Kidney malformations

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. 

Patients exhibit a broad spectrum of abnormalities, including liver and kidney dysfunction with hepatomegaly, high levels of copper and iron in the blood, severe neurologic defects, and skeletal malformations. 

There have been attempts to use nonhuman primates as tissue and organ donors. In the 1960s, several surgeons transplanted kidneys from baboons or chimps into humans, and the patients survived only a few months. Born with a malformed heart. Baby Fae received a baboon heart transplant in 1984. The procedure, her... 

B9 19 175 2 10.5 2 1.1 1 Malpositioned kidney 2 Malformed vertebral colmrm, spina bifida... 

F9 20 187 2 10.0 2 1.1 1 Dilated kidney, malpositioned kidney, gastroschisis, acaudia, malrotated hindlimbs, malformed caudal vertebrae 2 Dilated aortic arch... 

K9 18 146 2 11.1 2 1.4 1 Aortic arch fused 2 Malpositoned subclavian artery, small lungs, malformed kidney, marked dilated ureters... 

Mitochondrial disorders are not commonly regarded as causes of malformations. Facial features included round face, high forehead, small nose, and long flat philtrum, reminiscent of the fetal alcohol syndrome. Limb and trunk involvements included short hands, brachydactyly, hypoplasia of the distal and middle phalanges, hypoplastic nails, and the VACTERL [vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal (kidney) and/or radial anomalies, and preaxial limb anomalies (in front of or above the central axis of the limb)] association [50]. 

Prolonged contact between toluene and human skin may cause nonallergic contact dermatitis. Human exposure to toluene also causes nervous system symptoms and signs and excessive exposure may cause adverse effects on the kidney and liver. Adverse effects on the nervous system have been observed in experimental animals. In studies of spontaneous abortion, perinatal mortality and congenital malformations in humans, the numbers of cases were small and the mothers had also been exposed to other substances. Embryotoxicity that generally occurs concurrently with maternal toxicity has been seen in some studies in mice and rats but not rabbits (lARC, 1989a). 

Vitamin D3 is a precursor of the hormone 1,25-dihy-droxyvitamin D3. Vitamin D3 is essential for normal calcium and phosphorus metabolism. It is formed from 7-dehydrocholesterol by ultraviolet photolysis in the skin. Insufficient exposure to sunlight and absence of vitamin D3 in the diet leads to rickets, a condition characterized by weak, malformed bones. Vitamin D3 is inactive, but it is converted into an active compound by two hydroxylation reactions that occur in different organs. The first hydroxylation occurs in the liver, which produces 25-hydroxyvita-min D3, abbreviated 25(OH)D3 the second hydroxylation occurs in the kidney and gives rise to the active product 1,25-dihydroxy vitamin D3 24,25 (OH)2D3 (fig. 24.13). The hydroxylation at position 1 that occurs in the kidney is stimulated by parathyroid hormone (PTH), which is secreted from the parathyroid gland in response to low circulating levels of calcium. In the presence of adequate calcium, 25(OH)D3 is converted into an inactive metabolite, 24,25 (OH)2D3. The active derivative of vitamin D3 is considered a hormone because it is transported from the kidneys to target cells, where it binds to nuclear receptors that are analogous to those of typical steroid hormones. l,25(OH)2D3 stimulates calcium transport by intestinal cells and increases calcium uptake by osteoblasts (precursors of bone cells). 

The observed growth deficiencies are associated with an inability of the baby to catch up due to a slower than normal rate of development. Other infrequent outcomes include skeletal malformations such as deformed ribs and sternum, scoliosis, malformed digits, and microcephaly. Distinctive facial anomalies have been associated with a diagnosis of fetal alcohol syndrome small eye openings, epicanthal folds, failure of eyes to move in the same direction, short upturned nose, flat or absent groove between nose and upper lip, and thin upper lip. Visceral deformities may also be present heart defects, genital malformations, kidney, and urinary defects. 

The dipyridyl-based contact herbicides (Diquat, Paraquat) exhibit antifertility effects on spermatocytes and cause fetal malformations. In addition these compounds are severely damaging to lungs, kidneys, liver, heart and/or QI tract, and can be permanently disabling when not lethal. 

A number of developmental effects have been observed in animals acutely exposed to 2,3,7,8-TCDD by the oral route. The types of effects observed in the offspring of animals exposed to 2,3,7,8-TCDD include structural malformations-cleft palate and kidney anomalies, functional alterations-damage to the immune system and impaired development of the reproductive system, decreased growth, and fetal/newbom mortality. 

In rabbits, malformations were found with doses of 5 mg/kg/day, 150 mg/kg/day, and 500 mg/day, given between the seventh and eleventh days of pregnancy. There were abnormaUties of the extremities, skull, nose, and palate, as well as malformations of the kidneys. There seemed to be an increase in frequency with higher doses (173). 

Cerivastatin caused a significant increase in incomplete ossification of the lumbar center of the vertebrae in rats at an oral dose of 0.72 mg kg Cerivastatin did not cause any anomalies or malformations in rabbits at oral doses up to 0.7 mg kg These doses resulted in plasma levels about six times the human exposure (Cmax free) for rats and three times the human exposure for rabbits (Cmax free) at a human dose of 0.8 mg. Cerivastatin crossed the placenta and was found in fetal liver, gastrointestinal tract, and kidneys when pregnant rats were given a single oral dose of 2 mg kg... 

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