Chloral hydrate (Trichloroacetaldehyde)
CAS NO 302-17-0 (endorsed 2014)
Guideline
Based on health considerations, the concentration of chloral hydrate in drinking water should not exceed 0.1 mg/L.
Action to reduce chloral hydrate is encouraged, but must not compromise disinfection, as non-disinfected water poses significantly greater risk than chloral hydrate.
General description
Chloral hydrate may be formed as a byproduct during chlorination of water containing naturally occurring organic material. Contamination of drinking water due to industrial spills is unlikely in Australia but has occurred overseas. In the United States, chloral hydrate has been detected in a small number of supplies, with concentrations ranging from 0.00001 mg/L (10 ng/L) to 0.1 mg/L.
Chloral hydrate has been used as a sedative and hypnotic drug in humans at oral doses up to 14 mg/kg body weight. A typical adult dose as a sedative is 250 mg, three times per day (WHO 2005). However, therapeutic use is generally short-term.
Typical values in Australian drinking water
Testing undertaken of drinking water in South Australia between 2000 and 2012 detected up to 0.088 mg/L chloral hydrate (Amis 2012) while a survey conducted in Victoria in 2010 detected up to 0.04 mg/L (Department of Health 2011). Another study found concentrations of chloral hydrate in Australian drinking waters ranged from 0.0002 to 0.019 mg/L (Simpson and Hayes 1998).
Limiting formation in drinking water
The presence of chloral hydrate in drinking water can be minimised by removing naturally occurring organic matter from the source water, by reducing the amount of chlorine added, or by the use of alternative disinfectants.
Measurement
A solvent extraction procedure is suitable for the analysis of chloral hydrate (USEPA Method 551.1 1995). Chloral hydrate is extracted using methyl tert-butyl ether and analysed using gas chromatography with an electron capture detector. The limit of determination is approximately 0.000005 mg/L (5 ng/L). Standard Method 5710 D of the 21st edition of the Standard Methods for the Examination of Water and Wastewater can be used to analyse chloral hydrate as well as trihalomethanes (APHA et al. 2012).
Health considerations
Chloral hydrate is known to be rapidly absorbed in humans and quickly oxidised to trichloroacetic acid or reduced to trichloroethanol.
In its wide use as a sedative or hypnotic drug in humans, concentrated solutions have proved quite irritating to the gastrointestinal tract, and have caused nausea and vomiting. Side effects of the drug have included central nervous system depression, minor sensitivity reactions, and central nervous system excitement. Chronic use may result in development of tolerance, physical dependence and addiction. Addicts have been reported to take as much as 12 grams per day.
There have been a number of animal toxicity studies using rats and mice varying in duration from a few days to 2 years. In a 90-day drinking water study using mice, some enlargement of the liver was reported at doses from 16 mg/kg body weight per day. Other studies have reported that higher doses cause some liver toxicity.
A number of chronic studies have provided equivocal evidence for carcinogenicity (WHO 2005; Health Canada 2008). In a 2-year drinking water study in mice, the incidence of proliferative lesions in the liver was increased at concentrations of 120 mg/L (13.5 mg/kg/d, LOAEL) and above.
Chloral hydrate was mutagenic in tests with some strains of bacteria but did not bind to mouse liver DNA. It increased the frequency of chromosome aberrations in cultured cells and of bone marrow micronuclei in mice.
Derivation of guideline
The guideline value for chloral hydrate in drinking water was determined as follows:
where:
13.5 mg/kg body weight per day is the lowest effect level based on a 2-year drinking water study using mice where the incidence of liver proliferative lesions was increased at the lowest dose (George et al. 1982).
70 kg is the average weight of an adult.
0.8 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.
3000 is the safety factor in using the results of an animal study as a basis for human exposure (10 for interspecies variation, 10 for intraspecies variation, 10 for the use of a lowest effect level instead of a no-effect level, and 3 for limitations in the data relating to carcinogenicity).
The World Health Organization has no formal guideline value but notes a value of 0.1 mg/L could be calculated (WHO 2011).
An allocation factor of 80% is used as, except for therapeutic use, exposure is predominantly from chlorinated drinking water. This is the same approach taken by WHO (2011) and Health Canada (2008).
References
Amis A (2012). SA Water Drinking Water Quality January 2000-July 2012. Friends of the Earth, Melbourne.
APHA 5710-D Formation of other Disinfection By-Products (DBPs) (2012). Standard methods for the examination of water and wastewater. 22nd edition. APHA (American Public Health Association), AWWA (American Water Works Association) and WEF (Water Environment Federation), Washington, DC. p. 5.70.
Department of Health (2011). Section 22 notifications under the Safe Drinking Water Act 2003 for disinfection byproducts not regulated under schedule 2 of the Safe Drinking Water Regulations 2005. Drinking Water Regulation Guidance Note No.13, 2011. Victorian Government.
George, M., Moore, T., Kilburn, S., Olson, G.R. and DeAngelo, A.B. (2000). Carcinogenicity of chloral hydrate administered in drinking water to the male F344/N rat and male B6C3F1 mouse. Toxicologic Pathology, 28:610–618.
Health Canada (2008). Guidance on Chloral Hydrate in Drinking Water. Available at https://www.canada.ca/en/health-canada/services/publications/healthy-living/guidance-chloral-hydrate-drinking-water.html (accessed 14 January 2021)
Simpson KL and Hayes KP (1998). Drinking water disinfection by-products: an Australian perspective. Water Research, 32 (5): 1522-1528.
U.S. EPA (United States Environmental Protection Agency) (1995). Methods for the determination of organic compounds in drinking water — Supplement III. U.S. EPA, Washington, DC (EPA-600/R-95/131).
Water Corporation of Western Australia (2013). Routine testing data (Richard Walker, personal communication)
WHO (2005). Chloral Hydrate in Drinking-water Background document for development of WHO Guidelines for Drinking-water Quality. World Health Organisation, Geneva.
World Health Organization (2011). Guidelines for drinking-water quality, fourth edition.
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