Bromochloroacetonitrile

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 13(SRC), determined from a structure estimation method(2), indicates that bromochloroacetonitrile is expected to have very high mobility in soil(SRC). Volatilization of bromochloroacetonitrile from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.2X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Bromochloroacetonitrile is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.91 mm Hg(SRC), determined from a fragment constant method(4). Bromochloroacetonitrile has a hydrolysis rate constant of 5.3X10-6/sec at pH of 8.7(5), corresponding to a half-life of 36 hours(SRC). Bromochloroacetonitrile is a by-product of water chlorination and hydrolyzes quickly; therefore, biodegradation is not expected to be an important fate in the environment(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 13(SRC), determined from a structure estimation method(2), indicates that bromochloroacetonitrile 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 1.2X10-6 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 73 and 270 days, respectively(SRC). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.38(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Bromochloroacetonitrile has a hydrolysis rate constant of 5.3X10-6/sec at pH of 8.7(8), corresponding to a half-life of 36 hours(SRC). Bromochloroacetonitrile is a by-product of water chlorination and hydrolyzes quickly; therefore, biodegradation is not expected to be an important fate in the environment(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), bromochloroacetonitrile, which has an estimated vapor pressure of 0.91 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase bromochloroacetonitrile 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 410 days(SRC), calculated from its rate constant of 3.9X10-14 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bromochloroacetonitrile can be estimated to be 13(SRC). According to a classification scheme(2), this estimated Koc value suggests that bromochloroacetonitrile is expected to have very high mobility in soil.

/GENOTOXICITY/ ... The ability of halogenated acetonitriles (HAN) to induce single-strand breaks on the DNA of HeLa S3 cells was investigated using the single-cell gel electrophoresis (SCGE) assay, which could be a good tool with which to evaluate the genotoxicity of chlorinated water. The results were compared to those obtained in the Ames fluctuation test using the Salmonella typhimurium TA 100 strain without activation. With the Ames fluctuation test, a mutagenic effect was observed for chloroacetonitrile (MCAN), dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). No mutagenic effect was found with bromoacetonitrile (MBAN) or dibromoacetonitrile (DBAN). In the SCGE assay, all five HANs induced DNA damage in HeLa S3 cells, increasing the mean tail moment significantly. For each compound, a dose-effect relation was observed. ... Brominated acetonitriles were more genotoxic than chlorinated acetonitriles in the SCGE assay, and the genotoxicity increased with the number of halogenated atoms of the compound. This behavior had already been found with other genotoxicity tests.

/GENOTOXICITY/The haloacetonitriles produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells. trichloroacetonitrile (TCAN) was the most potent DNA strand breaker, and bromochloroacetonitrile (BCAN) greater than dibromoacetonitrile (DBAN) greater than dichloroacetonitrile (DCAN) greater than chloroacetonitrile (CAN), which was only marginally active.

/GENOTOXICITY/ Chlorinated and brominated haloacetonitriles (HAN) ... produced DNA strand breaks in cultured human lymphoblastic (CCRF-CEM) cells /treated for 1 hr with up to 3.0 mM dibromoacetonitrile/. /Chlorinated & brominated haloacetonitriles/

Bromochloroacetonitrile is formed during the chlorination of water(1-2). In experiments bromochloroacetonitrile was found in water treated with chlorine(1-2), chlorine with bromide(2), chlorine with ozone(1) and chloramination with bromide(2).

