Drinking Water and Health, Volume 7 Disinfectants and Disinfectant By-Products (1987) / Chapter Skim
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4 CHEMISTRY AND TOXICITY OF SELECTED DISINFECTANTS AND BY-PRODUCTS
4 CHEMISTRY AND TOXICITY OF SELECTED DISINFECTANTS AND BY-PRODUCTS
Pages 80-189
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From page 80... ...
For carcinogens, the multistage model was chosen for extrapolating from the high doses used in animal studies to the lower doses common in the environment of humans. This model appears to have a greater biological basis than most other models and in most cases is more conservative, usually producing higher estimates of risk at low doses.
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From page 81... ...
Given the absence of data on these noningestion routes, this report does not include specific estimates of their contribution to total exposure. Further, drinking water is not the only medium or source of exposure to many of the substances evaluated here.
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From page 82... ...
HEALTH ASPECTS Based on relatively early literature, the American Conference of Governmental Industrial Hygienists (ACGIH, 1986) recommends a threshold limit value (TLV' expressed as an 8-hour time-weighted average for workroom air of 1 ppm (approximately 3 mg/m3)
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From page 83... ...
CHLORINE DIOXIDE CAS No. 10049-04-4 C1O2 Chlorine dioxide is a reddish-yellow gas that freezes at-59.5°C, boils at 10°C, and is explosive in air at concentrations of about 4% or more.
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From page 84... ...
In both species ingestion of chlorine dioxide affects the mucosal surfaces of the alimentary tract and the chemical composition of nutrients and hormones within it, apparently by oxidation and covalent binding of bioavailable iodide, which is ubiquitous in the digestive tract. Absorption of the iodinated molecules may be the mechanism for inhibition of activity by the thyroid and for an accelerated decrease in the concentration of thyroxin in the blood.
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From page 85... ...
Ten normal volunteers ingested two 500-ml portions of water containing chlorine dioxide 4 hours apart every fourth day for a total of 6 dosing days. Each portion was consumed within 15 minutes.
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From page 86... ...
The chlorine dioxideexposed group had a significantly greater proportion of premature births, but this difference between the two communities disappeared when the effect of the age of the mother on premature parturition was taken into account. The only other significant difference after compensating for variations in feeding methods was a greater postnatal loss of weight by infants born into the exposed population.
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From page 87... ...
In another experiment from the same laboratory (Abdel-Rahman et al., 1984) , osmotic fragility was studied in rats given drinking water containing 10 to 1,000 mg chlorine dioxide/liter (about 1 to 100 mg/kg bw per day)
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From page 88... ...
(1985) gave female rats drinking water containing chlorine dioxide concentrations of 2, 20, or 100 mg/liter starting 2 weeks prior to mating and continuing through lactation, 21 days after parturition.
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From page 89... ...
(1986) investigated the effects of drinking water containing chlorine dioxide at 2 or 15 ppm on thyroid function and on plasma cholesterol in rabbits and pigeons.
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From page 90... ...
assuming that a 70-kg human consumes 2 liters of water daily, which contributes 20% of total intake: 3 mg/kg low/day x 70 kg x 0.2 0.21 mg/liter, or = 100 x 2 liters 210 ~g/liter. A SNARL may also be estimated for a 10-kg child consuming 1 liter of water daily, which contributes 20% of total intake: 3 mg/kg low/day x 10 kg x 0.2 100 x 1 liter CHLORAMINES Monochioramine CAS No.
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From page 91... ...
Under conditions that the reducing mechanisms in stomach fluid may overcome (Scully et al., 1986) , the transfer of a chlorine atom from monochloramine to organic amines or amino acids to form organic chloramines may be important (Isaac and Morris, 1980, 1983, 1985; Snyder and Margerum, 19821.
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From page 92... ...
92 DRINKING WATER AND HEALTH minutes at pH 6 (concentrations from Scully et al., 1985, 1986; rate data from Isaac and Morris, 19851. In this case the toxicological effects of monochloramine may be related to the organic chloramines formed by this chlorine transfer reaction.
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From page 93... ...
