メチルホスホン酸

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a structure estimation method(2), indicates that methyl phosphonic acid is expected to have very high mobility in soil(SRC). In soils with high metal content, methyl phosphonic acid may adsorb to metal oxide surfaces(3,4). Methyl phosphonic acid is expected to exist in the dissociated form in the environment based on its pKa of 2.12(5). Dissociated methyl phosphonic acid will not volatilize from moist or dry soils(SRC). Some microorganisms and bacterial cells have been shown to cleave the C-P bond producing methane gas(6-8); however, this occurs only when the C-P compound is the sole phosphorus source. Most soil environments are not characterized by a lack of phosphorus(7); therefore, biodegradation in soil may not be an important removal process(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from an estimation method(2), indicates that methylphosphonic acid is not expected to adsorb to suspended solids and sediment(SRC). A pKa of 2.12(3) indicates methyl phosphonic acid will exist almost entirely in the dissociated form at pH values of 5 to 9. Therefore volatilization from water surfaces is not expected to be an important fate process(SRC). The half-life for the OH radical reaction with methyl phosphonic acid in water can be estimated to be approximately 18 years based on an experimental rate constant of 1.2X10+8 /Mole/sec(4) and an average OH concn of 1X10-17(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of -0.70(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation in water to methane gas may be an important removal process if methyl phosphonic acid is the sole phosphorus source especially in marine water where there is a low phosphorus content(9).

ATMOSPHERIC FATE: A pKa of 2.12(1) indicates methyl phosphonic acid will exist almost entirely in the dissociated form in the ambient environment. Since dissociated compounds are not volatile, methyl phosphonic acid will only exist in the particulate phase in the atmosphere. Particulate phase methyl phosphonic acid will be removed from the atmosphere by wet and dry deposition(SRC). Based on its high water solubility, 2.0X10+4 mg/l(2), wet deposition will be an important atmospheric removal process(SRC).

The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 11.0 ug/l in industrial polluted waste water in the Federal Republic of Germany(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 2.4 ug/l in drainage water from an industrial waste deposit near Davamyran (Sweden) on March 26, 1980 and treated waste water from an industrial waste deposit in Kansas City (USA)(1).

The adsorption of methylphosphonic acid onto solid silt particles in a river sample was negligible(1). Based on a classification scheme(2), an estimated Koc value of 1(SRC), determined from a structure estimation method(3), indicates that methyl phosphonic acid is expected to have very high mobility in soil(SRC). In soils with high metal content, methyl phosphonic acid may adsorb to metal oxide surfaces(4,5). Methyl phosphonic acid is expected to exist in the dissociated form in the environment based on its pKa1 of 2.12 and pKa2 of 7.29(6). Dissociated methyl phosphonic acid is expected to be highly mobile in soil environments(SRC).

Methylphosphonic acid may be released to the environment during its production and use as a chemical warfare simulant(1). Methylphosphonic acid is a degradation product of the nerve agents sarin (GB), soman(2), and VX(3). It is also a degradation product of the two pesticides, O,O-bis(2,4,5-trichlorophenyl)methylphosphonate(4) and mecarphon (no longer being produced)(2) and O-ethyl S-2 diisopropyl-aminoethylmethyl-phosphonothioate(1). Methylphosphonic acid is a degradation product of the flame retardants dimethyl methyl phosphonate, Fyrol 58 and Antiblaze 19(5). Another source of methyl phosphonic acid in the environment may be methylphospholane dichloride(5). Therefore, methyl phosphonic acid may be released to the environment in waste streams during the production and use of these compounds(1,5).

Methyl phosphonic acid is expected to be resistant to biodegradation under environmental conditions(1-3). Compounds containing the C-P bond resist cleavage during metabolism in mammals and higher plants(4). In pure culture studies, the microorganism, Pseudomonas testosteroni, has been shown to cleave the C-P bond(5) and some bacterial cells were also shown to cleave the C-P bond(6,7); however, this occurs only when the C-P compound is the sole phosphorus source. Based on a pure culture study, the predominant degradation product of Escherichia coli growth on methyl phosphonic acid is methane gas(8).

An estimated BCF of 3 was calculated for methyl phosphonic acid(SRC), using an estimated log Kow of -0.70(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. Furthermore, methyl phosphonic acid will be highly dissociated under environmental conditions (pH 5-9) based on its pKa values (pKa1 of 2.12 and pKa2 of 7.29(4)) and methyl phosphonic acid in the dissociated form will not bioconcentrate in aquatic organisms(SRC).

Four genotoxic rat carcinogens, previously reported as negative in the standard hepatocyte/DNA repair assay, were studied in hepatocyte cultures derived from the livers of rats pretreated with the hepatic mixed function oxidase inducers, Aroclor and 3-methylcholanthrene. Cytembena and dimethyl hydrogen phosphite induced positive dose dependent DNA repair responses in Aroclor and 3-methylcholanthrene pretreated cultures, while 2,4-, 2,6-toluene diisocyanate, and ziram were negative for unschedule synthesis in cultures from both pretreatments. The results from this study indicate that pretreatment with hepatic mixed function oxidase inducers lowers the false negative detection rate of various genotoxic rat carcinogens and other organ specific genotopins and significantly increases the sensitivity of the in vitro rat hepatocyte/DNA repair assay.

