Appendix E: Chlorinated ketones

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Appendix E: Chlorinated Ketones

E. 1. I N T R O D U C T I O N The chemicals addressed in this appendix are the halogenated ketones, including 1, l',3,Y-tetrachloropropanone (l,l',3,3'-tetrachloroacetone), monochloropropanone, 1,1'-dichloropropanone, 1,3-dichloropropanone, 1,1,t-trichloropropanone (trichloroacetone), pentachloroacetone, hexachloroacetone, and 3-chloro-4-[dichloromethyl]-5-hydroxy-2(5H)-furanone (MX). These chemicals are relevant to the chapter on the chlorination of drinking water and wastewater and pulp and paper (Table E-1).

TABLE E- 1 CHLORINATED KETONES SELECTED FOR ASSESSMENT a Chemical

Drinking/Waste Water

Incineration

Solvents

Triehloroacetone

Pulp & Paper •

Tetrachloroacetone

•

1,1-Dichloropropanone

•

•

1,1,1 -Trichloropropanone

•

•

Diehloroeyclopentene- 1,2dione

•

3 -Chloro-4-[dichloromethyl]5-hydroxy-2(SH)-furanone

•

•

•

Aquatic assessment focused o n the chlorinated ketones as a group, with emphasis on the above chemicals.

E.2. S O U R C E S , P H Y S I C A L / C H E M I C A L PROPERTIES, AND ENVIRONMENTAL FATE E.2.1. Sources

E.2.1.1. Anthropogenic Sources Chlorinated ketones and furanones are produced during chlorination processes from precursor unchlorinated ketones and furanones naturally present in water. Chlorinated ketones and furanones that have been detected in drinking water and surface waters include 1,1'-dichloropropanone, l,l,l-trichloropropanone, and MX (IARC, 1991). These chemicals are likely produced during the chlorination of drinking water as a result of the reaction of chlorine with naturally occurring humic substances that contain the unchlorinated ketones and furanones (Merrick et al., 1987; Ringhand et al., 1988). Under laboratory conditions, MX was produced during the chlorination of drinking water, humic substances, amino acids, and wood pulp (Holmbom et al.. 1984; Kronberg and Vartiainen, 1988; Horth, 1989; Holmbom et al., 1990). l, l'-Dichloropropanone $835

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and 1,1, l-trichloropropanone were produced during the chlorination of drinking water and humic substances (Kopfler et al., 1985; Meier et al., 1985a). Chlorinated ketones and furanones have been identified as by-products from chlorine bleaching of wood pulp from kraft-type pulp mills (Merrick et al., 1987; Ringhand et al., 1988). M X is believed to arise from the reaction of chlorine with lignin during the bleaching process (Hemming et aL, 1986; Ringhand et aL, 1988). It is probable that other chlorinated ketones in bleach kraft pulp mill effluents are formed from the reaction between chlorine and lignin, since there appears to be a relationship between chlorination products from the chlorination of humic material (found in drinking water) and lignin (from wood pulp) (Coleman et aL, 1984; Kringstad et aL, 1985).

E.2.1.2. Natural Sources It is likely that chlorinated ketones and furanones are generated naturally as secondary metabolites of living organisms. Rhodophyta (red algae) has been reported to synthesize a wide variety of halogenated organic chemicals, from simple haloketones to complicated haloterpenes, using chloride, bromide, or iodide ions from seawater (Fenical, 1975; Gribble, 1992). Additional research and environmental monitoring are needed 1o identify possible natural sources of chlorinated ketones and furanones and the quantities of these chemicals that are released into the environment if natural sources are identified.

E.2.2. Physical/Chemical Properties The physical/chemical properties of selected ketones are summarized in Table E-2. Unless otheiwise indicated, all properties were measured at 25°C. All chlorinated ketones were reported to be unstable in water (Gurol et al., 1981; Meier et al., 1987a,b; Yamashita et al., 1987). Based on the information identified and an assessment of chemical structures, the log octanol/water partition coefficient would be low.

E.2.3. Environmental Fate E.2.3.1. Overview E.2.3.1.1. Air No information was identified in the literature reviewed concerning the fate of chlorinated ketones in the atmosphere.

TABLE E-2 SUMMARY OF SELECTED PHYSICAL/CHEMICAL PROPERTIES

Chemical Name

Molecular Weight (g/tool)

Vapor Pressure (Pa)

Solubility (g/m3)

Triehloroacetone

161.41 ~

NA

NA

0.93 b

Tetrachloroaeetone

195.85 ~

NA

NA

1.32 b

1,1 -Dichloropropanone

126.97 ~

NA

59,800 °

0.54 b

1,1,1 -Trichloropropanone

161.41 ~

NA

14,000 °

O.93b

Dichlorocyelopentene-1,2-dione

164.98

NA

NA

-0.53 b

3 -Chloro-4-[dichloromethyl]-5hydroxy-2(5H) -furanone

217.43 ~

NA

NA

1.07 b

Sources:

b NA

Sweet, 1987. Hanseh and Leo, 1979. ASTER Database, 1994 (calculated). Not available.