The subcellular distribution of 36Cl activity in rat liver preparations was similar at 24 hours following oral administration of either chloramineL36Cl] or chloride-36 (Abdel-Rahman et al., 1983; Sub and Abdel-Rahman, 1983~.
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From page 94... ...
(1981) administered drinking water containing chlorine, chloramine, chlorine dioxide, sodium chlorite, or sodium chlorate to adult male human subjects.
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From page 95... ...
The amount of oxidative damage was proportional to the amount of monochloramine formed. Furthermore, exposure of red blood cells to monochloramine also inhibited the hexose monophosphate shunt that protects red cells from oxidative damage.
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From page 96... ...
Fetner (1962) found that distilled water containing monochloramine produced chromosome breakage when it was used for soaking Vicia faba seeds.
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Selected Disinfectants and By-Products 97 abnormal anaphases. Monochloramine produced chromosome breakage at concentrations that exhibited little evidence of tissue damage.
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From page 98... ...
(1986) studied the effects of monochloramine on thyroid function and on plasma cholesterol in rabbits and pigeons.
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From page 99... ...
The melting point of sodium chlorite is between 1 80°C and 200°C. Chlorite is used for the on-site production of chlorine dioxide, in water purification, in paper pulp, and as a bleaching agent for textiles.
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From page 100... ...
administered 36Cl-labeled sodium chlorite and sodium chlorate to rats in a study of their absorption, distribution, and excretion Groups of four male rats drank 3 ml of solutions of chlorite (10 mg/liter) or chlorate (5 mg/liter)
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(1982) observed that one effect of ClO2 in African Green monkeys was a decrease in serum thyroxine.
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conducted controlled clinical investigations of volunteer human subjects exposed to sodium chlorite and sodium chlorate (as well as to some other materials)
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From page 103... ...
group-time interaction was found in the case of group mean corpuscular hemoglobin; however, linear trend regression analysis did not show a significant linear trend, and the physiological significance of this interaction was doubted. In a third phase of the study on sodium chlorite, three subjects found to be deficient in G-6-PD were given 500 ml of drinking water containing 5 mg chlorite/liter of water every day for 12 weeks, as in the second phase.
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From page 104... ...
group-time interaction in the case of group mean corpuscular hemoglobin and of group mean blood urea nitrogen, but linear regression analysis did not show a significant linear trend in the means of these effects, and they were judged not to be clinically significant. Observations in Other Species Acute Elects There were no studies available.
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From page 105... ...
(1979b) found that rats given drinking water containing NaClO2 at 100 mg/liter for 30 days had a mean concentration of glutathione in their red blood cells that was only 66.
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From page 106... ...
found an increase in mean corpuscular volume, in osmotic fragility and G-6-PD activity, and in the number of acanthocytes in A/J and C57L/J mice given drinking water containing 100 ppm (but not at 1 or 10 ppm) NaClO2, equivalent to 13-18 mg chlorite/ kg bw per day for 30 days.
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From page 107... ...
There were three groups of controls; two received distilled water and the third received water containing enough sodium chloride to be tonically equivalent to 1,000 ppm of sodium chlorite. There were seven female and seven male rats in each group except that no female rats were included in one of the drinking water controls.
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on Fisher's exact test or the chi-squared test. The investigators' conclusion on sodium chlorite was that a "potential promoting effect was suspected...." Developmental E~ects Suh et al.
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described effects of chlorite on several aspects of reproduction. Long-Evans rats ingested water containing sodium chlorite at 0, 1, 10, or 100 ppm for 66-76 days.
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Hematological effects have been observed both in humans and in laboratory animals. As in the case of chlorine dioxide, decreased thyroid function has been associated with exposure to chlorate and chlorite.
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From page 111... ...
Selected Disinfectants and By-Products 111 A SNARL may also be estimated for a 10-kg child consuming 1 liter of water daily, which contributes 20% of total intake: 0.034 mg/kg/day x 10 kg x 0.2 _ 0.007 mg/liter, or _ 7 ~g/liter. TR I HALOM ETHAN ES ChIoroform CAS No.
