Dietary cancer risk conditional cancerogens in produce of livestock fed on species of spurge (Euphorbiaceae). I. Skin irritant and tumor-promoting ingenane-type diterpene esters in E. peplus, one of several herbaceous Euphorbia species contaminating fodder of livestock

The hypothesis was proposed that there is a risk of dietary cancer from conditional cancerogens in produce of livestock polluted with irritants of the diterpene ester type, picked up by feeding on species of Euphorbiaceae (spurge). To challenge this, several herbaceous plants of the genus Euphorbia, widespread as weeds and contaminants of livestock fodder, were identified botanically and extracts of their aerial parts were tested for irritancy on the mouse ear. As compared to a standard probe of croton oil, the extracts of E. peplus, E. nubica and E. helioscopia displayed irritancy. The most active extract (that from E. peplus) was investigated by a fractionation procedure monitored by the mouse ear assay, and five molecularly uniform irritant Euphorbia factors Pe1-Pe5 were identified as diterpene ester-type toxins. Together these factors comprise at least 11 ppm in the aerial parts. They were characterized individually to carry the diterpene parent alcohols ingenol, 20-deoxyingenol, and 20-deoxyingenol-6 alpha, 7alpha-epoxide. The irritancy of the aerial plant parts was shown to be caused mainly by the Euphorbia factors Pe1 and Pe2 together. Upon chronic administration of these irritants and hyperplasiogens as principal cancerogenic risk factors in the mouse skin initiation/promotion bioassay, Pe1 and Pe2 were established as tumor promoters. These findings together support the initial hypothesis and suggest the need for further investigations to determine whether there is a consequent risk of dietary cancer.