Registration Dossier

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This Japanese paper with an abstract and presentation of results in English is considered as a reasonably well-documented publication. The study allows the derivation of a NOAEL value for developmental toxicity of Mg. Well-documented publication. Under physiological conditions, the hydroxyl- and carbonate ions released from calcined dolomitic lime following oral adminstration have been neutralised in the GI tract or released as CO2 and are therefore not relevant for consideration of systemic toxicity. Therefore for assessment of any systemic effects of calcined dolomitic lime following administration via the oral route, the magnesium ion Mg2+ is the chemical species of interest. In the current study, magnesium was administered in the form of magnesium chloride, the chloride ion being an ubiquitous component of mammalian mineral supply via the diet, omnipresent in body fluids and involved in osmoregulation, and therefore of limited toxicologically relevance at the tested doses. The objective of the study was the evaluation of any effects of magnesium. In view of the the limited relevance of the anionic counter-ions discussed here, magnesium released both from calcium magnesium carbonate oxide and magnesium chloride can be considered as analogous substances, and the results of the study can be used by read-across.

Data source

Reference
Reference Type:
publication
Title:
Teratogenicity study of magnesium chloride hexahydrate in rats
Author:
Usami, M.; et al.
Year:
1996
Bibliographic source:
Bull. Natl. Inst. Health Sci. 114, 16-20

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Teratogenicity test, not performed according to OECD 414, but fulfilling basic scientific principles for evaluating this endpoint.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
7791-18-6
EC Number:
616-575-1
Cas Number:
7791-18-6
IUPAC Name:
7791-18-6
Constituent 2
Reference substance name:
Magnesium chloride hexahydrate
IUPAC Name:
Magnesium chloride hexahydrate
Details on test material:
- Name of test material (as cited in study report): Magnesium chloride hexahydrate
- Physical state: solid
No further details are given.

Test animals

Species:
rat
Strain:
other: No details could be extracted from the Japanese publication.
Details on test animals or test system and environmental conditions:
No details could be extracted from the Japanese publication.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: MgCl2 x 6 H2O dissolved in distilled water was given to pregnant Wistar rats by gavage.
No further details could be drawn from the text, since the publication is written in Japanese.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No details available.
Details on mating procedure:
No details could be drawn from the Japanese publication.
Duration of treatment / exposure:
MgCl2 was given to rats from day 6-15 of pregnancy.
Frequency of treatment:
Once daily.
Duration of test:
The rats were killed on day 20 of gestation.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mg/kg bw/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
200 mg/kg bw/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
400 mg/kg bw/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
800 mg/kg bw/day
Basis:
nominal in water
No. of animals per sex per dose:
4 rats
Control animals:
yes
Details on study design:
No further details are given.

Examinations

Maternal examinations:
DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded on days 0, 1, 2, 3, 6, 9, 12, 15, 17 and 20.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule: Food consumption was recorded on days 1, 3, 6, 9, 12, 15, 17 and 20.

No further details could be extracted from the Japanese publication.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
- Other: sex ratio (male/female): Yes

No further details could be extracted from the Japanese publication.
Fetal examinations:
The pregnant rats were killed on day 20 of gestation and their foetuses were examined for malformations.
- External examinations: Yes: foetal weight
- Soft tissue examinations: Yes
- Skeletal examinations: Yes

No further details could be drawn from the Japanese publication.
Statistics:
No details could be extracted from the Japanese publication.
Indices:
No details could be extracted from the Japanese publication.
Historical control data:
No data available.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No toxic signs were observed in the dams.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
> 800 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
MgCl2 x 6 H2O caused no increased incidences of gross malformations and of visceral and skeletal variations in foetuses.
No toxic signs were observed in the foetuses.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 800 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
It was concluded that MgCl2 x 6 H2O is not teratogenic in this study. The NOAEL was estimated to be higher than 800 mg/kg bw/d for both the pregnant rats and rat foetuses. This dose level corresponds to a Mg dose of 95.7 mg/kg bw/d.