1.1. Synonyms

Chem. Abstr. Services Reg. No.: 83463-62-1

Chem. Abstr. Name: Bromochloroacetonitrile

IUPAC Systematic Name: Bromochloroacetonitrile

1.2. Structural and molecular formulae and molecular weight

1.3. Chemical and physical properties of the pure substance

1. Description: Liquid
2. Boiling-point: 138–140°C (Oliver, 1983)
3. Density: 1.68 (Trehy & Bieber, 1981)
4. Spectroscopy data: Mass spectroscopy data have been reported (Coleman et al., 1984).
5. Octanol/water partition coefficient (P): log P, 0.28 (calculated by the method of Leo et al., 1971)
6. Half-time in water at 25°C: 55 h at pH 8.32 (Trehy & Bieber, 1981)
7. Conversion factor¹: mg/m³ = 6.32 × ppm

1.1. Synonyms

Chem. Abstr. Services Reg. No.: 107-14-2

Chem. Abstr. Name: Chloroacetonitrile

IUPAC Systematic Name: Chloroacetonitrile

Synonyms: Chloracetonitrile; 2-chloroacetonitrile; alpha-chloroacetonitrile; chloromethyl cyanide; monochloroacetonitrile; monochloromethyl cyanide

1.2. Structural and molecular formulae and molecular weight

1.3. Chemical and physical properties of the pure substance

1. Description: Colourless liquid (Eastman Kodak Co., 1987; Sax & Lewis, 1987)
2. Boiling-point: 126–127°C (Weast, 1989)
3. Density: 1.193 at 20°C (Weast, 1989)
4. Spectroscopy data¹: Infrared, raman [7886]; Pouchert, 1981, 1985a,b), nuclear magnetic resonance (Sadtler Research Laboratories, 1980, proton [6783]; Pouchert, 1974, 1983) and mass spectral data [23] have been reported (STN International, 1989a).
5. Solubility: Very soluble in ethanol and diethyl ether (STN International, 1989a; Weast, 1989)
6. Octanol/water partition coefficient (P): log P, 0.23 (Chemical Information Systems, 1990) (g)
7. Conversion factor ²: mg/m³ = 3.09 × ppm

1.1. Synonyms

Chem. Abstr. Services Reg. No.: 3252-43-5

Chem. Abstr. Name: Dibromoacetonitrile

IUPAC Systematic Name: Dibromoacetonitrile

1.2. Structural and molecular formulae and molecular weight

1.3. Chemical and physical properties of the pure substance

1. Description: Liquid
2. Boiling-point: 169–170°C (Oliver, 1983)
3. Density: 2.369 (Trehy & Bieber, 1981)
4. Spectroscopy data¹: Infrared, raman [6434]; Pouchert, 1981, 1985a,b), nuclear magnetic resonance (Sadtler Research Laboratories, 1980, proton [2567], grating [883]; Pouchert, 1974, 1983) and mass spectral data (STN International, 1989a [162C]) have been reported.
5. Octanol/water partition coefficient (P): log P, 0.42 (calculated by the method of Leo et al., 1971)
6. Half-time in water at 25°C: 500 h at pH 7.4; 85 h at pH 8.3; 19 h at pH 9.0 (Bieber & Trehy, 1983)
7. Conversion factor²: mg/m³ = 8.13 × ppm

1.1. Synonyms

Chem. Abstr. Services Reg. No.: 3018-12-0

Chem. Abstr. Name: Dichloroacetonitrile

IUPAC Systematic Name: Dichloroacetonitrile

Synonyms: Dichloromethyl cyanide

1.2. Structural and molecular formulae and molecular weight

1.3. Chemical and physical properties of the pure substance

1. Description: Liquid
2. Boiling-point: 112–113°C (Weast, 1989)
3. Density: 1.369 at 20°C (Weast, 1989)
4. Spectroscopy data¹: Infrared, raman [4637, 4639]), nuclear magnetic resonance (Sadtler Research Laboratories, 1980, proton [23934]) and mass spectral data (Coleman et al., 1984) have been reported.
5. Solubility. Soluble in ethanol (Weast, 1989) and methanol (STN International, 1989a)
6. Octanol/water partition coefficient (P): log P, 0.14 (Chemical Information Systems, 1990)
7. Half-time in water at 25°C: 30 h at pH 8.3; 0.75 h at pH 9.77 (Bieber & Trehy, 1983)
8. Conversion factor²: mg/m³ = 4.50 × ppm

