were closely related to each other (Figure 1).

[FIGURE 1 OMITTED]

Association between the chemical concentrations among the three types of tissues. Correlation of organochlorine pesticide pesticide, biological, physical, or chemical agent used to kill plants or animals that are harmful to people; in practice, the term pesticide is often applied only to chemical agents.  concentrations among the three types of tissues is shown in Table 5. Some organochlorine pesticides showed no association between MS versus CS and/or between CS versus UC. Between MS versus CS, HCB, HCHs, heptachlor epoxide, and PCBs with chlorines showed a relatively high correlation coefficient (r > 0.7). Between CS versus UC, HCHs, p,p'-DDE, and PCBs with 5-8 chlorines showed relatively high correlation (r > 0.7). Comparing MS and UC, HCHs and PCBs with 4-7 chlorines showed a relatively high correlation coefficient (r > 0.7).

Association between the chemical concentrations in UC and maternal age. Several studies have reported that chemical concentrations were dependent upon maternal age at delivery (Mori et al. 2003; Rhainds et al. 1999). Our present results confirmed that HCHs, pentaCBs, hexaCBs, heptaCBs, and octaCBs showed such correlation (Table 5). A significant correlation was found between CS versus UC and age versus UC (r = 0.75; Table 5). Also, relatively significant correlation was found between MS versus UC and age versus UC (r = 0.64; Table 5). However, we found no correlation between MS versus CS and age versus UC (r = 0.04; Table 5). That is, HCHs, pentaCBs, hexaCBs, and heptaCBs tended to show relatively high association of concentrations in CS versus UC and MS versus UC. Also, these chemicals showed high correlation coefficients between the chemical concentrations in UC of first babies and maternal age.

Discussion

We investigated the distribution of organochlorine pesticides and PCBs in three types of tissues (UC, CS, and MS). We analyzed the chemical contamination See: contamination.  status mainly on a lipid basis because the liposolubility rate is thought to be a major factor influenced by rates of accumulation and elimination from tissues and organs (Parham et al. 1997) and because the existing differences depend principally on lipid content of the tissues (Henriksen et al. 1998). Several studies have reported that the concentration levels of persistent chemicals showed association between cord blood and maternal blood (Sala et al. 2001; Waliszewski et al. 2000; Walker et al. 2003). In our study, we found strong correlation between MS versus CS (Table 5) in some organochlorine pesticides and PCB congeners. Also, Grandjean et al. (2001) showed high associations between cord blood and UC. The tendency was confirmed in our study of HCHs, p,p'-DDE, and some PCB congeners (Table 5). However, we found no report that compared the concentration levels among UC, CS, and MS. Hence, we compared the data among these three tissues.

In the present study, we found that the chemical concentrations were often higher in UC than in CS on a lipid basis, and the detection rates and the concentrations in CS were often lower than in MS and UC. In past studies, chemical concentrations were higher in adipose tissues adipose tissue (ăd`əpōs'): see connective tissue.
adipose tissue
 or fatty tissue

Connective tissue consisting mainly of fat cells, specialized to synthesize and contain large globules of fat, within a
 than in serum (Lopez-Carrillo et al, 1999; Pauwels et al. 2000), and in other studies, concentrations were higher in serum lipid serum lipid Any major lipid in the circulation–total cholesterol, HDL, LDL, TGs. See Cholesterol, Triglyceride.  than in breast tissues (Waliszewski et al. 2003). Moreover, as suggested by Pauwels et al. (2000), the concentration levels of persistent chemicals varied dramatically depending on the tissues (Tables 1 and 3). One of the reasons for the confusion may be the pharmacokinetics pharmacokinetics /phar·ma·co·ki·net·ics/ (fahr?mah-ko-ki-net´iks) the action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion.  of chemicals in blood. Mohammed et al. (1990) and Noren et al. (1999) reported that chemicals in blood are bound to lipoproteins Lipoproteins
The packages in which cholesterol and triglycerides travel throughout the body.