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From page 112... ...
The health effects of this byproduct of drinking water disinfection were reviewed in Volume 3 of Drinking Water and Health (NRC, 1980, pp. 205-2064; the following material updates and reevaluates that information.
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From page 113... ...
The possible modifiers investigated were SKF-525A, an inhibitor of mixed-function oxidase; the antioxidants vitamin E and N,N'-diphenyl-p-phenylenediamine (DPPD) ; and a depletor of cellular glutathione, diethylmaleate.
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From page 114... ...
HEALTH EFFECTS Observations in Humans Because chlorination can lead to the formation of chloroform or other chlorocarbons in drinking water, there has been interest in the cancer incidence among persons whose drinking water has been chlorinated as compared with those whose drinking water has not been so treated. Several epidemiological studies have indicated an association between water chlorination and increased mortality rates from cancer (Cantor et al., 1977, 1978, 1985; Cragle et al., 1985; Kuzma et al., 1977; Page et al., 1976~.
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studied the association of the use of drinking water containing trihalomethanes (THMs) with cancer mortality in 923 U.S.
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From page 116... ...
Improved ventilation of the work area lowered the concentration of chloroform in the ambient air to a mean of 28% of that existing before the improvement and enabled employees to perform their duties comfortably. Physical examinations of 10 employees believed to have been exposed to concentrations of chloroform vapor ranging from 77 to 237 ppm (370 to 1,138 mg/m3)
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From page 117... ...
Selected Disinfectants and By-Products 117 numbers of people in the groups volunteered to be tested for the separate parameters listed.) Hepatomegaly was found in 25% of the employees exposed to chloroform for a comparatively long time, in 12.8% of the employees exposed to chloroform for a shorter time, in 8.7% of the people who had had viral hepatitis, and in 3.7% of the control group.
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From page 118... ...
(1982a) gave rats drinking water containing chloroform concentrations of 5, 50, or 500 ppm for 28 days.
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From page 119... ...
among high-dose males and in all treated groups of females; hexobarbital sleeping times were increased in all groups and significantly so in mid- and high-dose females. High-dose males had increased blood glucose and decreased humoral immunity.
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From page 120... ...
Groups of 30 mice were given water containing 200-, 400-, 600-, 900-, 1,800-, or 2,700-ppm concentrations of chloroform. Two control groups similar to those in the rat experiment were included.
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From page 121... ...
Significant increases in red blood cells (RBCs) and hemoglobin at 12 months among the rats exposed to chloroform concentrations of 200, 900, and 1,800 ppm indicated some hemoconcentration, but significant differences were not seen among these same groups at 18 months.
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(1980) studied the mutagenicity of various compounds known or believed to be produced by treatment with chlorine or chlorine dioxide.
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From page 123... ...
At doses of 1.2 and 2.4 g/kg bw, there was extensive necrosis in all liver lobules, whereas at 0.6 g/kg bw there was necrosis in some lobes. Another bioassay of possible carcinogenicity was performed by the National Cancer Institute (NCI, 19769.
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From page 124... ...
124 DRINKING WATER AND HEALTH week rest period. The investigation was conducted in several parts: First, ICI mice, 52 of each sex per dose level, were given chloroform in toothpaste at doses of 17 or 60 mg/kg bw per day; controls (104 of each sex)
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From page 125... ...
(1982) also reported that water consumption was decreased in rats in a dose-related manner, but water intake tended toward normal at the two lower doses near the end of the study.
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From page 126... ...
intraperitoneally in doses of 0, 5, or 20 mg/kg bw to 15-day-old outbred CD- 1 Swiss mice. At weaning, at 5 weeks of age, 23 to 29 mice at each dose level were given drinking water containing 1,800-ppm concentrations of chloroform.
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From page 127... ...
Selected Disinfectants and By-Products 127 urea nitrogen (BUN) in those given the corn oil solutions but not in those receiving the Emulphor suspensions.
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From page 128... ...
