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SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

2-Chloroethyl ethyl sulfide may be decomposed by strong mineral acids to yield toxic hydrogen chloride fumes and heat.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 149(SRC), determined from a structure estimation method(2), indicates that 2-chloroethyl ethyl sulfide is expected to have high mobility in soil(SRC). Volatilization of 2-chloroethyl ethyl sulfide from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.9X10-4 atm-cu m/mole(SRC), using a fragment constant estimation method(3). However, based upon measured hydrolysis rates in ethanol-water and acetone-water systems, the extrapolated hydrolysis half-life of 2-chloroethyl ethyl sulfide in pure water at 25 °C is about 44 sec(5). Therefore, the dominant environmental fate process in moist soil will be hydrolysis. The potential for volatilization of 2-chloroethyl ethyl sulfide from dry soil surfaces may exist(SRC) based upon a vapor pressure of 3.4 mm Hg(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 149(SRC), determined from an estimation method(2), indicates that 2- chloroethyl ethyl sulfide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 4.9X10-4 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 16 hrs and 11 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 9(SRC), from an estimated log Kow of 2.16(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low. However, the only important environmental fate process for 2-chloroethyl ethyl sulfide in water is hydrolysis. 2-Chloroethyl ethyl sulfide hydrolyzes faster in pure water than it dissolves(8); based upon measured hydrolysis rates in ethanol-water and acetone-water systems, the extrapolated hydrolysis half-life in pure water at 25 °C is about 44 sec(8,9). The products from the aqueous hydrolysis of 2-chloroethyl ethyl sulfide are 2-hydroxyethyl ethyl sulfide, HCl and an alcohol(10,11). Due to rapid hydrolysis, environmental fate processes such as bioconcentration, volatilization, adsorption, photolysis and biodegradation are not important(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2-chloroethyl ethyl sulfide, which has a vapor pressure of 3.4 mm Hg at 25 °C(2), is expected to exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase 2-chloroethyl ethyl sulfide 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 32 hr(SRC), calculated from its rate constant of 1.2X10-11 cu cm/molecule-sec at 25 °C(3) determined using a structure estimation method(3). 2-Chloroethyl ethyl sulfide rapidly hydrolyzes upon contact with water(4), therefore, contact with rainfall or moist conditions existing in fog and clouds may contribute to the atmospheric degradation of the compound(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for 2-chloroethyl ethyl sulfide can be estimated to be 149(SRC). According to a classification scheme(2), this estimated Koc value suggests that 2-chloroethyl ethyl sulfide is expected to have high mobility in soil. However, before 2-chloroethyl ethyl sulfide can leach from soil, it will be hydrolyzed. A study indicates that 2-chloroethyl ethyl sulfide hydrolyzes faster in pure water than it dissolves(3); based upon measured hydrolysis rates in ethanol-water and acetone-water systems, the extrapolated hydrolysis half-life in pure water at 25 °C is about 44 sec(3).

Blistering agent. Effects may be delayed up to 12 hr.

Tumor necrosis factor (TNF) is a monokine produced by monocytes and macrophages in response to different stimuli. To determine whether vesicant agents such as half-mustard gas (H-MG; chemical structure: ClCH2CH2SCH2CH3) may induce the release of TNF-alpha in human monocytes (THP-1), ELISA experiments were conducted at different post exposure times. The results indicate that: (1) Significant increases in the TNF-alpha (pg mL-1) concentration were observed as a function of time when THP-1 cells were exposed to 100 uL of 2 M half-mustard gas. A specific serine-type protease inhibitor, Nalpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this laboratory detected the generation of spin adducts of 2-methyl-2-nitrosopropane (MNP) having a resemblance to 2-methyl-2-nitrosopropane-adducts generated from hydrogen atom abstraction of protein constituents. The EPR/Spin Trapping data indicate the trapping of by-products of protein degradation after exposure to half-mustard gas. TNF-alpha may play a role as a biochemical marker for pathophysiological changes induced by half-mustard gas or related agents.