l o g Ko~

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Water~Sediment

Chlorinated ketones and furanones have often been detected in drinking water or pulp mill effluents as by-products of chlorination processes (Merrick et aL, 1987; Ringhand et al., 1988; IARC, 1991). No information was found on the environmental fate of 1, l'-dichloropropanoneand 1,1,1-trichloropropanone. However, based on their physical/chemical properties their environmental fate would be similar to chloroacetones, which would generally be unstable in water. Using chloroacetones as models for chlorinated ketones, the number of chlorine atoms contained in a molecule would greatly alter the stability of chlorinated ketones (Yamashita et al., 1987). For example, the order of stability in water among three specific chloroacetones is 1,3-dichloroacetone > pentachloroacetone > hexachloroacetone. Increasing the number of chlorine atoms decreases the stability of the chloroacetone by activating the carbonyl moiety toward nucleophilic attack by water. Chloroacetones are most stable at low temperature and low pH, but degrade rapidly as temperature and pH increase. Under laboratory conditions, hexachloroacetone was shown to be extremely unstable in aqueous solution, even at an acidic pH, and could not be detected within 6 hr in water at a temperature of 15°C and a pH of 4, 6, 7, or 8. However, at a pH of 4.0 and a temperature of 0°C, 70% of the original concentration of hexachloroacetone still remained in aqueous solution after 24 hr. The degradation of 1,3-dichloroacetone was most rapid at a basic (elevated) pH and at high temperature. At a temperature of 15°C and a pH of 8, more than 96% of 1,3-dichloroacetone decomposed within the first 48 hr. Under acidic conditions 1,3dichloroacetone was also more stable. Exposure to sunlight increased the degradation rate slightly. An increase in temperature significantly decreased the stability of 1,3-dichloroacetone (Yamashita et al., 1987). The reaction between 1,1,1-trichloroacetone and water was found to be a first-order reaction, in the pH range of 6 to 8. The stability of 1,1,1-trichloroacetone in water decreased dramatically as pH increased. Hydrolysis of 1,1,1-trichloroacetone resulted in the formation of chloroform. Chloroform formation occurred immediately, suggesting a one-step reaction or formation of an intermediate, which decomposed immediately to chloroform and the corresponding acid (Gurol et al., 1981), trichloroacetic acid. The stability as affected by temperature and pH has been studied for MX (Meier et al., 1987a). MX undergoes pH-dependent ring-chain tautomerism, from a ring form to an open chain form, which has been identified as (E)-2-chloro-3-(dichloromethyl)-4-oxo-2-butenoic acid (E-MX) (Ringhand et al., 1988). Tautomerism occurred in the pH range of 4.5 to 6 (Holmbom et al., 1989). Thus, under acidic conditions MX was favored, whereas under basic conditions E-MX was the most dominant.

E.2.3.1.3. Soil No information was identified concerning the fate of chlorinated ketones in soil.

E.2.3.2. Fugacity Modeling No fugacity modeling could be performed for 1, l'-dichloropropanone, 1,1,1-trichloropropanone, or MX because of their instability and consequent rapid degradation in water. E.3. H A Z A R D

ASSESSMENT

The chlorinated ketones discussed here are by-products of chlorination processes, whether of drinking or wastewater or of pulp. Since chlorinated ketones that may be produced during chlorine bleaching of wood pulp would be discharged into the aquatic environment, these chemicals are discussed with respect to potential adverse effects on organisms in the aquatic environment. Chemicals produced by the chlorine disinfection of drinking water are considered in the human health hazard assessment.

E.3.1. Human Health Hazard Assessment

E.3.1.1. Bioavailability, Metabolic Conversion, Pharmacokinetics, and Bioaccumulation No studies were identified which evaluated the bioavailability, metabolism, or bioaccumulation of haloketones after oral ingestion, inhalation, or dermal exposure.

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E.3.1.2. Mammalian Toxicology (Laboratory Animal and Biochemical Studies)

L e t h a l Effects Acute studies with hexachloroacetone indicated an oral LDso of 1550 mg/kg body wt in male Wistar rats, a dermal LDso of 2980 mg/kg body wt in male albino rabbits, and LCs0'S of 660 and 360 ppm in albino rats after 3- and 6-hr inhalation exposures, respectively (BorzeUeca and Lester, 1965). The oral LDs0 for MX was 128 mg/kg in Swiss-Webster mice (Meier et aL, 1987a).

N o n l e t h a l Effects Liver toxicity was observed in mice receiving a single dose of 325 mg 1,1-dichloroacetone/kg body wt. No effects on liver were observed following exposures to a single dose of 130 mg 1, l-diehloroacetone/kg body wt (Laurie et al., 1986).

R e p r o d u c t i v e Effects Signs of maternal toxicity and fetotoxicity were reported in mice receiving a dose of 15 mg l,l',3,3'tetrachloroacetone via gavage on Days 6 to 15 of gestation (John et ak, 1983).

D e v e l o p m e n t a l Effects In one developmental toxicity assay, no effects were observed in rabbits dosed with 10 mg l,l',3,3'tetrachloroacetone (John et al., 1983).

