What is polychlorinated biphenyl toxin

Prenatal uptake of polychlorinated biphenyls: Pathogenetic significance of the current pollution in Germany

MEDICINE

Summary
Polychlorinated biphenyls (PCB) are ubiquitous substances with carcinogenic and teratogenic properties. In addition to food (90 percent), the main source of intake for humans is also contaminated sites in housing and building materials. Due to their chemical persistence, PCBs accumulate in the organism throughout their life, whereby intake begins prenatally through free transplacental transfer from mother to fetus. Based on the research results of the author, findings on the pathogenetic significance of prenatal PCB uptake are presented against the background of the development of pollution over the past 15 years. The prenatal PCB uptake has decreased by about 90 percent during this period, so that the human PCB exposure in Germany is now in a low dose range, which appears to be very unlikely to result in health consequences from this group of substances, including postnatal absorption through breast milk leaves. Using the example of the cumulative uptake of tobacco-specific carcinogens and PCBs in children of smoking mothers, however, it becomes clear that the organism is exposed to a large number of xenobiotics, although the interactions between the substances and the possible health risks are still largely unknown.

Key words: polychlorinated biphenyls, environmental medicine, cancer risk, teratogenesis, exposure to harmful substances

Summary
Prenatal Uptake of Polychlorinated Biphenyls: Course of Pollution During the Past 15 Years and Pathogenetic Relevance
Polychlorinated biphenyls (PCBs) are ubiquitous compounds with carcinogenic and teratogenic properties. Main source of uptake for men is
via diet (90 per cent) and residual pollution in housings. PCBs accumulate in the food chain and human organism due to their chemical
persistence. The uptake begins as early as during pregnancy because PCBs can easily cross the placenta from mother to fetus. Based upon research of the author, data about the pathogenetic relevance of PCBs in Germany during the past 15 years are presented. The prenatal uptake of PCBs has declined by 90 per cent during this time period, thus only very low level PCB exposure today is still present in humans. Health impairment due to this exposure including the postnatal uptake with mother's milk seems very unlikely. On the other hand, coincidental uptake of PCBs and tobacco-specific carcinogens in offspring of smoking women raises concern that the organism is exposed to a variety of xenobiotics whose chemical and biological interactions as well as their possible harmful properties are still unknown and have to be elucidated.

Key words: polychlorinated biphenyls, environmental medicine, risk for cancer, teratogenesis

Polychlorinated biphenyls (PCB) consist of two interconnected phenolic rings to which one to a maximum of ten chlorine atoms can bind (Figure). A total of 209 individual compounds or congeners are conceivable (26). The PCB substance class was first described at the end of the 19th century and has been industrially produced on a large scale since 1920 (48). Because of their chemical stability and heat resistance, they have been used in a wide variety of uses; Among other things, they were used as lubricants, plasticizers, hydraulic oils and insulating agents in transformers (2, 3, 48). Through gradual entry into the environment, whether through uncontrolled waste disposal, targeted dissemination as a component of pesticides, industrial accidents or continuous emissions from transformers as well as sealing and jointing compounds, PCBs have spread worldwide due to their poor degradability and chemical persistence and are ubiquitous today (2 , 5, 7, 17). From the environmental media, PCBs get into vegetable feed and food, accumulate in the food chain due to their good fat solubility and are finally deposited at the end of the food chain in the human organism (23), where the higher chlorinated PCBs have a half-life of up to several years accumulate for life (28, 30, 42).
Due to proven carcinogenic and teratogenic properties of PCBs, their use in open systems was banned in the USA in 1974 and in Germany in 1978 (2, 5). Since the regulation banning PCBs, polychlorinated terphenyls and restricting vinyl chloride came into force in Germany in 1989, use in closed systems has also been prohibited (52). Nonetheless, PCBs are still contained in old systems and devices, such as transformers, and emission sources can still be found today in buildings in which PCB-containing grout has been used (7, 16). In the first place (90 percent), however, are contaminated food, namely dietary fats of animal origin, here in particular fish fat in adulthood and breast milk in infancy, now the predominant source of intake of PCBs in humans (20, 43, 44, 45, 46, 50, 51 , 53). The geographical differences in PCB contamination within Germany that were occasionally described in previous years (47, 49, 55) are therefore no longer to be expected. This was also confirmed in an extensive comparative study by the author's working group in 1998 on prenatal pollution in a rural small town area and a metropolitan area in Germany (34, 37).
