Dietary cancer risk from conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae): III. Milk of lactating goats fed on the skin irritant Herb Euphorbia peplus is polluted by tumor promoters of the ingenane diterpene ester type

Special procedures were developed to investigate poisonous milk of lactating goats fed experimentally on aerial parts of the herb Euphorbia peplus L. In extracts of the milk, weakly irritant in the mouse-ear assay, three diterpene ester toxins were detected by techniques of high-performance liquid chromatography. They are of the ingenane structural type: Euphorbia factor Pel (ingenol 20-acetate 3-angelate), Euphorbia factor Pe2 (20-deoxyingenol 3-angelate) and Euphorbia factor Pe4 (20-deoxyingenol-6alpha,7alpha-epoxide 3-angelate). From goats milk collected 15 days after cessation of the experimental feeding period, extracts were completely free of diterpene ester toxins. The toxins polluting the milk are identical to diterpene ester entities occurring in the aerial parts of E. peplus. Of these, Euphorbia factors Pel and Pe2 are known as promoters of tumors of mouse skin. Apart from the toxic Euphorbia factors, the non-toxic parent alcohol ingenol was also detected in the milk. It is absent in the plant, and may have been generated metabolically from a certain portion of the toxic diterpene esters picked up by the goats from their fodder. The results presented here provide, for the first time, data for a novel interpretation of the locally high incidence of esophageal cancer observed in certain areas in the Caspian littoral of Iran, associated with a greater consumption of goat's (and sheep's) milk.