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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Characterization and toxicological behavior of synthetic amorphous hydrophobic silica
Author:
Lewinson, J. et al.
Year:
1994
Bibliographic source:
Regul Toxicol Pharmacol. 20(1 Pt 1):37-57

Materials and methods

Principles of method if other than guideline:
One-generation reproduction study over two breeding sequences
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aerosil R 972 (Fumed Hydrophobic Silica, FHS)
- Analytical purity: >99.8%

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: (P) Males: 131 g; Females: 120 +/- 4 g
- Diet (e.g. ad libitum): powder diet Altromin (Altromin GmbH, Germany)
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 +/- 2

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): the test compound was mixed into the powder diet Altromin (supplied by Altromin GmbH), and adapted weekly to the food consumption and the body weight gain.
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 1/5
Duration of treatment / exposure:
6 months
Frequency of treatment:
Continuous
Duration of test:
Two breeding sequences
Doses / concentrations
Remarks:
Doses / Concentrations:
500 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
10
Control animals:
yes, plain diet

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Time schedule for examinations: daily

HAEMATOLOGY
- Hemoglobin, erythrocytes, leukocytes, and blood smears were examined at week 0 and then monthly, but not during pregnancy and lactation.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOEL
Effect level:
500 mg/kg bw/day (nominal)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOEL
Effect level:
500 mg/kg bw/day (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

There were no changes in behavior, appearance, or occurrence of clinical symptoms in the parental treatment and control groups. The body weight gain and food consumption were comparable in treated and control groups. No differences were seen in the hematological parameters or in organ weights at autopsy during pathological examination. Reproductive performance was not altered in the treated rats. The results of the pathological examination of the parents were comparable to those found in the simultaneously performed chronic 6 -month study described in the same publication.

After the first mating procedure, at week 8, 15 rats became pregnant, 6 in the control group and 9 in the treated group. Seven dams from each group were pregnant after the second mating period after week 17. There were no treatment-related effects in the litter size or birth weights. This was true for all parameters evaluated (s. table). Physical or behavioral abnormalities were not observed and runts did not occurred in either breeding experiment. Hematomas on the heads of three pups were seen only in the litter of one control animal. The development of the progeny during lactation was without adverse effects. The weight gains of both generations were normal. After 4 weeks the pups were examined for gross pathology. No treatment-related changes were found. Therefore, a dose of 500 mg/kg was concluded to be the no-observed effect level for developmental and reproductive toxicity in this study.

Developmental parameters for progeny and pregnant female rats fed 500 mg/kg test material for 6 months.

 

Control group

Treated group

 

Litter 1

Litter 2

Litter 1

Litter 2

Pre-treatment period (weeks)

-

-

8

17

Number of females

10

10

10

10

Number pregnant

6

7

9

7

Number of pups

62

60

91

70

Mean litter size

10.3

8.6

10.1

8.6

Mean birth weight (g)

5.1

5.3

5.6

5.5

Dead pups

2

1

0

2

Runts

0

0

0

0

Gross anomalies and other changes

3*

0

0

0

Breeding rate (%):

Birth

Week 1

Week 2

Week 3

Week 4

 

100

90

84

84

84

 

100

97

93

92

92

 

100

97

96

92

92

 

100

93

76

76

76

* Hematomas on the heads of three pups in the same litter were observed.

Applicant's summary and conclusion