Chloroacetic acids: chloroacetic acid, dichloroacetic acid (DCA), trichloroacetic acid (TCA)

(endorsed 1996)

Guideline

Based on health considerations, the concentrations of chloroacetic acids in drinking water should not exceed the following values:

chloroacetic acid 0.15 mg/L

dichloroacetic acid 0.1 mg/L

trichloroacetic acid 0.1 mg/L

General description

Chloroacetic acids are produced in drinking water as by-products of the reaction between chlorine and naturally occurring humic and fulvic acids. Concentrations reported overseas range up to 0.16 mg/L, and are typically about half the chloroform concentration.

The chloroacetic acids are used commercially as reagents or intermediates in the preparation of a wide variety of chemicals. Monochloroacetic acid can be used as a pre-emergent herbicide, dichloroacetic acid as an ingredient in some pharmaceutical products, and trichloroacetic acid as a herbicide, soil sterilant and antiseptic.

Typical values in Australian drinking water

Based on preliminary data, concentrations of chloroacetic acids in Australian drinking waters range from 0.01 mg/L to 0.1 mg/L for chloroacetic acid, from 0.003 mg/L to 0.05 mg/L for dichloroacetic acid, and from 0.001 mg/L to 0.1 mg/L for trichloroacetic acid.

Limiting formation in drinking water

The formation of chloroacetic acids in drinking water can be minimised by removing naturally occurring organic matter from the source water, reducing the amount of chlorine added, or using alternative disinfectants.

Measurement

The chloroacetic acids can be analysed by a liquid–liquid extraction procedure (USEPA Draft Method 552 1990). In this method the sample is adjusted to pH 11.5 and extracted with methyl tert-butyl ether (MTBE) to remove neutral and basic compounds. The sample is then acidified to pH 0.5 and the chloroacetic acids extracted into MTBE. The dried extracts are methylated, and the esters analysed by gas chromatography using electron capture detection. Limits of determination are lower than 0.001 mg/L.

Health considerations

Chloroacetic acids would be expected to be absorbed after ingestion in view of their water solubility, but there are no data to confirm this assumption. Dichloroacetate is rapidly metabolised to glyoxylate and oxalate by the liver, but no data are available on how the other chloroacetic acids are metabolised.

Dichloroacetic acid has been used in humans to control blood sugar and cholesterol levels. There are no studies on the short- or long-term exposure of humans to chloroacetic acid or trichloroacetic acid.

In rats and mice fed chloroacetic acid for two years, survival was decreased in rats at doses of 15–30 mg/kg body weight per day, whereas in mice, survival was affected at 100 mg/kg body weight per day (males) but not at 50 mg/kg body weight per day. There was no evidence of carcinogenic activity.

Rats given dicholoroacetic acid by gavage at 3 months developed brain lesions and increases in mean liver, kidney and adrenal weight at doses from 125 mg/kg body weight per day. Similar effects were observed at 3 months in dogs fed encapsulated dichloroacetate at 50 mg/kg body weight per day. Mice receiving dichloroacetate in their drinking water for a year had decreased body weight at doses from 410 mg/kg body weight per day, increased liver weight at doses from 77 mg/kg body weight per day, and an increase in the incidence of hepatocellular carcinomas and adenomas at doses from 295 mg/kg body weight per day.

Trichloroacetic acid administered in drinking water to rats for 90 days significantly increased liver peroxisomal activity at a dose of 355 mg/kg body weight per day. A 12-month drinking water study in mice reported increases in liver weight and hepatocellular carcinomas at doses from 178 mg/kg body weight per day.

No data are available on the genotoxicity of dichloroacetic acid. Trichloroacetic acid and chloroacetic acid are not mutagenic in tests using bacteria, but have shown some mutagenic activity in some mammalian cells.

Derivation of guidelines

The guideline values for the chloroacetic acids in drinking water were determined as follows:

i) Chloroacetic acid:

$$\text{ 0.15 mg/L   } = \dfrac{\text{ 15 mg/kg body weight per day x 70 kg x 0.2   }}{\text{ 2 L/day x 500   }} \times \dfrac{\text{ 5   }}{\text{ 7   }}$$

where:

• 15 mg/kg body weight per day is the lowest effect level based on a 2-year feeding study using rats (NTP 1992).

• 70 kg is the average weight of an adult.

• 0.2 is the proportion of total daily intake attributable to the consumption of water.

• 2 L/day is the average amount of water consumed by an adult.

• 500 is the safety factor in using the results of an animal study as a basis for human exposure (10 for interspecies variations, 10 for intraspecies variations and 5 for use of the low-effect level, which is close to the no-effect level).

• 5/7 is used to convert data based on a 5-day week feeding study to a 7-day week equivalent.

The 2004 World Health Organization (WHO) Guidelines do not have a health-based guideline for chloroacetic acid.

ii) Dichloroacetic acid:

$$\text{ 0.1 mg/L } = \dfrac{\text{ 7.6 mg/kg body weight per day x 70 kg x 0.2 }}{\text{ 2 L/day x 500 }}$$

where:

• 7.6 mg/kg body weight per day is the no-effect level based on a 90-day drinking water study using mice (DeAngelo et al. 1991).

• 500 is the safety factor in using the results of an animal study as a basis for human exposure (10 for interspecies variations, 10 for intraspecies variations and 5 for limited evidence of carcinogenicity).

• Other factors are as above.

The 2004 WHO provisional guideline value of 0.05 mg/L includes a factor of 10 for carcinogenicity. On review this was considered to be excessive and a lower factor was used.

iii) Trichloroacetic acid:

$$\text{ 0.1 mg/L } = \dfrac{\text{ 36 mg/kg body weight per day x 70 kg x 0.2 }}{\text{ 2 L/day x 2000 }}$$

where:

• 36 mg/kg body weight per day is the no-effect level based on a 90-day drinking water study using male rats (Mather et al. 1990).

• 2000 is the safety factor in using the results of an animal study as a basis for human exposure (10 for interspecies variations, 10 for intraspecies variations, 10 for evidence of carcinogenicity in animals and 2 because a less than lifetime study was used but chronic studies are available).

• Other factors are as above.

The 2004 WHO has a health-based guideline value of 0.2 mg/L for trichloroacetic acid.

References

DeAngelo AB, Daniel FB, Stober JA, Olsen GR (1991). The carcinogenicity of dichloroacetic acid in the male B6C3F mouse. Fundamental and Applied Toxicology, 16:337–347.

Mather GC, Exon JH, Koller LD (1990). Subchronic 90 day toxicity of dichloroacetic acid and trichloroacetic acid in rats. Toxicology, 64:71–80.

NTP (National Toxicology Program) (1992). Toxicology and carcinogenesis studies of monochloroacetic acid in F344/N rats and B6C3F1 mice (gavage studies). NTP TR 396, NIH Publication No. 92-2851. United States Department of Health and Human Services, Public Health Service, National Institute of Health.

USEPA Draft Method 552 (1990). Determination of haloacetic acids in drinking water by liquid–liquid extraction, derivatization, and gas chromatography with electron capture detection. United States Environmental Protection Agency, Environmental Monitoring and Support Laboratory (EMSL), Cincinnati, Ohio.

WHO (World Health Organization) (2004). Guidelines for Drinking-water Quality. 3rd Edition, WHO, Geneva, Switzerland.

WHO (World Health Organization) (2006). Guidelines for Drinking-water Quality. 3rd Edition, First Addendum. WHO, Geneva, Switzerland.