Non-carcinogenic effects of TCDD in animals

Abstract

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.

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

“…Numerous experimental studies showed that TCDD may suppress both humoral and cell-mediated immune responses (Birnbaum and Tuomisto 2000;Kerkvliet 2002). Inhibition of immunoglobulin secretion has been demonstrated in multiple animal species (Birnbaum and Tuomisto 2000;Nohara et al 2002;Vorderstrasse et al 2001), as well as in human lymphocytes cultivated in vitro (Sulentic et al 2000). Zober et al (1994) found an increased incidence of infectious and parasitic diseases in a small retrospective cohort study of TCDD-exposed workers, but clinical diagnoses were ill-defined.…”

“…The immune system is one of its most sensitive targets (Birnbaum and Tuomisto 2000). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals (Birnbaum and Tuomisto 2000;Holsapple et al 1991;Nohara et al 2002). In humans, increased incidence of and mortality from lymphatic tumors have been found in exposed subjects, even though there is a lack of consistency among studies (Bertazzi et al 2001;IARC 1997).…”

“…The immune system is one of its most sensitive targets (Birnbaum and Tuomisto 2000). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals (Birnbaum and Tuomisto 2000;Holsapple et al 1991;Nohara et al 2002).…”

“…2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD) has a long biological half-life in humans (> 7 years) and induces carcinogenicity and severe developmental, endocrinologic, immunologic, and reproductive toxicity in animal experiments (Birnbaum and Tuomisto 2000;Dragan and Schrenk 2000;IARC 1997). The immune system is one of its most sensitive targets (Birnbaum and Tuomisto 2000).…”

Development and characterization of monoclonal antibodies against human aryl hydrocarbon receptor

“…The aryl hydrocarbon receptor can be activated by exogenous chemicals, such as halogenated aromatic hydrocarbons, non-halogenated polycyclic aromatic hydrocarbons, and other dioxin-like chemicals (DLCs), as well as endogenous compounds, such as 6-formylindolo-[3,2-b]-carbazole, bilirubin and lipoxinA4 (Denison and Nagy, 2003;Nguyen and Bradfield, 2007). The activation of AhR by these compounds leads to regulation of the expression of a battery of genes resulting in diverse biological and toxicological effects, including dermal, hepatic, cardiac and immunotoxic response, wasting syndrome, reproductive and developmental toxicities (Beischlag et al, 2008;Flaveny et al, 2010;Birnbaum and Tuomisto, 2000;Bock, 1994).…”