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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
immunotoxicity: sub-chronic oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Immunotoxicologic evaluation of chlorine-based drinking water disinfectants, sodium hypochlorite and monochloramine
Author:
Jerry H. Exon, Loren D. Koller, Connie A. O'Reilly and Peter Bercz
Year:
1987
Bibliographic source:
Toxicology, 44, 257-269.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male sprague-Dawley rats were exposed to tested substance in the drinking water from weaning to 12 weeks of age. Spleen and thymus weights, antibody production, delayed-type hypersensitivity (DTH) reactions, natural killer cell (NKC) cytotoxicity, oxidative metabolism response (i.e. chemiluminescence - CL) , phagocytosis by macrophages, production of 2 immunoregulatory cytokines, interleukin 2 (IL2) and prostaglandin E2 (PGE2) were measured.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloramide
EC Number:
234-217-9
EC Name:
Chloramide
Cas Number:
10599-90-3
Molecular formula:
ClH2N
IUPAC Name:
chloranamine
Test material form:
other: in solution
Details on test material:
- Name of test material (as cited in study report): Monochloramine

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Washington State University, Laboratory Animal Resources.
- Age at study initiation: 3 weeks
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: 4/cage
- Diet : ad libitum
- Water : ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data but in controlled condition
- Humidity (%): no data but in controlled condition
- Air changes (per hr): no data but in controlled condition
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: drinking water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Monochloramine was prepared under conditions of alkaline pH (>8.0) by adding 0.01 M sodium hypochlorite to 0.1 M ammonium chloride mixed in 0.01 M sodium hydroxide-sodium chloride. The final monochloramine solution was diluted in deionized water to concentratios of 9, 19 or 38 ppm.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
9 weeks (from 3 to 12 weeks of age)
Frequency of treatment:
daily (via drinking water)
Doses / concentrations
Remarks:
Doses / Concentrations:
9, 19, 38 ppm
Basis:
nominal in water
No. of animals per sex per dose:
12 males
Control animals:
yes

Examinations

Observations and clinical examinations performed and frequency:
No observations and clinical examinations were performed during the time course of the study.
Sacrifice and pathology:
No necropsies were performed.
Cell viabilities:
Not performed.
Humoral immunity examinations:
- Method: Antibody to KLH was elicited by injecting 1 mg KLH/rat 0 and 8 days prior to termination and analized by an indirect enzyme-linked immunosorbent assay (ELISA)
- Dose groups: 9, 19, and 38 ppm
- No. of animals: 12
Specific cell-mediated immunity:
DELAYED-TYPE HYPERSENSITIVITY (DTH) REACTION: Yes
- Method: The DTH reaction wes elicited by sensitizing s.c. with 100 µg of bovine serum albumin (BSA), followed 7 days later by challenge in the right footpad with heat-aggregated BSA and sham-injection in the left footpad with saline.
- Dose groups: 9, 19, 38 ppm
- No. of animals: 12

Non-specific cell-mediated immunity:
not performed
Other functional activity assays:
IL-2 synthesis by adherent resident peritoneal cells (ARPC)
- method: The synthesis of IL-2 was measured by a double antibody radioimmunoassay in supernatants of ARPC stimulated with LPS for 18h.
- Dose groups: 9, 19, 38 ppm
- No. of animals: 12

Chemiluminescence (oxidative metabolism) by adherent resident peritoneal cells:
- method: Chemiluminescent was assessed by activating peritoneal macrophage with phorbal-12-myristate-13-acetate (PMA) in the presence of lumisol and quantitating light emission as CPM on a scintillation counter at various times.
- Dose groups: 9, 19, 38 ppm
- No. of animals: 12
Positive control:
No
Statistics:
The data was analyzed by computerized statstical techniques developed by Statistical Analysis Systems (SAS). Statistical analysis was by analysis of variance (ANOVA) and least squares mean comparisons to control values.

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Gross pathological findings:
not examined
Details on results:
A dose-dependent decrease in raw or adjusted spleen weight compared to controls was observed in rats treated with monochloramine. Reduced spleen weights were significantly different from controls in the 38 ppm monochloramine-treated group. antibody synthesis was significantly (p<= 0.05) suppressed in rats which were treated with 9 or 19 ppm monochloramine. This effect on antibody production was inverse to the exposure level of monochloramine. The PGE2 levels produced by macrophages of rats exposed to 19 or 38 ppm monochloramine was significantly (p<= 0.05) greater than controls and directly related to dose. No significant effects on body weights, DTH reactions, NKC cytotoxicity, IL2 synthesis, macrophage CL or phagocytosis were apparent following monochloramine treatment.

Specific immunotoxic examinations

Cell viabilities:
not examined
Humoral immunity examinations:
effects observed, treatment-related
Specific cell-mediated immunity:
no effects observed
Non-specific cell-mediated immunity:
not examined
Other functional activity assays:
effects observed, treatment-related
Description (incidence and severity):
see field "details on results" for more details
Other findings:
not examined

Effect levels

Dose descriptor:
other: Immunotoxicity
Basis for effect level:
other: see 'Remark'
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, rats exposed to the higher doses of monochloramine had reduced spleen weights (38 ppm), decreased antibody synthesis (9 and 19 ppm) and augmented PGE2 production (19 and 38 ppm). Then, monochloramine is not particularly strong immunodepressant.
Executive summary:

In the present study, the immunotoxic effects of subchronic exposure of rats to drinking water treated with monochloramine were determined. A comprehensive battery of immunoassays were used to assess immune competence of each animal by examining alterations of major populations of cells which mediate immune responses (i.e. B and T lymphocytes, natural killer cells and macrophages), major types of immune responses (i.e. humoral, T cell-mediated, macrophage-mediated and natural killer cell-mediated) and production of potent immune regulating cytokines (i.e. lymphocyte-derived interleukin 2 and macrophage-derived PGE2). The immunoassays used were antibody production to a T-dependent antigen; delayed-type hypersensitivity reaction; phagocytosis, oxidative metabolism and prostaglandin (PGE2) production by macrophages; natural killer cell (NKC) cytotoxicity reaction; and production of T cell-derived interleukin 2 (IL2). A dose-dependent decrease in spleen weight compared to controls was observed in rats treated with monochloramine. Reduced spleen weights were significantly different from controls in the 38 ppm monochloramine-treated group. Antibody synthesis was significantly suppressed in rats which were treated with 9 or 19 ppm monochloramine. This effect on antibody production was inverse to the exposure level of monochloramine. The PGE2 levels produced by macrophages of rats exposed to 19 or 38 ppm monochloramine was significantly greater than controls and directly related to dose. Nevertheless, these changes were not considered to be biologically significant. No significant effects on body weights, DTH reactions, NKC cytotoxicity, IL2 synthesis, macrophage CL or phagocytosis were apparent following monochloramine treatment.