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EC number: 200-272-2 | CAS number: 56-40-6
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
No study required since no adverse effects on reproductive organs were seen in the available repeated dose toxicity studies with glycine and N-acetylglycine.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
Prenatal developmental toxicity (similar to OECD 414), oral, rat:
NOAEL developmental toxicity = ≥ 855 mg/kg bw/day
NOAEL maternal toxicity = ≥ 855 mg/kg bw/day
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- analytical purity of test substance not specified, limited documentation, only organogenesis covered (days 6-15 of gestation)
- 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
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 206-215 g
- Housing: individually in mesh bottom cages
- Diet (ad libitum)
- Water (ad libitum): tap water
ENVIRONMENTAL CONDITIONS
- temperature and humidity-controlled quarters - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- VEHICLE
- Amount of vehicle (if gavage): 1 to 3 mL/kg bw - 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
- Dose / conc.:
- 9 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 40 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 185 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 855 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 23 (control group, 185 mg/kg bw/d dose group, 250 mg/kg bw/d Aspirin)
21 (9 mg/kg bw/d)
22 (40, 855 mg/kg bw/day) - Control animals:
- yes, sham-exposed
- other: positive control: 250 mg/kg bw/d Aspirin
- 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 implantations: Yes
- Number of resorptions: Yes
- Other: number of live and dead fetuses was recorded and the urigenital tract of each dam was examined in detail for anatomical normality - Fetal examinations:
- Number of live and dead fetuses were recorded and body weights of the live pups were recorded.
- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [one-third per litter]
- Skeletal examinations: Yes: [two-thirds per litter]
- Head examinations: Yes - Details on maternal toxic effects:
- Maternal toxic effects:no effects. Remark: no treatment-related effects
- Dose descriptor:
- NOAEL
- Effect level:
- >= 855 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects. Remark: no treatment-related effects
Details on embryotoxic / teratogenic effects:
Besides the effects listed in Table 1-3 (see " Any other information on resutls incl. tables"), the following soft tissue abnormalities were found in the positive control group pups delivered by different dams: acrania, craniocele; spina bifida, subcutaneous edema. - Dose descriptor:
- NOAEL
- Effect level:
- >= 855 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The test substance had no effect on intrauterine development.
Reference
Table 1: Average maternal body weights (in g)
Day |
|||||
|
0 |
6 |
11 |
15 |
20 |
Dose group |
|
|
|
|
|
Sham |
206 |
236 |
260 |
283 |
352 (23) |
Positive Control |
214 |
236 |
252 |
270 |
309 (23) |
9 mg/kg bw TS |
209 |
230 |
246 |
275 |
344 (21) |
40 mg/kg bw TS |
215 |
240 |
262 |
286 |
351 (22) |
185 mg/kg bw TS |
207 |
227 |
250 |
273 |
243 (23) |
855 mg/kg bw TS |
207 |
229 |
246 |
277 |
343 (22) |
- TS: test substance
- number of surviving dams in parentheses
