2,3,5-Trimethylphenyl Methylcarbamate

Biological Exposure Indices (BEI) [ACGIH] - Acetylcholinesterase activity in red blood cells = 70% of individual's baseline; Butylcholinesterase activity in serum or plasma = 60% of individual's baseline; Sample at end of shift; [TLVs and BEIs]

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Chronically high (>10 years) exposure leads to neuropsychological consequences including disturbances in perception and visuo-motor processing (A15321).

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Chronically high (>10 years) exposure leads to neuropsychological consequences including disturbances in perception and visuo-motor processing (A15321).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 470(SRC), determined from a measured water solubility of 58 mg/l(2) and a regression-derived equation(3), indicates that 2,3,5-trimethacarb is expected to have moderate mobility in soil(SRC). Volatilization of 2,3,5-trimethacarb from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.2X10-7 atm-cu m/mole(SRC), calculated from trimethacarb's vapor pressure, 5.1X10-5 mm Hg(2), and water solubility, 58 mg/l(2). 2,3,5-Trimethacarb is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). The half-life of trimethacarb in a sterile soil was 60 days(2), which suggests hydrolysis is expected to be an important fate process for 2,3,5-trimethacarb. The half-life of 2,3,5-trimethacarb in an aerated, dry, Drummer-Catlin soil mixture was 42 days(4), which suggests biodegradation will be important in soils.

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 470(SRC), determined from a measured water solubility of 58 mg/l(2)and a regression-derived equation(3), indicates that 2,3,5-trimethacarb is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.2X10-7 atm-cu m/mole(SRC), based upon trimethacarb's vapor pressure, 5.1X10-5 mm Hg(2), and water solubility, 58 mg/l(2). According to a classification scheme(4), an estimated BCF of 60(SRC), from its water solubility and a regression derived equation(3), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Hydrolysis is expected to be an important environmental fate process for 2,3,5-trimethacarb based upon estimated hydrolysis half-lives of 4 and 37 days at pH values of 7 and 8, respectively(5). No biodegradation data is available for 2,3,5-trimethacarb in water, however a half-life of about 42 days in a pristine-soil indicates that 2,3,5-trimethacarb will be moderately biodegradeable in water(6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), trimethacarb, which has a vapor pressure of 5.1X10-5 mm Hg at 25 °C(2), is expected to exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 2,3,5-trimethacarb is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 18 hours(SRC), calculated from its rate constant of 2.1X10-11 cu cm/molecule-sec at 25 °C (SRC) determined using a structure estimation method(3). Particulate-phase 2,3,5-trimethacarb may be removed from the air by wet and dry deposition(SRC).

Inhalation (L793) ; oral (L793); dermal (L793)

Inhalation (L793) ; oral (L793); dermal (L793)

2,3,5-Trimethylphenyl methylcarbamate is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

Trimethacarb is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Carbamates form unstable complexes with chlolinesterases by carbamoylation of the active sites of the enzymes. This inhibition is reversible. A cholinesterase inhibitor suppresses the action of acetylcholine esterase. Because of its essential function, chemicals that interfere with the action of acetylcholine esterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop.

As with organophosphates, the signs and symptoms are based on excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate poisonings tend to be of shorter duration because the inhibition of nervous tissue acetylcholinesterase is reversible, and carbamates are more rapidly metabolized. Muscle weakness, dizziness, sweating and slight body discomfort are commonly reported early symptoms. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Contraction of the pupils with blurred vision, incoordination, muscle twitching and slurred speech have been reported. (L795)

As with organophosphates, the signs and symptoms are based on excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate poisonings tend to be of shorter duration because the inhibition of nervous tissue acetylcholinesterase is reversible, and carbamates are more rapidly metabolized. Muscle weakness, dizziness, sweating and slight body discomfort are commonly reported early symptoms. Headache, salivation, nausea, vomiting, abdominal pain and diarrhea are often prominent at higher levels of exposure. Contraction of the pupils with blurred vision, incoordination, muscle twitching and slurred speech have been reported. (L795)

The Koc of 2,3,5-trimethacarb is estimated as 470(SRC), using a measured water solubility of 58 mg/l(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that 2,3,5-trimethacarb is expected to have moderate mobility in soil(SRC).

Two trials for malaria control carried out in Nigeria with Landrin lasted for 2 & 4 days, respectively. there were no complaints among the operators & residents, although in one of the trials a water shortage prevented operators form washing & bathing after work as frequently as planned. Whereas moderate to pronounced inhibition of whole-blood cholinesterase was observed in some sprayers at the end of the day's work, this was considerably less than that observed in the same sprayers when spraying propoxur at other times.

2,3,5-Trimethacarb's production may result in its release to the environment through various waste streams; it's use as an ingredient in the insecticide trimethacarb(1) will result in its direct release to the environment(SRC). The insecticide trimethacarb is a reaction product consisting of 3,4,5-trimethylphenyl methylcarbamate and 2,3,5-trimethylphenyl methylcarbamate in a ratio between 3.5:1 and 5:1(1).

2,3,5-Trimethacarb was degraded 15% in a pristine Drummer-Catlin soil mixture over a 2 week incubation period(1). However when the soil was pre-treated with carbofuran (1 application of 5 ug/g of carbofuran and incubated for 42 days) the amount biodegraded was 34% and when pre-treated with trimethacarb (2,3,5- and 3,4,5-isomers) the amount biodegraded was 75% over a 2 week period(1). After 42 days roughly 50% of the added 2,3,5-trimethacarb had been degraded from the pristine soil, while over 90% had been degraded in the treated soils(1). It was also observed that the rate of biodegradation was slightly greater for 3,4,5-trimethacarb when compared to 2,3,5-trimethacarb(1). Methyl carbamate and phenyl carbamate insecticides such as carbaryl, carbofuran, propoxur, propham, and phenmedipham are reported as being moderately to highly biodegradable under aerobic conditions and moderately biodegradeable under anaerobic conditions(2,3), which suggests 2,3,5-trimethacarb will also be biodegradeable under similar conditions(SRC).