Transplacental transfer

Mutagenicity, carcinogenicity and teratogenicity are discussed in detail in Part II, Chapter 9. 

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There are very limited data on the kinetics and metabolism of organotins in laboratory mammals. A widespread distribution of organotins throughout body tissues has been observed. Transplacental transfer seems to occur, whereas transfer across the blood-brain barrier is limited, since brain levels are usually low. The only compound for which data are available on metabolites is dibutyltin, which has butyl(3-hydroxybutyl)tin as its major metabolite. Limited information suggests quite rapid metabolism and elimination, with half-lives of several days. Much of an oral dose of dioctyltin was eliminated in the faeces, with the remainder in urine. 

Information on the transplacental transfer of americium in humans is not available directly, but the information from experiments with americium and other actinides has been used to derive biokinetic models and perform dosimetric models for the human (NCRP 1998 NRC 1996 Sikov and Kelman 1989). Studies in animals that received parenteral injections of americium have shown that absorbed americium is transferred to the fetus (Hisamatsu and Takizawa 1983 Paquet et al. 1998 Sasser at al. 1986 Schoeters et al. 1990 Weiss et al. 1980) (see Section 3.4.2.1). Limited reports indicate that241 Am may induce fetal death and teratogenic effects in rodents (Moskalev et al. 1969 Rommerein and Sikov 1986). 

Information on the transplacental transfer of americium in humans is not available. Studies in animals that received parenteral injections of americium have shown that absorbed americium is transferred to the fetus (Hisamatsu and Takizawa 1983 Paquet et al. 1998 Sasser at al. 1986 Schoeters et al. 1990 Weiss et al. 1980). 

Transplacental transfer of lead in humans has been demonstrated in a number of studies, and lead has been identified in umbilical cord blood. In the work of Bellinger et al. (1987a), the mean lead concentration in umbilical cord blood from a sample size of 11,000 women was 6.6 3.2 pg/dL. In a study of 236 pregnant women in Glasgow, Scotland, the geometric mean PbB levels were 14 pg/dL for... 

Finnegan LP (1979). Pathophysiological and behavioural effects of the transplacental transfer of narcotic drugs to the foetuses and neonates of narcotic-dependent mothers. United Nations Office on Drugs and Crime. Available at http //www.unodc.org/unodc/en/ bulletin/bulletin 1979-01-01 3 page002.html n05... 

Ingebrigtsen, K., I. Nafstad, and R.A. Andersen. 1984. Distribution and transplacental transfer of paraquat in rats and guinea-pigs. Gen. Pharmacol. 15 201-204. 

S irenians are characterized by hemochorial placentation, a model which favors a more important role for transplacental transfer of immunoglobulins, and less via colostrum. 

Yorty, J.L. and Bonneau, R.H., Transplacental transfer and subsequent neonate utilization of herpes simplex virus-specific immunity are resilient to acute maternal stress, J. Virol., 77, 6613, 2003. 

T. Heikkinen, U. Ekblad, and K. Laine. Transplacental transfer of amitriptyline and nortriptyline in isolated perfused human placenta. Psychopharmacology (Berl). 153 450-454 (2001). 

D.W. Fowler, M.J. Eadie, and R.G. Dickinson. Transplacental transfer and biotransformation studies of valproic acid and its glucuronide(s) in the perfused human placenta. J Pharmacol Exp Ther. 249 318-323 (1989). 

Heptachlor epoxide was measured in a strip of skin, fat, and subcutaneous tissue from 68 children who died in the perinatal period and ranged from not detected (nondetectable) to 0.563 ppm (mean 0.173) (Zavon et al. 1969). In 10 other stillborn infants, heptachlor epoxide levels measured in various tissues were as follows brain (nondetectable), lung (0.17 0.07 ppm), adipose (0.32 0.10 ppm), spleen (0.35 0.08 ppm), liver (0.68 0.50 ppm), kidney (0.70 0.28 ppm), adrenal (0.73 0.27 ppm), and heart (0.80 0.30 ppm) (Curley et al. 1969). In another study, the following heptachlor epoxide levels were measured in extracted lipids from mothers and newborn infants maternal adipose tissue (0.28 0.31 ppm), maternal blood (0.28 0.46 ppm), uterine muscle (0.49 0.51 ppm), fetal blood (1.00 0.95 ppm), placenta (0.50 0.40 ppm), and amniotic fluid (0.67 1.16 ppm) (Polishuk et al. 1977a). These data provide evidence of transplacental transfer to the fetus. 

In two three-generation studies with rats administered heptachlor, heptachlor epoxide, or a mixture of the two in the diet, the number of resorbed fetuses increased and the fertility decreased with succeeding generations. No adverse effects on reproductive capacity were reported in male mice receiving single oral doses of 7.5 or 15mg/kg heptachlor heptachlor epoxide (25% 75%) in a dominant lethal assay. Heptachlor epoxide has been found in tissues of stillborn infants, indicating transplacental transfer. ... 

Facilitated diffusion is a carrier-mediated mechanism of transplacental transfer. It is important for endogenous substances, such as glucose. It is also the mechanism for some drugs, e.g. the antibiotic cefalexin. Active transport is a carrier-mediated process that requires energy against an electrochemical or concentration gradient. Amino acids and calcium are transported by this mechanism. Only a few drugs, such as a-methyidopa and 5-fluorouracil, are transferred by active transport. 

No studies were located regarding distribution in humans after dermal exposure to aluminum or its compounds. Elevated levels of aluminum have been observed in the liver, brain, lung, and kidneys of Swiss mice dermally exposed to 0.4 g/day aluminum chloride (0.04 g Al/day) for 20 days during gestation (Anane et al. 1997). Elevated levels of aluminum were also observed in the fetus, providing evidence of transplacental transfer of aluminum. 

Schecter A, P pke O, Ball M. 1990a. Evidence for transplacental transfer of dioxins from mother to fetus Chlorinated dioxinal dibenzofuran levels in the livers of stillborn infants. Chemosphere 21 1017-1022. 

As detailed in Section 3.2.2.6 Developmental Effects, DEHP and/or metabolites administered during gestation can induce increased incidences of resorptions, fetal deaths and malformations in rats and mice (Hellwig et al. 1997 Ritter et al. 1987 Shiota and Mima 1985 Tomita et al. 1982a Tyl et al. 1988 Yagi et al. 1980). While this might be interpreted as evidence of transplacental transfer of these substances, the possibility that the effects result from toxicity to the dams cannot be ruled out. 

Route of exposure is defined as the portal of entry to the body. Pathway is defined as the course that the contaminant takes from its source to the exposure medium, and then to the portal of entry. For a given source, exposure media and exposure routes can define the pathways. Depending upon the life stage of the child, exposure media can include amniotic fluid, breast milk, air, water, soil/dust/ sediments, food, and objects/surfaces. Exposure routes include transplacental transfer, inhalation, ingestion, dermal absorption, and indirect (non-dietary) ingestion. 

Denning DW, Allen R, Wilkinson AP, Morgan MR (1990) Transplacental transfer of aflatoxin in humans. Carcinogenesis, 11(6) 1033-1035. 

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