Toxicokinetics of prenatal PCB uptake
The accumulation of pollutants begins in humans already in utero through the free transplacental transfer of PCBs from the mother to the unborn child (29, 35, 37). While Winneke et al. Recently again highlighted the importance of breastfeeding for the child’s PCB uptake and brought it into causal connection with the neurological deficits of these children at the age of 42 months (53), it is still unanimously assumed that if In general, prenatal pollutant accumulation is of crucial importance with regard to possible neurological sequelae in children (22, 39).
With regard to the toxicokinetics of prenatal PCB uptake in humans, the author's working group was able to show that the level of pollution increases almost linearly with maternal age (30, 37), with newborns from a 40-year-old mother compared to the children from a 20-year-old mother. year old woman have up to 500 percent higher concentrations of the higher chlorinated PCB congeners 138, 153 and 180. In contrast to earlier studies from 1984/85 (29), the low-chlorinated PCB congeners 28, 52 and 101 were no longer detectable in current studies from 1994 to 1998 (30, 37). This shows that short-term, acute PCB exposure can no longer be observed in the general population today (3).
Furthermore, a significant dependence of the neonatal PCB concentration on the length of pregnancy was found (37), with newborns of the 42nd week of pregnancy having PCB concentrations 3.5 times higher than newborns of the 38th week of pregnancy. Correlations between the birth weight, the sex of the children and the neonatal PCB concentration could not be proven in any of the author's studies.
The relationship between prenatal PCB exposure and maternal age reflects the continuous increase in PCB concentrations in the human organism with increasing age (25). The dependence on the length of pregnancy also confirms the free transplacental transfer of these organochlorine compounds from the mother to the fetus. In view of the limited information that is currently available on the mechanisms of transplacental transfer of these substances in humans (27), three points seem worth discussing in this context:
- PCBs evidently accumulate more rapidly prenatally than in later life, especially more rapidly than in the first decade of life. However, as already mentioned, the postnatal intake of organochlorine compounds nowadays takes place almost exclusively through food, and most industrially manufactured infant and toddler foods are residue-free or only minimally contaminated with organochlorine compounds (9, 48). In 1996, Brussaard et al. Found the lowest daily PCB intake in small children and the highest in adult men (6). Conversely, PCBs can be freely filtered transplacentally due to their lipophilicity and accumulate in the fetal adipose tissue, which suggests and explains a significant prenatal accumulation of these substances in the fetal organism (41).
- While the prenatal accumulation of pollutants increases almost linearly with maternal age, it is noticeable that the child's PCB exposure towards the end of pregnancy does not appear to increase linearly, but almost exponentially (37). A decrease in the filtration capacity of the placenta in the sense of a decrease in its barrier function against any noxious agents may play a role here.
le (13, 29). In addition, this increase may be an expression of an increased accumulation of pollutants due to the rapid increase in fetal adipose tissue towards the end of pregnancy (57).
- Given these findings, if one asks whether pregnancies should be prematurely terminated in order to protect the newborn from increased PCB exposure, or whether pregnancies over a certain age should be completely discouraged for this reason, these questions are clearly no based on current knowledge answer. If you look at the neonatal PCB exposure in Germany 15 years ago, the concentrations at that time were significantly higher than those found today in children of a 40-year-old mother in the 42nd week of pregnancy (3, 29).
In addition, there has been such a significant decrease in overall pollution in recent years that the concentration of PCBs is now in the low dose range, the pathogenetic significance of which can at best achieve biological-toxicological relevance in conjunction with other pollutants.