1.1. Synonyms

Chem. Abstr. Services Reg. No. : 545-06-2

Chem. Abstr. Name: Trichloroacetonitrile

IUPAC Systematic Name: Trichloroacetonitrile

Synonyms: Cyanotrichloromethane; 2,2,2-trichloroacetonitrile; trichloro-methyl cyanide; trichloromethylnitrile

1.2. Structural and molecular formulae and molecular weight

1.3. Chemical and physical properties of the pure substance

1. Description: Colourless liquid (Budavari, 1989; Sax & Lewis, 1987)
2. Boiling-point: 85.7°C (Budavari, 1989)
3. Melting-point: −42°C (Weast, 1989)
4. Density: 1.4403 at 25/4°C (Weast, 1989)
5. Spectroscopy data¹: Infrared (Sadtler Research Laboratories, 1980 prism [38232,429%]; grating [17218, 23996]; Pouchert, 1981,1985a,b) and mass spectral data [383]; Coleman et al., 1984) have been reported.
6. Solubility: Insoluble in water (STN International, 1989a)
7. Conversion factor²: mg/m³ = 5.91 × ppm

1.4. Technical products and impurities

Chloroacetonitrile is available at 98- > 99% purity, dibromoacetonitrile at 95–97% purity, dichloroacetonitrile at 95–98% purity and trichloroacetonitrile at ≥ 98% purity (Riedel-de Haën, 1986 Eastman Kodak Co., 1987; American Tokyo Kasei, 1988; Fairfield Chemical Co., 1988; Pfaltz & Bauer, 1988; Aldrich Chemical Co., 1990).

The trade name for trichloroacetonitrile is Tritox.

(a) Production

Chloroacetonitrile was synthesized by Bisschopinck in 1873 by the reaction of chloroacetamide with phosphoric anhydride (STN International, 1989b). It has been produced commercially by the high-temperature chlorination of acetonitrile (Movsum-Zade et al., 1977).

Dibromoacetonitrile and dichloroacetonitrile have been synthesized by the reaction of N-bromosuccinimide (or N-chlorosuccinimide) with cyanoacetic acid (Trehy & Bieber, 1981). Bromochloroacetonitrile has been synthesized by the reaction of a mixture of N-chlorosuccinimide and N-bromosuccinimide with cyanoacetic acid, and fractional distillation of the resulting mixture of haloacetonitriles (Pereira et al., 1984a; Bull et al., 1985). Bromochloroacetonitrile has also been synthesized by the bromination of chloroacetonitrile with bromine (Trehy & Bieber, 1981).

Trichloroacetonitrile was synthesized by Bisschopinck in 1873 by the reaction of trichloroacetamide with phosphoric anhydride (STN International, 1989b). It has been produced commercially by reaction of acetonitrile with chlorine or sulfonyl chloride in the presence of a catalyst at elevated temperatures (Dow Chemical Co., 1975). Trichloroacetonitrile has also been synthesized from ethyl trichloroacetate and aqueous ammonia and by reaction of methylnitrile, hydrochloric acid and chlorine gas (Budavari, 1989).

(b) Use

Chloroacetonitrile has reportedly been used as a fumigant and as a chemical intermediate; trichloroacetonitrile has reportedly been used as an insecticide (Sax & Lewis, 1987).

(c) Regulatory status and guidelines

No regulatory standards or guidelines have been published for exposures to halogenated acetonitriles.

(a) Natural occurrence

None of the halogenated acetonitriles is known to occur as a natural product.

(b) Water and sediments

Dichloroacetonitrile was detected in tap-water samples taken from two buildings in Durham, NC, USA (McKinney et al., 1976).

In a two-year study of trace organic compounds in drinking-water in Philadelphia, PA, Suffet et al. (1980) tested samples collected at three treatment plants and one hotel, which originated from two surface water (river) sources. Dichloroacetonitrile was identified in four of nine samples originating from the Delaware River but in neither of the two samples originating from the Schuylkill River. No quantitative analysis was performed.

Three dihaloacetonitriles (bromochloroacetonitrile, dibromoacetonitrile and dichloroacetonitrile) were identified in chlorinated ground- and surface water supplies in southern Florida (USA). Although individual concentrations were not determined, the highest total concentration of dihaloacetonitriles found was 42 µg/l in a chlorinated well-water supply. The relative concentrations of the three dihaloacetonitriles varied considerably from supply to supply, and none was found in water supplies that had been lime-softened. Experimental chlorination of lakewater samples confirmed that dihaloacetonitriles were formed in the chlorination process (Trehy & Bieber, 1980, 1981).

