Product Code Database
Ethion (C9H22O4P2S4) is an organophosphate insecticide. It is known to affect the neural enzyme acetylcholinesterase and disrupt its function.
Ethion monoxon is an inhibitor of the neuroenzyme cholinesterase (ChE), which normally facilitates Action potential transmission; secondary damage thus occurs in the brain. Because the chemical structure of ethion monoxon is similar to that of an organophosphate, its mechanism of poisoning is thought to be the same. See the figure, "Inhibition of cholinesterase by ethion monoxon." The figure depicts enzyme inhibition as a two-step process. Here, a Hydroxy group (OH) from a Serine in the active site of ChE is Phosphorylation by an organophosphate, causing enzyme inhibition and preventing the serine hydroxyl group from participating in the hydrolysis of another enzyme called Acetylcholine (Ach). The phosphorylated form of the enzyme is highly stable, and depending on the R and groups attached to phosphorus, this inhibition can be either reversible or irreversible.
In a study conducted among rats, it was found that ethion is readily Metabolism after oral administration. Rat urine samples contained four to six polar water-soluble ethion Metabolite.
A study among chickens revealed more about spontaneous ethion distribution in the body. In a representative study, liver, muscle, and fat tissues were examined after 10 days of ethion exposure. In all three cases, ethion or ethion derivatives were present, indicating that it is widely spread in the body. Chicken eggs were also investigated, and 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. In the investigated chickens, about six polar water-soluble metabolites were also found to be present.
In a study performed on goats, heart and kidney tissues were investigated after a period of ethion exposure, and in these tissues, ethion-derivatives were found. This study indicates that the highest levels were found in the liver and kidneys, and the lowest levels in fat. Derivatives were also detected in the goats' milk.
After solvent partitioning of urine from rats that had been fed ethion, it became clear that the metabolites found in the urine were 99% dissolved in the aqueous phase. This means that only non-significant levels (<1 %) were present in the organic phase and that the metabolites are very Hydrophile.
In a parallel study in goats, radioactive labeled ethion with incorporated 14C was used. After identification of the 14C residues in organs of the goats, such as the liver, heart, kidneys, muscles and fat tissue, it appeared that 0.03 ppm or less of the 14C compounds present was non-metabolized ethion. The metabolites ethion monoxon and ethion dioxon were also not detected in any samples with a substantial threshold (0.005-0.01 ppm). In total, 64% to 75% of the metabolites from the tissues were soluble in methanol. After the addition of a protease, another 17% to 32% were solubilized. In the aqueous phase, at least four different radioactive metabolites were found. However, characterization of these compounds was repeatedly unsuccessful due to their high volatility. One compound was trapped in the kidney and was identified as formaldehyde. This is an indication that the 14C of ethion is used in the formation of natural products.
When being exposed through skin contact, the lowest dose to kill a rat was found to be 150 mg/kg for males and 50 mg/kg for females. The minimum survival time was 6 hours for female rats and 3 hours for male rats, and the maximum time of death was 3 days for females and 7 days for males. The LD50 was 245 mg /kg for male rats and 62 mg/kg for female rats.
When being exposed through ingestion, 10 mg/kg/day and 2 mg/kg/day showed no histopathological effect on the respiratory track of rats, nor did 13-week testing on dogs (8.25 mg/kg/day).
LD50 values for pure ethion in rats is 208 mg/kg, and for technical ethion is 21 to 191 mg/kg. Other reported oral LD50 values are 40 mg/kg in mice and guinea pigs. Furthermore, inhalation of ethion is very toxic - during one study which was looking at chemical purity ethion, an LC50 of 2.31 mg/m^3 was found in male rats and of 0.45 mg/m^3 in female rats. Other data reported a 4-hour LC50 in rats of 0.864 mg/L.
In a study determining the LD50 of ethion, 80 male and 60 female adult rats were dermally exposed to ethion dissolved in xylene. The lowest dose to kill a rat was found to be 150 mg/kg for males and 50 mg/kg for females. The minimum survival time was 6 hours for females and 3 hours for males, while the maximum time of death was 3 days for females and 7 days for males. The LD50 was 245 mg /kg for males and 62 mg/kg for females. Skin contact with organophosphates, in general, may cause localized sweating and involuntary muscle contractions. Other studies found the LC50 via the dermal route to be 915 mg/kg in guinea pigs and 890 mg/kg in rabbits.
Ethion can also cause slight redness and inflammation to the eye and skin that will clear within 48 hours. It is also known to cause blurred vision, pupil constriction and pain.