The development of lung neoplasms following chronic dimethyl hydrogen phosphite administration was studied in rodents. Male Fischer 344 rats and B6C3F1 mice of both sexes received dimethyl hydrogen phosphite by oral gavage in doses of 0, 100, or 200 mg/kg body weight 5 days a week for 103 weeks, while female rats received dimethyl hydrogen phosphite via the same route in doses of 0, 50, or 100 mg/kg for an identical period of time. A dose related toxicity was observed in the lungs of dimethyl hydrogen phosphite treated male and female rats. Lung lesions were most prevalent among high dose male rats, which received twice the dimethyl hydrogen phosphite dose administered to high dose female rats. These pulmonary lesions included alevolar epithelial hyperplasia, chemically related pneumonia, alveolar/bronchiolar adenoma, alveolar/bronchiolar carcinoma, and squamous cell carcinoma. Dimethyl hydrogen phosphite administration also caused the development of neoplastic and non neoplastic lesions in the forestomachs of male rats, with a similar but less pronounced effect being noted in female rats. The non neoplastic lesions associated with dimethyl hydrogen phosphite administration included mineralization of the cerebellum in male rats and focal calcification of the testes in male mice. The authors conclude that evidence of dimethyl hydrogen phosphite carcinogenicity is clear in male rats and equivocal in female rats, while no evidence exists to support dimethyl hydrogen phosphite carcinogenicity in mice of either sex.

Pathological and biochemical effects induced by dimethyl hydrogen phosphite were studied in rats. Male Fischer 344 rats were administered 0 or 200 mg/kg dimethylhydrogen phosphite by oral gavage for 4, 5, or 6 wk. Some animals were treated for 4 wk and maintained for 1 or 2 wk of recovery. No overt signs of toxicity were seen in any animals. The weights of the forestomachs of treated rats were significantly increased. The other organ weights were not significantly affected by dimethyl hydrogen phosphite. Forestomach weights of rats treated for 4 wk returned to the control value after 1 wk of recovery. Epithelial hyperplasia, hyperkeratosis, subepithelial inflammation, and edema were seen in the forestomachs of rats given dimethyl hydrogen phosphite for 6 wk. No treatment related changes were seen in the glandular stomach or lungs. Serum angiotensin converting enzyme activity was increased in all treated rats. Angiotensin converting enzyme activity in rats treated for 4 wk decreased to near the control value after 2 wk recovery. The nonprotein sulfhydryl content of the forestomach was increased and carboxylesterase activity in the forestomach and lungs was reduced in rats given dimethyl hydrogen phosphite for 6 wk. In rats given a single oral or iv dose of 1000 mg/kg dimethyl hydrogen phosphite, and killed 0.5 to 8 hr later, nonprotein sulfhydryl content was significantly reduced in that dimethyl hydrogen phosphite, a known forestomach carcinogen for Fischer 344 rats, induces early and possibly preneoplastic changes in the forestomach.

The resistance of methyl phosphonic acid to hydrolysis, photolysis, and thermal decomposition has been thoroughly substantiated in the literature(1-5). Methyl phosphonic acid in the ionized form can be oxidized to phosphoric acid when treated with ozone in an aqueous medium(6-7). The half-life for the OH radical reaction with methyl phosphonic acid in water can be estimated to be approximately 18 years based on an experimental rate constant of 1.2X10+8 /Mole/sec(8) and an average OH concn of 1X10-17(9). Oxidation of methyl phosphonic acid in basic solution has been shown to occur by a photochemically initiated reaction(10). Methylphosphonic acid is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(11) nor to directly photolyze due to the lack of absorption in the environmental UV spectrum(>290 nm).

SURFACE WATER: Compounds containing the phosphorus-methyl linkage expressed as methyl phosphonic acid were quantitatively reported at concn ranging from 0.35-1.23 ug/l in samples taken from the river Rhine, Netherlands and at concn of 0.21 and 0.25 ug/l in two samples from the river Muese, Netherlands in the period of August, 1975 to April, 1978(1). The analytical method first hydrolyzed the sample so that all compounds containing the P-CH3 bond would be converted to methyl phosphonic acid and then the methyl phosphonic acid was esterifed to trimethyl methylphosphonate for analytical detection(1). In the same study, concn of P-CH3 bond expressed as methyl phosphonic acid were reported at concn of 0.25 ug/l and 0.5 ug/l in Maarsseveen Lake and Viagtwedde Lake, respectively(1).

SURFACE WATER: The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.09 ug/l in water from the river Meuse (Dinant, Belgium) in April, 1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.39 ug/l in industrially polluted water from the river Schelde (Helchin, Belgium) in April, 1980 and 0.17 ug/l in water from the river Renkajoki (Renko, Finland) sampled on April 22, 1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.11 ug/l in water from the River Bow (Canada), sampled 60 km from the glacier source on May 13, 1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.31 ug/l in industrial polluted water from the river South Saskatchewan, sampled at 450 km from the source and 250 km from Calgary (Canada) on May 21, 1980(1).

SURFACE WATER: The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.45 ug/l in surface water in the Federal Republic of Germany. The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.29 ug/l in industrially polluted surface water from the river Tervajoki sampled at Janankala (Finland) on May 5, 1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.18 ug/l in water from the Lake of Maarseveen (The Netherlands) on August 4, 1980. The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to range from 0.21-2.65 ug/l in industrial polluted water from the river Rhine, sampled at Bergambacnt (The Netherlands) in the period of 1979-1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.02 ug/l in water from the lake Gittsjon (Sweden) beneath the ice on April 11, 1980(1). The concn of P-CH3 bond expressed as methyl phosphonic acid was reported to be 0.30 ug/l in water from the river Ume (Gimonas, Sweden) on April 21, 1980(1).