Registration Dossier

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:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals 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.