Table 2.
We Are Confident of the Following | We Consider the Following Likely, but Requiring Confirmation | Broad Themes to Be Pursued in Future Investigations |
---|---|---|
Forms of inorganic mercury (HgCl2, vapor, amalgam) induce systemic autoimmune disease in rats (transient) and mice, and exacerbates systemic autoimmune disease in lupus-prone mice; Several mineral oil components and certain other hydrocarbons can induced an acute inflammatory arthritis in some rat strains; The mineral oil component 2,6,10,14-tetramethylpentadecane (TMPD or pristane) induces lupus-like disease and inflammatory arthritis in several strains of mice; For a limited number of pathogens there is a clear association with development of autoimmune diseases; Excess iodine increases the incidence of autoimmune thyroiditis in genetically predisposed animal models. |
Gold causes (transient) nephropathy in rats. Gold and silver cause autoimmune responses, but not autoimmune disease, in mice; but the ability of silver and gold to exacerbate spontaneous autoimmune disease requires study; Silica exacerbates autoimmune disease but more studies are needed using more species/strains and a wider range of doses and exposure routes; Trichloroethylene (TCE) exacerbates systemic autoimmunity although responses are often limited and transient. Studies of autoimmune liver disease are needed with additional species/strains and in developmental studies; TCDD exposure during fetal or early neonatal development may promote autoimmunity; Organochlorine pesticides may enhance lupus-like disease in a predisposed mouse strain; Sunlight/ultraviolet (UV) light exposure exacerbates lupus in genetically prone mice. |
Studies should be “shaped by what is observed in humans, not by what is possible in mice” [53]; Studies should not be restricted to a “gold standard” animal model. Multiple models should be investigated to reflect human genetic heterogeneity; When using spontaneous disease models it is important to consider whether environmental exposures directly impacts idiopathic autoimmunity, or reflects environmental factor-specific autoimmunity; More studies on the effects of environmental factor exposure on expression of autoimmunity during different stages of life (gestational to adulthood) are needed. |