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Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1951
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1951
Report date:
1951

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Non-iodized sodium chloride, hereafter referred to as "salt" was fed to rats in their diets for periods of 90 days. A group of 40 Carworth Farms, Wistar strain, albino rats was selected after a preliminary observation period. The animals were randomized among the 8 cages so that each cage contained 5 male or 5 female rats. The basic diet was the modified Food Research Laboratory Diet 2C which consisted of dried whole milk, ground whole wheat, inactivated yeast, U.S.P liver extract, and iodized salt. The iodized salt was present as 2% of the basic diet. The diets were continuously available in McCollum-type food cups. Groups of five males and 5 females received diets that contained 32, 8, 2, and 0% added salt respectively. In terms of total salt added plus that in the basic diet of these groups the percentages were 34, 10, 4, and 2%.

GLP compliance:
no
Remarks:
Study was conducted before GLP guidance was established
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium chloride
EC Number:
231-598-3
EC Name:
Sodium chloride
Cas Number:
7647-14-5
Molecular formula:
NaCl
IUPAC Name:
sodium chloride
Specific details on test material used for the study:
- Name of test material (as cited in study report): Sodium Chloride
- Physical state: Salt
- Lot/batch No.: E 277

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Carwoth Farms

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Mixing appropriate amounts with (Type of food):The basfe diet was the modified Food Research Laboratory Diet 2C which consisted of dried whole milk, ground whole wheat, inactivated yeast, U.S.P. liver extract,and iodised salt. The iodized salt was present as 2% of the basic diet.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
90 days
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 other: %
Remarks:
% in diet of added salt, equals 0 mg/kg/day
Dose / conc.:
2 other: %
Remarks:
% in diet of added salt, equals 1.33 g/kg/day
Dose / conc.:
8 other: %
Remarks:
% in diet of added salt, equals 5.73 g/kg/day
Dose / conc.:
32 other: %
Remarks:
% in diet of added salt, equals 31.04 g/kg/day
No. of animals per sex per dose:
5 males and 5 females per dose.
Control animals:
yes, plain diet
Details on study design:
no data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data
- Time schedule:no data
- Cage side observations checked in table were included.: No data

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:No data

BODY WEIGHT: Yes


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):


Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
None of the 40 rats used in this study died. At the end of 91 days of doses, the rats were weighed and sacrificed, Portions of kidney, liver and lung were taken for histopathological examination. Livers and kidneys were weighed and the mean organ weight, expressed as percentage of body weight was calculated. These data, as well as those obtained on body weight gain and diet consumption were satatistically analysed for the sexes separately and combined.
Statistics:
The experimental data were statistically evaluated.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
None of the 40 rats used in this study died. No adverse clinical signs of toxicity were reported.
Mortality:
no mortality observed
Description (incidence):
None of the 40 rats used in this study died.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
When the body weight data were examined separately by sex, each group of male rats was found to have gained statistically significantly less weight than did the male controls (+92.6 g, +161.6 g, +217.6 g, and +236.8 for the 32, 8, 2, and 0% added salt groups). For females the weight gain was +70.6 g, +97.4 g, +95.0 g and 112.0 g 32, 8, 2, and 0% added salt groups.
Food consumption and compound intake (if feeding study):
not examined
Description (incidence and severity):
Whe
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Endocrine findings:
not examined
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
The mean liver weights of the high dose group (combined) were statistically lower than the controls. The mean kidney weights of the high dose group were significantly higher in comparison to the control. Nevertheless, no pathological changes were seen by during histopathological examination.
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
The mean liver weights of the high dose group (combined) were statistically lower than the controls. The mean kidney weights of the high dose group were significantly higher in comparion to the control. Nevertheless, no pathological changes were seen by during histopathological examination.
Histopathological findings: neoplastic:
not specified
Other effects:
not examined

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 330 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Please refer to study results as attached.

Applicant's summary and conclusion

Conclusions:
In a sub-chronic repeated dose toxicity study the NOAEL for Sodium chloride was established to be < 1330 mg/kg/day.
Executive summary:

In a sub-chronic repeated dose toxicity study, a group of 5 males and 5 female Wistar rats were fed with diets for 91 days, which contained additionally 32, 8, 2 and 0% Sodium chloride in excess of the 2% already present as a normal constituent of basic FRL-2C rat diet.

None of animals died during the study. At the end of 91 days of doses, the rats were weighed and sacrificed. Portions of kidney, liver, and lung were taken for histopathological examination. Livers and kidneys were weighed and the mean organ weight, expressed as percentage of the body weight, calculated.

When the body weight data were examined separately by sex, each group of male rats was found to have gained statistically significantly less weight than did the male controls (+92.6 g, +161.6 g, +217.6 g, and +236.8 for the 32, 8, 2, and 0% added salt groups). For females the weight gain was +70.6 g, +97.4 g, +95.0 g and 112.0 g for the 32, 8, 2, and 0% added salt groups. The mean liver weights of the high dose group (combined) were statistically lower than the controls. The mean kidney weights of the high dose group were significantly higher in comparison to the control. Nevertheless, no pathological changes were seen during histopathological examination.

Based on the results, the NOAEL is considered to be less than 1330 mg Sodium chloride/kg/day.