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Toxicological information

Developmental toxicity / teratogenicity

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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-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
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

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:
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1 % sodium chloride
Basis:
nominal in water
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.