Ethion

Ethion (C9H22O4P2S4) is an organophosphate insecticide. Ethion is known to affect a neural enzyme called acetylcholinesterase and prevent it from working. Ethion (C9H22O4P2S4) is an organophosphate insecticide. Ethion is known to affect a neural enzyme called acetylcholinesterase and prevent it from working. Ethion was one of many substances that were approved for use based on data from Industrial Bio-Test Laboratories, which prompted the Food and Agriculture Organization and World Health Organization to recommend its reanalysis in 1982. In the 1950s, Ethion was first registered in the USA as an insecticide. However, the usage of ethion has varied during the years due to overall crop values and weather conditions. For example, 1999 was a very dry year; the drought reduced yields, and the usage of ethion became less economically advantageous. Since 1998, serious studies for the risk assessment of ethion have been conducted by (among others) the EPA (United States Environmental Protection Agency). The risk assessments for ethion were presented at a July 14, 1999 briefing with stakeholders in Florida, which was followed by an opportunity for public comment on risk management for this pesticide. Ethion is produced under controlled pH conditions, by making dibromomethane react with O,O-diethyl hydrogen phosphorodithioate in ethanol. Another method of manufacturing is the reaction of methylene bromide and the sodium salt of O,O-diethylphosphorodithoate. It can also be made with an reaction of O,O-Diethyl dithiophosphoric acid and formaldehyde. It is known that ethion is small and lipophilic molecule and because it has these characteristics rapid absorption across cell membranes is expected. This absorption from skin, lungs and the gut to the blood will happen via passive diffusion. Furthermore, ethion is changed in the liver, via desulfuration, into its active metabolite: ethion monoxon. Due to this change happening in the liver the primary place of damage it expected to be the liver. Ethion monoxon is an inhibitor of the neuro enzyme cholinesterase (ChE). ChE is a facilitator of nerve impulse transmission, secondary of damage is thus the brain. Because ethion monoxon is an organophosphate its mechanism of action is thought to be the same. This mechanism works as follows (see the figure 'Inhibition of cholinesterase by ethion monoxon.'): a hydroxyl group from a serine residue in the active site from ChE is phosphorylated by the organophosphate, thereby inhibiting the enzyme. The inhibition is a result of the inability of the serine hydroxyl group to participate in the hydrolysis of another enzyme called acetyl choline(Ach). In the figure it is indicated that inhibition reaction is a two step process. The phosphorylated form of the enzyme is highly stable, and depending on the R and R’ groups attached to the phosphorus this inhibition is reversible or irreversible. Goats exposed to ethion showed clear distinctions in excretion, absorption half-life and bioavailabilities. These differences depend on the method of administration. Intravenous injection resulted in a half-life time of 2 hours, while oral administration resulted in a half-life time of 10 hours. Dermal administration lead to a half-life time of even 85 hours. These differences in half-life times can be completed with a difference in bioavailability. The bio-availability of ethion in oral administration was less than 5%, whereas the bio-availability of dermal administration of ethion was 20%. In a study conducted among rats, after oral administration it was found that ethion is quite readily metabolized. The metabolization products in found in urine are four to six polar water-soluble products. A study among chickens reveals more about the ethion distribution in the body. After 10 days of ethion exposure liver, muscle, and fat tissues were examined. In all three cases ethion or ethion derivatives were present, indicating that it is widely spread in the body. Also chicken eggs were investigated. It was found that the egg white reaches a steady ethion derivative concentration after four days while the concentration in yolk was still rising after ten days. Also in the investigated chicken about six polar water-soluble metabolites were found. In a goat study, also heart in kidney tissue was investigated after a period of ethion exposure, and in these tissue ethion-derivatives were found. This study also indicates that the highest level were found in the liver and kidneys and the lowest levels in fat. In goat milk derivatives were also present.