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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Test method was similar to OECD guideline 417, but only male animals were used. Although the study was not conducted according to the recommended guidelines, it provides scientific valid information to assess the metabolism of the substance. No GLP.

Data source

Reference
Reference Type:
publication
Title:
Metabolism and Pharmacokinetics of Alternate Drinking Water Disinfectants.
Author:
Abdel-Rahman MS, Courit D, BulIt RJ
Year:
1982
Bibliographic source:
Environmental Health Perspectives Vol. 46, pp. 19-23.

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
Deviations:
yes
Remarks:
(Only male animals were used)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Chlorite
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 50-170 g
- Diet (e.g. ad libitum): Food was available ad libitum.
- Water (e.g. ad libitum): It was available 20 hours/day

.ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ºC
- Humidity (%): 50 %
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Duration and frequency of treatment / exposure:
20 h/day, 7 days/week, for 12 months.
Doses / concentrations
Remarks:
Doses / Concentrations:100 mg/L
No. of animals per sex per dose:
7 male rats per group (two groups)
Control animals:
yes
Details on dosing and sampling:
After one year, rats were killed and blood collected in heparinized tubes. Tissue samples of liver, kidney, spleen, brain, and testes were homogenized in isotonic sucrose medium. Tissue homogenate or blood sample (3 mL) was extracted by 5 mL pentane. The pentane layer was then separated by centrifugation at 1000 g for 5 min. A gas chromatograph equipped with an electron capture detector was used for the quantitation of chloroform in each sample, with bromodichloromethane being used as the internal standard.

Results and discussion

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
The administration of test substance elevated chloroform levels in the liver and brain but not in the blood.

Any other information on results incl. tables

The administration of test substance elevated chloroform levels in the liver and brain but not in the blood.

Applicant's summary and conclusion

Conclusions:
The administration of test substance elevated chloroform levels in the liver and brain but not in the blood.
Executive summary:

The formation of chloroform was investigated in two groups of 7 male Sprague-Dawley rats that received 36Cl-labelled sodium chlorite at 100 mg/L in drinking-water for 20 h/day, 7 days/week, for 12 months. After one year, rats were killed and blood collected in heparinized tubes. Tissue samples of liver, kidney, spleen, brain, and testes were homogenized in isotonic sucrose medium. Tissue homogenate or blood sample (3 mL) was extracted by 5 mL pentane. The pentane layer was then separated by centrifugation at 1000 g for 5 min. A gas chromatograph equipped with an electron capture detector was used for the quantitation of chloroform in each sample, with bromodichloromethane being used as the internal standard.

The administration of test substance elevated chloroform levels in the liver and brain but not in the blood.