Malformation

In laboratory tests, appHcation of DMAC to the skin of pregnant rats has caused fetal deaths when the dosages were close to the lethal dose level for the mother. Embryonal malformations have been observed at dose levels 20% of the lethal dose and higher. However, when male and female rats were exposed to mean DMAC concentrations of 31,101, and 291 ppm for 6 h per day over several weeks, no reproductive effects were observed (6). 

The incidence of congenital malformations such as cryptorchidism (undescended testes) and hypospadias (malformation of the penis) may have increased, but... 

World Health Organization, Congenital Malformations Worldwide A Reportfrom the International Clearinghouse for Birth Defects Monitoring Systems, Elsevier, Oxford, 1991, p. 113. 

Amphibians. Amphibians are highly susceptible to endocrine disruption during development of the larval form and during metamorphosis. The action of metamorphosis is triggered and controlled by the thyroid gland via an increase in triiodothyronine and a decrease in thyroxine, and differs greatly between oviparous and viviparous species. Experimentally, it has been shown that disruption during this sensitive period can lead to malformations and adverse impacts on immune and reproductive functions. 

In order to discuss the biological mechanisms involved in the aetiology of genital tract malformations, testicular cancer and lowered sperm counts, some knowledge of the processes involved in the differentiation and development of the male reproductive tract and determination of normal testicular function is required. An early embryo has the potential to develop either a male or a female... 

The first known incidence of pollution from approved herbicides was identified in 1972 in Essex, where tomato plants grown by commercial producers became malformed. The plants had been watered from public water supplies fed from a reservoir. The reservoir in turn abstracted water from a river supplemented by a water transfer scheme, from the River Cam in Cambridgeshire. Pollution from a factory manufacturing 2,3,6-TBA was identified as the cause and the problem was subsequently resolved by treating the effluent. 

In addition to direct effects of chemical compounds on the fetus, metabolic disturbances in the mother, such as diabetes or hyperthermia, or deficiencies of calories or specific nutrients such as vitamin A, zinc, and folic acid may lead to teratogenesis. Compounds that inhibit placental functions may also induce malformations, e.g., by inhibiting placental circulation. For example, hydroxyurea disrupts the placental circulation and induces malformations. In addition, it also induces DNA damage. 

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. 

Mi sbildung,/. malformation deformity, missbilligen, v.t. disapprove of, oppose. Missbrauch, m. misuse, abuse, missen, v.t. miss dispense with. 

Mice homozygous for an ETA receptor gene disruption show craniofacial malformations, such as cleft palate, micrognathia, microtia and microglossia. ETA (—/—) mice die shortly after birth due to respiratory failure. Mice with an ET-l-null mutation show the same cranciofacial malformations and, in addition, cardiovascular disorders (e.g. septal defects, abnormal cardial outflow tract, aortic arch and subclavian arteries). 

LRP2/ megalin Loss-of-function (familial, autosomal recessive) Donnai-Barrow syndrome (brain malformation, renal tubular deficiency, diaphragmatic hernia)... 

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

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