Bromochloroacetonitrile and dibromoacetonitrile were identified in stored, chlorinated Rhine water in The Netherlands. The concentrations of bromochloroacetonitrile before and after chlorination were < 0.1 and 3 µg/l, respectively, and those of dibromoacetonitrile, < 0.1 and 1 µg/l (Zoeteman et al., 1982).

Analysis of chlorinated drinking-water samples from ten cities in Ontario, Canada, showed dichloroacetonitrile at 0.3–8.1 µg/l and bromochloroacetonitrile at not detected (< 0.1 µg/l) to 1.8 µg/l. Neither was detected in any of the raw water samples tested; dibromoacetonitrile was not detected in either the raw-water or drinking-water samples. When chlorine was reacted with fulvic acid (a major component of humic substances found in natural waters) for 4–120 h, dichloroacetonitrile was produced in concentrations of 3.5–6.5 µg/l, and bromochloroacetonitrile was not detected (< 0.1 µg/l); when chlorine was reacted with a blue-green alga, dichloroacetonitrile occurred at 0.5–3.5 µg/l and bromochloroacetonitrile at not detected to 0.6 µg/l; after reaction with a green alga, dichloroacetonitrile occurred at 0.3–1.0 µg/l and the bromine compound at not detected to 1.1 µg, indicating that dihaloacetonitriles can be produced by chlorinating aquatic humic substances and algae under conditions used for water treatment (Oliver, 1983).

Samples collected following prechlorination of raw water in 1984 from a drinking-water treatment plant at Cholet, France, contained dichloroacetonitrile at 0.14 µg/l and trichloroacetonitrile at 0.11 µg/l (Bruchet et al., 1985).

Samples of chlorinated wastewater from an extended aeration treatment plant in the USA contained 7–14 µg/l dichloroacetonitrile. Chlorinated lakewater samples from West Palm Beach, FL, contained 5–19 µg/l dichloroacetonitrile and those from Gainsville, FL, 10–17 µg/l (chlorine contact time, 5–70 min). Experimental studies confirmed that dichloroacetonitrile is formed when amino acids, such as aspartic acid, tyrosine and tryptophan, are chlorinated (Trehy et al., 1986, 1987).

Treated water at 10 Canadian sites along the Great Lakes in the spring contained dichloroacetonitrile at a mean concentration of 0.3 µg/l. It was not detected (detection limit, 0.1 µg/l) in treated water samples during the summer or winter or in any of the raw-water samples (Otson, 1987).

Treatment plant samples collected from 29 US community water systems (using free chlorine disinfection) in 1984 and 1985 contained bromochloroacetonitrile at 0.2–9.4 µg/l (25 of 29 sites), dibromoacetonitrile at 0.3–11 µg/l (14 of 29 sites) and dichloroacetonitrile at 0.2–21 µg/l (27 of 29 sites). Distribution samples from the system contained bromochloroacetonitrile at 0.4–10 µg/l (21 of 26 sites), dibromoacetonitrile at 0.2–2.5 µg/l (11 of 26 sites) and dichloroacetonitrile at 0.3–24 µg/l (21 of 26 sites) (quantification limits, 0.2–0.3 µg/l) (Reding et al., 1989).

Water samples collected from 10 US utilities in 1985 (using free chlorine disinfection, in one of which ammonia was added before distribution) contained bromochloroacetonitrile at < 10 µg/l at all of seven sites for which data were available, dibromoacetonitrile at < 10 µg/l at three of the seven sites and dichloroacetonitrile at < 10 µg/l at all of 10 sites; trichloroacetonitrile was not found at any of the eight sites for which data were available (Stevens et al., 1989).

Samples of finished water were taken from 35 US utilities in spring, summer, autumn and winter, 1988–89. The median concentrations (µg/l) of halogenated acetonitriles measured were: bromochloroacetonitrile, 0.50–0.70; dibromoacetonitrile, 0.48–0.54; dichloroacetonitrile, 1.1–1.2; and trichloroacetonitrile, not detected (detection limits, < 0.012 and < 0.029, according to season) (Krasner et al., 1989).

