Pesticides and Skin Diseases in Man - Pesticides: Evaluation of Environmental Pollution - page 527

(HCB)—a fungicide formerly used for seed treatment (Ezendam et al. 2004). It appears,
however, that skin lesions can develop in response to HCB also in the T cell-independent
manner. Lesions in the T cell-depleted rats, though developed more slowly, were simi-
lar in appearance; histopathological examination indicated the important roles of mono-
nuclear phagocytes and eosinophils in skin reactions to HCB (Michielsen et al. 1999).
Exposure of mice to parathion or methoxychlor enhanced the rates of sensitization upon
a subsequent exposure to environmental haptens, which may seem somewhat paradoxi-
cal as both pesticides alone possess immunosuppressive rather than immunostimulatory
effects, probably via apoptosis of thymus-dependent lymphocytes (Fukuyama et al. 2010a,b).
Pesticides may also possess pharmacological properties, for example, the organophos-
phate insecticide malathion causes long-term modulation in the physiological function of
the cutaneous vasculature through its influence on both neuronal and nonneuronal ace-
tylcholinesterase (Boutsiouki and Clough 2004). The insecticide bisphenol-methoxychlor
has estrogen-like properties (Sakabe et al. 1998). Chlorinated pesticides may interfere with
the metabolism of vitamin A (retinoid) in the skin, resulting in disturbances of keratiniza-
tion within the pilosebaceous duct, which in turn result in occupational acne (Coenraads
et al. 1994). The herbicide propanil induces chloracne in humans and hyperkeratosis in
rabbits (Kimbrough 1980). Although, typically referred to as “chloracne,” the comedogenic
effect seems not restricted to organochlorine pesticides as it was also observed in the case
of zineb (Kimura et al. 1998).
Although the undisputed major risk factor for skin cancer is UV exposure, animal
studies indicate that inflammation and histological changes are more pronounced in
the pesticide-exposed skin (Kimura et al. 1998). Arsenic, but possibly also other pes-
ticides, is capable of inducing cancer independently from sunlight exposure. Arsenic
causes DNA damage in keratinocytes via generation of hydroxyl radicals (Shi et al.
2004). This carcinogenic effect may occur via upregulation of mitogen-activated protein
(MAP) kinase cascades and subsequent upregulation of genes including c-fos and c-jun
(Cooper et al. 2004). Furthermore, arsenic pesticides cause increases in granulocyte/
macrophage colony-stimulating factor (GM-CSF) in the epidermis and transforming
growth factor-alpha (TGF-α)—both factors known to be promoters of skin tumor for-
mation (Luster et al. 1995; Germolec et al. 1998). Upregulation of matrix-degrading pro-
teases such as matrix metalloproteinase 9 (MMP-9) via epidermal growth factor (EGF)
may also play an important role in arsenic-induced skin carcinogenesis (Cooper et al.
2004). Also, the nonarsenic herbicide paraquat was demonstrated to cause genotoxic
effects on human lymphocytes, manifested by an increased number of chromosomal
aberrations (Jovtchev et al. 2010).
16.4 Pesticides and Autoimmunity
Autoimmunity is an unfavorable breakage of the immunologic tolerance toward the
body's own antigens. This is a systemic phenomenon; however, numerous autoimmune
diseases involve the skin. Pesticide exposure is a suspected risk factor for autoimmune dis-
eases (Holsapple 2002); and a higher prevalence of antinuclear antibodies (ANA) related
to connective tissue diseases was observed among rural residents (Spiewak and Stojek
2003). Long-term exposure to insecticides was demonstrated to be a significant risk factor
for two autoimmune connective tissue diseases—rheumatoid arthritis and systemic lupus