Developmental toxicity structural abnormalities

As part of the assessment of reproductive toxicity testing there is a regulatory requirement that fetuses from treated dams are examined for developmental and structural abnormalities by soft tissue examination. Current guidelines (1, 2) stipulate that this is performed in two laboratory species, one rodent (rat or mouse) and one non-rodent (routinely rabbit), in order to assess the safety of a test compound before, or in case, humans are exposed. 

Toxicologists nowadays take a broad view of developmental toxicity they consider not only structural but also functional abnormalities to qualify as adverse, as long as they were produced as a result of exposures incurred in utero. Thus, for example, the developmental effects of chronic alcohol abuse by pregnant women, known as fetal alcohol syndrome (FAS), are characterized not only by the presence of certain craniofacial abnormalities, but also by a variety of disabilities such as shortened attention span, speech disorders, and restlessness. Although fully expressed physical deformities included in FAS are associated with heavy drinking, debate continues on the level of alcohol consumption, if any, that is without these more subtle effects on behavior. 

It is critical that the examiner is familiar with the normal appearance of skeletal structures including the variants which are typical for the strain or breed of animals that is being used. Therefore, a good historical database of spontaneous abnormalities which occur in the strain of animals used is essential for a proper assessment of skeletal abnormalities observed in a prenatal developmental toxicity study. 

Developmental toxicity, defined in its widest sense to include any adverse effect on normal development either before or after birth, has become of increasing concern in recent years. Developmental toxicity can result from exposure of either parent prior to conception, from exposure of the embryo or fetus in utero or from exposure of the progeny after birth. Adverse developmental effects may be detected at any point in the life span of the organism. In addition to structural abnormalities, examples of manifestations of developmental toxicity include fetal loss, altered growth, functional defects, latent onset of adult disease, early reproductive senescence and shortened life span. 

Results from animal studies indicate that in utero exposure to PBBs and exposure to PBBs through mothers milk can produce embryolethal effects, structural abnormalities, growth retardation, liver effects, and neurological effects in offspring. Developmental toxicity has been observed in studies with hexabromobiphenyl and octabromobiphenyl commercial mixtures, but not with commercial... 

Developmental toxicity includes any detrimental effect produced by exposures during embryonic development, and the effect may be temporary or overt physical malformation. Adverse effects include death, structural abnormalities, altered growth, and... 

It is assumed that all four manifestations of developmental toxicity (death, structural abnormalities, growth alterations, and functional deficits) are of concern. 

Developmental toxicity Adverse effects on the developing organism. Adverse developmental effects may be detected at any point in the life span of the organism. Major manifestations of developmental toxicity include death of the developing embryo, induction of structural abnormalities (teratogenicity), altered growth, and functional deficiency. 

SAFETY PROFILE A poison by intravenous and subcutaneous routes. Moderately toxic by ingestion and intraperitoneal routes. Human teratogenic effects by an unspecified route developmental abnormalities of the central nervous system effects on embryo or fetus fetal death, extra embryonic structures. Human reproductive effects by an unspecified route stillbirth. An experimental teratogen. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and irritating fumes. 

Maternal cocaine use can affect reproduction by adversely affecting the pregnancy. In addition, cocaine use may directly injure the fetus and/or produce behavioral and developmental abnormalities in the neonate. Indirect toxicities of cocaine abuse may result in severe health consequences including child neglect and abuse, loss of family structure, an increased risk of AIDS, and congenitally acquired sexually transmitted diseases (Benowitz 1992). A study of data from 72 U.S. Poison Control Centers in 1990 that analyzed 1.7 million... 

Mutagenic carcinogenicity unknown caused birth defect and developmental abnormalities in blood and lymphatic systems in rats low toxicity in animals in humans, ingestion may cause paresthesias and affect the teeth and supporting structure LD50 oral (mice) 12,750 mg/kg. 

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