Topical Permethrin Exposure Causes Thymic Atrophy and Persistent Inhibition of the Contact Hypersensitivity Response in C57BI/6 Mice

Abstract

Permethrin was applied to the shaved dorsal interscapular region of female C57Bl/6 mice at doses of 0.5 or 1.5 µ l/day in corn oil and neat 5.0 µ l/day. These doses corresponded to approximately 22, 66, and 220 mg/kg/day topical permethrin. Mice were exposed in this manner either daily for 10 or 30 consecutive days, or every other day for 7 or 14 exposures. Body weight was not affected by any of the treatment regimens. However, thymic weight was decreased and splenic weight was increased by 1.5 or 5.0 µ l permethrin/day, 2 days after termination of 10 consecutive days of topical chemical exposure. Cell surface antigen expression did not change in any treatment group on thymocytes (CD4, CD8), splenocytes (CD45R, Thy 1.2), or bone marrow cells (CD45, CD45R). A persistent, dose-related inhibition of the contact hypersensitivity (CH) response occurred in mice at all exposure levels of permethrin tested.

Cis-Urocanic Acid Increases Immunotoxicity and Lethality of Dermally Administered Permethrin in C57BL/6N Mice

“…The single topical exposure to permethrin caused a limited but significant depression of thymic weight, paralleled by a near significant ( p = .09) decrease in thymic cellularity. These data support previous observations in which subacute topical permethrin caused a severe reduction in thymic organ weight and cellularity (Punareewattana et al 2000). Although cUCA alone did not affect thymic weight or cellularity in the present mice, coexposure to topical permethrin and cUCA appeared to significantly exacerbate the thymolytic effects of permethrin alone.…”

“…et Bacci, Nakamura, and Streilein 1996;El-Ghorr and Norval 1997;Hart et al 1997). Likewise, prolonged or acute exposure to permethrin depressed the functional competency of immune cells in vivo and in vitro (Blaylock et al 1995;Diel et al 1998;Punareewattana et al 2000Punareewattana et al , 2001Prater et al in press). These data raised questions about adverse immune effects that…”

Early Pesticide Exposure and Later Mortality in Rural Africa: A New Hypothesis

“…The children studied were of an age such that limited OC exposure would be predicted, with cypermethrin likely predominating. As previously mentioned, one of the more consistent findings in animal studies that have examined the immunotoxicity of pyrethroids is thymic atrophy (Rashatwar and Matsumura, 1985;Enan et al, 1996;Madsen et al, 1996;Punareewattana et al, 2000). At least for the thymic size study, a transplacental contribution to immunotoxicity may have been limited; thymic index measurements in week-old infants were arithmetically but nonsignificantly lower in hungry season births (p = 0.06).…”

“…Enan et al (1996) found that deltamethrin (a type-II pyrethroid) produced atrophy of the thymus of BALB/c mice in a dose-and time-dependent fashion. Punareewattana et al (2000Punareewattana et al ( , 2001) exposed mice to topical permethrin, and observed decreased thymic weight, increased splenic weight, inhibited macrophage function, and reduced antibody production. Prater et al (2005) reported persistent, dose-related inhibition of the contact hypersensitivity response in mice after topical exposure to permethrin.…”

Molecular mechanisms of cis‐urocanic acid and permethrin‐induced alterations in cutaneous immunity

“…Chemical exposure is also thought to contribute to depressed CH response and lead to an increased incidence of the development of infectious or neoplastic skin disease. The effects of the pyrethroid insecticide permethrin on systemic immunity include thymic atrophy and hypocellularity, inhibition of natural killer cell activity, and inhibition of lymphocyte proliferative responses to T cell mitogens (5–8). However, although previous exposure to topical permethrin has been shown to result in highly persistent reduction of the CH response, the molecular mechanisms are currently poorly characterized.…”