Mentioned in: Lipoproteins Test

lipoproteins
(lip´ōprō´tēns),
n.
 and albumin albumin (ălby`mən) [Lat.,=white of egg], member of a class of water-soluble, heat-coagulating proteins. Albumins are widely distributed in plant and animal tissues, e.g.  rather than being dissolved in lipid, and the distribution in plasma vary according to the chemicals. It is possible that a free form of chemicals is distributed by simple equilibrium, but distribution or transport of bound form of chemicals to protein in blood is more complicated, so the chemical concentration in CS might be lower than in MS and UC. Further studies on the distribution of contaminants in different body tissues and fetal tissues are required.

In conclusion, we believe that UC is the best sample to assess fetal contamination status of persistent chemicals. There is a possibility that assessment based on the contamination levels in CS result in an underestimation.
Table 1. Organochlorine pesticide concentrations (pg/g-lipid) in three
types of tissue.

Organochlorine       Detection (a)
pesticide, tissue         (%)             Mean [+ or -] SD

HCB
  MS                      100        15,500 [+ or -] 6,220
  CS                      100        10,900 [+ or -] 3,680 **
  UC                       95        17,700 [+ or -] 6,360 (##)
HCHs
  MS                      100        27,400 [+ or -] 10,630
  CS                      100        33,800 [+ or -] 19,300
  UC                      100        36,200 [+ or -] 14,920 **
p,p'-DDT
  MS                       80         3,380 [+ or -] 3,240
  CS                        0                  --
  UC                       50         5,550 [+ or -] 7,160 **
o,p'-DDT
  MS                       15            38 [+ or -] 104
  CS                        0                  --
  UC                        0                  --
p,p'-DDE
  MS                      100        89,700 [+ or -] 33,600
  CS                      100        33,000 [+ or -] 16,500 **
  UC                      100        79,600 [+ or -] 26,200 (##)
p,p'-DDD
  MS                       85           766 [+ or -] 982
  CS                        0                  --
  UC                       15           215 [+ or -] 527
cis-Chlordane
  MS                      100           240 [+ or -] 165
  CS                        0                  --
  UC                       70         1,220 [+ or -] 1,230 **
trans-Chlordane
  MS                       95           320 [+ or -] 257
  CS                       20           198 [+ or -] 449
  UC                       55           644 [+ or -] 848 **
Oxychlordane
  MS                       85         2,640 [+ or -] 4,160
  CS                       40           978 [+ or -] 1,630
  UC                       60         2,120 [+ or -] 2,100
trans-Nonachlor
  MS                      100         7,230 [+ or -]  2,840
  CS                       80         3,780 [+ or -] 6,470
  UC                      100         7,660 [+ or -] 2,580
Dieldrin
  MS                       70           495 [+ or -] 454
  CS                        0                  --
  UC                       45         1,970 [+ or -] 3,170 *
Endosulfan
  MS                       90           380 [+ or -] 267
  CS                        0                  --
  UC                       70         2,090 [+ or -] 2,440 **
Heptachlor                                     --
  MS                       25           150 [+ or -] 272
  CS                        0                  --
  UC                       10           505 [+ or -] 1,620
Heptachlor epoxide
  MS                      100           142 [+ or -] 729
  CS                       95         1,580 [+ or -] 844
  UC                      100         2,790 [+ or -] 1,280 **,(##)

Organochlorine                    25th
pesticide, tissue    Minimum   percentile   Median