Sulfur mustard and 2-chloro ethyl ethyl sulfide (CEES, a sulfur mustard analog) is known to have immediate (minutes), long-term (hours to days), and toxic effects on human skin. Research was directed toward developing a single in vitro assay that might reflect both these short-term and long-term effects of this vesicating agent on normal human epidermal keratinocytes (NHEK) in vitro. Such an assay system would be useful in identifying and developing sulfur mustard therapeutic agents. Normal human epidermal keratinocytes were exposed to the monofunctional sulfur mustard analog 2-chloro ethyl ethyl sulfide for a variety of times. The effects of 2-chloro ethyl ethyl sulfide on normal human epidermal keratinocytes nuclei were assessed using the membrane-permeable SYTO nuclear stains, whereas the effects of 2-chloro ethyl ethyl sulfide on normal human epidermal keratinocytes metabolism were determined by using the nontoxic mitochondria dye Alamar blue. 2-chloro ethyl ethyl sulfide enhanced SYTO binding in a concentration-dependent manner to the nucleus immediately subsequent to a 2-hr exposure, whereas 2-chloro ethyl ethyl sulfide had relatively little effect on metabolic activity at this time. Fifteen to 36 hr subsequent to 2-chloro ethyl ethyl sulfide exposure, however, Alamar blue revealed a robust, sulfur mustard-dependent effect on mitochondrial activity. To determine if both these indicator dyes could be used simultaneously, normal human epidermal keratinocytes were exposed to 2-chloro ethyl ethyl sulfide and stained with the SYTO nuclear stain 2 hr subsequent to exposure. This procedure was followed by assay of the same cell cultures with Alamar blue at 36 hr subsequent to initial 2-chloro ethyl ethyl sulfide exposure. The data indicate that this nuclear/mitochondrial double-label technique can be used to monitor the short- and long-term effects of sulfur mustard on the same culture of normal human epidermal keratinocytes.

2-Chloroethyl ethyl sulfide's production and use as a simulant for mustard and in studies involving decontamination, detection, contact hazards, and clothing protection(1) may result in its release to the environment through various waste streams(SRC).

2-Chloroethyl ethyl sulfide and its hydrolysate, ethyl 2-hydroxyethyl sulfide, may undergo reductive cleavage of the sulfide bond to yield thiols which are further susceptible to biodegradation under both aerobic and anaerobic conditions(1).

An estimated BCF of 9 was calculated for 2-chloroethyl ethyl sulfide(SRC), using an estimated log Kow of 2.16(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low. 2-Chloroethyl ethyl sulfide hydrolyzes faster in pure water than it dissolves(4); based upon measured hydrolysis rates in ethanol-water and acetone-water systems, the extrapolated hydrolysis half-life in pure water at 25 °C is about 44 sec(4). Therefore, bioconcentration in aquatic organisms is not an important environmental fate process(SRC).

The Henry's Law constant for 2-chloroethyl ethyl sulfide is 4.9X10-4 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 2-chloroethyl ethyl sulfide is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 16 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 11 days(SRC). 2-Chloroethyl ethyl sulfide's Henry's Law constant(1) indicates that volatilization from moist soil surfaces may occur(SRC). However, volatilization will not be an important fate process becuase of its rapid hydrolysis rate. 2-Chloroethyl ethyl sulfide hydrolyzes faster in pure water than it dissolves(4); based upon measured hydrolysis rates in ethanol-water and acetone-water systems, the extrapolated hydrolysis half-life in pure water at 25 °C is about 44 sec(4). The potential for volatilization of 2-chloroethyl ethyl sulfide from dry soil surfaces may exist(SRC) based upon a vapor pressure of 3.4 mm Hg(3).

TREATMENT OF LYSOSOMES FROM A HEAVY MITOCHONDRIAL (3500 G) RAT LIVER FRACTION OF MALE SPRAGUE-DAWLEY RATS WITH 2-CHLOROETHYL ETHYL SULFIDE RESULTED IN SLIGHT RELEASE OF 3 MARKER ENZYMES. ARYL SULFATASE APPEARED TO BE RELEASED AT LOWER CONCN OF THE ALKYLATING AGENT THAN EITHER BETA-GLUCURONIDASE OR ACID PHOSPHATASE. DIRECT LYSOSOMAL LABILIZATION PROBABLY IS NOT INVOLVED IN THE CYTOTOXIC ACTION OF SULFUR MUSTARDS.

Adult Drosophila melanogaster males injected with 0.15 + or - 0.05 ul solutions of mustard gases or 0.25 + or - 0.05 ul of alkyl nitrosoquanidines and mated with virgin females. Phenotypic analysis of the progeny (F1 and F2) from such matings showed that the cmpd had selective mutagenicity for heterochromatic loci in the order: bis(2-chloroethyl) sulfide > MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) > ethyl 2-chloroethyl sulfide > ENNG (N-ethyl-N'-nitro-N-nitrosoguanidine). The order of selective mutagenicity for euchromatic loci was: one > four > three > two.

