Glycerides, C12-18 di- and tri-

Developmental toxicity / teratogenicity

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

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1970

Reference 2

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
3 mL/kg
Basis:
actual ingested

Doses / concentrations 2

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