Bromochloroacetonitrile

Group 3: Not classifiable as to its carcinogenicity to humans

Volume 52: (1991) Chlorinated Drinking-water; Chlorination By-products; Some Other Halogenated Compounds; Cobalt and Cobalt Compounds

1999

1998

An estimated BCF of 3 was calculated in fish for bromochloroacetonitrile(SRC), using an estimated log Kow of 0.38(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 bromochloroacetonitrile is estimated as 1.2X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bromochloroacetonitrile 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 37 days(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 270 days(SRC). Bromochloroacetonitrile's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Bromochloroacetonitrile is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 0.91 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Bromochloroacetonitrile was tested in a limited carcinogenicity study in female SEN mice by skin application, in an initiation/promotion study in female SEN mice by skin application and in a screening assay for lung tumors in female strain A/J mice by oral administration. No skin tumor was produced after skin application in mice. In the initiation/promotion study, in which bromochloroacetonitrile was applied topically as six equal doses over a two-week period, followed by repeated doses of 12-O-tetradecanoylphorbol 13-acetate for 20 weeks, there was a small increase in the number of mice with tumors in the highest dose group: control, 9/105; intermediate dose, 7/37 (nonsignificant); highest dose (total dose 4800 mg/kg bw), 8/37 (p < 0.05). In orally treated mice, an increase in the proportion of animals with lung tumors and number of tumors per mouse was observed: control, 3/31 and 0.1; treated group (10 mg/kg bw, three times per week, eight weeks), 10/32 and 0.34 (p < 0.05)

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The developmental toxicity of acetonitrile and 5 halogenated derivatives was examined with an in vivo teratology screen adapted for use in the Long-Evans rat. The screen was extended to an evaluation of growth till postnatal Days 41-42, and weight of several organs at sacrifice. Acetonitrile was without developmental effects even at doses toxic to the dam. Of the halogenated compounds, treatment with trichloroacetonitrile (TCAN) and dichloroacetonitrile (DCAN) resulted in reduced fertility and increased early implantation failure. There was no effect on litter size in females bearing live litters, but pup birth weight was reduced in all litters exposed to halogenated compounds. Perinatal survival of the pups was adversely impacted by DCAN and TCAN. Postnatal growth until Day 4 was reduced by DCAN and bromochloroacetonitrile (BCAN) while growth untll Day 42 was consistently affected only by TCAN. Some general observations were made on the usefulness of the criteria used in the screen, and TCAN, the most toxic of the halogenated compounds, was selected for further in-depth evaluation.

/GENOTOXICITY/ ... Dichloroacetonitrile, but not dibromoacetonitrile, is an effective inducer of aneuploidy in oocytes of Drosophila melanogaster. Following inhalation exposure of ZESTE adult females, dichloroacetonitrile (8.6 ppm) induced highly significant increments in the frequencies of sex chromosome loss and gain. Sodium cyanide was also found to be a highly effective inducer of germline aneuploidy, suggesting that cyanide toxicity may contribute to potency of nitriles as inducers of aneuploidy.

/GENOTOXICITY/ ... Microplate-based Chinese hamster ovary (CHO) cell assays /were used/ for chronic cytotoxicity and acute genotoxicity, we analyzed 7 haloacetonitriles (HANs): iodoacetonitrile (IAN), bromoacetonitrile (BAN), dibromoacetonitrile (DBAN), bromochloroacetonitrile (BCAN), chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). The cytotoxic potency (%C1/2 values) ranged from 2.8 uM (DBAN) to 0.16 mM (TCAN), with a descending rank order of DBAN > IAN approximately BAN > BCAN > DCAN > CAN > TCAN. HANs induced acute genomic DNA damage; the single cell gel electrophoresis (SCGE) genotoxicity potency ranged from 37 uM (IAN) to 2.7 mM (DCAN). The rank order of declining genotoxicity was IAN > BAN approximately DBAN > BCAN > CAN > TCAN > DCAN. The accompanying structure-activity analysis of these HANs was in general agreement with the genotoxicity rank order. ... As a chemical class, the HANs are more toxic than regulated carbon-based drinking water disinfection byproducts, such as the haloacetic acids...

The rate constant for the vapor-phase reaction of bromochloroacetonitrile with photochemically-produced hydroxyl radicals has been estimated as 3.9X10-14 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 410 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Bromochloroacetonitrile has a hydrolysis rate constant of 5.3X10-6/sec at pH of 8.7(2), corresponding to a half-life of 36 hours(SRC).