Thirty-five 4-week-old male B6C3F~ mice imbibed drinking water containing DENA in doses of 10 mg/liter for 4 weeks, after which they were given various chlorinated hydrocarbons, including chloroform, in their drinking water at the maximum tolerated dose (MTD) or at one-third of the MTD (1,800 or 600 mg of CHCl3/liter of water)
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From page 129... ...
The carcinogenicity of dibromochloromethane was assessed by the National Toxicology Program in a 2-year rodent bioassay (Dunnick et al., 1985; NIP, 1985~. Both sexes of Fischer 344 rats and B6C3F~ mice were Savaged 5 days per week for 104 weeks (rats)
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From page 130... ...
The estimation of carcinogenic risk calculated in Table 4-8 takes these factors into consideration. In the National Toxicology Program study of dibromochloromethane, results in B6C3F~ male mice show some or equivocal evidence, but not clear evidence, of carcinogenicity.
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From page 131... ...
. bAssuming daily consumption of 1 liter of water containing the compound in a concentration of 1 ~g/liter.
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. bAssuming daily consumption of 1 liter of water containing the compound in a concentration of 1 1lg/liter.
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From page 133... ...
. bAssuming daily consumption of 1 liter of water containing the compound in a concentration of 1 ~g/liter.
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From page 134... ...
Liver cells from male rats were incubated with t2-~4C] DCA, and labeled amino acids were assayed, as were such enzymes as cx-ketoisocaproate dehydrogenase and pyruvate dehydrogenase (PDH)
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From page 135... ...
DCA decreased glucose synthesis from lactate, pyruvate, and alanine in isolated rat hepatocytes, but it did not decrease such synthesis from substrates that do not involve pyruvate carboxylase, viz., propionate or glycerol (Demaugre et al., 19781. The DCA also inhibited pyruvate carboxylation in isolated mitochondria, but only after a period of preincu
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From page 136... ...
HEALTH EFFECTS Observations ~n Humans In a study of the metabolic effects of DCA in man (Stacpoole et al., 1978) , daily oral doses of 3-4 g (43-57 mg/kg bw per day if body weights
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From page 137... ...
Levels of plasma insulin, free fatty acid, and glycerol were unaffected. Plasma cholesterol levels were not affected by treatment in one patient, and, in the other patients, depressed cholesterol levels returned toward pretreatment levels after treatment stopped.
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From page 138... ...
or unlabeled sodium dichloroacetate was given by vein to four human subjects (two at 10 and two at 20 mg/kg bw in 100 ml of saline)
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From page 139... ...
As mentioned earlier, the half-lives for the four human subjects varied between 20 and 36 minutes. Subchronic Effects Katz et al.
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From page 140... ...
, in a study of renal toxicity of chloroacetic acids, reported that DCA and TCA at lower doses did not affect food consumption,
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From page 141... ...
No effects were observed at 0.3 g/liter, equivalent to about 25 ma/ kg bw per day. Impaired growth in male rats from DCA occurred only at the highest concentration in drinking water, 7.5 g/liter; however, in female rats, there was weight loss after exposure to drinking water containing 1.875 g/liter.
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From page 142... ...
] 42 DRINKING WATER AND HEALTH weakness or paralysis in rats dosed orally with DCA for 90 consecutive days to rats at 125, 500, and 2,000 mg/kg bw per day.
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From page 143... ...
The committee estimated SNARLs as: 60 mg/kg/day x 70 kg x 0.2 1,000 x 2 liters 25 mg/kg/day x 70 kg x 0.2 1,000 x 2 liters 0.420 mg DCA/liter, or 420 fig DCA/liter; 0.175 mg TCA/liter, or 175 fig TCA/liter. SNARLS may also be estimated for a 10-kg child consuming 1 liter of water daily, which contributes 20% of total intake: 60 mg/kg/day x 10 kg x 0.2 1,000 x 1 liter 25 mg/kg/day x 10 kg x 0.2 1,000 x 1 liter HALOALDEHYDES ChIoroacetaldehyde CAS No.
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From page 144... ...
Chloral hydrate produces rapid anesthesia in man, and thus its reaction product, trichloroethanol, must be rapidly absorbed from the gastrointestinal tract (Gilman et al., 1985, pp.
