Human teratogen

More than 900 teratogens have been identified in experimental animals. However, only about 30 human teratogens have been identified. Human teratogens have been listed in Table 5.20. In this section, some of the best-known Teratogenic compounds are briefly described. 

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. 

Known to be a human teratogen based on clear evidence from human data,... 

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. 

A single dose of nevirapine (200 mg) is effective in the prevention of transmission of HIV from mother to newborn when administered to women at the onset of labor and followed by a 2-mg/kg oral dose to the neonate within 3 days after delivery. There is no evidence of human teratogenicity. However, resistance has been documented after this single dose. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

Saquinavir is subject to extensive first-pass metabolism by CYP3A4 and functions as a CYP3A4 inhibitor as well as a substrate thus, there are many potential drug-drug interactions (Table 49-4). A decreased dose of saquinavir is recommended when -administered with nelfinavir. Increased saquinavir levels when -administered with omeprazole necessitate close monitoring for toxicities. Digoxin levels may increase if co administered with saquinavir and should therefore be monitored. Liver function tests should be monitored if saquinavir is -administered with delavirdine or rifampin. There is no evidence of human teratogenicity from saquinavir there is short-term safety data for both mother and infant. 

The widely cited FDA system for teratogenic potential (Table 59-2) is an attempt to quantify teratogenic risk from A (safe) to X (definite human teratogenic risk). This system has been criticized as inaccurate and impractical. For example, several drugs have been labeled "X" despite extensive opposite human safety data (eg, oral... 

Despite the great interest in and notoriety of thalidomide as a teratogen, the underlying mechanisms of its teratogenicity are still not clear. It is, however, of particular interest in being a well-established human teratogen. 

This is a sedative drug with low adult toxicity, which proved to be a very potent human teratogen, causing phocomelia (shortening of the limbs) and other defects when taken between the third and eighth week. In some cases, only a few doses were taken, but on the critical days (e.g., days 24-27 for phocomelia of arms). It is not readily reproducible in laboratory animals (e.g., rats). Mechanism is unknown, but a metabolite suspected, possibly produced by cytochrome P-450. A number of metabolites are produced and some chemical breakdown occurs. Phthalylglutamic acid metabolite is teratogenic in mice. Thalidomide may acylate nucleic acids and polyamines. The S-enantiomer is more embryotoxic than the R-enantiomer. 

The Food and Drug Administration (FDA) maintains a computerized human teratogen Information system as part of Its adverse drug reaction reporting... 

Little, J. M. Friedman, R. Bost, L. Gerrity, S. Mize and VI. Singleton, Teratogen Information System authoritative information on potential human teratogens for clinicians, J. Am. Coll. Toxicol., 4 (1985) 367. 

Barr, M. 1997. Lessons from human teratogens ACE inhibitors. Teratology 56(6) 373. 

Human teratogens and chemicals that have an effect on human reproduction Chemicals that are irritants to the skin, eyes, and respiratory system (data from human exposure or animal tests)... 

SAFETY PROFILE Human poison by ingesdon. Poison by ingesdon, intraperitoneal, and intravenous routes. A human teratogen with developmental abnormahdes of the circulatory system. Experimental reproducdve effects. Human systemic effects by ingesdon distorted percepdons, euphoria, excitement, hallucinadons. When heated to... 

SAFETY PROFILE Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. A human teratogen that causes developmental abnormalities of the central nervous system. Experimental reproductive effects including other teratogenic effects. A habit-forming stimulant. When heated to decomposition it emits very toxic fumes of SOx and NO. See also other benzidrine compounds and SULFATES. 

SAFETY PROFILE Poison by intravenous and intramuscular routes. Moderately toxic by subcutaneous and intraperitoneal routes. Human teratogenic effects by unspecified route developmental abnormalities of the eye and ear. An experimental teratogen. Other experimental reproductive effects. Mutation data reported. A derivative of streptomycin has anesthetic properties. When heated to decomposition it emits toxic fumes of NOx. 

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