Non-carcinogenic effects of TCDD in animals.

Exposure to TCDD and related chemicals leads to a plethora of effects in multiple species, tissues, and stages of development. Responses range from relatively simple biochemical alterations through overtly toxic responses, including lethality. The spectrum of effects shows some species variability, but many effects are seen in multiple wildlife, domestic, and laboratory species, ranging from fish through birds and mammals. The same responses can be generated regardless of the route of exposure, although the administered dose may vary. The body burden appears to be the most appropriate dosimetric. Many of the effects often attributed to TCDD are associated with relatively high doses: lethality, wasting, lymphoid and gonadal atrophy, chloracne, hepatotoxicity, adult neurotoxicity, and cardiotoxicity. Changes in multiple endocrine and growth factor systems have been reported in a manner which is tissue, sex, and age-dependent. The most sensitive adverse effects observed in multiple species appear to be developmental, including effects on the developing immune, nervous, and reproductive systems. Such effects have been observed at maternal body burdens in the range of 30-80 ng/kg in both non-human primates and rodents. Biochemical effects on cytokine expression and metabolizing enzymes occur at body burdens which are within a factor of ten of the clearly adverse developmental responses. Thus, effects on the immune system, learning, and the developing reproductive system of multiple animals occur at body burdens which are close to those present in the background human population.