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From page 145... ...
Dogs given doses of either chloral hydrate or TCE excreted most of the TCEA produced within their bodies as TCEA glucuronide in urine. The concentration of chloral in venous blood plasma fell as that of TCEA rose
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From page 146... ...
found that an aldehyde dehydrogenase prepared from rabbit liver mitochondria has converted chloral hydrate to TCAA. Observations in Humans Toxic doses of chloral hydrate (approximately 10 g in humans)
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From page 147... ...
reported that trichloroethylene and trichloroacetaldehyde produced damage to lungs, but not to livers, of rats given daily injections intraperitoneally of 0.2 to 2.0 g/kg bw for 5 days. This procedure reduced the mixed function oxidase activity of pulmonary microsomes by 25% to 50%.
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From page 148... ...
administered chloral hydrate to CD-1 mice in the drinking water for 90 days. A 14-day range-finding study had
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From page 149... ...
were significantly different from those of corresponding controls (p < 0.051. To the extent that a pattern is evident from these results, it seems that the liver was most affected by this repeated exposure to chloral hydrate, with males being more affected than females.
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From page 150... ...
However, the humoral immune function of female mice exposed to chloral hydrate for 90 days was depressed. There were fewer splenic antibody-forming cells produced against sheep erythrocytes, 36% fewer in females given 0.07 mg/ml and 40% fewer in those given 0.7 mg/ml.
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From page 151... ...
developed tumors of the stomach. Because chloroacetaldehyde is a metabolite of the carcinogen vinyl chloride, it was tested for carcinogenic activity along with chloroethylene oxide in an initiation-promotion mouse skin experiment (Zajdela et al., 1980~.
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From page 152... ...
A group of halogenated acroleins (propenals) are formed in the chlorination of water containing humic acids and wood pulp.
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From page 153... ...
Toxicity data are lacking for these compounds. The acute oral LDso values for the chloroacetaldehydes in rats are approximately 100 to 300 mg/kg bw; and effects on weight gain, organ-to-body-weight ratios, and lung pathology were found after 12 weeks of study with doses in the approximate range of 2-5 mg/kg bw of monochloroacetaldehyde.
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From page 154... ...
There are insufficient data to assess their toxicity, and there are no good measures of their concentration in drinking water because they are difficult to analyze. They are direct-acting mutagens and are postulated intermediates in the metabolism of chloroethylenes, compounds that are known or suspected carcinogens.
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From page 155... ...
Observations in Other Species Acute Elects Borzelleca and Lester (1965) determined the oral LDso in male Wistar rats for hexachloroacetone to be 1,550 mg/kg bw.
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From page 156... ...
There are insufficient data available for the committee to estimate suggested no-adverse-effect levels (SNARLs) or to perform other r~sk as sessments.
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From page 157... ...
were administered at 0.2, 2.0, arid 15 mung bw; He highest dose level represented 5-10% of He oral LDso of 2 rnM/kg bw determined for rats. The rats eliminated 84% of He administered dose in 48 hours; total recoveries from tissue and excrete were greater Han 95%.
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From page 158... ...
MFO is mixed function oxidase.
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From page 159... ...
(1986) also reported the following oral LDsoS for DBAN: in male CD-1 mice, 289 mg/kg bw; in CD-1 females, 303 mg/kg bw; in male Charles River CD rats, 245 mg/kg bw; and in Charles River CD females, 361 mg/kg bw.
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From page 160... ...
}60 DRINKING WATER AND HEALTH proteins albumin and globulin, alkaline phosphatase (ALP) , 5'-nucleotidase, glucose, and phosphorous; and increases in cholesterol and blood urea nitrogen (BUN)
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From page 161... ...
for DCAN may be calculated based on the NOEL of 8 mg/kg bw per day assuming that a 70kg human consumes 2 liters of water daily, which contributes 20% of the total intake: 8 mg/kg low/day x 70 kg x 0.2 1,000 x 2 liters _ 0.056 mg/liter, or 56 1lg/liter.
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From page 162... ...