Genotoxicity Studies to assess the in vitro toxicity of monochloropropanone, 1, l-dichloropropanone, and 1,3-dichloropropanone showed that all three chloropropanones were cytotoxic to suspensions of male rat hepatocytes at concentrations of 0.5 to 10 mmol (Merrick et al., 1987). The mutagenie potential of the chloropropanones to Salmonella typhimurium was also tested. Monochloropropanone was nonmutagenic, while 1,1-dichloropropanone and 1,3-dichloropropanone were both mutagenic without metabolic activation. The 1,3-dichloropropanone isomer was found to be more potent than l, 1-dichloropropanone isomer. Positive mutagenicity results have been reported in bacterial assays using S. typhirnurium (TAI00) without metabolic activation for the following haloketones: 1,1-Dichloropropanone (Meier et al., 1985b), l,l,ltrichloropropanone (Meier et al., 1985b), 1,1,3,3-tetrachloropropanone (Meier et al., 1985b), and MX (Hemming et aL, 1986; Meier et al., 1987b; Kronberg and Vartiainen, 1988). Trichloroacetone was mutagenic to S. typhimurium strains TA1535, TA97, TA98, and TA100, but not to strains TA1537 and TA1538 (Nestmann et al., 1985). Addition of exogenous metabolic activation ($9) had no effect. Tetrachloroacetone was found to be mutagenic in strains TA98 and TA 100, with $9 enhancing the effects in TA98 only. Negative results were found with strains TA1535, TA1537, TA1538, and TA97. Pentachloroacetone induced mutagenic effects in strains TA97, TA98, and TA100, with $9 slightly increasing the effects in strain TA97 and TA98, but not in strain TAI00. Negative results with pentachloroacetone were found with strains TA 1535, TA 1537, and TA 1538. Hexachloroacetone was found to be mutagenie to both TA98 and TAI00. MXwas mutagenic inS. typhimurium strains TA1535, TA1538, TA92, TA97, TA98, TA100, and TAI02 without metabolic activation (Meier et al., 1987a), In the presence of metabolic activation, the mutagenicity of MX to strain TA100 was greatly reduced. MX-induced chromosomal aberrations in Chinese hamster ovary cells after 6 to 8 hr of exposure to very low doses (4 #g/ml) without the presence of exogenous

POTENTIAL ADVERSE EFFECTS OF CHLORINATED CHEMICALS

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metabolic activation. With metabolic activation, MX induced chromosomal aberrations after 2 hr of exposure, but at higher doses (75 #g/ml). In an in vivo genotoxicity bioassay, micronuclei were not induced in mouse bone marrow when MX was administered by oral gavage at doses of up to 70% of the LDs0. MX has been found to account for 20 to 50% of the mutagenic potential of chlorinated drinking water (Meier et al., 1987b; Backlund et al., 1989).

Carcinogenicity Short-term carcinogenicity assays (i.e., lung adenoma assay and skin painting initiation-promotion assays) were negative for 1,1-dichloroacetone (Bull and Robinson, 1985), 1,1,1-trichloroacetone (Bull and Robinson, 1985), and 1,1',3,Y-tetrachloroacetone (Theiss et al., 1977). Positive results were observed in similar assays conducted with 1,3-dichloroacetone (Robinson et al., 1986).

E.3.1.3. Mechanisms of Toxicity Monochloropropanone, 1,1-dichloropropanone, and 1,3-dichloropropanone have been shown to react directly with reduced glutathione (GSH) in vitro (Merrick et al., 1987). In cytotoxicity studies, monochloropropanone, 1,1-dichloropropanone, and 1,3-dichloropropanone led to a rapid decline in cellular GSH levels. In addition, a number of haloketones were strongly mutagenic in bacterial assays. This information is suggestive of a mechanism of action involving the direct interaction of haloketones with cell macromolecules, possibly including DNA.

E.3.2, A q u a t i c W i l d l i f e H a z a r d A s s e s s m e n t

E.3.2.1. Bioavailability, Metabolic Conversion, Pharmacokinetics, and Bioaccumulation No studies were identified that evaluated the bioavailability, metabolic conversion, or bioaccumulation of haloketones in aquatic species.

E.3.2.2. Laboratory Studies Information on the toxicity of chlorinated ketones in aquatic wildlife was limited. Only one study was available, an acute bioassay of trichloroacetone and tetrachloroacetone using the rainbow trout (McKague et aL, 1990). The 96-hr LCs0's reported for tri- and tetrachloroacetone were 2.3 and 11.0 mg/liter, respectively.

E.3.3. Terrestrial W i l d l i f e H a z a r d A s s e s s m e n t No information was identified on the potential bioavailability, metabolism, bioaccumulative potential, or acute lethality of chlorinated ketones in terrestrial wildlife. However, the responses of terrestrial wildlife to these chemicals would not be expected to be different from those reported in laboratory animals.

E.3.4. O t h e r E n v i r o n m e n t a l Effects No information was identified linking chlorinated ketones to other environmental effects such as ozone depletion, acid rain, and forest decline.

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APPENDIX E REFERENCES

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