Glycerol trioctanoate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

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

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A teratogenicity study in mice was conducted in 1970, prior to any OECD guideline adoption.

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:

1,3-bis(octanoyloxy)propan-2-yl octanoate

Test animals

Species:

mouse

Strain:

other: ICR-JCL

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 4-8 weeks
- Diet: ad libitum
- Water: ad libitum

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1.2% Tween 80/0.8% Span 80 in water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
The test substance was mixed with 1.2% (w/v)Tween 80 and 0.8% (w/v) Span 80 in water. The emulsion was prepared with Manton Gaulin Homgenizer.

VEHICLE
- Justification for use and choice of vehicle: low water solubility

Analytical verification of doses or concentrations:

no

Details on mating procedure:

No detailed information is available.

Duration of treatment / exposure:

Day 7-12 of gestation

Frequency of treatment:

daily

Duration of test:

Day 18 of gestation

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

1 908 mg/kg bw/day (actual dose received)

Remarks:

2 mL/kg; calculated based on a density value of 0.954 g/mL

Doses / concentrations 2

Dose / conc.:

9 540 mg/kg bw/day (actual dose received)

Remarks:

10 mL/kg; calculated based on a density value of 0.954 g/mL

No. of animals per sex per dose:

20 parental females

Control animals:

other: physiological saline or soybean oil

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: on Days 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

General toxicity (maternal animals)

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Maternal developmental toxicity

Number of abortions:

not specified

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

not specified

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

not specified

Changes in number of pregnant:

no effects observed

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)

Key result

Dose descriptor:

NOAEL

Effect level:

9 540 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity: no adverse effects

Maternal abnormalities

Key result

Abnormalities:

no effects observed

Results (fetuses)

Fetal body weight changes:

no effects observed

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

no effects observed

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

not examined

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
External abnormalities: cleft palate was observed in 1 foetus of control, 1 foetus of the 2 mL/kg bw/day dose group and 3 foetuses of the 10 mL/kg bw/day dose group. No cleft palate was found in foetuses receiving soybean oil. Club foot was observed in 1 foetus of control, 4 foetuses of the soybean oil control group, 3 foetuses of the 2 mL/kg bw/day dose group and 4 foetuses of the 10 mL/kg bw/day dose group.
Skeletal abnormalities: Two foetuses showed assimilation of the ribs in the 2 mL/kg bw/day dose group. One foetus showed assimilation of the cervical vertebra in the 10 mL/kg bw/day dose group. However, these effects did not follow a clear dose-dependency.

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

9 540 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: teratogenicity: no adverse effects

Fetal abnormalities

Key result

Abnormalities:

no effects observed

Overall developmental toxicity

Key result

Developmental effects observed:

no

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 (saline)	20	232 (11.6 ± 0.39)	116	104	220	1.28 ± 0.023	11	1	12 (5.2)
Soybean oil	20	223 (11.1 ± 0.46)	101	114	215	1.26 ± 0.021	6	2	8 (3.6)
2 mL/kg	20	231 (11.5 ± 0.29)	113	107	220	1.29 ± 0.023	9	2	11 (4.8)
10 mL/kg	20	232 (11.6 ± 0.40)	107	112	219	1.26 ± 0.030	12	1	13 (5.6)

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. (%)		Number of fetuses: Type
	Ex	Sk
Control (saline)	3 (1.4)	0	1: Curled tail 1: Cleft palate 1: Club foot
Soybean oil	4 (1.9)	0	4: Club foot
2 mL/kg	4 (1.8)	2 (0.9)	1: Cleft palate 3: Club foot 2: Assimilation of the ribs
10 mL/kg	7 (3.2)	1 (0.5)	3: Cleft palate 4: Club foot 1: Assimilation of the cervical vertebra

Ex: external malformation

Sk: skeletal malformation

Applicant's summary and conclusion

Conclusions:

CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.