HCB
  MS                  3,600      10,000     16,000
  CS                  5,200       8,800     11,000
  UC                     ND      16,000     18,000
HCHs
  MS                 13,000      22,000     26,000
  CS                 12,000      24,000     28,000
  UC                 18,000      26,000     30,000
p,p'-DDT
  MS                     ND       1,000      2,400
  CS
  UC                     ND          ND      1,100
o,p'-DDT
  MS                     ND          ND         ND
  CS                     --          --         --
  UC                     --          --         --
p,p'-DDE
  MS                 19,000      71,000     93,000
  CS                 14,000      22,000     28,000
  UC                 29,000      64,000     78,000
p,p'-DDD
  MS                     ND         200        360
  CS                                 --         --
  UC                     ND          ND         ND
cis-Chlordane
  MS                     63         110        200
  CS                                 --         --
  UC                     ND          ND      1,200
trans-Chlordane
  MS                     ND         160        240
  CS                     ND          ND         ND
  UC                     ND          ND        290
Oxychlordane
  MS                     ND         620      1,200
  CS                     ND          ND         ND
  UC                     ND          ND      1,900
trans-Nonachlor
  MS                  2,000       5,600      7,000
  CS                     ND       1,400      1,900
  UC                  2,500       6,200      6,700
Dieldrin
  MS                     ND          ND        440
  CS                     --          --         --
  UC                     ND          ND         ND
Endosulfan
  MS                     ND         280        340
  CS                     --          --         --
  UC                     ND          ND      1,600
Heptachlor
  MS                     ND          ND         ND
  CS                                 --         --
  UC                     ND          ND         ND
Heptachlor epoxide
  MS                    310         950      1,200
  CS                     ND       1,100      1,500
  UC                    160       2,000      2,700

Organochlorine          75th
pesticide, tissue    percentile   Maximum

HCB
  MS                   17,800      31,000
  CS                   12,000      18,000
  UC                   20,000      28,000
HCHs
  MS                   30,000      55,000
  CS                   39,000     100,000
  UC                   45,000      69,000
p,p'-DDT
  MS                    5,100      11,000
  CS
  UC                    9,300      19,000
o,p'-DDT
  MS                       ND         340
  CS                       --          --
  UC                       --          --
p,p'-DDE
  MS                  110,000     150,000
  CS                   42,000      75,000
  UC                   90,000     140,000
p,p'-DDD
  MS                      950       3,800
  CS                       --          --
  UC                       ND       1,600
cis-Chlordane
  MS                      330         660
  CS                       --          --
  UC                    1,700       4,400
trans-Chlordane
  MS                      430       1,200
  CS                       ND       1,400
  UC                    1,200       3,000
Oxychlordane
  MS                    3,900      19,000
  CS                    1,600       6,300
  UC                    3,700       6,100
trans-Nonachlor
  MS                    9,000      14,000
  CS                    3,800      30,000
  UC                    8,300      14,000
Dieldrin
  MS                      770       1,600
  CS                       --          --
  UC                    2,200       9,600
Endosulfan
  MS                      460       1,100
  CS                       --          --
  UC                    2,900       9,400
Heptachlor
  MS                      100         700
  CS                       --          --
  UC                       ND       6,500
Heptachlor epoxide
  MS                    1,700       3,000
  CS                    1,900       3,400
  UC                    3,500       6,000

ND, not detected.

* Detection rate is shown as a percentage (n = 20). * p < 0.05 and
** p < 0.001 compared with MS. (##) p < 0.001 compared with CS.

Table 2. Organochlorine pesticide concentrations (pg/g-wet) in three
types of tissue.

Organochlorine       Detection (a)
pesticide, tissue         (%)            Mean [+ or -] SD