The mutagenic and lethal effects of a monofunctional sulfur mustard, 2-chloroethylsulfide, have been studied in a number of repair deficient variants of Escherichia coli K12, B/r and B. The results indicate that 2-chloroethylsulfide induces a (pre)mutational lesion which is subject to Uvr+- excision repair. Extensive 2-chloroethylsulfide induced mutagenesis can occur in extra-Uvra- and recA-UvrB- variants suggesting that the majority of the mutations in Uvr- bacteria do not arise from error prone repair. It is hypothesized that 2-chloroethylsulfide alkylates guanine at the O6 position (R-O6G) and that this R-O6G which is Uvr+-excisable is directly mutagenic by producing G-C to A-T transitions during replication. Reduced levels of induced mutation frequencies observed in an endonuclease II deficient variant lead /the authors/ to postulate that, in contrast to Uvr- bacteria, 2-chloroethylsulfide induced mutation in wild type cells arise from error prone repair of apurinic sites. Analysis of the lethal actions of 2-chloroethylsulfide indicates that the lesion produced is largely unexcisable by the Uvr+ system. Host cell reactivation of 2-chloroethylsulfide treated Tr bacteriophage shows that the production of the (pre)lethal lesion is dependent on both the initial dose and post treatment incubation. The efficient repair of the (pre)lethal lesion requires both endonuclease I and polymerase I. Moreover, deficiences of these 2 enzymes rendered bacteria more sensitive to the cytotoxic action of 2-chloroethylsulfide . It is postulated that the lethal mechanism of 2-chloroethylsulfide involves: (1) alkylation at the N3 position of adenine and the N7 position of guanine; (2) spontaneous depurination of these alkylated bases; and (3) production of apurinic sites which are lethal unless repaired by the endonuclease II-polymerase I excision repair system.

When neuroblastoma cells (N18) in vitro were exposed to the bifunctional alkylating agent di-2-chloroethyl sulfide (HS), the specific activity of acetylcholinesterase began to rise rapidly after an initial lag period of 1 to 2 days. The 5 fold increase in enzyme activity at 4 days after exposure to 0.5 ug/ml di-2-chloroethyl sulfide accompanied a 25 fold rise in the rate of reappearance of acetylcholinesterase activity following essentially irreversible inhibition. Based on previous experience with acetylcholinesterase synthesis in serum deprived neuroblastoma cells, this behavior indicates induction of the enzyme. Vinblastine blocked the concomitant large increase in neurite extension which was stimulated by di-2-chloroethyl sulfide, but left acetylcholinesterase induction unaffected. ... Since enzyme activity was inversely related to the ability of the monolayer cells to form microcolonies, acetylcholinesterase induction is dependent upon inhibition of cell division and independent of neurite extension. The monofunctional analog of di-2-chloroethyl sulfide, 2-chloroethyl sulfide, produced similar effects, but much higher concn were required.

The rate constant for the vapor-phase reaction of 2-chloroethyl ethyl sulfide with photochemically-produced hydroxyl radicals has been estimated as 1.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 32 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 2-Chloroethyl ethyl sulfide is highly susceptible to hydrolysis reactions(2). It hydrolyzes faster in pure water than it dissolves(3); based upon measured hydrolysis rates in ethanol-water and acetone-water systems (0.025 to 0.20 mole fraction organic solvent), the extrapolated hydrolysis rate constant in pure water at 25 °C is 0.0158/sec, which corresponds to a half-life of about 44 sec(3,4). The products from the aqueous hydrolysis of 2-chloroethyl ethyl sulfide are 2-hydroxyethyl ethyl sulfide, HCl(5) and an alcohol(2). Hydrolysis under acidic conditions is a reversible reaction(2). Primary hydrolysis products expected under acidic conditions are an alcohol, 2-hydroxyethyl ethyl sulfide, hydrogen chloride or a chloride salt(2). The similar compound bis(2-chloroethyl)sulfide (also known as mustard gas) hydrolyzes rapidly like 2-chloroethyl ethyl sulfide, but has been known to persist for periods of years in soil and water environments when released in bulk quantities as a warfare agent(6); the persistence results from a very slow dissolution rate in water and a formation of a film or crust around pockets of the compound which prevents contact with soil and water(6); bulk environmental releases of 2-chloroethyl ethyl sulfide may act similarly(SRC).

2-Chloroethyl ethyl sulfide's production and use as a simulant for mustard and in studies involving decontamination, detection, contact hazards, and clothing protection may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 3.4 mm Hg at 25 °C indicates 2-chloroethyl ethyl sulfide will exist solely in the vapor-phase in the ambient atmosphere. Vapor-phase 2-chloroethyl ethyl sulfide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 32 hrs. If released to soil, 2-chloroethyl ethyl sulfide is expected to have high mobility based upon an estimated Koc of 149. Volatilization from moist soil surfaces will not be an important fate process due to its hydrolysis rate; the extrapolated hydrolysis half-life of 2-chloroethyl ethyl sulfide in pure water at 25 °C is about 44 sec. Due to rapid hydrolysis, leaching will in soil will not be important. 2-Chloroethyl ethyl sulfide may volatilize from dry soil surfaces based upon its vapor pressure. If released into water, biodegradation, photolysis, bioconcentration, volatilization and adsorption will not be important fate processes because of the rapid hydroysis rate. The extrapolated hydrolysis half-life of 2-chloroethyl ethyl sulfide in pure water from studies in ethanol-water and acetone water at 25 °C is about 44 sec. Occupational exposure to 2-chloroethyl ethyl sulfide may occur through inhalation and dermal contact with this compound at workplaces where 2-chloroethyl ethyl sulfide is produced or used. (SRC)