TABLE 2-2 Representative Human Developmental Toxicants

Agent

Use

Developmentally Toxic Dosage

Adverse Effects

13-cis retinoic acid

Treatment of cystic acne

0.4-1.5 mg/kg/d

Craniofacial and cardiovascular malformations and intellectual deficits

Aminopterin

Folate antagonist

1-2 mg/kg/d

Abortion, central nervous system and craniofacial defects, and growth retardation

Angiotensin converting enzyme inhibitors

Antihypertensive

Therapeutic dose (differs for each)

Fetal death, stillbirth, oligohydramnios, growth retardation, hypotension, and renal failure

Cigarette smoke

Stimulant

>20/day

Growth retardation and facial defects

Coumarin derivatives

Anticoagulants

Therapeutic dose (differs for each)

Facial defects, limb anomalies, growth retardation, and neonatal respiratory distress

Cyclophosphamide

Antineoplastic

4 mg/kg/d

Limb and facial defects

Diethylstilbestrol

Synthetic estrogen

0.1-3 mg/kg/d

Reproductive tract malformations and vaginal cancer

Diphenylhydantoin

Anticonvulsant

8 mg/kg/d

Craniofacial defects, growth retardation, fetal loss, and intellectual deficit

Etretinate

Treatment of psoriasis

0.5-1 mg/kg/d

Limb, ear, cardiac, and thymic defects

Lead

Environmental contaminant

10-15 µg/dl/blooda

Abortion, growth retardation, and neurobehavioral deficits

Lithium

Bipolar disorder

3-5 mg/kg/d

Cardiac defects

Methylmercury

Environmental contaminant

10 µg/kg/db

Central nervous system defects

Penicillamine

Chelator

20 mg/kg/d

Connective tissue defects

Polychlorinated biphenyls

Environmental contaminant

 

Growth retardation, hyperpigmentation, and neurobehavioral deficitb

Thalidomide

Sedative/ hypnotic

0.7-3 mg/kg/d

Structural malformations (particularly reduction defects of the limbs and ears)

Valproic acid

Anticonvulsant

5-10 mg/kg/d

Neural tube closure defects

a The dosage of lead needed to reach these blood levels is dependent on route of exposure. Typically, humans are exposed to lead through a combination of inhalation and oral ingestion.

b There is uncertainty about the dosage associated with adverse effects.



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