Malathion is an organophosphorus insecticide, exposure to which leads to skin inflammation, possibly through the inhibition of acetylcholinesterase and the subsequent increase in tissue levels of non-neuronal acetylcholine (ACh) (Boutsiouki et al. 2001). This study, which was approved by the local Ethics Committee, investigates the longer term effects of acute exposure to a single low dose of malathion. Malathion (1 % in aqueous gel) or vehicle was applied for 5 h under occlusive dressing to the skin of one forearm of eleven healthy volunteers all of whom gave written, informed consent. The cutaneous vascular response to ACh (2 %), delivered by iontophoresis (maximum current 200 µA for 60 s) was assessed using scanning laser Doppler imaging, < 1 h and at 24 h after removal of the malathion.

Malathion significantly increased skin blood flow (274 ± 88 laser Doppler perfusion units (PU); mean ± S.E.M.) < 1 h after removal compared with vehicle control (150 ± 29 PU; n = 6, P < 0.04, Student’s paired t test), which was still present 24 h later (142 ± 13 vs. 115 ± 5 PU; n = 5, P < 0.04). Iontophoresis of ACh into control treated skin caused a vasodilatation within the area of delivery (direct response), which was surrounded by a neurogenic flare (indirect response). The size of the ACh-induced neurogenic flare was significantly enhanced by malathion < 1 h after its removal (2.4 ± 0.4 cm², n = 11) vs. control (1.2 ± 0.3 cm², P < 0.001). Twenty-four hours later, no significant difference was observed between the size of the flare at malathion and control treated sites, which were 2 ± 0.7 and 1.2 ± 0.35 cm², respectively (n = 5). The mean blood flux at the site of delivery of ACh at < 1 h and 24 h after malathion exposure was not significantly different from control treated skin. However, as indicated by the differences in the slopes of the recovery from the maximum response to ACh, malathion 24 h after its removal did significantly increase the duration of both the direct (-8.2 ± 2.3 cm² min^-1) and indirect (-3.9 ± 1.5 cm² min^-1) response to ACh compared with control (-12.4 ± 1.4 and -7 ± 2.3 cm² min^-1, respectively; n = 5, P < 0.04). These responses were similar to those seen at < 1 h. These data confirm that the microvascular response to exogenous ACh is modulated by acute exposure to a single low dose of malathion and that this modulation lasts for at least 24 h. We hypothesise that this is a result of the maintained inhibition of endogenous acetylcholinesterase both at the blood vessel wall and the nerves modulating the neurogenic vasodilator response in human skin.This work was supported by the Sir Jules Thorn Charitable Trust.

Boutsiouki, P., Thompson, J.T. & Clough, G.F. (2001). Arch Tox. 75, 321-328.