, fumigants, fungicides, insecticides, rat extermination, and tear gas. The American Conference of Governmental Industrial Hygienists has set 0.1 ppm (~0.7 mg/m3)
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From page 163... ...
Selected Disinfectants and By-Products 163 CHEMISTRY AND ENVIRONMENTAL FATE In 1980, de Greef et al. reported that tap water from 13 major water supplies of The Netherlands contained chloropicrin in concentrations of about 0.01 ~g/liter, whereas tap water from 7 water supplies that had undergone chlorination contained up to 3.0 ~g/liter.
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From page 164... ...
] 64 DRINKING WATER AND HEALTH In the vapor phase, Moilanen et al.
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From page 165... ...
687) determined the oral LDso of
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From page 166... ...
In a study undertaken for the National Cancer Institute (NCI, 1978) , the mean daily dose of chloropicrin that resulted in no significant decrease in growth of male and female mice or in their probability of survival was 32 mg/kg bw.
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From page 167... ...
Despite that fact, the report concluded that the occurrence of these tumors of the stomach was not significant under the Bonferroni criterion. In 1980, 2 years after publication of the results of the study performed for the National Cancer Institute, Griesemer and Cueto (1980)
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From page 168... ...
Chloropicrin had mild mutagenic activity in the fruit fly when ingested. No information on mutagenic and carcinogenic activities of Chloropicrin in vertebrate or mammalian species seems to exist other than one assay of its carcinogenic activity in the mouse and the rat performed for NCI.
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From page 169... ...
Selected Disinfectants and By-Products 169 CHLOROPHENOLS MONOCH LOROPH ENOLS 2-Chlorophenol, o-ChIoropheno' CAS No. 95-57-S DICH LOROPH ENOLS 2,4-Dichlorophenol CAS No.
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From page 170... ...
The data are summarized in Table 4-14. Acute oral toxicity data for 2,4-pop are summarized in Table 4-15.
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From page 171... ...
171 ~ ~ U~ _ _ __ _ oo .
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From page 172... ...
(1981) reported that 2,4-pop was negative in the hepatocyte unscheduled DNA synthesis and in a modified Ames assay.
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From page 173... ...
P 117 in Documentation of the Threshold Limit Values and Biological Exposure Indices, 5th ed.
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From page 174... ...
1986. Mechanistic aspects of ingested chlorine dioxide on thyroid function: Impact of oxidants on iodide metabolism.
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From page 175... ...
1984. The effects of chronic administration of chlorine dioxide, chlorite and chlorate to normal healthy adult male volunteers.
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From page 176... ...
1982. Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate.
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From page 177... ...
1981. Controlled clinical evaluations of chlorine dioxide, chlorite and chlorate in man.
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From page 178... ...
1949. The Effect on Rats of Chronic Administration of Sodium Chlorite and Chlorine Dioxide in the Drinking Water.
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From page 179... ...
1984. The effects of chronic administration of chlorine dioxide, chlorite and chlorate to normal healthy adult male volunteers.
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From page 180... ...
1980. Cytochrome P-450 mediated genetic activity and cytotoxicity of seven halogenated aliphatic hydrocarbons in Saccharomyces cerevisiae.
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From page 181... ...
. NTP Technical Report Series No.
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From page 182... ...
1978. Characterization of oxalate as a catabolite of dichloroacetate responsible for the inhibition of gluconeogenesis and pyruvate carboxylation in rat liver cells.
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From page 183... ...
1948. The metabolic fate of chloral hydrate.
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From page 184... ...
1958. The enzymic oxidation of chloral hydrate to trichloroacetic acid.
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From page 185... ...
1981. Pulmonary toxicity of chloral hydrate and trichloroacetaldehyde.
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From page 186... ...
P 134 in Documentation of the Threshold Limit Values and Biological Exposure
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From page 187... ...
National Cancer Institute Carcinogenesis Technical Report Series No.
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From page 188... ...
1981. Chemically-induced unscheduled DNA synthesis in primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds.
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From page 189... ...
1977. Acute toxicity and skin corrosion data for some organic and inorganic compounds and aquaeous solutions.
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