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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: dominant lethal assay
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): FDA-Compound 71-41 = Silene, calcium silicate (hydrated)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Flow laboratories
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 300-350 g
- Fasting period before study: no data
- Housing: 1-5 rats / cage
- Diet (e.g. ad libitum): commercial 4% fat diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 4-11 days

ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
physiological saline
Details on mating procedure:
- M/F ratio per cage: 1 M / 2 F
- Length of cohabitation: 5 days
- After 2 days of rest, the male rat was housed with two other females for 5 days. This was repeated for 8 weeks (7 weeks in the subacute study).
- After successful mating each pregnant female was caged (how): 2 feamles / cage
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Acute: single administration, subacute: 5 days.
Frequency of treatment:
One dose per day.
Details on study schedule:
The females were killed 14 days after separation from the males.
Doses / concentrations
Remarks:
Doses / Concentrations:
15, 150, 1500, 5000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control:
Triethylene melamine

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
Litter observations:

Corpora lutea, early fetal deaths, late fetal deaths, total implantations per uterine horn.
Statistics:
t-tests, regression analyses, Freeman-Tukey transformations, chi-square test, Armitage's trend.
Reproductive indices:
fertility index, average number of implantations, average corpora lutea, average preimplantation losses, average resorptions, dead implants/total implants

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

No differences in fertility index, preimplantation losses or embryo resorptions were observed between the calcium silicate groups and the control animals.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
5 000 mg/kg bw/day
Sex:
male
Basis for effect level:
other: Dominant lethal test negative.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Calcium silicate did not have any fertility effects in rats studied by the dominant lethal assay.
Executive summary:

The toxicity of calcium silicate was studied by the dominant lethal assay after exposure of male rats given with oral doses up to 5000 mg/kg for 1 or 5 days (Litton 1974). No differences in fertility index, preimplantation losses or embryo resorptions were observed between the calcium silicate groups and the control animals.