Registration Dossier
Registration Dossier
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EC number: 215-664-9 | CAS number: 1338-41-6
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: Comparable to guideline study (analytical purity of test substance not specified, limited documentation, only organogenesis covered (days 6-15 of gestation)).
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 972
- Report date:
- 1972
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- (analytical purity of test substance not specified, limited documentation, only organogenesis covered (days 6-15 of gestation))
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- D-glucitol
- EC Number:
- 200-061-5
- EC Name:
- D-glucitol
- Cas Number:
- 50-70-4
- Molecular formula:
- C6H14O6
- IUPAC Name:
- D-glucitol
- Details on test material:
- - Name of test material (as cited in study report): FDA 71-31, sorbitol
- Physical state: fine white crystalline material
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 218-235 g
- Housing: singly
- Diet (ad libitum)
- Water (ad libitum): tap water
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 1 mL/kg bw/day - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: cohoused
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- day 6-15 of gestation
- Frequency of treatment:
- daily
- Duration of test:
- 20 days
- No. of animals per sex per dose:
- 20 (control group)
22 (positive control group; 350 mg/kg bw/day)
21 (74 mg/kg bw/day)
23 (16, 1600 mg/kg bw/day) - Control animals:
- yes, sham-exposed
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on days 0, 6, 11, 15, and 20 of gestation
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- daily observation, but no recording
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20 (caesarean section under surgical anesthesia) - 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 resorptions: Yes - Fetal examinations:
- - External examinations: Yes: [all pups per litter]
- Soft tissue examinations: Yes: [one-third pf pups per litter]
- Skeletal examinations: Yes: [two-thirds of pups per litter], (cleared in potassium hydroxide, stained with alizarin red dye and examined)
- Head examinations: Yes
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Effect levels (maternal animals)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 600 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:
Soft tissue abnormalities found: In the positive control group, one to two pups of 7 different dams showed exencephaly and spina bifida.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 600 mg/kg bw/day (nominal)
- 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: Average maternal body weights (in g)
|
Day |
||||
|
0 |
6 |
12 |
18 |
29 |
Dose group |
|
|
|
|
|
Sham |
235 |
252 |
271 |
290 |
359 (20) |
Positive Control |
224 |
244 |
258 |
273 |
322 (22) |
16 mg/kg bw TS |
219 |
235 |
254 |
278 |
339 (23) |
74 mg/kg bw TS |
225 |
244 |
264 |
286 |
353 (21) |
350 mg/kg bw TS |
225 |
246 |
264 |
284 |
347 (22) |
1600 mg/kg bw TS |
218 |
237 |
259 |
281 |
352 (23) |
- TS: test substance
- number of surviving dams in parentheses
Table 2: Litter response (caesarean section data)
Dose group |
Sham |
Positive Control |
16 mg/kg bw TS |
74 mg/kg bw TS |
350 mg/kg bw TS |
1600 mg/kg bw TS |
Pregnancies |
|
|
|
|
|
|
Total No. |
20 |
22 |
23 |
21 |
22 |
23 |
Died or aborted (before day 17) |
0 |
0 |
0 |
0 |
0 |
0 |
To term (on day 17) |
20 |
22 |
23 |
21 |
22 |
23 |
Corpora lutea |
|
|
|
|
|
|
Total No. |
230 |
250 |
250 |
240 |
235 |
279 |
Average/dam mated |
9.58 |
10.4 |
10.4 |
10.4 |
9.8 |
11.6 |
Live litters |
|
|
|
|
|
|
Total No. |
20 |
18 |
23 |
21 |
22 |
23 |
Implant Sites |
|
|
|
|
|
|
Total No. |
219 |
232 |
244 |
214 |
224 |
271 |
Average/dam |
10.9 |
10.6 |
10.6 |
10.2 |
10.2 |
11.8 |
Resorptions |
|
|
|
|
|
|
Total No. |
8 |
51 |
11 |
4 |
4 |
16 |
Dams with 1 or more sites resorbed |
5 |
9 |
5 |
2 |
4 |
7 |
Dams with all sites resorbed |
0 |
3 |
0 |
0 |
0 |
0 |
% partial resorptions |
25 |
40.9 |
21.7 |
9.52 |
18.2 |
30.4 |
% complete resorptions |
-- |
13.6 |
-- |
-- |
-- |
-- |
Live fetuses |
|
|
|
|
|
|
Total No. |
211 |
181 |
233 |
210 |
219 |
255 |
Average/dam |
10.6 |
8.23 |
10.1 |
10.1 |
9.96 |
11.1 |
Sex ratio (M/F) |
1.04 |
0.83 |
1.01 |
0.87 |
0.79 |
0.82 |
Dead Fetuses |
|
|
|
|
|
|
Total No. |
0 |
0 |
0 |
0 |
1 |
0 |
Dams with 1 or more dead |
-- |
-- |
-- |
-- |
1 |
0 |
Dams with all dead |
-- |
-- |
-- |
-- |
0 |
-- |
% partial dead |
-- |
-- |
-- |
-- |
4.55 |
-- |
% all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average fetus weight (g) |
3.51 |
2.55 |
3.75 |
3.52 |
3.86 |
3.69 |
Table 3: Summar of skeletal findings
Dose group |
Sham |
Positive Control |
16 mg/kg bw TS |
74 mg/kg bw TS |
350 mg/kg bw TS |
1600 mg/kg bw TS |
Live Fetuses (at term) |
141/20 |
121/18 |
156/23 |
150/21 |
147/22 |
172/23 |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
18/10 |
102/17 |
24/11 |
32/15 |
15/12 |
22/16 |
Scrambled |
-- |
-- |
-- |
-- |
-- |
-- |
Bipartite |
-- |
4/3 |
-- |
1/1 |
-- |
-- |
Fused |
-- |
-- |
-- |
-- |
-- |
-- |
Extra |
-- |
-- |
-- |
-- |
-- |
-- |
Missing |
-- |
56/15 |
-- |
2/2 |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
Ribs |
-- |
-- |
-- |
-- |
-- |
-- |
Incomplete oss. |
-- |
9/6 |
-- |
-- |
-- |
-- |
Fused/Split |
-- |
8/4 |
-- |
-- |
-- |
-- |
Wavy |
4/4 |
20/12 |
6/3 |
4/4 |
9/6 |
-- |
Less than 12 |
-- |
3/2 |
-- |
-- |
-- |
-- |
More than13 |
-- |
60/16 |
-- |
-- |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
Vertebrae |
-- |
-- |
-- |
-- |
-- |
-- |
Incomplete oss. |
1/1 |
86/18 |
6/3 |
4/2 |
1/1 |
2/2 |
Scrambled |
-- |
-- |
-- |
-- |
-- |
-- |
Fused |
-- |
4/2 |
-- |
-- |
-- |
-- |
Extra ctrs. oss. |
-- |
-- |
-- |
-- |
-- |
-- |
Scoliosis |
-- |
10/5 |
-- |
-- |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
| Skull | ||||||
Incomplete Closure |
11/8 | 68/17 | 14/7 | 18/9 | 15/8 | 8/7 |
Missing |
-- | 11/7 | -- | -- | -- | -- |
| Extremities | ||||||
| Incomplete Oss. | -- | 7/6 | -- | -- | -- | -- |
| Miscellaneous | ||||||
Hyoid; missing |
8/6 | 80/17 | 15/9 | 19/9 | 5/4 | 8/7 |
Hyoid; reduced |
3/3 | 3/3 | 1/1 | 3/3 | 1/1 | 1/1 |
Applicant's summary and conclusion
- Conclusions:
- The test substance had no effect on intrauterine development.
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