Toxic plants as possible human teratogens

r r a t o g e n s are substances that cause birth defects. Although nongenetic deformities have been recorded throughout human history, evidence that they could be caused by exposure to toxic chemicals did not appear until the 1930s, and it was the 1961 Thalidomide episode that generated today’s public concern over teratogenic chemicals. Compounds as chemically diverse as vitamin D, quinine, aspirin, marijuana cannabinols, and 2,4-D have shown some evidence of teratogenicity in laboratory rodents. We now suspect that toxic constituents of common plants may contribute to human birth defects. Birth defects in domestic animals are commonplace. In 1960, Wayne Binns and his USDA co-workers discovered that a severe skull deformity known as “monkey-faced lamb,” which had been thought hereditary, could be produced by feeding a toxic range plant, Veratrum californicurn, to the dams during early pregnancy. Another deformity commonly observed by ranchers was “crookedcalf disease,” characterized by bone abnormalities in the forelimbs and, to a lesser extent, spine and skull (scoliosis and cleft palate); K.A. Wagnon proposed that range lupines (Lupinus species) might be the cause, and Binns later proved it with feeding experiments in pregnant cows. More detailed investigation by Richard Keeler over the past few years shows that crooked-calf disease can be directly attributed to ingestion of a specific lupine alkaloid, known as anagyrine, by the mother at some time during the second or third month of pregnancy. In September 1980, a baby boy born in the mountainous backcountry of northwestern California (Trinity County) was brought to the U.C. Medical Center in Sacramento with severe bone deformities in his arms and hands, including a partial absence of forearm bones (radial aplasia) and absent thumbs. Extensive medical histories and genetic analyses of his parents indicated that the probable cause was environmental rather than hereditary, and his mother feared that somehow exposure to 2,4-D spraying was responsible; popular association of forest spraying and a reportedly high incidence of birth defects in northwestern California and south-