Pathogenetic significance of prenatal pollutant accumulation
Concerns about possible harm to health from the accumulation of PCBs in the environment first arose in Sweden in 1966 (24); the general public learned of the potential dangers of PCBs in 1968. In the so-called yusho disaster on the Japanese island of Kyushu, more than 10,000 people were poisoned by PCB-contaminated rice oil (yusho).
ten chlorine acne led to uncharacteristic general symptoms, respiratory complaints, and endocrinological and immunological disorders in the victims (1, 10, 14). With regard to their neurological development, many of the children affected exhibited muscular hypotension, apathy, or psychomotor retardation (15). Of 128 children exposed intrauterine, who were followed up in a comprehensive study, most showed persistent disorders of their psycho-intellectual or neuromotor development, with intrauterine dystrophy or neurological symptoms in the neonatal period being associated with a poor prognosis (56). Similar accidents were repeated in Taiwan in 1979 (PCB-contaminated rice oil, Yu Chen) and Finland in 1982 (explosion in a cardboard factory), with symptoms in Taiwan being comparable to those in Japan (8). The workers in the cardboard factory in Finland, on the other hand, did not suffer any permanent health damage (Federal Institute for Consumer Health Protection and Veterinary Medicine, personal communication 1999). While in all these accidents the actual toxic effect was initially ascribed to the PCB, we now know that a large part of the toxicity was caused by the simultaneous release of furans, heavy metals and other organochlorine compounds (35).
More recent studies also suggest that neurological sequelae can be expected even with significantly lower prenatal PCB exposure, as has been observed among other things in the general American population (40). Gladen et al. Found a clear association between prenatal PCB exposure and lower development scores in the Bayley Scales of Psychomotor Development at the ages of 18 and 24 months (11, 12). Other study groups even succeeded in demonstrating a dose-dependent effect between prenatal PCB exposure and later neurological and psychomotor developmental disorders in children up to the age of 4 years (21). Corresponding European studies produced comparable results (18, 19, 54, 35). Animal studies have also been able to confirm the various observations made in humans (40). Overall, these studies made it clear that prenatal PCB exposure is much more dangerous with regard to subsequent neurological damage than the sometimes much higher postnatal exposure to breast milk (22, 40). One explanatory hypothesis for this is the greater vulnerability of the fetal nervous system to external noxa (22).
The prenatal PCB exposure in Germany has been over 90 since 1984
Percent decreased (table) (29, 36, 38). Against this background, the results of the studies mentioned, most of which were collected 10 to 15 years ago and projected onto today's conditions, appear more than doubtful. Consequential health damage from prenatal PCB exposure nowadays appears to be very unlikely per se. If at all, additive effects due to the simultaneous accumulation of other biological-chemical toxins should be discussed. Nevertheless, another study was recently published that ascribes a causal role to breastfeeding for the later development of neurological sequelae in children (53). The authors found significantly increased PCB concentrations (the sum of the three higher chlorinated PCB congeners 138, 153 and 180 was calculated) in the serum of children who were breastfed for longer than four months (mean PCB concentration 1.77 ng / mL) im Compared to 0.68 ng / mL in previously weaned children (2 weeks to 4 months) and bottle-fed peers (0.36 ng / mL). This postnatal PCB exposure was causally related to deficits in the Bayley Scales of Infant Development in the longer breastfed children aged 30 and 42 months.
While the reference values ​​determined for PCBs in newborns (38) agree with the values ​​of this new study in comparison to the author's surveys, the corresponding reference values ​​for umbilical cord blood in the German general population in 1994 were 0.96 ng / mL. These values ​​are higher than in previously weaned children if the samples were taken at the age of 42 months (29, 53). In 1984 the PCB reference values ​​in umbilical cord blood were 1.37 ng / mL (29) and were almost in the range that is found today in long-term breastfed children at the age of 42 months. According to the cited study (53), such exposure should be able to cause motor and mental deficits. However, since these are values ​​in the low dose range, no consequential damage to human health is to be expected, including breastfeeding with breast milk (39).
