Prophylactic administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using terbufos sulfone.

Poisoning with organophosphorus compounds (OPCs) poses a serious threat worldwide. OPC-induced mortality can be significantly reduced by prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors. The only American Food and Drug Administration (FDA)-approved substance for such pre-treatment (to soman exposure) is presently pyridostigmine, although its efficacy is controversial. In search for more efficacious and broad-spectrum alternatives, we have assessed in vivo the mortality-reducing efficacy of a group of five compounds with known AChE inhibitory activity (pyridostigmine, physostigmine, ranitidine, tacrine and K-27), when given in equitoxic dosage (25% of LD01 ) 30 min before exposure to the OPC terbufos sulfone. Protection was quantified in rats by determining the relative risk of death (RR) using Cox analysis, with RR = 1 for animals given only terbufos sulfone, but no pre-treatment. All tested AChE inhibitors reduced terbufos sulfone-induced mortality significantly (p ≤ 0.05) as compared with the non-treatment group (RR = 1: terbufos sulfone only). Best in vivo protection from terbufos sulfone-induced mortality was achieved, when K-27 was given before terbufos sulfone exposure (RR = 0.06), which was significantly (P ≤ 0.05) superior to the pre-treatment with all other tested compounds, for example tacrine (RR = 0.21), pyridostigmine (RR = 0.28), physostigmine (RR = 0.29) and ranitidine (RR = 0.33). The differences in efficacy between tacrine, pyridostigmine, physostigmine and ranitidine were not statistically significant. Prophylactic administration of an oxime (such as K-27) in case of imminent OPC exposure may be a viable option.

Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.

Assessment of occupational exposure to malathion and bifenthrin in mosquito control sprayers through dermal contact.

OBJECTIVE: To assess occupational exposure of malathion and bifenthrin concentrations by dermal contact and urinary 3-(2-chloro-3, 3, 3-trifluoro-1-propenyl)-2, 2-dimethyl-cyclopropanecarboxylic (TFP) acid, health symptoms developed and the relationship between bifenthrin concentrations and TFP acid in urine of the mosquito control sprayers. MATERIAL AND METHOD: The aerosols of these two pesticides were collected using 100 cm2 cotton patches attached on the skin of upper legs of 54 volunteer of mosquito control sprayers. Their urine samples were also collected before and after application. RESULTS: These subjects exposed to average malathion and bifenthrin concentrations of 0.18 and 0.32 microg/cm2, respectively After application, the average concentration of urinary TFP acid in the sprayers was 39.22 +/- 0.77 mg/g creatinine ranging from 0.58 to 261.19 mg/g creatinine. A significant difference was found between urinary TFP acid levels before and after application (p < 0.001) but the bifenthrin concentrations through dermal contact and urinary TFP acid levels were not significantly correlated (p > 0.05). CONCLUSION: The mosquito control sprayers had dermal contact with smoke of malathion and bifenthrin and some sprayers developed health symptoms after exposure. They should use protective clothing made ofplastic, nylon or polyester to protect sprayers from skin contact.