Fumes, silica

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

No toxicological data were available for silica fume and, therefore, a read-across approach was used. The dissolution, composition and surface properties were the most important parameters considered when deciding which substances can be used for read-across.

Based on the composition, surface characteristics, and bioaccessibility data, silica fume was assumed to have toxicological properties similar to those of sparingly synthetic amorphous silicas. Therefore read-across was carried out using available toxicological studies with synthetic amorphous silica (SAS).

Details on the read-across approach are presented in Iuclid section 13.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

toxicity to reproduction

Remarks:

other: dominant lethal assay

Type of information:

experimental study

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.

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)

GLP compliance:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system 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

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.

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

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

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

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

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

Dose descriptor:

NOAEL

Effect level:

5 000 mg/kg bw/day

Sex:

male

Basis for effect level:

other: Dominant lethal test negative.

Remarks on result:

other: Dominant lethal test negative

Basis for effect level:

other: reprotoxicity

Remarks on result:

other: not specified

Reproductive effects observed:

not specified

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.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Fumes, silica

EC Number:

273-761-1

EC Name:

Fumes, silica

Cas Number:

69012-64-2

Molecular formula:

SiO2

IUPAC Name:

silanedione

Details on test material:

- Name of test material (as cited in study report): high grade silica fume; low grade silica fume
- Analytical purity: high grade: SiO2 96.4% (w/w); low grade: SiO2 83.8% (w/w)