Furthermore, the human organism and the growing fetus are exposed to a large number of xenobiotics, the interaction of which with regard to consequential health damage is not known. For example, it is unclear whether and to what extent maternal smoking during pregnancy increases the incidence of malignant diseases in the offspring. In this context, the transplacental transfer of tobacco-specific carcinogens from the mother to the fetus was demonstrated for the first time (31, 32). Independently of this, it has been shown that newborns from smoking mothers have significantly higher PCB concentrations than children from passive or non-smoking mothers (33, 37). It is off
Animal experiments know that the tobacco-specific carcinogens and PCBs identified by the author develop a pronounced cocarcinogenic effect when they act on the organism at the same time (4).
Here it becomes clear that it is possible that it is only the interaction of different pollutants that has biological-toxicologically relevant effects on the human organism and that the interactions of various environmental pollutants in the human organism are not yet understood. There is an extremely extensive need for research here.
In summary, it can be concluded that the PCB exposure of humans in Germany today is in the low dose range and that damage to health that can be attributed to this alone is very unlikely.
Acknowledgments: My special thanks go to Prof. Dr. J. Angerer and Dipl.-Ing. K.-H. Schaller, Institute for Occupational, Social and Environmental Medicine of the Friedrich-Alexander-Universität Erlangen-Nürnberg, for the implementation of the pollutant analyzes and the willing and friendly support and advice in all environmental medicine issues.

Manuscript submitted: December 3, 2001, revised version accepted: April 23, 2002

How this article is cited:
Dtsch Arztebl 2002; 99: A 2262-2265 [Issue 34-35]

The numbers in brackets refer to the bibliography, which is available from the author in an offprint and on the Internet (www.aerzteblatt.de).

Author's address:
Priv.-Doz. Dr. med. Gerd-Michael Lackmann
Reinstorfweg 10a
21107 Hamburg
Email: [email protected]
Akiyama K, Ohi G, Fujitani K, Yagyu H, Ogino M, Kawana T: Polychlorinated biphenyl residues in maternal and cord blood in Tokyo metropolitan area. Bull Environ Contam Toxicol 1975; 14: 588-592. MEDLINE
American Council on Science and Health - Position paper: Public health concerns about environmental polychlorinated biphenyls (PCBs). Exotoxicol Environ Saf 1997; 38: 71-84. MEDLINE
Angerer J, Göen T, Schaller KH, Lackmann GM, Töllner U: Prenatal exposure to polychlorinated biphenyls and hexachlorobenzene: A comparison of the values ​​from 1984/85 and 1994/95. Umweltmed Forsch Prax 1996; 1: 78-82.
Beebe LE, Kim YE, Amin S, Riggs CW, Kovatch RM, Anderson LM: Comparison of transplacental and neonatal initiation of mouse lung and liver tumors by N-ni-trosodimethylamine (NDMA) and 4- (methylnitrosamino) -1- (3 -pyridyl) -1-buta-none (NNK) and promotability by a polychlorinated biphenyls mixture (Aroclor 1254). Carcinogenesis 1993; 14: 1545-1548. MEDLINE
Bleeker I, Fischer AB, Tilkes F, Eikmann T: PCB concentrations in human blood. Umweltmed Forsch Prax 1999; 4: 84-96.
Brussaard JH, Dokkum van W, Paauw van der CG, Vos de RH, Kort de WLAM, Löwik MRH: Dietary intake of food contaminants in The Netherlands (Dutch Nutrition Surveillance System). Food Add Contam 1996; 13: 561-573. MEDLINE
Burkhardt U, Bork M, Balfanz E, Leidel J: Indoor pollution from polychlorinated biphenyls (PCB) in permanently elastic sealing compounds. Public Health 1990; 52: 567-574. MEDLINE
Chen YC, Guo YL, Hsu CC, Rogan WJ: Cognitive development of Yu-Cheng ("oil disease") children perinatally exposed to heat-degraded PCBs. JAMA 1992; 268: 3213-3218. MEDLINE
German Research Foundation (DFG): Polychlorinated Biphenyls: Inventory of analysis, occurrence, kinetics and toxicology. Communication VIII, Weinheim: Verlag Chemie 1988.
