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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:
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 mice
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tricaprylin
- Physical state: light yellow clear liquid
- Analytical purity: no data
- Other: not soluble in water but in ethanol, chloroform, acetone, benzene and ether

Test animals

Species:
mouse
Strain:
other: ICR-JCL
Details on test animals 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2 and 10 mL/kg
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1908 and 9540 mg/kg bw/day
Basis:
other: calculated based on a density value of 0.954 g/mL
No. of animals per sex per dose:
20 P 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

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:
9 540 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: 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)

Dose descriptor:
NOAEL
Effect level:
9 540 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

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. (%)

Type

Ex

Sk

Control

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