Triaziquon

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.13(2) and a regression-derived equation(3), indicates that triaziquone is expected to have very high mobility in soil(SRC). Volatilization of triaziquone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.3X10-16 atm-cu m/mole(SRC), obtained using a fragment constant estimation method(4). Triaziquone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-6 mm Hg(SRC), determined from a fragment constant method(5).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 20(SRC), determined from a log Kow of -0.13(2) and a regression-derived equation(3), indicates that triaziquone 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 9.3X10-16 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis may be an important environmental fate process since triaziquone contains aziridine groups(SRC); aziridine has a hydrolysis half-life of 154 days at pH 7 and 25 °C(7).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), triaziquone, which has an estimated vapor pressure of 3.4X10-6 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 triaziquone 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 13 hours(SRC), calculated from its rate constant of 3.1X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). The rate constant for the vapor-phase reaction of triaziquone with ozone has been estimated as 3.5X10-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(4). This corresponds to an atmospheric half-life of about 3.3 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(5). Particulate-phase triaziquone may be removed from the air by wet and dry deposition(SRC).

The Koc of triaziquone is estimated as 20(SRC), using a log Kow of -0.13(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that triaziquone is expected to have very high mobility in soil.

/CASE REPORTS/ Three patients, one with an adenocarcinoma of the colon with metastases to the lung, one with a mammary carcinoma with metastases to the lymph nodes and one with a squamous-cell carcinoma of the bronchus without metastases, were treated with triaziquone for 52, 17 and 42 months, respectively. In one case androgens were given also. Leucopenia was evident in all three cases, and at autopsy, 10 months to 4 and one-half years after the end of treatment, atypical reticulum-cell growths described as "neoplastic reticulosis" were found in the bone marrow, spleen and lymph nodes. Treatment of a myosarcoma with triaziquone for one and one-half years was associated with the later occurrence of a monocytic leukemia; a course of radiation had been given also.

Triaziquone's production and use as a research chemical and antineoplastic agent(1) may result in its release to the environment through various waste streams(SRC). Triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany(2).

An estimated BCF of 3.2 was calculated for triaziquone(SRC), using a log Kow of -0.13(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 triaziquone is estimated as 9.3X10-16 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that triaziquone is expected to be essentially nonvolatile from water surfaces(2). Triaziquone's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected(SRC). Triaziquone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.4X10-6 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Acute Exposure/ T(1;13)70H/+ male mice were treated with hydroxyurea (HU) and Trenimon (T). ... HU and T produce large gaps in the spermatogenic line. The surviving population between the gaps was analysed at diakinesis--metaphase I and metaphase II. We found by autoradiography a considerable retardation of the development from resting primary spermatocytes (RPS) to metaphase I and II as compared to untreated T70H/+ males. Furthermore we found increased chiasma frequencies in diakinesis--metaphase I (MI) and reduced nondisjunction frequencies at anaphse I as a result of the treatments applied.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Forty-eight male BR 46 rats, 100 days old, were injected intravenously once weekly with 0.03 mg/kg bw triaziquone (7% of the LD50) for 52 weeks (total dose, 1.56 mg/kg bw). After 16 +/- 3 months, 11/45 (24%) animals had developed malignant tumors at various sites, and benign tumors were found in 4/45 animals. The malignant tumors were 5 sarcomas of the abdominal cavity, 1 lung squamous-cell carcinoma, 1 liver-cell carcinoma, 1 hemangiosarcoma of the salivary gland, 1 hemangiosarcoma of the kidney, 1 ear-duct carcinoma and 1 subcutaneous sarcoma. The benign tumours were 2 adenomas of the bronchus and 2 subcutaneous fibromas. After 23 +/- 5 months, 4/65 control rats had developed malignant tumors (3 mammary sarcomas and 1 phenochromocytoma) and 3 animals had benign tumors (2 thymomas and 1 mammary fibroma).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Forty male BR 46 rats, 100 days of age, were injected intravenously once weekly with 0.03 mg/kg bw triaziquone for about 25 weeks. Thereafter the same dose was administered intraperitoneally for another 33 weeks (total dose, 1.74 mg/kg bw). After 16 +/- 2 months, 8 animals developed malignant tumors: 3 abdominal sarcomas, 1 reticulosarcomatosis, 1 myeloid leukemia, 1 fibrosarcoma of the ribs, 1 lung carcinoma and 1 carcinoma of the kidney. Four animals had benign tumors: 1 an adenoma of the kidney in addition to a fibroma of the skin, 1 an adenoma of the bronchus, 1 a fibroma of the skin and 1 a thymoma. Among 50 control rats, 1 thymoma occurred within a period of 26 months.

/GENOTOXICITY/ ... Alkylation of DNA in vitro by triaziquone /has been reported/.

For more Non-Human Toxicity Excerpts (Complete) data for TRIAZIQUONE (14 total), please visit the HSDB record page.

The rate constant for the vapor-phase reaction of triaziquone with photochemically-produced hydroxyl radicals has been estimated as 3.1X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of triaziquone with ozone has been estimated as 3.5X10-18 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). This corresponds to an atmospheric half-life of about 3.3 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(4). Hydrolysis may be an important environmental fate process since triaziquone contains aziridine groups(SRC); aziridine has a hydrolysis half-life of 154 days at pH 7 and 25 °C(5).

Occupational exposure to triaziquone may occur through inhalation and dermal contact with this compound at workplaces where triaziquone is produced or used(SRC). However, exposure may be limited(SRC), since triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany(1). Exposure would be expected to be limited to individuals receiving triaziquone as drug for cancer treatment(SRC).

Triaziquone's production and use as a research chemical and antineoplastic agent may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 3.4X10-6 mm Hg at 25 °C indicates triaziquone will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase triaziquone 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 13 hours. A half-life of 3.3 days was estimated for the reaction of vapor-phase triaziquone with ozone. Particulate-phase triaziquone will be removed from the atmosphere by wet and dry deposition. If released to soil, triaziquone is expected to have very high mobility based upon an estimated Koc of 20. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 9.3X10-16 atm-cu m/mole. Triaziquone is not expected to volatilize from dry soil surfaces based upon its estimated vapor pressure. If released into water, triaziquone 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 3.2 suggests the potential for bioconcentration in aquatic organisms is low. Aziridine has a hydrolysis half-life of 154 days at pH 7 and 25 °C; since triaziquone contains aziridine groups, hydrolysis may be an important environmental fate for triaziquone. Occupational exposure to triaziquone may occur through inhalation and dermal contact with this compound at workplaces where triaziquone is produced or used. However, exposure may be limited since triaziquone was not produced commercially in the US (as of 1975); it has been produced for research purposes and was manufactured in West Germany. Exposure would be expected to be limited to individuals receiving triaziquone as drug for cancer treatment. (SRC)

This chemical has been tested in the US as an insect chemosterilant, but it is believed that problems associated with its application to insects, its toxicity and environmental effects have prevented its use in this way on a commercial basis.

MEDICATION

Research chemical and antineoplastic agent