Fujiwara K: Environmental and food contamination with PCBs in Japan. Sci Total Environ 1975; 4: 219-247. MEDLINE
Gladen BC, Rogan WJ, Hardy P, Thullen J, Tingelstad J, Tully M: Development after exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene transplacentally and through human milk. J Pediatr 1988; 113: 991-995. MEDLINE
Gladen BC, Rogan WJ: Effects of perinatal polychlorinated biphenyls and dichlorodiphenyl dichloroethene on later development. J Pediatr 1991; 119: 58-63. MEDLINE
Gregus Z, Klaassen CD: Hepatic disposition of xenobiotics during prenatal and early postnatal development. In: Polin RA, Fox WW, Ed .: Fetal and Neonatal Physiology. Philadelphia: WB Saunders, 1992. Vol. 2, 1103-1122.
Guo YL, Yu ML, Hsu CC, Rogan WJ: Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-up of the Taiwan Yucheng cohort. Environ Health Perspect 1999; 107: 715-719. MEDLINE
Harada M: Intrauterine poisoning: Clinical and epidemiological studies and significance of the problem. Bull Inst Constit Med (Kumamoto University) 1976; 25 (Suppl.): 1-69.
Heudorf U, Angerer J: Current PCB exposure of a resident population in Germany 1998. Umweltmed Forsch Prax 2000; 5: 137-142.
Heudorf U, Salzmann N, Angerer J, Wittsiepe J: Biomonitoring on PCDD / F and on PCBs with greatly increased indoor air pollution. Umweltmed Forsch Prax 1996; 1: 6-12.
Huisman M, Koopman-Esseboom C, Brouwer M et al .: The Dutch PCB / dioxin study. Influence of maternal dietary habits on the pre- and postnatal exposure to xenobiotics. Organohalogen Comp 1993; 14: 81-84.
Huisman M, Koopman-Esseboom C, Lanting CI et al .: Neurological condition in 18-month-old children perinatally exposed to polychlorinated biphenyls and dioxins. Early Hum Dev 1995; 43: 165-176. MEDLINE
Jacobson JL, Jacobson SW: Dose-response in perinatal exposure to polychlorinated biphenyls (PCBs): The Michigan and North Carolina cohort studies. Toxicol Industrial Health 1996; 12: 435-445. MEDLINE
Jacobson JL, Jacobson SW: Intellectual impairment in children exposed to poly-chlorinated biphenyls in utero. N Engl J Med 1996; 335: 783-789. MEDLINE
Jacobson JL, Jacobson SW: Postnatal exposure to PCBs and childhood development. Lancet 2001; 358: 1568-1569. MEDLINE
Jensen AA: Polychlorobiphenyls (PCBs), polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) in human milk, blood and adipose tissue. Sci Total Environ 1987; 64: 259-293. MEDLINE
Jensen S: Report of a new chemical hazard. New Sci 1966; 32: 612-623.
Kappos AD, Schümann A, Angerer J: Reference values ​​for the PCB congeners No. 138, 153 and 180 and their sum in human blood. Umweltmed Forsch Prax 1998; 3: 135-143.
Kimbrough RD: Polychlorinated biphenyls (PCBs) and human health: An update. CRC Crit Rev Toxicol 1995; 25: 133-163. MEDLINE
Koppe JG, Olie K, Wijnen van J: Placental transport of dioxins from mother to fetus. II. PCBs, dioxins and furans and vitamin K metabolism. Dev Pharmacol Ther 1992; 18: 9-13. MEDLINE
Koss G: Polychlorinated Biphenyls (PCB). In: Marquardt H, Schäfer SG, Hrsg .: Textbook of Toxicology. Heidelberg: Spektrum Akademischer Verlag 1997: 416-434.
