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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Adequate documentation of protocol and results.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1974
Reference Type:
publication
Title:
Final Report on the Safety Assessment of Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and sodium Erythorbate
Author:
F. Alan Andersen, Cosmetic Ingredient Expert Review Panel
Year:
1999
Bibliographic source:
International Journal of Toxicology 1999 18 (suppl. 3): 1-26

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): FDA 71-68 (Sodium erythorbate)
- Physical state: Fine white powdered material

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS

- Age at study initiation: Adult
- Housing:Individually in mesh-bottom cages
- Diet: ad libitum
- Water: Tap water ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature controlled
- Humidity (%): Humidity controlled

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
Females were mated with young adult males and observation of the vaginal sperm plug was considered Day 0 of gestation. (One male was not permitted to impregnate more than one female per group).
Duration of treatment / exposure:
Days 6-15 days of gestation
Duration of test:
All dams were subjected to caesarean section on day 20.
Doses / concentrations
Remarks:
Doses / Concentrations:
9.0, 41.8, 194.0, or 900.0 mg/kg bw/day
Basis:

No. of animals per sex per dose:
Positive control: 22 animals
0, 900 mg/kg bw/day: 24 animals
9, 41.8 mg/kg bw/day: 20 animals
194 mg/kg bw/day: 21 animals
Control animals:
yes, sham-exposed
other: Positive control (Aspirin 250 mg/kg bw/day)

Examinations

Maternal examinations:
CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily for appearance and behaviour

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

FOOD CONSUMPTION: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: Urogenital tract was examined for anatomical abnormality.
Ovaries and uterine content:
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
-Other: live and dead fetuses

See Table 1:Reproductive and developmental toxicity of Sodium Erythorbate in Wistar rats
Fetal examinations:
- External examinations: Yes: [all per litter]. All fetuses were examined grossly for presence of external congenital abnormalities.
- Soft tissue examinations: Yes:. One third of the fetuses of each litter underwent detailed visceral examinations employing the Wilson technique.
- Skeletal examinations: Yes: The remaining two third of fetuses were cleared in potassium hydroxide, stained with Alizarin Red S dye and examined for skeletal defects.
- Head examinations: Yes
-Other: Body weight of live pups

Indices:



See Table 1:Reproductive and developmental toxicity of Sodium Erythorbate in Wistar rats

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no data

Details on maternal toxic effects:
No statistically significant differences were observed in number of pregnancies, corpus lutea, implantation rates, live births, resorptions, dams with >1 site resorbed, dams with all sites resorbed, % partial resorptions, complete resorptions, number live fetuses (average/dam) betwen treated and control groups. Abnormalities were observed in rats given aspirin.

See Table 1:Reproductive and developmental toxicity of Sodium Erythorbate in Wistar rats and Appendix II - Individual Reproduction Data

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
900 mg/kg bw/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
900 mg/kg bw/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No statistically significant differences in average fetus weight or number of live fetuses examined at term in rats of the negative control group or in rats given Sodium Erythorbate. No gross, skeletal or soft tissue morphological abnormalities were observed in rats of the negative control group or in rats given Sodium Erythorbate. Abnormalities were observed in rats given aspirin.

See Table 1:Reproductive and developmental toxicity of Sodium Erythorbate in Wistar rats and Appendix II - Individual Reproduction Data

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Table 1:Reproductive and developmental toxicity of Sodium Erythorbate in Wistar rats

Endpoint

 

 

Treatment group

 

 

Negative

control

Positive

control

9.0 mg/kg bw/day

41.8 mg/kg bw/day

194.0 mg/kg bw/day

900.0 mg/kg bw/day

Pregnancies

(total no./no. to term)

20/20

20/20

20/20

20/20

20/20

20/20

No. corpora lutea (average/dam)

268 (11.2)

252 (11.5)

266 (13.3)

257 (12.9)

270 (12.9)

254 (10.6)

No. live litters

19

20

20

20

20

20

No. implant sites (average/dam)

244 (12.2)

227 (11.4)

237 (11.9)

233 (11.7)

238 (11.9)

234 (11.7)

No. resorptions

13

46

2

2

3

4

Dams with >1 site resorbed

5

11

2

2

3

4

Dams with all sites resorbed

1

 

 

 

 

 

% Partial resorptions

25.0

55.0

10.0

10.0

15.0

20.0

% Complete resorptions

0.96

1.10

0.82

0.94

0.84

1.09

No. live fetuses (average/dam)

231 (11.6)

181 (9.05)

235 (11.8)

231 (11.6)

230 (11.5)

230 (11.5)

M/F ratio

0.96

1.10

0.82

0.94

0.84

1.09

No. dead fetuses

 

 

 

 

5

 

Dams with >1 dead

 

 

 

 

1

 

Dams with all dead

 

 

 

 

 

 

% Partial dead

 

 

 

 

5.00

 

% All dead

 

 

 

 

 

 

Average fetus weight (g)

3.95

2.62

3.96

3.95

3.87

3.92

Live fetuses examined at term*

161/19

129/20

166/20

161/20

160/20

161/20

Stemebrae-incomplete

ossification

28/10

52/16

55/15

21/11

56/16

27/14

Stemebrae-bipartite

 

11/6

 

 

 

 

Stemebrae-fused

 

1/1

 

 

 

 

Stemebrae-extra

 

2/2

 

 

 

 

Stemebrae-missing

8/2

106/20

13/5

8/5

21/10  -

4/4

Ribs-incomplete ossification

 

19/8

 

 

 

1/1

Ribs-fused/split

 

5/3

 

 

 

 

Ribs-wavy

18/8

52/14

8/5

14/7

8/5

12/4

Ribs->13

4/3

39/14

2/1

 

2/2

2/1

Vertebrae-incomplete

ossification

7/2

60/16

 

 

7/4

1/1

Vertebrae-extra centers of

ossification

 

2/1

 

 

 

 

Skull-incomplete closure

30/12

54/15

17/10

16/8

15/5

26/13

Skull-missing

 

1/1

 

 

 

 

Extremities-incomplete

ossification

 

7/2

 

 

 

 

Miscellaneous-hyoid missing

22/9

52/16

16/8

19/9

16/8

23/11

Miscellaneous-hyoid reduced

21/11

5/2

15/10

15/7

14/7

14/10

*Numerator = number of fetuses affected; denominator = number of litters affected.

Study report attachments:

Appendix II - Individual Reproduction Data

Applicant's summary and conclusion

Conclusions:
The administration of up to 900 mg/kg bw/day of 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone to pregnant Wistar rats had no clearly discernible effect on nidation or on maternal or fetal survival.
Executive summary:

In a developmental toxicity study (FDABF-GRAS-350) 2,3-didehydro-3-O-sodio-D-erythro-hexono-1,4-lactone was administered to groups of Wistar rats by gavage at dose levels of 0.0, 9.0, 41.8, 194.0, or 900.0 mg/kg bw/day from days 6 through 15 of gestation.

No statistically significant differences were observed in number of pregnancies, corpus lutea, implantation rates, live births, resorptions, dams with >1 site resorbed, dams with all sites resorbed, % partial resorptions, complete resorptions, number live fetuses (average/dam) betwen treated and control groups. The maternal NOAEL is 900 mg/kg bw/day.

There were no treatment-related effects in developmental parameters (average fetus weight, number of live fetuses, gross, skeletal or soft tissue morphological abnormalities) The developmental NOAEL is 900 mg/kg bw/day.