Lead teratogenicity

Levine, F., Muenke, M., 1991. VACTERL association with high prenatal lead exposure similarities to animal models of lead teratogenicity. Pediatrics 87, 390—392. 

The effects of a teratogen on a fetus depend on the timing of the exposure, i.e., at which stage of organogenesis the exposure takes place. Exposure to a teratogen before implantation usually leads to death and abortion of the fetus. How-... 

FAS is normally characterized by growth retardation, anomalies of the head and face, and psychomotor dysfunctions. Excessive consumption of ethyl alcohol may lead to malformations of the heart, extremities, and kidneys. Since consumption of ethyl alcohol is socially acceptable and prevalent even in pregnant women, the risks associated with the use of ethyl alcohol are remarkable. However, it should be kept in mind that there are several chemical compounds in tlie occupational environment that may also cause malformations even at low doses. The oc-cupationally-important known human teratogens include methyl mercury, ethyl alcohol, PCB compounds, tobacco smoke, lead, TCDD, 2,4,5- F, carbon monoxide, nitrogen dioxide, gasoline, and fluoride. 

Women of reproductive potential prescribed efavirenz should be counseled on its potentially teratogenic effects and the importance of birth control. Additionally, nevirapine, nelfinavir, ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir have been shown to decrease the concentrations of estrogens and/or progestins in oral contraceptives, which could lead to failure.2 For patients prescribed these drugs, barrier forms of contraception are preferred to prevent pregnancy. DepoProvera may be... 

Teratogen Any substance that leads to structural or functional abnormality in the fetus, including death. 

The data from the only available animal study (Prigge and Greve 1977) indicate that inhaled lead is not teratogenic. However, it impaired heme synthesis in both rat dams and fetuses. In this study, dams were exposed to 1, 3, or 10 mg lead/m3 (chemical species not provided) throughout gestation (days 1-21). Maternal and fetal ALAD were inhibited at all exposure levels in a dose-related manner, and fetal (but not maternal) hematocrit and body weight were decreased at the 10-mg/m3 lead level. These results suggest that the fetuses were more sensitive to lead-induced toxicity than were the dams. 

Twenty-three teratogenicity studies in which lead compounds (acetate or nitrate) were administered in the drinking water or feed or by gavage to rats and mice have shown no evidence that lead causes... 

Developmental Effects. Evidence from human studies on congenital anomalies as an end point (Emhart et al. 1985, 1986 McMichael et al. 1986 Needleman et al. 1984) indicate no association between prenatal exposure to low levels of lead and the occurrence of major congenital anomalies. This conclusion is further supported by developmental toxicity studies conducted in rats and mice these studies provide no evidence that lead compounds (acetate or nitrate) are teratogenic when exposure is by natural routes (i.e., inhalation, oral, dermal). Intravenous or intraperitoneal injection of lead compounds (acetate, chloride, or nitrate) into pregnant rats, mice, or hamsters, however, has produced malformations in several studies reviewed by EPA (1986a). 

Carpenter SJ. 1982. Enhanced teratogenicity of orally administered lead in hamsters fed diets deficient in calcium or iron. Toxicology 24 259-271. 

Kennedy GL, Arnold DW, Calandra JC. 1975. Teratogenic evaluation of lead compounds in mice and rats. Food Cosmet Toxicol 13 629-632. 

Needleman HL. 1988. The neurotoxic, teratogenic, and behavioral teratogenic effects of lead at low dose A paradigm for transplacental toxicants. Prog Clin Biol Res 281 279-287. 

The ability to form carbon—carbon bonds in a controlled manner around an alkene is the subject of continuing intense research [49,134—136], These compounds are stable and, due to the considerably different reactivities of the C—Zr and C—B bonds, allow for selective and sequential reactions with a variety of electrophiles. Temarotene 58 is a retinoid of interest [137] because it shows no sign of hypervitaminosis A and it is not teratogenic, presumably due to the lack of a polar group [138,139], The published synthesis of temarotene-type compounds is long and leads to mixtures of diastereo-isomers, from which the desired product is eventually isolated [140—142], However, the synthesis of temarotene 58 by the method of Srebnik et al. [130] is straightforward, as outlined in Scheme 7.18. 

Most cases of mercury poisoning led to handicap, chronic disease, or death. The most frequent symptoms include numbness of limbs, lips and tongue, speech abnormalities, limb function disorders, visual acuity disorders, deafness, and muscular atrophy. Insomnia, hyperactivity, and coma have also been reported. Methylmercury penetrates the blood-brain barrier and causes central nervous system injuries. Mercury also has a teratogenic effect, leading to congenital abnormalities or congenital Minamata disease. 

High concentrations of vitamin A in pregnancy tend to be teratogenic leading to birth defects. Hence vitamin A is contraindicated in pregnancy. 

The activity of vitamin A is related to vision process, tissue differentiation, growth, reproduction, and the immune system. A deficiency of this micronutrient mainly leads to visual problems, impaired immune function, and growth retardation in children. Hypervitaminosis could lead to hepatotoxicity, affect bone metabolism, disrupt lipid metabolism, and teratogenicity [417]. The isomerization of P-carotene, due to technological processes in foods, leads to a reduction of the vitamin A activity it is therefore important to analyze it. 

In Europe, the developmental toxicity testing (including teratogenicity) of new cosmetic ingredients is performed according to the Cosmetics Directive 76/768/EEC only alternatives leading to full replacement of animal experiments should be used. This chapter presents the three scientifically validated animal alternative methods for the assessment of embryotoxicity the embryonic stem cell test (EST), the micromass (MM) assay, and the whole embryo culture (WEC) assay. 

Right now, in Europe, there are three validated in vitro assays aimed at evaluating embryotoxicity (teratogenicity) potential. Three of these assays were submitted to extensive intra- and interlaboratory validations lead by the European Center for Validation of Alternative Methods (ECVAM) (3) ... 

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