Soybean oil, epoxidised, reaction products with methanol and water

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:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Soybean oil, epoxidized

EC Number:

232-391-0

EC Name:

Soybean oil, epoxidized

Cas Number:

8013-07-8

IUPAC Name:

8013-07-8

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

- Housing: individually in polycarbonate cages containing autoclaved sawdust and equipped with a water bottle.
- pelleted Diet ad libitum
- Water ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

soya oil

Duration of treatment / exposure:

days 6 to 15 of pregnancy inclusive

Frequency of treatment:

daily

Duration of test:

to day 20 of pregnancy

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 300, 1000 mg/kg kg/day
Basis:

No. of animals per sex per dose:

25 mated females at the beginning 9 weeks old

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes


BODY WEIGHT: Yes
Body weight was recorded for each female on days 2, 6, 9, 12, 15 and 20 of pregnancy.


FOOD CONSUMPTION: Yes
The quantity of food consumed was measured for each female at the intervals day 2 - day 6, day 6 - day 9, day 9 - day12, day 12 - day 15 and day 15 - day 20. Food intake per animal and per day was calculated using the difference between the amount of food given and left in each feeder.


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: heart, lung, liver, kidneys, stomach, intestines

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: all per litter
- Skeletal examinations: Yes: all per litter

Statistics:

The mean values were compared by one-way analysis of variances and Dunnett's test. Percentage values were compared by Fisher's exact probability test.

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 clinical signs, no deaths and no abortions were noted in any of the groups. The mean food consumption and body weight gain of the females with completed pregnancy were similar in the control and treated groups. No treatment-related macroscopic changes were observed at necropsy of the
females.

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day

Basis for effect level:

other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No external malformations were observed in foetuses of the treated control group. No treatment related soft-tissue anomalies or malformations were noted. No dose-related effects were noted on the incidence of the skeletal variations, anomalies or malformations.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Summary of maternal and fetal data:

Dose mg/kg/day	0	100	300	1000
Females pregnant	23	24	18	20
Dams with viable fetuses	23	24	18	20
Corpora Lutea (TOTAL)	410	440	323	360
No per animal (MEAN)	17.8	18.3	17.9	18.0
Implantation Sites (TOTAL)	342	339	257	272
Preimplantation Loss (TOTAL)	68	101*	66	88**
Preimplantation Loss (%)	16.6	23.0	20.4	24.4
Fetuses (N)	333	330	253	269
No. per animal (MEAN)	14.5	13.8	14.1	13.4
No. per animal (S.D.)	2.0	3.0	1.9	3.7
Live Fetuses (N)	333	330	253	268
No. per animal (MEAN)	14.5	13.8	14.1	13.4
No. per animal (S.D.)	2.0	3.0	1.9	3.7
Resorptions: early (N)	6	7	3	3
No. per animal (MEAN)	0.3	0.3	0.2	0.2
No. per animal (S.D.)	0.5	0.6	0.4	0.5
Resorptions: late (N)	3	2	1	0
No. per animal (MEAN)	0.1	0.1	0.1	0.0
No. per animal (S.D.)	0.3	0.3	0.2	0.0
Postimplantation los (TOTAL)	9	9	4	4
No. per animal (MEAN)	0.4	0.4	0.2	0.2
No. per animal (S.D.)	0.7	0.6	0.4	0.5
Viable male fetuses (N)	164	176	139	150
Viable male fetuses (%)	49.2	53.3	54.9	56.0
Female fetuses (N)	169	154	114	118
Female fetuses (%)	50.8	46.7	45.1	44.0
Fetal Body Weight (g) (MEAN)	3.94	4.03	4.02	4.08

Statistical key: *=P<0.05 **=P<0.0

Fetal anomalies and malformations

Litters evaluated (N)	23	24	18	20
Fetuses evaluated (N)	162	160	122	130

Abnormalities: dilated renal pelvis

Fetal incidence (N)	0	0	3	3
Fetal incidence (%)	0.0	0.0	2.5	2.3
Litter incidence (N)	0	0	2	3
Litter incidence (%)	0.0	0.0	11.1	15.0

Ureter-dilatation

Fetal incidence (N)	0	0	2	1
Fetal incidence (%)	0.0	0.0	1.6	0.8
Litter incidence (N)	0	0	2	1
Litter incidence (%)	0.0	0.0	11.1	5.0

Malformations: ventricular cerebral dilatation

Fetal incidence (N)	0	0	1	0
Fetal incidence (%)	0.0	0.0	0.8	0.0
Litter incidence (N)	0	0	1	0
Litter incidence (%)	0.0	0.0	5.6	0.0

Applicant's summary and conclusion

Conclusions:

The test substance EPOXYDISED SOYBEAN OIL (ESBO) when administered daily by oral route (gavage) to pregnant female Sprague-Dawley rats during organogenesis at the dose levels of 100, 300 and 1000 mg/kg bw/day was well tolerated by the dams at all the dose levels and was neither embryotoxic or teratogenic.