Lackmann GM, Göen T, Töllner U, Schaller KH, Angerer J. PCBs and HCB in serum of full-term German neonates. Lancet 1996; 348: 1035. MEDLINE
Lackmann GM, Angerer J, Salzberger U, Töllner U: Influence of maternal age and duration of pregnancy on serum concentrations of polychlorinated biphenyls and hexachlorobenzene in full-term neonates. Biol Neonate 1999; 76: 214-219. MEDLINE
Lackmann GM, Salzberger U, Töllner U, Chen M, Carmella SG, Hecht SS: Metabolites of a tobacco-specific carcinogen in the urine of newborns. J Natl Cancer Inst USA 1999; 91: 459-465. MEDLINE
Lackmann GM, Salzberger U, Hecht SS, Töllner U: Smoking during pregnancy: New findings on the influence on the fetus and the newborn child. Dtsch Arztebl 1999; 96: A 2080-2083 [booklet 33]. FULL TEXT
Lackmann GM, Angerer J, Töllner U: Parental smoking and neonatal serum levels of polychlorinated biphenyls and hexachlorobenzene. Pediatr Res 2000; 47: 598-601. MEDLINE
Lackmann GM, Angerer J, Salzberger U, Schaller KH, Töllner U, Lenard HG: Prenatal exposure to organochlorine compounds: Comparative study in a rural small town area and a metropolitan area in Germany. Monthly Children's Health 2001; 149: 283-287.
Lackmann GM: Prenatal, transplacental transmission of polychlorinated biphenyls and hexachlorobenzene in humans. Part I: Background and current state of research. Umweltmed Forsch Prax 2001; 6: 87-96.
Lackmann GM: Prenatal, transplacental transmission of polychlorinated biphenyls and hexachlorobenzene in humans. Part II: Development of neonatal pollution in Germany over the past 15 years. Umweltmed Forsch Prax 2001; 6: 165-171.
Lackmann GM: Prenatal, transplacental transmission of polychlorinated biphenyls and hexachlorobenzene in humans. Part III: Personal influencing factors (gestational age, birth weight, maternal age, parents' tobacco consumption) and geographical differences. Umweltmed Forsch Prax 2001; 6: 275-285.
Lackmann GM: Polychlorinated biphenyls and hexachlorobenzene in full-term neonates - Reference values ​​updated. Biol Neonate 2002; 81: 82-85. MEDLINE
Lackmann GM: Effect of polychlorinated biphenyls on psychodevelopment. Lancet 2002: 359: 1437-1438. MEDLINE
Landrigan PJ: Pesticides and polychlorinated biphenyls: An analysis of the evidence that they impair children's neurobehavioral development. Mol Genet Metabol 2001; 73: 11-17. MEDLINE
Lanting CI, Huisman M, Muskiet FAJ, Paauw van der CG, Essed CE, Boersma ER: Polychlorinated biphenyls in adipose tissue, liver, and brain from nine still-borns of varying gestational ages. Pediatr Res 1998; 44: 222-225. MEDLINE
Lehnert G, Angerer J, Göen T, Schaller KH: Reference values ​​for persistent hazardous substances using the example of the concentrations of polychlorinated biphenyls in human serum. Arbeitsmed Sozialmed Umweltmed 1994; 29: 454-458.