(a) Oral administration

Mouse: In a screening assay based on the enhanced induction of lung tumours, groups of 40 female strain A/J mice, 10 weeks old, were given 10 mg/kg bw chloroacetonitrile, dichloroacetonitrile, trichloroacetonitrile, bromochloroacetonitrile or dibromoacetonitrile [purity unspecified] in 10% Emulphor by oral gavage three times per week for eight weeks. A group of 40 animals given 10% Emulphor only served as controls. Survival at the end of the study (at nine months of age) was: control, 31/40; chloroacetonitrile-treated, 28/40; dichloroacetonitrile-treated, 30/40; trichloroacetonitrile-treated, 32/40; bromochloroacetonitrile-treated, 32/40- and dibromoacetonitrile-treated, 31/40. The numbers of animals with lung tumours and the average numbers of tumours per animal were: control, 3/31 and 0.1; chloroacetonitrile-treated, 9/28 and 0.43 (p < 0.05); dichloroacetonitrile-treated, 7/30 and 0.23; trichloroacetonitrile-treated, 9/32 and 0.38 (p < 0.05); bromochloroacetonitrile-treated, 10/32 and 0.34 (p < 0.05); dibromoacetonitrile-treated, 5/31 and 0.19 (Bull & Robinson, 1985).

(b) Skin application

Mouse: In a series of three initiation-promotion experiments, groups of 40 female Sencar mice [age unspecified] were given topical applications of 200, 400 or 800 mg/kg bw chloroacetonitrile (> 99% pure), dichloroacetonitrile (> 99% pure), trichloroacetonitrile (98% pure), bromochloroacetonitrile (93% pure) or dibromoacetonitrile (96% pure) in 0.2 ml acetone three times per week for two weeks. Two weeks following the last application of the halogenated acetonitrile, 1.0 µg 12-O-tetradecanoylphorbol 13-acetate (TPA) was applied topically three times per week for 20 weeks. Animals were observed for one year. The numbers of animals with skin tumours and the numbers of squamous-cell papillomas and carcinomas are given in Table 1 (Bull et al., 1985). [The Working Group noted that the results were variable and were derived from three separate studies not conducted simultaneously.]

In another experiment, groups of 40 female Sencar mice [age unspecified] were given topical applications of 800 mg/kg bw chloroacetonitrile, dichloroacetonitrile, trichloroacetonitrile or bromochloroacetonitrile or 400 mg/kg bw dibromoacetonitrile at the same purity described above in 0.2 ml acetone three times per week for 24 weeks. A group of 40 female mice given topical applications of acetone on the same schedule served as controls. No skin tumour occured (Bull et al., 1985). [The Working Group noted that the duration of the study was not specified.]

(a) Experimental systems

(iv) Genetic and related effects (Table 3)

Table 3.

Genetic and related effects of bromochloroacetonitrile.

The genetic and related effects of the haloacetonitriles considered have been reviewed (Bull, 1985).

Bromochloroacetonitrile

Mutation was induced in Salmonella typhimurium. Sister chromatid exchange was induced in Chinese hamster ovary (CHO) cells and DNA strand breaks in human lymphoblast cell lines. In mice dosed for five days, neither micronuclei in bone marrow nor abnormal sperm morphology was induced.

Chloroacetonitrile

Chloroacetonitrile did not induce mutation in a single study with S. typhimurium. Sister chromatid exchange was induced in one study using Chinese hamster ovary (CHO) cells, and DNA strand breaks (weakly) were induced in another using a human lymphoblast cell line. In mice dosed for five days, neither micronuclei in bone marrow nor abnormal sperm morphology was induced.

Dibromoacetonitrile

Dibromoacetonitrile was not mutagenic in either S. typhimurium or Drosophila melanogaster. Sister chromatid exchange was induced in Chinese hamster ovary (CHO) cells and DNA strand breaks in human lymphoblast cell lines. In mice dosed for five days, neither micronuclei in bone marrow nor abnormal sperm morphology was induced.

Dichloroacetonitrile

Dichloroacetonitrile induced mutation in S. typhimurium and in one study in D. melanogaster. Mitotic recombination was not induced in yeast. Dichloroacetonitrile induced sister chromatid exchange in Chinese hamster ovary (CHO) cells and DNA strand breaks (weakly) in a human cell line. In mice dosed for five days, neither micronuclei in bone marrow nor abnormal sperm morphology was induced.

Trichloroacetonitrile

Trichloroacetonitrile did not induce mutation in S. typhimurium. Sister chromatid exchange was induced in Chinese hamster ovary (CHO) cells and DNA strand breaks in human cell lines. In mice dosed for five days, neither micronuclei in bone marrow nor abnormal sperm morphology was induced.

(b) Humans

No data were available to the Working Group.