Immunotoxicology and Its Application in Risk Assessment

Abstract

Immunotoxicology is the study of undesired modulation of the immune system by extrinsic factors. Toxicological assessments have demonstrated that the immune system is a target following exposure to a diverse group of xenobiotics including ultraviolet radiation, chemical pollutants, therapeutics, and recreational drugs. There is a well-established cause and effect relationship between suppression of the immune response and reduced resistance to infections and certain types of neoplasia. In humans, mild-to-moderate suppression of the immune response is linked to reduced resistance to common community-acquired infections, whereas opportunistic infections, which are very rare in the general population, are common in individuals with severe suppression. Xenobiotic exposure may also result in unintended stimulation of immune function. Although a cause and effect relationship between unintended stimulation of the immune response and adverse consequences has yet to be established, evidence does suggest that hypersensitivity, autoimmunity, and pathological inflammation may be exacerbated in susceptible populations exposed to certain xenobiotics. Xenobiotics can act as allergens and elicit hypersensitivity responses, or they can modulate hypersensitivity responses to other allergens such as pollen or dust mite by acting as adjuvants, enhancing the development or expression of hypersensitivity. Allergic contact dermatitis, allergic rhinitis, and asthma are the most commonly encountered types of hypersensitivity reactions resulting from chemical exposure. The immunologic effectors and mechanisms involved in autoimmune reactions are the same as those associated with responses to foreign antigens; however, the reactions are directed against the host's own cells. Thus, chemicals that induce immune suppression, nonspecific immunostimulation, or hypersensitivity may also impact autoimmunity. Risk assessment for immunotoxicity should be performed using the same approaches and principles for other noncancer effects. However, since xenobiotics may have effects on more than one aspect of immune function, immunotoxicity data should be evaluated separately for evidence of suppression, stimulation, hypersensitivity, and autoimmunity.

Immunotoxicology: challenges in the 21st century and in vitro opportunities

“…the authors have contributed to many that have already been published (Gennari et al, 2005;Corsini, 2006;Carfì et al, 2007;Corsini and Roggen, 2009;Galbiati et al, 2010;lankveld et al, 2010;Pfaller et al, 2010). Immunotoxicology in general is also well covered in reviews and book chapters (Descotes, 2004(Descotes, , 2006Kadow et al, 2009;Dietert, 2010;House, 2010;Rooney et al, 2012), and is even the subject of entire textbooks (Dean et al, 1994;House et al, 2006), though arguably the latter may no longer be entirely up to date. that is why this review is not another attempt to sum up the state of the art but to ask some fundamental but out of the box questions.…”

Lack of autoantibody induction by mercury exposure in artisanal gold mining settings in Colombia: Findings and a review of the epidemiology literature

“…Taking into account the previous scenarios, we hypothesized the combination of organic and inorganic species of Hg, as well as infectious diseases status, may exert a different effect on immune function and, as a consequence, foster an environment conducive to development of an autoimmune-like phenomenon. In fact, it has been claimed that the risk of autoimmune diseases is influenced not only by a genetic component, but also by environmental exposure to both pathogens and xenobiotics (Rioux & Abbas, 2005;Rooney et al, 2012;Smyk et al, 2012). In this way, the proposed phenomenon may alternatively explain the changes observed among populations noted by Silva et al (2004), where people exposed to inorganic Hg from gold mining activities and methyl-Hg via fish consumption (median ¼ 4 mg Hg/L urine), as well as malaria status (490%) had more prevalent ANA + compared to those exposed only to methyl-Hg (51% versus 3.6% for titres 41:40 and 17% versus 1% for titres 41:80; median ¼ 8 mg Hg/g hair).…”

Toxicology: a discipline in need of academic anchoring—the point of view of the German Society of Toxicology

“…Adverse effects of substances can be mediated by the immune system (IPCS 2012 ; Rooney et al 2012 ). A reaction of the immune system contributes to conditions such as allergic contact dermatitis and asthmatic symptoms.…”