Teratogens ethanol

Following the development of the test, an in-house validation was conducted to evaluate the performance of FETAX compared to the results in the rat and/or rabbit. Thirteen reference chemicals were tested including eight compounds known to be teratogenic in rats and/or rabbits (caffeine, retinoic acid, hydroxyurea, ethanol, cyclophosphamide, nicotine, acetylsalicylic acid, dexametha-sone) and five non-teratogens (isoniazid, saccharin, paracetamol, penicillin G, sildenafil). The estimation of teratogenicity in rats and rabbits was based on published data (9). 

For some agents for example valproic acid and ethanol, a threshold concentration must be reached before teratogenicity is induced and the effect is therefore related to the maximum plasma concentration For others such as retinoids and cyclophos-... 

A few comments Beyond water, ethanol is perhaps the most commonly used solvent in chemistry. It has also been used extensively in some countries as fuel. As a result, its presence in the environment, aquatic and atmospheric, is increased. Ethanol in great doses has been recognized as a human teratogen, well before experimental studies in animals were undertaken. However, the consumption of alcohol via drinks and beverages covers any adverse effects due to ethanol s presence in the environment. 

The mechanisms that underlie ethanol s teratogenic effects are unknown. Ethanol rapidly crosses the placenta and reaches concentrations in the fetus that are similar to those in maternal blood. The fetal liver has little or no alcohol dehydrogenase activity, so the fetus must rely on maternal and placental enzymes for elimination of alcohol. 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

Nowhere are the effects of the permeability of the placental membrane more graphic than in the incidence of fetal alcohol syndrome (FAS) in the children of alcoholic mothers. FAS produces distinctive anatomical features and mental retardation. Ethanol is called a teratogen because it causes genetic malfunction. Recall that thalidomide was a teratogen. 

Noxious substances inhaled when smoking, caffeine absorbed from coffee or other drinks, ethanol-uptake from alcoholic drinks are examples of potentially neurobehavioral teratogens absorbed by pregnant women as part of everyday social life patterns. 

Effects of low doses of alcohol are considered to be not as dramatic as those of heavy drinking. The occurrence of teratogenic effects decreases when addicted women cut down on alcohol intake or stop drinking altogether after the first trimester (refs. 51, 52). However, McLeod et al. (ref. 60)) found a disappearance followed by a decreased level of fetal breathing movements for 3 hours after the intake of a low dose of alcohol (0.25 g/kg). Therefore, if these movements have a function in the development of the fetus, regular social drinking may have some noxious effects as well. In addition, rat studies have shown that postnatal ethanol treatment can still cause... 

One clear example of a known teratogen for which warning can be effective is ethanol, but warnings alone are not the whole story. Alcohol consumption... 

Very many chemicals are recognized teratogens in animals a significantly smaller subset of these is known or suspected to be developmental neurotoxicants in humans. Some of the more significant of the latter group include ethanol, which causes a constellation of effects ranging from fetal alcohol syndrome to alcohol-related neurodevelopmental disorder maternal smoking of tobacco (fetal tobacco syndrome) excess vitamins A and D heavy metals, particularly... 

In addition to phocomelias, other teratogenic effects include eye and ear abnormalities, esophageal and duodenal atresias, and defects in internal organs such as the heart and kidneys. Congenital defects of the kidneys and nervous system may persist throughout life. Very large doses taken with ethanol have been associated with transient hypotension. Bradycardia has been rarely reported with therapeutic use. Acute toxicity appears infrequent. 

Nelson BK, Conover DL, Brightwell WS, et al. Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxy-ethanol and radiofrequency radiation in rats. Teratology 1991 43(6) 621 34. 

Some single organic solvents, for example, toluene, xylene, and ethanol, are known teratogens. Regretfully, many of the studies in the literature lump all organic solvent exposures together and fail to identify the specific... 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

Mixtures of ethanol with other toxic chemicals produce unanticipated effects with greater teratogenic effects than ethanol or its mixture partners alone. The following study illustrates this phenomenon. 

Ethanol is a teratogen partly because it inhibits embryonic cellular proliferation. Maternal alcoholism causes fetal alcohol syndrome, which is characterized by abnormal function of the central nervous system, microcephaly, cleft palate, and micrognathia. 

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