Trichloroacetaldehyde (chloral hydrate) (endorsed 20XX) CAS NO 302-17-0 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 Page 1 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: 0.1 mg/L = 13.5 mg/kg body weight per day 70 kg 0.8 2 L/day 3000 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 2000) 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 http://www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/chloral_hydratechloral/index-eng.php#b2_4 (accessed 15 July 2013) 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) Page 2 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. Page 3 Monochloramine (endorsed 20XX) CAS NO 10599-90-3 GUIDELINE Based on health considerations, the concentration of monochloramine in drinking water should not exceed 3 mg/L (equivalent to 5 mg Cl as Cl2/L). Monochloramine has an odour threshold of 0.5mg/L. GENERAL DESCRIPTION Monochloramine is used as a disinfectant for drinking water supplies. Its use as an alternative to chlorine is becoming more widespread. Although it is less effective than chlorine as an oxidising agent, it persists for a longer time in lengthy pipelines; contact times with microorganisms are consequently longer and concentrations of byproducts such as trihalomethanes are reduced. Where monochloramine is used overseas as a primary disinfectant, concentrations range from 1.5 to 2.5 mg/L. Monochloramine, dichloramine and trichloramine can be formed when water containing ammonia is chlorinated. At neutral pH and above, monochloramine is the main product and is more persistent, and for this reason chloramination should occur at pH >8. Conditions that favour the formation of dichloramine and trichloramine should be avoided because these compounds have lower taste and odour thresholds than monochloramine. Monochloramine has an odour threshold of 0.5 mg/L. TYPICAL VALUES IN AUSTRALIAN DRINKING WATER Monochloramine is used as a disinfectant in some Australian reticulated supplies, and concentrations up to 45 mg/L (as total chlorine) have been applied at the start of long distribution systems to achieve concentrations ranging from 0.5-1.5 mg/L at the ends of distribution systems. TREATMENT OF DRINKING WATER Monochloramine can be removed from drinking water by the use of granular activated carbon, or by reducing agents such as sodium sulphite or sodium bisulphite. MEASUREMENT The concentration of monochloramine in drinking water can be determined by the DPD ferrous titrimetric method (APHA Method 4500-Cl Part F 2012). The limit of determination is 0.1 mg/L. This method measures monochloramine in terms of mg Cl as Cl2/L and not NH2Cl. The guideline value for monochloramine as NH2Cl can be converted to mg Cl as Cl2/L based on molecular weights by multiplying the guideline value as follows: guideline value monochloramine (as NH2Cl) x 71 = guideline value as Cl2/L 51.5 where: 71 is the molecular weight of chlorine (Cl2). 51.5 is the molecular weight of monochloramine (NH2Cl). Page 4 HEALTH CONSIDERATIONS In studies with rats it has been shown that monochloramine is readily absorbed and does not accumulate in tissues. It is metabolised rapidly to the chloride ion and excreted in urine in mammals. No specific toxic effects have been reported for monochloramine from either short-term or long-term studies. However, monochloramine is toxic to fish. In humans, short-term exposure to concentrations of up to 24 mg/L of monochloramine in drinking water did not produce adverse effects. Similarly, volunteers given water containing up to 5 mg/L of monochloramine for 12 weeks did not exhibit adverse effects. Acute haemolytic anaemia has been reported in haemodialysis patients when tap water containing chloramines was used for dialysis. Carcinogenicity studies have reported a slight increase in the incidence of mononuclear cell leukaemia in female rats exposed to monochloramine for 2 years, at doses of approximately 10 mg/kg bodyweight per day. There was no evidence of carcinogenic activity in male rats, or male and female mice. Monochloramine exhibited weak mutagenic activity in one test using bacteria but was negative in another test. It did not induce chromosome aberrations in mammalian cells. Based on inadequate evidence in humans and experimental animals, the International Agency for Research on Cancer concluded that chloramines are not classifiable as to their carcinogenicity to humans (Group 3) (IARC 2004). No data are available on the health effects of dichloramine or trichloramine in drinking water. DERIVATION OF GUIDELINE The guideline value for monochloramine in drinking water was derived as follows: 3 mg/L = 9.4 mg/kg bodyweight per day x 70 kg 2 L/day x 100 where: 9.4 mg/kg bodyweight per day is the no-observed-adverse-effect level (NOAEL) based on 2-year drinking water study using rats (NTP 1992). A similar value was obtained from a human study but this was of a limited duration. 70 kg is taken as the average weight of an adult. 2 L/day is the estimated maximum amount of water consumed by an adult. 100 is the safety factor applied to the NOAEL derived from an animal study (10 for interspecies variations, and 10 for intraspecies variations). Where monochloramine is measured by determining mg Cl as Cl2 by standard DPD ferrous titrimetric methods (as described above, under Measurement) the equivalent guideline value is: 5 mg/L = 9.4 mg/kg bodyweight per day x 70 kg x 71 (molecular weight Cl2) 2 L/day x 100 x 51.5 (molecular weight NH2Cl) It is assumed that all monochloramine intake is from drinking-water. Page 5 REFERENCES APHA Method 4500-Cl Part F (2012). Chlorine (residual): DPD Ferrous Titrimetric method. 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.. IARC (International Agency for Research on Cancer) (2004). Chloramine. IARC Monograph Vol 84, IARC Publications, Lyon. NTP (National Toxicology Program) (1992). Toxicology and carcinogenesis studies of chlorinated water and chloraminated water in F344/N rats and B6C3F1 mice (drinking water studies). NTP, Technical Report No. 392, Publication No. 92-2847. United States Department of Health and Human Services, National Institute of Health. Page 6