Oil shale, thermal processing waste

Developmental toxicity / teratogenicity

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 for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Silane, dichlorodimethyl-, reaction products with silica

EC Number:

271-893-4

EC Name:

Silane, dichlorodimethyl-, reaction products with silica

Cas Number:

68611-44-9

IUPAC Name:

68611-44-9

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 or test system 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)

1

Dose descriptor:

NOEL

Effect level:

500 mg/kg bw/day (nominal)

Basis for effect level:

other: maternal toxicity

2

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.