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Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication which meets basic scientific principles. No soft tissue and head examinations were performed in foetuses.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1970
Reference Type:
secondary source
Title:
Final report on the safety assessment of Trilaurin, Triarachidin, Tribehenin, Tricaprin, Tricaprylin, Trierucin, Triheptanoin, Triheptylundecanoin, Triisononanoin, Triisopalmitin, Triisostearin, Trilinolein, Trimyristin, Trioctanoin, Triolein, Tripalmitin
Author:
Cosmetic Ingredient Review (CIR)
Year:
2001
Bibliographic source:
Int J Toxicol. 2001;20 Suppl 4:61-94

Materials and methods

Principles of method if other than guideline:
Teratogenicity study in rabbits
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Glycerol trioctanoate
EC Number:
208-686-5
EC Name:
Glycerol trioctanoate
Cas Number:
538-23-8
Molecular formula:
C27H50O6
IUPAC Name:
propane-1,2,3-triyl trioctanoate

Test animals

Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Kansai Institute for Experimental Animals, Japan
- Weight at study initiation: 2.5-3.8 kg
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-25
- Humidity (%): 55-60

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No detailed information is available.
Duration of treatment / exposure:
Day 7-16 of gestation
Frequency of treatment:
daily
Duration of test:
Day 29 of gestation
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3 mL/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
2862 mg/kg bw/day
Basis:
other: calculated based on a density value of 0.954 g/mL
No. of animals per sex per dose:
8 P females
Control animals:
other: physiological saline
Details on study design:
- Dose selection rationale: in a preliminary study, mortality was observed after administration of the test substance at 5 and 10 mL/kg bw/day. Therefore, a dose of 3 mL/kg bw/day was selected for treatment in this study.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 7 and 18 of gestation
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: No
Fetal examinations:
- External examinations: Yes: [all per litter]
- Soft tissue examinations: No
- Skeletal examinations: Yes: [all per litter]
- Head examinations: No

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 differences were observed between test substance administration group, control group and soybean oil administration group.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
2 862 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
External abnormalities: hydrocephalus (1 foetus) and absence of the head (1 foetus) was observed in the soybean oil group.
Skeletal abnormalities: Division of the skull was observed in 4 foetuses of the control group and 1 foetus of the soybean oil group. One foetus of the soybean oil group showed assimilation of the ribs.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
2 862 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Table 1. Effects on foetuses of parental females treated with the test substance (2 and 10 mL/kg) and soybean oil

Groups

No of mothers

No. of fetuses

Live fetuses

Dead

No.

Mean body weight (g)

No. of resorbed fetuses

No. of dead fetuses

Total (%)

M.

F.

M.+F.

Control

8

69 (8.6 ± 1.36)

35

23

58

36.2 ± 2.55

7

4

11 (15.9)

Soybean oil

8

65 (8.1 ± 1.26)

34

28

62

38.6 ± 2.21

2

1

3 (4.8)

3 mL/kg

8

72 (9.0 ± 0.60)

28

33

61

34.9 ± 1.47

4

7

11 (15.3)

M.: male, F.: female

Mean ± standard error

Table 2. Malformations in foetuses of parental females treated with the test substance (2 and 10 mL/kg) and soybean oil

Group

Malformed

No. (%)

Type

Ex

Sk

Control

0

4 (6.9)

4: Division of the skull

Soybean oil

2 (3.2)

2 (3.2)

1: Hydrocephalus

1: Absence of the head

1: Assimilation of the ribs

1: Division of the skull

3 mL/kg

0

0

 

Ex: external malformation

Sk: skeletal malformation

Applicant's summary and conclusion