HCB
  MS                      100          120 [+ or -] 55.2
  CS                      100         23.9 [+ or -] 8.42 **
  UC                       95         19.6 [+ or -] 6.52 **
HCHs
  MS                      100          208 [+ or -] 84.7
  CS                      100         74.5 [+ or -] 39.3 **
  UC                      100         39.8 [+ or -] 7.8 **,(##)
pp'-DDT
  MS                       80        26.40 [+ or -] 26.5
  CS                        0                 --
  UC                       50         5.76 [+ or -] 7.53 *
op'-DDT
  MS                       15         0.32 [+ or -] 0.89
  CS                        0                 --
  UC                        0                 --
pp'-DDE
  MS                      100        680.0 [+ or -] 277
  CS                      100         71.9 [+ or -] 30.7 **
  UC                      100         86.5 [+ or -] 26.1 **,(#)
pp'-DDD
  MS                       85         6.11 [+ or -] 7.99
  CS                        0                 --
  UC                       15         0.26 [+ or -] 0.63
cis-Chlordane
  MS                      100         1.81 [+ or -] 1.25
  CS                        0                 --
  UC                       70         1.20 [+ or -] 1.19
trans-Chlordane
  MS                       95         2.46 [+ or -] 2.45
  CS                       20         0.41 [+ or -] 0.90
  UC                       55         0.68 [+ or -] 0.91 *
Oxychlordane
  MS                       85        22.80 [+ or -] 45.4
  CS                       40         2.19 [+ or -] 3.45
  UC                       60         2.48 [+ or -] 2.50
trans-Nonachlor
  MS                      100        55.00 [+ or -] 23.2
  CS                       80         8.02 [+ or -] 12.1 **
  UC                      100         8.52 [+ or -] 3.17 **
Dieldrin
  MS                       70         3.75 [+ or -] 3.30
  CS                        0                 --
  UC                       45         2.02 [+ or -] 3.01
Endosulfan
  MS                       90         2.90 [+ or -] 2.07
  CS                        0                 --
  UC                       70         2.83 [+ or -] 2.61
Heptachlor
  MS                       25         1.44 [+ or -] 2.58
  CS                        0                 --
  UC                       10         0.57 [+ or -] 1.82
Heptachlor epoxide
  MS                      100        10.70 [+ or -] 5.67
  CS                       95         3.51 [+ or -] 1.80 **
  UC                      100         2.89 [+ or -] 1.03 **

Organochlorine                    25th
pesticide, tissue    Minimum   percentile   Median

HCB
  MS                    20          81        120
  CS                    13          20         23
  UC                    ND          17         20
HCHs
  MS                   100         160        190
  CS                    33          49         70
  UC                    17          29         35
pp'-DDT
  MS                    ND         8.0         17
  CS                    --          --         --
  UC                    ND          ND        1.0
op'-DDT
  MS                    ND          ND         ND
  CS                    --          --         --
  UC                    --          --         --
pp'-DDE
  MS                   190         480        640
  CS                    26          50         72
  UC                    31          76         88
pp'-DDD
  MS                    ND         1.6        2.7
  CS                    --          --         --
  UC                    ND          ND         ND
cis-Chlordane
  MS                  0.54        0.70        1.3
  CS                    --          --         --
  UC                    ND          ND        1.1
trans-Chlordane
  MS                    ND         1.2        1.9
  CS                    ND          ND         ND
  UC                    ND          ND       0.25
Oxychlordane
  MS                    ND         4.9         11
  CS                    ND          ND         ND
  UC                    ND          ND        2.3
trans-Nonachlor
  MS                    15          38         53
  CS                    ND         3.1        4.3
  UC                   2.9         6.8        7.9
Dieldrin
  MS                    ND          ND        3.4
  CS                    --          --         --
  UC                    ND          ND        2.7
Endosulfan
  MS                    ND           2        2.6
  CS                    --          --         --
  UC                    ND          ND        1.9
Heptachlor
  MS                    ND          ND         ND
  CS                    --          --         --
  UC                    ND          ND         ND
Heptachlor epoxide
  MS                   2.3         6.9          9
  CS                    ND         2.4        3.3
  UC                   0.3         2.2        3.1

Organochlorine          75th
pesticide, tissue    percentile   Maximum

HCB
  MS                     140         230
  CS                      25          46
  UC                      23          33
HCHs
  MS                     240         430
  CS                      82         190
  UC                      48          95
pp'-DDT
  MS                      42          90
  CS                      --          --
  UC                      11          27
op'-DDT
  MS                      ND           3
  CS                      --          --
  UC                      --          --
pp'-DDE
  MS                     900       1,200
  CS                      95         130
  UC                      94         150
pp'-DDD
  MS                     7.1          30
  CS                      --          --
  UC                      ND         2.1
cis-Chlordane
  MS                     2.6         4.8
  CS                      --          --
  UC                     2.0         4.4
trans-Chlordane
  MS                     3.1          12
  CS                      ND         2.9
  UC                     1.1         2.9
Oxychlordane
  MS                      24         210
  CS                     3.6          12
  UC                     4.5         6.9
trans-Nonachlor
  MS                      68         100
  CS                     9.7          56
  UC                    10.3          17
Dieldrin
  MS                     5.9          10
  CS                      --          --
  UC                     2.6         8.5
Endosulfan
  MS                     3.9         8.4
  CS                      --          --
  UC                     3.3          10
Heptachlor
  MS                     1.2         7.2
  CS                      --          --
  UC                      ND         7.2
Heptachlor epoxide
  MS                      13          24
  CS                     4.2         7.3
  UC                     3.5         5.1