Testing on rats with 10 mg/kg/day and 2 mg/kg/day showed no Histopathology effect on the respiratory tract, nor did 13 week testing on dogs (8.25 mg/kg/day). values for pure ethion in rats of 208 mg/kg, and for technical-grade ethion of 21 to 191 mg/kg,. Other reported oral LD50 values (for the technical product) are 40 mg/kg in mice and guinea pigs. In a group of six male volunteers no differences in blood pressure or pulse rate were noted, neither in mice or dogs. Diarrhea did occur in mice orally exposed to ethion, severe signs of neurotoxicity were also present. The effects were consistent with cholinergic over stimulation of the gastrointestinal tract.
No hematological effects were reported in an experiment with six male volunteers, nor in rats or dogs. The volunteers did not show differences in muscle tone after intermediate-duration oral exposure, nor did the testing animals to different exposure. It is however knows that ethion can result in muscle tremors and . The animal-testing studies on rats and dogs showed no effect on the kidneys and liver, but a different study showed an increased incidence in orange-colored urine. The animal-testing studies on rats and dogs did also not show dermal or ocular effects.
Rabbits, receiving 2.5 mg/kg/day of ethion showed a decrease in body weight, but no effects were seen at 0.6 mg/kg/day. The decrease body, combined with reduced food consumption, was observed for rabbits receiving 9.6 mg/kg/day . Male and female dogs receiving 0.71 mg/kg/day did not show a change in body weight, but dogs receiving 6.9 and 8.25 mg/kg/day showed reduced food consumption and reduced body weight.
In a study with human volunteers, a decrease of Blood plasma cholinesterase was observed during 0.075 mg/kg/day (16% decrease), 0.1 mg/kg/day (23% decrease) and 0.15 mg/kg/day (31%decrease) treatment periods. This was partially recovered after 7 days, and fully recovered after 12 days. No effect on erythrocyte acetylcholinesterase was observed, nor signs of adverse neurological effects. Another study showed severe neurological effects after a single oral exposure in rats. For male rats, salivation, tremors, nose bleeding, urination, diarrhea, and convulsions occurred at 100 mg/kg, and for female rats, at 10 mg/kg. In a study with albino rats, it was observed that brain acetylcholinesterase was inhibited by 22%, erythrocyte acetylcholinesterase by 87%, and plasma cholinesterase by 100% in male rats after being fed 9 mg/kg/day of ethion for 93 days. After 14 days of recovery, plasma cholinesterase recovered completely, and erythrocyte acetylcholinesterase recovered 63%. There were no observed effects at 1 mg/kg/day. In a study involving various rats, researchers observed no effects on erythrocyte acetylcholinesterase at 0, 0.1, 0.2, and 2 mg/kg/day of ethion. In a 90-day study on dogs, in which the males received 6.9 mg/kg/day and the females 8.25 mg/kg/day, ataxia, emesis, miosis, and tremors were observed. Brain and erythrocyte acetylcholinesterase were inhibited (61-64% and 93-04%, respectively). At 0.71 mg/kg/day in male dogs, the reduction in brain acetylcholinesterase was 23%. There were no observed effects at 0.06 and 0.01 mg/kg/day. Based on these findings, a minimal risk level of 0,002 mg/kg/day for oral exposure for acute and intermediate duration was established. Researchers also calculated a chronic-duration minimal risk level of 0.0004 mg/kg/day.
In one study, in which rats received a maximum of 1.25 mg/kg/day, no effects on reproduction were observed. In a study on pregnant river rats, eating 2.5 mg/kg/day, it was observed that the fetuses had increased incidence of delayed ossification of pubes. Another study found that the fetuses of pregnant rabbits, eating 9.6 mg/kg/day had increased incidence of fused sterna centers.
In case of skin exposure, it is advised to wash and rinse with plenty of water and soap to reduce exposure. In case of inhalation, fresh air is advised to reduce exposure.
Treating the ethion-exposure itself is done in the same way as exposure with other organophosphates. The main danger lies in respiratory problems - if symptoms are present, then artificial respiration with an endotracheal tube is used as a treatment. The effect of ethion on muscles or nerves is counteracted with atropine. Pralidoxime can be used to act against organophosphate poisoning, this must be given as fast as possible after the ethion poisoning, for its efficacy is inhibited by the chemical change of ethion-enzyme in the body that occurs over time.
In a chronic toxicity study, rats were fed 0, 0.1, 0.2 or 2 mg/kg/day ethion for 18 months, and no severe toxic effects were observed. The only significant change was a decrease of cholinesterase levels in the group with the highest dose. Therefore, the NOEL of this study was 0.2 mg/kg. The oral LD50 for pure ethion in rats is 208 mg/kg. The dermal LD50 in rats is 62 mg/kg, 890 mg/kg in rabbits, and 915 mg/kg in guinea pigs. For rats, the 4-hour LD50 is 0.864 mg/L ethion.
|
|
