Cholinesterase activity decrease

M (decreased plasma 67-88%, erythrocyte 9-20%, and brain 76-79% cholinesterase activity)... 

When methyl parathion was given orally to rats at doses of 1.5 mg/kg and to guinea pigs at 50 mg/kg, plasma, erythrocyte, and brain cholinesterase activity was maximally inhibited within 30 minutes after administration. In rodents of both species that died after acute intoxication, brain cholinesterase levels decreased to 20% of control values and often to 5-7% (Miyamoto et al. 1963b). The species difference in susceptibility to orally administered methyl parathion is noted in Section 3.2.2.1. 

Permethrin, a pyrethrin pesticide, decreased the inhibition of brain cholinesterase activity by methyl parathion, but methyl parathion decreased the LD50 of permethrin when the two pesticides were simultaneously administered to rats (Ortiz et al. 1995). The potentiation of permethrin lethality may be due to the inhibition by methyl parathion of carboxylesterase, which metabolizes permethrin. 

Consistent decreases in plasma cholinesterase may not have been observed in rats and dogs because they were treated with lower doses of diisopropyl methylphosphonate. In general, depression of plasma cholinesterase, also known as pseudocholinesterase or butyrylcholinesterase, is considered a marker of exposure rather than an adverse effect. Depression of cholinesterase activity in red blood cells (acetylcholinesterase) is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity. It is considered an adverse effect. Acetylcholinesterase is found mainly in nervous tissue and erythrocytes. Diisopropyl methylphosphonate was not found to inhibit RBC... 

Although this study (Hart 1980) did not identify an effect level, the NOAEL is below the LOEL found in all studies examining the toxicity of diisopropyl methylphosphonate. The LOEL for diisopropyl methylphosphonate is 262 mg/kg/day for male mink and 330 mg/kg/day for female mink (Bucci et al. 1997), doses at which statistically significant decreases in plasma cholinesterase (butyrylcholinesterase) but not RBC cholinesterase (acetylcholinesterase) activity were observed (Bucci et al. 1997). In general, a decrease in plasma cholinesterase activity is considered to be a marker of exposure rather than a marker of adverse effect, while a decrease in RBC acetylcholinesterase activity is a neurological effect thought to parallel the inhibition of brain acetylcholinesterase activity and is thus considered an adverse effect. Diisopropyl methylphosphonate was not found to inhibit red blood cell cholinesterase at doses at which plasma cholinesterase was significantly inhibited. No effects were observed in males at 45 mg/kg/day (Bucci et al. 1997) or at 63 mg/kg/day (Bucci et al. 1994), and no effects were observed in females at 82 mg/kg/day (Bucci et al. 1994), or at 57 mg/kg/day (Bucci et al. 1997). 

Most displayed decreased blood cholinesterase activity. Many were observed to have affective syndromes (anxiety, fear, aggression), sometimes accompanied by symptoms of depression. Disruption of memory was noted. Vision problems are also caused by long-term contact with OPPs [A64]. In cotton growing regions with intensive OPP use, the number of spontaneous miscarriages and stillbirths was higher than elsewhere [3]. 

In the mid-1950s, octamethyl pyrophosphoramide was tested on wheat in the Stavropol Krai, and in the Kiev Oblast on gardens [A2]. Octamethyl pyrophosphoramide concentrations were 1.0-3.0 mg/m3 when fruit trees were manually sprayed, and 0.5 mg/m3 in the signaler s work zone when sprayed from the air [58]. The MPC, established considerably later, was much lower 0.02 mg/ m3. When spraying cotton from the air in Tajikistan, the concentrations were 0.8-1.5 mg/m3 in the air of the field airport, and 3.0 mg/m3 in the signaler s work zone. Workers were observed to have decreased cholinesterase activity. 

It will be shown below that D.F.P. is rapidly destroyed in vitro and in vivo.2 Therefore, the recovery of serum cholinesterase activity is not representative of a reversal of enzyme inhibition, but is indicative of synthesis of new enzyme proteins. Since the regeneration rate of serum cholinesterase in patients with liver damage is significantly depressed as contrasted with that in the normal patient, it is concluded that the ability of such patients to synthesize this particular enzyme protein is decreased. This constitutes evidence for the view that the fiver is a primary locus for the formation of serum cholinesterase. 

The MRL is based on a NOAEL of 0.5 mg/m3 for decreased acetylcholinesterase activity in rats exposed to disulfoton 4 hours/day for 5 days in a study by Thyssen (1978). The NOAEL was adjusted for intermittent exposure, converted to a human equivalent concentration, and divided by an uncertainty factor of 30 (3 for extrapolation from animals to humans and 10 for human variability). Inhibition of erythrocyte cholinesterase activity and unspecified behavioral disorders were observed at 1.8 mg/m, and unspecified signs of cholinergic toxicity were observed at 9.8 mg/m. Similar effects were observed in rats or mice exposed to higher concentrations for shorter duMtions (Doull 1957 Thyssen 1978). The NOAEL value of 0.5 mg/m is supported by another study, in which no significant decrease in the activity of brain, serum, or submaxillary gland cholinesterase was found in rats exposed to 0.14-0.7 mg/m for 1 hour/day for 5-10 days (DuBois and Kinoshita 1971). Mild depression of erythrocyte cholinesterase activity was reported in workers exposed by the inhalation and dermal routes (Wolfe et al. 1978). 

The MRL was based on a NOAEL of 0.009 mg/kg/day for decreased brain cholinesterase activity in F a pups in a multigeneration feeding study in rats by Hixson and Hathaway (1986). At the LOAEL of... 

Although some steroids have been reported to reduce the toxic effects of some insecticides, the steroid ethylestrenol decreased the rate of recovery of depressed cholinesterase activity in disulfoton- pretreated rats (Robinson et al. 1978). The exact mechanism of this interaction was not determined. Ethylestrenol alone caused a small decrease in cholinesterase activity, and, therefore, resulted in an additive effect. Rats excreted less adrenaline and more noradrenaline when given simultaneous treatments of atropine and disulfoton compared with rats given disulfoton alone (Brzezinski 1973). The mechanism of action of disulfoton on catecholamine levels may depend on acetylcholine accumulation. In the presence of atropine, the acetylcholine effect on these receptors increases the ability of atropine to liberate catecholamines. 

An acute-duration inhalation MRL for disulfoton of 0.006 mg/m3 was derived. The MRL is based on a NOAEL of 0.5 mg/m for lethargy and decreased cholinesterase activity in rats exposed for 4 hours/day, 5 days/week (Thyssen 1978). 

A chronic-duration oral MRL for disulfoton of 6x10-5 mg/kg/day was derived. The MRL is based on a LOAEL value of 0.06 mg/kg/day for decreased cholinesterase activity in female rats in a chronic feeding study (Hayes 1985). 

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