ND, not detected.

(a) Detection rate is shown as a percentage (n = 20). * p < 0.05
and ** p < 0.001 compared with MS. (#) p < 0.05 and (##) p < 0.001
compared with CS.

Table 3. PCB concentrations (pg/g-lipid) in three types of tissue.

              Detection (a)
PCB, tissue        (%)              Mean [+ or -] SD          Minimum

MonoCBs
  MS                25           8.4 [+ or -] 30.5                ND
  CS                 0                  --                        --
  UC                95           480 [+ or -] 405 *               ND
DiCBs
  MS                70            44 [+ or -] 37                  ND
  CS                 0                  --                        --
  UC                80           354 [+ or -] 276 **              ND
TriCBs
  MS               100         1,630 [+ or -] 639                720
  CS                65         1,630 [+ or -] 1770                ND
  UC                90         1,210 [+ or -] 977                 ND
TetraCBs
  MS               100         7,000 [+ or -] 2120             4,000
  CS                95         4,360 [+ or -] 3750 **             ND
  UC                95         3,190 [+ or -] 2,200 **            ND
PentaCBs
  MS               100        15,000 [+ or -] 4,630            7,700
  CS               100        12,700 [+ or -] 6,080 **         3,700
  UC               100        13,200 [+ or -] 6,100 *          5,100
HexaCBs
  MS               100        25,600 [+ or -] 8,410           11,000
  CS               100        31,200 [+ or -] 11,000 **       14,000
  UC               100        32,600 [+ or -] 12,000 **       13,000
HeptaCBs
  MS               100         9,640 [+ or -] 3,610            3,900
  CS               100        12,300 [+ or -] 5,420 **         3,500
  UC               100        15,200 [+ or -] 5,860 **,(##)    7,700
OctaCBs
  MS               100         1,750 [+ or -] 718                590
  CS                75         1,700 [+ or -] 1,380               ND
  UC               100         3,130 [+ or -] 1,360 **,(##)    1,700
NonaCBs
  MS                70           212 [+ or -] 174                 ND
  CS                35           146 [+ or -] 291                 ND
  UC                50           148 [+ or -] 221                 ND
DecaCBs
  MS                85           114 [+ or -] 65                  ND
  CS                35           130 [+ or -] 257                 ND
  UC                55           148 [+ or -] 173 *               ND
Total PCBs
  MS               100        61,500 [+ or -] 18,400          29,000
  CS               100        63,800 [+ or -] 23,300          31,000
  UC               100        70,000 [+ or -] 26,100 *,(#)    34,000

                 25th                  75th
PCB, tissue   percentile   Median   percentile   Maximum

