Sodium chloride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

other: publication

Adequacy of study:

weight of evidence

Study period:

1962

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The publication contains sufficient information to permit a meaningful evaluation of study results

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

The Teratogenic Induction of Hypertension

Author:

Grollman A & Grollman EF

Year:

1962

Bibliographic source:

J.Clin.Invest. 41 (4), 710-714

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

not specified in the publication

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

sodium chloride

Details on test material:

- Name of test material (as cited in study report): sodium chloride

Test animals

Species:

rat

Strain:

other: Piebald from McCollum-Evans strain

Details on test animals or test system and environmental conditions:

not specified in the publication

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on exposure:

Duration of test - 2 years
Rats were exposed to 2% in drinking water from:
- day -7 to end of gestation,
- day 5 to end of gestation,
- day 14 to end of gestation and
another group of rats were exposed to 1% in drinking water from day -7 to end of gestation. Their offspring/s were examined up to 2 years for blood pressure.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

not specified in the publication

Details on mating procedure:

as determined by the presence of a vaginal plug or spematozoa in the vaginal smear

Duration of treatment / exposure:

Duration of test - 2 years
Rats were exposed to 2% in drinking water from:
- day -7 to end of gestation,
- day 5 to end of gestation,
- day 14 to end of gestation and
another group of rats were exposed to 1% in drinking water from day -7 to end of gestation. Their offspring/s were examined up to 2 years for blood pressure.

Frequency of treatment:

daily

Duration of test:

Duration of test - 2 years

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
1 % sodium chloride
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2 % sodium chloride
Basis:
nominal in water

No. of animals per sex per dose:

Controls - 10 litters - 88 (number of offspring surviving after 1 year)
High NaCl intake -
-7 (day of treatment initiation) - 4 litters - 29 (number of offspring surviving after 1 year)
5 (day of treatment initiation) - 1 litter - 5 (number of offspring surviving after 1 year)
14 (day of treatment initiation) - 2 litters - 12 (number of offspring surviving after 1 year)

NaCl (1%) as drinking water -
-3 (day of treatment initiation) - 3 litters - 16 (number of offspring surviving after 1 year)

Control animals:

yes

Details on study design:

Offsprings were examined up to 2 years for blood pressure. Kidney and heart were weighed and examined microscopically at the end of the experiment. Groups of 1-10 litters were used.

Examinations

Maternal examinations:

not specified in the publication

Ovaries and uterine content:

not specified in the publication

Fetal examinations:

not specified in the publication

Statistics:

not specified in the publication

Indices:

not specified in the publication

Historical control data:

not specified in the publication

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Effect on blood pressure was significantly increased at 1 year of age in all the groups treated with 2 % NaCl but to a lesser extend when females were treated from day 14 of gestation.
At 1 % NaCl the effect was hardly detectable. Cardiac hypertrophy was found in the hypertensive animals. No effect on kidney was found.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no data

Details on embryotoxic / teratogenic effects:
not specified in the publication

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

not applicable

Applicant's summary and conclusion

Conclusions:

Effect on blood pressure was significantly increased at 1 year of age in all the groups treated with 2 % NaCl but to a lesser extend when females were treated from day 14 of gestation.
At 1 % NaCl the effect was hardly detectable. Cardiac hypertrophy was found in the hypertensive animals. No effect on kidney was found.

Executive summary:

Sodium chloride was administered at 1 and 2 percent in drinking water to groups of rats over a period of 2 years and their offspring examined up to 2 years for blood pressure. Kidney and heart were weighed and examined microscopically at the end of the experiment. Groups of 1 to 10 litters were used.

Effect on blood pressure was significantly increased at 1 year of age in all the groups treated with 2% sodium chloride but to a lesser extent when females were treated from day 14 of gestation.

At 1% sodium chloride the effect was hardly detectable. Cardiac hypertrophy was found in the hypertensive animals and no effects on kidney were found.