Docosanoic acid, ester with 1,2,3-propanetriol

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Reference 2

Reference Type:

publication

Title:

Teratologic Evaluation of Glycerine

Author:

NTIS US Department of Commerce

Year:

1974

Bibliographic source:

PB-234 876

Materials and methods

Principles of method if other than guideline:

Pre-natal developmental toxicity study in rats exposed on Days 6-15 of gestation by oral gavage. Examinations of uterine content included: No. of implantation sites, resorptions and live and dead fetuses. Examination of fetuses included: body weight, sex, external abnormalities, visceral (1/3 of fetuses) and skeletal (2/3 of fetuses) examinations.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

Details on test material:

- Name of test material (as cited in study report): FDA 71-89 (Glycerol; glycerine)
- Physical state: water-white syrupy liquid
- Analytical purity: no data

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 214-230 g (on Day 0 of gestation)
- Housing: Animals were individually housed in mesh bottom cages.
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified, reported as controlled.
- Humidity (%): Not specified, reported as controlled.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: The test material was prepared and doses calculated according to Table 1.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: presumably 1/1
- Proof of pregnancy: vaginal plug referred to as Day 0 of pregnancy

Duration of treatment / exposure:

10 days (Day 6-15 of gestation)

Frequency of treatment:

daily

Duration of test:

20 days

Doses / concentrations

Remarks:

Doses / Concentrations:
13.1, 60.8, 282 and 1310 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

Negative control: 25
Positive control: 29
13.1 mg/kg bw/day: 25
60.8 mg/kg bw/day: 28
282 mg/kg bw/day: 25
1310 mg/kg bw/day: 25

Control animals:

yes, concurrent vehicle

other: positive control: Aspirin (250 mg/kg bw/day)

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included: appearance and behaviour with particular attention to food consumption and weight

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 11, 15 and 20 of gestation

FOOD CONSUMPTION: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day 20
- Organs examined: urogenital tract

Ovaries and uterine content:

The uterine content was examined after termination: Yes
Examinations included:
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of live and dead fetuses: Yes

Fetal examinations:

- Body weight: Yes: all live pups per litter
- Sex ratio: Yes: all live pups per litter
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: two thirds per litter

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
MORTALITY
No mortality occurred.

BODY WEIGHT
No treatment-related effects observed.

FOOD CONSUMPTION
Not reported.

CLINICAL SIGNS
Not reported.

PREGNANCIES AND LIVE LITTERS (No. of pregnant animals or live litters/No. total mated animals)
No treatment-related effects observed.

Negative control: 23/25
Positive control: 24/29
13.1 mg/kg bw/day: 24/25
60.8 mg/kg bw/day: 22/28
282 mg/kg bw/day: 22/25
1310 mg/kg bw/day: 21/25

ABORTIONS
There were no abortions.

IMPLANTATIONS (mean value per dam)
No treatment-related effects observed.

Negative control: 11.4
Positive control: 10.9
13.1 mg/kg bw/day: 11.0
60.8 mg/kg bw/day: 12.4
282 mg/kg bw/day: 12.0
1310 mg/kg bw/day: 11.2

RESORPTIONS (Total No. of resorptions/No. of dams involved/No. of dams examined)
No treatment-related effects observed.

Negative control: 2/2/23
Positive control: 40/11/24
13.1 mg/kg bw/day: 4/1/24
60.8 mg/kg bw/day: 1/1/22
282 mg/kg bw/day: 4/2/22
1310 mg/kg bw/day: 3/2/21

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 310 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:
MORTALITY
There were no dead fetuses in the negative control and treatment groups.
In the positive control group, 3 dams showed 1 dead fetus each.

BODY WEIGHT (Mean fetus body weight in g)
No treatment-related effects observed.

Negative control: 3.80
Positive control: 2.37
13.1 mg/kg bw/day: 3.76
60.8 mg/kg bw/day: 3.89
282 mg/kg bw/day: 3.86
1310 mg/kg bw/day: 3.83

LIVE FETUSES
No treatment-related effects on number of viable fetuses and sex ratio.
- Mean No. of viable fetuses per dam:
Negative control: 11.0
Positive control: 9.08
13.1 mg/kg bw/day: 10.8
60.8 mg/kg bw/day: 12.3
282 mg/kg bw/day: 11.8
1310 mg/kg bw/day: 11.1

- Sex ratio (m/f):
Negative control: 0.77
Positive control: 1.06
13.1 mg/kg bw/day: 0.90
60.8 mg/kg bw/day: 0.94
282 mg/kg bw/day: 1.02
1310 mg/kg bw/day: 0.83

EXTERNAL EXAMINATIONS
No external abnormalities reported.

SOFT TISSUE EXAMINATIONS
No soft tissue abnormalities were observed in the negative control and treatment groups.
In the positive control group, 15 out 24 litters showed 1-3 pups with visceral abnormalities each. Abnormalities included: meningoencephalocele, anopia, cleft palate, harelip, encephalomyelocele, gastroschisis, umbilical hernia and hydrocephalus.

SKELETAL EXAMINATIONS
Delayed ossification was observed in all control and treatment groups without evidence for a relationship to treatment (Table 2).

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 310 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 2. Summary of skeletal findings (No. fetuses affected/No. of litters affected)

Findings	Dose level (mg/kg bw/day)
	Negative control	Positive control	13.1	60.8	282	1310
Live fetuses examined	183/23	157/24	180/24	189/22	182/22	163/21
Sternebrae
Incomplete ossification	54/16	78/21	52/17	37/14	35/11	47/15
Bipartite	-	21/15	-	2/2	-	-
Fused	-	1/1	-	-	-	-
Missing	11/6	131/23	15/7	9/6	6/4	2/2
Ribs
Incomplete ossification	1/1	9/5	-	-	-	1/1
Fused/split	-	13/7	-	-	-	-
Wavy	26/10	46/17	25/12	5/5	11/8	9/6
Less than 12	-	3/2	-	-	-
More than 13	-	126/24	1/1	-	-	3/1
Vertebrae
Incomplete ossification	45/14	115/23	15/9	14/9	12/5	10/5
Skull
Incomplete closure	34/11	71/19	22/9	26/15	18/9	35/13
Missing	-	7/5	-	-	-	-
Extremities
Incomplete ossification	-	2/2	-	-	-	-
Miscellaneous
Hyoid; reduced	36/13	77/21	10/8	23/11	17/10	19/10
Hyoid; reduced	25/10	9/7	14/9	11/8	26/9	14/7