MonoCBs
  MS                ND         ND         28         110
  CS                --         --         --          --
  UC               100        470        640       1,400
DiCBs
  MS                ND         44         67         120
  CS                --         --         --          --
  UC               220        370        450       1,200
TriCBs
  MS              1200       1400      2,000       2,900
  CS                ND      1,500      2,200       6,700
  UC               560       1100      1,800       3,900
TetraCBs
  MS             7,400      7,100      8,000      12,000
  CS             1,800      3,300      5,600      14,000
  UC             2,100      3,000      4,000      10,000
PentaCBs
  MS            11,000     15,000     18,000      25,000
  CS             8,000     13,000     17,000      24,000
  UC             7,900     12,000     18,000      25,000
HexaCBs
  MS            20,000     26,000     30,000      42,000
  CS            23,000     31,000     38,000      51,000
  UC            24,000     35,000     40,000      53,000
HeptaCBs
  MS             7,400      8,600     12,000      17,000
  CS             8,000     12,000     13,500      23,000
  UC            11,000     14,000     20,000      29,000
OctaCBs
  MS             1,500      1,800      2,500       3,100
  CS               830      1,400      2,600       4,400
  UC             2,100      2,700      3,900       5,900
NonaCBs
  MS                ND        220        290         530
  CS                ND         ND        200       1,200
  UC                ND         60        210         910
DecaCBs
  MS                91        115        150         240
  CS                ND         ND        220       1,100
  UC                ND         96        255         570
Total PCBs
  MS            46,000     61,000     72,000      96,000
  CS            44,000     63,000     77,000     110,000
  UC            47,000     73,000     88,000     130,000

ND, not detected.

(a) Detection rate is shown as a percentage (n = 20). * p < 0.05
and ** p < 0.001 compared with MS. (#) p < 0.05 and (##) p < 0.001
compared with CS.

Table 4. PCB concentrations (a) (pg/g-wet) in three types of tissue.

              Detection (a)
PCB, tissue        (%)              Mean  [+ or -] SD         Minimum

MonoCBs
  MS                25          0.10 [+ or -] 0.21             ND
  CS                 0                     --                  --
  UC                95          0.52 [+ or -] 0.47             ND
DiCBs
  MS                70          8.65 [+ or -] 0.28             ND
  CS                 0                     --                  --
  UC                80          0.38 [+ or -] 0.30             ND
TriCBs
  MS               100          13.0 [+ or -] 6.14              6.1
  CS                65          3.78 [+ or -] 4.42 **          ND
  UC                90          1.38 [+ or -] 1.15 **, (#)     ND
TetraCBs
  MS               100          53.2 [+ or -] 17.75            22
  CS                95          9.59 [+ or -] 8.32 **          ND
  UC                95          3.69 [+ or -] 3.13 **, (##)    ND
PentaCBs
  MS               100           115 [+ or -] 42.3             51
  CS               100          27.5 [+ or -] 12.8 **           8.6
  UC               100          14.6 [+ or -] 7.54 **, (##)     5.2
HexaCBs
  MS               100           195 [+ or -] 68.4             90
  CS               100          69.3 [+ or -] 25.9 **          26
  UC               100          36.1 [+ or -] 15.3 **, (##)    16
HeptaCBs
  MS               100          73.3 [+ or -] 26.7             34
  CS               100          27.9 [+ or -] 13.8 **           6.2
  UC               100          17.1 [+ or -] 8.26 **, (##)     8.6
OctaCBs
  MS               100          14.5 [+ or -] 5.57              4.6
  CS                75          4.03 [+ or -] 3.96 **          ND
  UC               100          3.57 [+ or -] 1.86 **, (#)      1.4
NonaCBs
  MS                70          1.54 [+ or -] 1.26             ND
  CS                35          0.32 [+ or -] 0.64             ND
  UC                50        0.17 * [+ or -] 0.27 *           ND
DecaCBs
  MS                85          0.87 [+ or -] 0.50             ND
  CS                35          0.29 [+ or -] 0.58             ND
  UC                55          0.18 [+ or -] 0.23 **          ND
Total PCBs
  MS               100           467 [+ or -] 154             220
  CS               100           139 [+ or -] 56.4 **          56
  UC               100          77.4 [+ or -] 35.5 **, (##)    35

                 25th                   75th
PCB, tissue   percentile   Median    percentile   Maximum