Restum JC, Bursian SJ, Giesy JP et al .: Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginow Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit growth and survival, and selected biological parameters. J Toxicol Environ Health 1998; 54: 343-375. MEDLINE
Rylander L, Strömberg U, Hagmar L: Decreased birthweight among infants born to women with a high dietary intake of fish contaminated with persistent organochlorine compounds. Scand J Work Environ Health 1995; 21: 368-375. MEDLINE
Stewart P, Darvill T, Lonky E, Reihman J, Pagano J, Bush B: Assessment of prenatal exposure to PCBs from maternal consumption of Great Lakes fish: An analysis of PCB pattern and concentration. Environ Res 1999; 80: S87-S96. MEDLINE
Summer CL, Giesy JP, Bursian SJ et al .: Effects induced by feeding organochlorine-contaminated carp from Saginaw Bay, Lake Huron, to laying white leghorn hens. II. Embryotoxic and teratogenic effects. J Toxicol Environ Health 1996; 49: 409-438. MEDLINE
Teufel M, Niessen KH, Sartoris J et al .: Chlorinated hydrocarbons in fat tissue: Analyzes of residues in healthy children, tumor patients, and malformed children. Arch Environ Contam Toxicol 1990; 19: 646-652. MEDLINE
Teufel M: Significance of environmental pollution with polychlorinated biphenyls in childhood. Pediatrician 1997; 28: 1360-1368.
Teufel M: PCB exposure of children in East and West Germany. Klin Pediatr 1992; 204: 348-354. MEDLINE
Federal Environment Agency (Commission “Human Biomonitoring”). Reference values ​​for the PCB congeners No. 138, 153 and 180 and their sum in human blood. Bundesgesundhbl 1998; 41: 416-428.
Federal Environment Agency (Human Biomonitoring Commission). Substance monograph PCB - reference values ​​for blood. Bundesgesundhbl 1999; 42: 511-521.
Ordinance on the prohibition of polychlorinated biphenyls, polychlorinated terphenyls and the restriction of vinyl chloride (PCB, PCT and VC prohibition ordinance) of July 18, 1989. BGBI Part I. 1989: 1482.
Walkowiak J, Wiener JA, Fastabend A et al .: Environmental exposure to polychlorinated biphenyls and quality of the home environment: Effects on psychodevelopment in early childhood. Lancet 2001; 358: 1602-1607. MEDLINE
Winneke G, Bucholski A, Heinzow B et al. Developmental neurotoxicity of poly-chlorinated biphenyls (PCBs): Cognitive and psychomotor functions in 7-month old children. Toxicol Lett 1998; 102-103: 423-428. MEDLINE
Wuthe J, Piechotowski I, Päpke O et al .: First data on background levels of non-ortho and mono-ortho PCBs in blood of residents from southern Germany. Chemosphere 1996; 32: 567-574. MEDLINE
Yu ML, Hsu CC, Gladen BC, Rogan WJ: In utero PCB / PCDF exposure: Relation of developmental delay to dysmorphology and dose. Neurotoxicol Teratol 1991; 13: 195-202. MEDLINE
Ziegler EE, O'Donnell AM, Nelson SE et al .: Body composition of the reference fetus. Growth 1976; 40: 329-341. MEDLINE
1. Akiyama K, Ohi G, Fujitani K, Yagyu H, Ogino M, Kawana T: Polychlorinated biphenyl residues in maternal and cord blood in Tokyo metropolitan area. Bull Environ Contam Toxicol 1975; 14: 588-592. MEDLINE
2. American Council on Science and Health - Position paper: Public health concerns about environmental polychlorinated biphenyls (PCBs). Exotoxicol Environ Saf 1997; 38: 71-84. MEDLINE
3. Angerer J, Göen T, Schaller KH, Lackmann GM, Töllner U: Prenatal exposure to polychlorinated biphenyls and hexachlorobenzene: A comparison of the values ​​from 1984/85 and 1994/95. Umweltmed Forsch Prax 1996; 1: 78-82.
4. Beebe LE, Kim YE, Amin S, Riggs CW, Kovatch RM, Anderson LM: Comparison of transplacental and neonatal initiation of mouse lung and liver tumors by N-ni-trosodimethylamine (NDMA) and 4- (methylnitrosamino) -1- (3 -pyridyl) -1-buta-none (NNK) and promotability by a polychlorinated biphenyls mixture (Aroclor 1254). Carcinogenesis 1993; 14: 1545-1548. MEDLINE
5.