Thiodiglycolic acid

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that thiodiglycolic acid is expected to have very high mobility in soil(SRC). Volatilization of thiodiglycolic acid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.4X10-14 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Thiodiglycolic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.5X10-5 mm Hg(SRC), determined from a fragment constant method(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 12(SRC), determined from a structure estimation method(2), indicates that thiodiglycolic acid is not 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 4.4X10-14 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). The estimated pKa of thiodiglycolic acid is 3.4(5), indicating that this compound will partially exist in the dissociated form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(6). According to a classification scheme(7), an estimated BCF of 3(SRC), from an estimated log Kow of -1.2(SRC) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Thiodiglycolic acid is stable to hydrolysis(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), thiodiglycolic acid, which has an estimated vapor pressure of 5.5X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase thiodiglycolic acid 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 28 hrs(SRC), calculated from its rate constant of 1.4X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase thiodiglycolic acid may be removed from the air by wet and dry deposition(SRC). Thiodiglycolic acid is stable to photolysis(4).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for thiodiglycolic acid can be estimated to be 12(SRC). According to a classification scheme(2), this estimated Koc value suggests that thiodiglycolic acid is expected to have very high mobility in soil. However, adsorption of thiodiglycolic acid was found to vary with soil type; observed maximum sorption capacities ranged from 19.9 mg/kg (53% sand, 14% silt, 33% clay, pH 8.5, 0.5% OM) to 427.4 mg/kg (43% sand, 21% silt, 36% clay, pH 4.7, 0.4% OM)(3). The estimated pKa of thiodiglycolic acid is 3.4(4), indicating that this compound will partially exist in the dissociated form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(5).

Thiodiglycolic acid's production and use as a detection agent of copper, lead, mercury, and silver(1) may result in its release to the environment through various waste streams(SRC). In soil, thiodiglycolic acid was shown to be a biodegradation product of thiodiglycol, a hydrolysis product of bis(2-chloroethyl) sulfide (mustard gas)(2).

An estimated BCF of 3 was calculated for thiodiglycolic acid(SRC), using an estimated log Kow of -1.2(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(SRC).

The Henry's Law constant for thiodiglycolic acid is estimated as 4.4X10-14 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that thiodiglycolic acid is expected to be essentially nonvolatile from water surfaces(2). Thiodiglycolic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.5X10-5 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Acute Exposure/ Thiodiglycolic acid (50 mg/kg) administered to rats inhibited the carnitine-dependent oxidation of [1-14C]palmitic acid by 55%, but affected neither the oxidation of [1-14C]octanoic acid, which is carnitine-independent, nor the oxidation of [1, 4-14C]succinic acid, a marker of Kreb's cycle activity. Additionally, thiodiglycolic acid (30 microM) inhibited oxidation of palmitic acid but not palmitoyl-L-carnitine in isolated rat liver mitochondria, indicating that it either sequesters carnitine or inhibits carnitine palmitoyltransferase I. This study elucidates a specific mitochondrial dysfunction induced by thiodiglycolic acid which may contribute to the adverse effects associated with ifosfamide chemotherapy.

/ALTERNATIVE IN VITRO TESTS/ Our previous studies in mice indicated that the exposure to vinyl chloride (VC) produced a state of immunostimulation. The metabolism of VC was an important factor in this phenomenon. Two known metabolites of VC, namely thiodiglycolic acid and N-acetyl-S-(hydroxyethyl)-cysteine produced little or no effect when added to mouse splenic lymphocyte cultures in vitro but in vivo administration of thiodiglycolic acid produced apparent immune stimulation in mice.

The rate constant for the vapor-phase reaction of thiodiglycolic acid with photochemically-produced hydroxyl radicals has been estimated as 1.4X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 28 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Thiodiglycolic acid is not expected to undergo hydrolysis in the environment(2); concentrations of 20 and 50 mg/l were tested at pHs of 4, 7, and 11 and resulted in 100% recovery of the thiodiglycolic acid after 48 and 96 hours(2). Also, thiodiglycolic acid does not directly photolyze(2). Initial concentrations of 50 and 20 mg/l thiodiglycolic acid were sunlight irradiated for 14 days with final concentrations reported at 49.4 and 19.5 mg/l, respectively; results for the dark controls were 49.2 and 19.8 mg/l, respectively(2).

Thiodiglycolic acid's production and use as detection agent for copper, lead, mercury, and silver may result in its release to the environment through various waste streams. In soil experiments, thiodiglycolic acid was shown to be a biodegradation product of thiodiglycol which is a hydrolysis product of bis(2-chloroethyl) sulfide (mustard gas). If released to air, an estimated vapor pressure of 5.5X10-5 mm Hg at 25 °C indicates thiodiglycolic acid will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase thiodiglycolic acid 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 28 hrs. Particulate-phase thiodiglycolic acid will be removed from the atmosphere by wet and dry deposition. Thiodiglycolic acid is stable to photolysis. If released to soil, thiodiglycolic acid is expected to have very high mobility based upon an estimated Koc of 12. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 4.4X10-14 atm-cu m/mole. The estimated pKa of thiodiglycolic acid is 3.4, indicating that this compound will partially exist in the dissociated form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts. If released into water, thiodiglycolic acid is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process as indicated by 100% recovery of test compound following testing at various pH values for 96 hrs. Occupational exposure to thiodiglycolic acid may occur through inhalation and dermal contact with this compound at workplaces where thiodiglycolic acid is produced or used. (SRC)

Used for detection of copper, lead, mercury, and silver; A major metabolite of vinyl chloride monomer and ifosfamide (anti-cancer drug) in human urine; [HSDB]

Detection of copper, lead, mercury, silver.

Analytical reagent

Acetic acid, 2,2'-thiobis-: ACTIVE

Thioglycolic acid is manufactured by the reaction of monochloracetic acid or its salts with alkali hydrosulfides ... in aqueous medium, under controlled conditons of pressure, temperature, pH, concentration, to give a higher yield of thioglycolate salt and minimize the formation of such by-products as thiodiglycolic and dithiodiglycolic acids. The reaction mixture is acidified to liberate thioglycolic acid, which is extracted from the aqueous solution into an organic solvent, such as an ether, and then purified by vacuum distillation.