MonoCBs
  MS           ND           ND         0.02         0.68
  CS           --           --        --           --
  UC            0.16         0.36      0.82         1.7
DiCBs
  MS           ND            0.35      0.52         0.89
  CS           --           --        --           --
  UC            0.24         0.36      0.50         1.2
TriCBs
  MS            8.5         10        15           31
  CS           ND            3.6       4.8         17
  UC            0.45         1.3       1.8          4.4
TetraCBs
  MS           40           50        65           91
  CS            4.2          6.9      13           35
  UC            2.4          2.9       4.5         15
PentaCBs
  MS           81          110       140          190
  CS           19           26        34           54
  UC           10           13        18           37
HexaCBs
  MS          140          210       240          340
  CS           51           68        88          130
  UC           26           35        43           78
HeptaCBs
  MS           55           73        94          120
  CS           19           26        32           61
  UC           12           16        20           43
OctaCBs
  MS           11           15        18           26
  CS            1.4          3.4       5.1         16
  UC            2.1          3.4       4.3          8.3
NonaCBs
  MS           ND            1.6       2.5          3.8
  CS           ND           ND         0.52         2.7
  UC           ND            0.065     0.26         1.1
DecaCBs
  MS            0.73         0.86      1.0          1.7
  CS           ND           ND         0.49         2.5
  UC           ND            0.094     0.33         0.85
Total PCBs
  MS          340          490       570          780
  CS          100          130       180          270
  UC           57           73        91          190

ND, not detected.

(a) Detection rate is shown as a percentage (n = 20).
* p < 0.05 and ** p < 0.001 compared with MS.
(#) p < 0.05 and (##) p < 0.001 compared with CS.

Table 5. Correlation coefficients (r) of chemicals among tissues
and between maternal age and chemical concentrations in UC of
first babies.

                                                            Between
                                                            maternal
                                                            age and
                                                         concentrations
                                Among tissues (a)        in UC of first
                                                            babies
                     MS vs. CS   CS vs. UC   MS vs. UC    (age vs. UC)

HCB                    0.73        0.30        0.39          -0.16
HCHs                   0.72        0.76        0.80           0.83
p,p'-DDE               0.46        0.76        0.29           0.28
cis-Chlordane           --          --         0.03          -0.02
trans-Nonachlor        0.18        0.20        0.11           0.47
Endosulfan              --          --         0.19          -0.20
Heptachlor epoxide     0.72        0.22        0.02           0.10
TriCBs                  --          --         0.35          -0.03
TetraCBs               0.51        0.41        0.73           0.37
PentaCBs               0.83        0.89        0.84           0.75
HexaCBs                0.87        0.87        0.82           0.76
HeptaCBs               0.68        0.85        0.72           0.85
OctaCBs                0.32        0.70        0.47           0.81
NonaCBs                 --          --         -0.25           --
DecaCBs                 --          --         0.40            --
Total PCBs             0.82        0.82        0.81           0.80
Correlation            0.04        0.75        0.64            --
  coefficients
  (r) (b)
  between "among
  tissues" and
  age vs. UC

--, not calculated.

(a) The values shown were calculated when the detection rate
in the tissue was [greater than or equal to] 70%.
(b) Total PCBs were excluded from this calculation.


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Hideki Fukata, (1,2) Mariko Omori, (1,2,3,4) Hisao Osada, (2,5) Emiko Todaka, (2,4,6) and Chisato Mori (2,4)

(1) Department of Environmental Medical Science, (2) Environmental Health Science Project for Future Generations, (3) Department of Reproductive Medicine, and (4) Department of Bioenvironmental bi·o·en·vi·ron·men·tal  
adj.
Having to do with the relationship between the environment and living organisms: Bioenvironmental engineers are studying the effects of toxic chemicals on life in the area. 
 Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; (5) Department of Obstetrics and Gynecology obstetrics and gynecology

Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system.
, Chiba University Hospital, Chiba, Japan; (6) Center for Environment, Health and Field Sciences, Chiba University, Kashiwa, Japan

Address correspondence to C. Mori, Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670 Japan. Telephone: 81-43-226-2017. Fax: 81-43-226-2018. E-mail: cmori@faculty.chiba-u.jp

This work was supported by grants from the Ministry of the Environment (Government of Japan) and the Ministry of Education, Culture, Sports, Science and Technology (Government of Japan).

Received 16 June 2004; accepted 14 December 2004.
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Title Annotation:Research
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Publication:Environmental Health Perspectives
Date:Mar 1, 2005
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