A plethora of effects have been reported to occur in multiple animal studies following exposure to PCDDs, PCDFs and PCBs. The most extensive dataset on dose-response effects is available for 2,3,7,8-TCDD; less information is available for the other dioxin-like compounds. Therefore the focus of the evaluation of the animal data is on the effects of 2,3,7,8-TCDD.
Due to the multitude of different effects at various dose levels the most sensitive toxic and biochemical endpoints are presented in Table 1. In this table information on the lowest daily doses or body burdens resulting in the observed effects are included. The effects observed are each characterized either as an adverse (toxic) effect or as a biochemical and functional effect. The biochemical effects observed at the lowest body burdens, or tissue concentrations are early expressions of cascades of events induced by dioxin-like compounds that may or may not result in adverse effects in the animal or its progeny.
Among the most sensitive endpoints (on a body burden basis) are: endometriosis, developmental neurobehavioral (cognitive) effects, developmental reproductive (sperm counts, female urogenital malformations) effects, and immunotoxic effects, both adult and developmental . The most sensitive biochemical effects are CYP1A1/2 induction, EGF-receptor down-regulation and oxidative stress (Table 1).
The lowest doses giving rise to statistically significant effects in the most sensitive endpoints following exposure, have resulted in body burdens (e.g. 3 to 73 ng of TCDD/kg) in the exposed animals that overlap, at the lower end, the range of body burdens expressed as TEQ that are found in the general population in industrialized countries exposed to background levels of PCDDs, PCDFs and PCBs.