Effects of Subchronic Exposure of Rats to Dichloramine and Trichloramine in Drinking Water
Abstract
The subchronic toxicity of 0.2-200 ppm dichloramine and 0.2-90 ppm trichloramine in the drinking water of rats was investigated using biochemical, hematological, and histopathological parameters. Animals in the highest dose groups consumed 5-15% less fluid than controls with no significant decrease in body weight gain. No clinical signs of toxicity were observed in either case. Both males and females dosed with 90 ppm trichloramine had significantly increased relative kidney/body weights and the females had increased hepatic glutathione S-transferase and UPD-glucuronosyltransferase activities. No significant changes were detected in other xenobiotic metabolizing enzymes or in serum biochemistry, urine biochemistry, or hematology. Both dichloramine and trichloramine induced minimal to mild adaptive histopathological changes in thyroids and kidneys of animals of both sexes. Dichloramine, but not trichloramine, was associated with histological changes in the gastric cardia characterized by epithelial hyperplasia at concentrations of 2 ppm and above in the males and 200 ppm in the females. This study indicates that dichloramine produced mild histological effects at drinking water concentrations of >0.2 ppm in males (0.019 mg/kg/day) and >2 ppm in females (0.26 mg/kg/day) while trichloramine produced biochemical and mild histological effects at levels of >2 ppm both in males (0.23 mg/kg/day) and in females (0.29 mg/kg/day).
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The authors concluded that trichloramine produced mild histological effects at doses >0.23 mg/kg bw/day in males and >0.29 mg/kg bw/day in females.
“The authors concluded that trichloramine produced mild histological effects at doses >0.23 mg/kg bw/ day in males and >0.29 mg/kg bw/day in females (Nakai et al. 2000).”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
Trichloramine induced minimal to mild adaptive histopathological changes in thyroid and kidneys in both sexes, with relative kidney weights increased at the highest dose.
“Trichloramine induced minimal to mild adaptive histopathological changes in thyroid and kidneys in both sexes.The histopathological changes described in the thyroid were reduced follicle size, colloid density and vesiculation of nuclei.Relative kidney weights were increased in both sexes at the highest dose.”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
In rats, 13-week trichloramine in drinking water increased hepatic glutathione S-transferase and uridine diphosphate glucuronosyltransferase activities in females at 13 mg/kg/day, with no significant changes in other xenobiotic metabolizing enzyme activities or hematological and biochemical parameters.
“Increases in hepatic glutathione S-transferase and uridine diphosphate glucuronosyltransferase activities were detected in females receiving 13 mg/kg bw/day.No significant changes were detected in other xenobiotic metabolizing enzyme activities or hematological and biochemical parameters.”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
In rats, 13-week dichloramine in drinking water caused no significant changes in xenobiotic metabolizing enzyme activities or hematological and biochemical parameters, but induced minimal to mild adaptive histopathological changes in thyroid and kidneys and gastric cardia epithelial hyperplasia at >=0.19 mg/kg/day in males and >=2.5 mg/kg/day in females.
“No significant changes were detected in xenobiotic metabolizing enzyme activities or in hematological and biochemical parameters.Dichloramine induced minimal to mild adaptive histopathological changes in thyroid and kidneys in both sexes (no statistical analysis for individual dose levels).”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
In the only study located, male and female rats administered dichloramine in drinking water (0.019-24 mg/kg bw/day) for 13 weeks showed minimal to mild histological effects in thyroid, kidneys or gastric cardia from 0.19 mg/kg bw/day in males and from 2.5 mg/kg bw/day in females.
“In the only study located, male and female rats were administered dichloramine in drinking water (0.019-24 mg/kg bw/ day) for 13 weeks.Minimal to mild histological effects in thyroid, kidneys or gastric cardia were observed from 0.19 mg/ kg bw/day in males and from 2.5 mg/kg bw/day in females, respectively (Table 5 and Section 10) (Nakai et al. 2000).”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
It is unclear how the effect levels in the Nakai et al. (2000) trichloramine study were derived from the results presented in the paper.
“It is unclear how these effect levels were derived from the results presented in the paper.”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
In the only long-term study located, male and female rats administered trichloramine in drinking water (0.020-13 mg/kg bw/day) for 13 weeks showed minimal to mild histological effects in thyroid and kidneys at doses >0.23 mg/kg bw/day in males and >0.29 mg/kg bw/day in females, and increased hepatic enzyme activities among females only (13 mg/kg bw day).
“In the only long-term study located, male and female rats were administered trichloramine in drinking water (0.020-13 mg/kg bw/day) for 13 weeks.Minimal to mild histological effects in thyroid and kidneys were observed at doses > 0.23 mg/kg bw/day in males and > 0.29 mg/kg bw/ day in females, respectively.Increased hepatic enzyme activities were observed among females only (13 mg/kg bw day) (Nakai”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
In the only animal study located, mild histopathological effects in kidneys, thyroid and gastric cardia were observed among male and female rats administered dichloramine in drinking water for 13 weeks.
“In the only animal study located, mild histopathological effects in kidneys, thyroid and gastric cardia were observed among male and female rats administered dichloramine in drinking water for 13 weeks (Nakai et al. 2000).”
From Inorganic chloramines: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting (2020) · cites this paper as Nakai et al. 2000
Cites
Massin, N., Bohadana, A. B., Wild, P., Héry, M., Toamain, J. P., & Hubert, G. (1998) · Occupational and Environmental Medicine · doi:10.1136/oem.55.4.258 · Cited by 181 · see citing works
Exposure to chloramines in the atmosphere of indoor swimming pools
HERY, M. (1995) · The Annals of Occupational Hygiene · doi:10.1016/0003-4878(95)00013-5 · Cited by 167 · see citing works
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Wastensson, G., & Eriksson, K. (2020) · Critical Reviews in Toxicology · doi:10.1080/10408444.2020.1744514 · Cited by 30 · see citing works
- Authors
- Nakai, J. S., Poon, R., Lecavalier, P., Chu, I., Yagminas, A., & Valli, V. E.
- Affiliations
- Health Canada (CA)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Nakai, Jamie S.
- ORCID
- Poon, Raymond
- Venue
- Regulatory Toxicology and Pharmacology
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 31
- Issue
- 2
- Pages
- 200-209
- ISSN
- 0273-2300 (ISSN-L)
- OpenAlex
- W2075448498
- Cited by
- 3
- References
- 2
- Citations by year
- 2020: 1 · 2015: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Regulatory Toxicology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Environmental Toxicology and Ecotoxicology
- Keywords
- dichloramine, trichloramine, subchronic toxicity, drinking water exposure, kidney weight, UDP-glucuronosyltransferase, xenobiotic metabolism, thyroid histopathology, sex differences, rats
- MeSH terms
- Benzenesulfonamides, Administration, Oral, Animals, Chlorides, Drinking, Eating, Female, Gastric Mucosa, Glutathione Transferase, Kidney, Liver, Male, Organ Size, Spleen, Sulfonamides, Glucuronosyltransferase, Water Pollutants, Chemical, Water Supply, Weight Gain, Rats, Sprague-Dawley, Nitrogen Compounds, Rats
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