Table 2: Litter response (caesarean section data)
Dose group |
Sham |
Positive Control |
9 mg/kg bw TS |
40 mg/kg bw TS |
185 mg/kg bw TS |
855 mg/kg bw TS |
Pregnancies |
|
|
|
|
|
|
Total No. |
23 |
23 |
21 |
22 |
23 |
22 |
Died or aborted (before day 20) |
0 |
0 |
0 |
0 |
0 |
1 |
To term (on day 20) |
23 |
23 |
21 |
22 |
23 |
22 |
Corpora lutea |
|
|
|
|
|
|
Total No. |
268 |
270 |
244 |
267 |
265 |
253 |
Average/dam mated |
11.2 |
11.3 |
10.2 |
11.1 |
11.0 |
10.5 |
Live litters |
|
|
|
|
|
|
Total No. |
23 |
15 |
21 |
22 |
23 |
22 |
Implant Sites |
|
|
|
|
|
|
Total No. |
253 |
256 |
233 |
253 |
251 |
252 |
Average/dam |
11.0 |
11.1 |
11.1 |
11.5 |
10.9 |
11 |
Resorptions |
|
|
|
|
|
|
Total No. |
12 |
106 |
8 |
15 |
6 |
4 |
Dams with 1 or more sites resorbed |
6 |
16 |
6 |
11 |
5 |
3 |
Dams with all sites resorbed |
0 |
8 |
0 |
0 |
0 |
0 |
% partial resorptions |
26.1 |
69.6 |
28.6 |
50.0 |
21.7 |
13.6 |
% complete resorptions |
-- |
34.8 |
-- |
-- |
-- |
-- |
Live fetuses |
|
|
|
|
|
|
Total No. |
240 |
150 |
225 |
238 |
245 |
248 |
Average/dam |
10.4 |
6.52 |
10.7 |
10.8 |
10.7 |
10.8 |
Sex ratio (M/F) |
0.81 |
0.95 |
0.67 |
0.68 |
0.55 |
0.76 |
Dead Fetuses |
|
|
|
|
|
|
Total No. |
1 |
0 |
0 |
0 |
0 |
0 |
Dams with 1 or more dead |
1 |
-- |
-- |
-- |
-- |
1 |
Dams with all dead |
0 |
-- |
-- |
-- |
-- |
-- |
% partial dead |
4.35 |
-- |
-- |
-- |
-- |
-- |
% all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average fetus weight (g) |
3.91 |
2.63 |
3.81 |
3.81 |
3.92 |
3.75 |
Table 3: Summary of skeletal findings
Dose group |
Sham |
Positive Control |
9 mg/kg bw TS |
40 mg/kg bw TS |
185 mg/kg bw TS |
855 mg/kg bw TS |
Live Fetuses (at term) |
161/23 |
99/15 |
148/21 |
159/22 |
164/23 |
167/22 |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
15/11 |
94/16 |
10/9 |
8/7 |
11/8 |
13/9 |
Scrambled |
-- |
-- |
-- |
-- |
-- |
-- |
Bipartite |
-- |
1/1 |
-- |
1/1 |
-- |
-- |
Fused |
-- |
-- |
-- |
-- |
-- |
-- |
Extra |
-- |
-- |
-- |
-- |
-- |
-- |
Missing |
2/1 |
64/14 |
-- |
-- |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
Ribs |
||||||
Incomplete oss. |
1/1 |
12/6 |
-- |
-- |
-- |
-- |
Fused/Split |
3/2 |
4/3 |
-- |
-- |
-- |
-- |
Wavy |
5/2 |
27/11 |
12/8 |
12/6 |
4/3 |
1/1 |
Less than 12 |
-- |
3/3 |
-- |
1/1 |
-- |
1/1 |
More than13 |
-- |
26/9 |
-- |
-- |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
Vertebrae |
||||||
Incomplete oss. |
3/1 |
75/14 |
3/3 |
-- |
2/1 |
4/4 |
Scrambled |
-- |
-- |
-- |
-- |
-- |
-- |
Fused |
-- |
2/2 |
-- |
-- |
-- |
-- |
Extra ctrs. oss. |
-- |
-- |
-- |
-- |
-- |
-- |
Scoliosis |
-- |
7/4 |
-- |
-- |
-- |
-- |
Other |
-- |
-- |
-- |
-- |
-- |
-- |
| Skull | ||||||
| Incomplete closure | 19/11 | 69/13 | 16/10 | 28/10 | 14/8 | 20/10 |
| Craniostosis | -- | 1/1 | -- | -- | -- | -- |
| Miscellaneous | ||||||
| Hyoid; missing | 9/4 | 73/15 | 11/6 | 13/8 | 9/7 | 15/9 |
| Hyoid; reduced | 3/2 | 1/1 | -- | -- | 1/1 | -- |
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 855 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Comparable to guideline study (Klimisch = 2).
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Prenatal developmental toxicity of the test substance was investigated in a study equivalently performed as described in OECD 414. Wistar rats received the test substance by oral gavage from gestation day 6 to 15 at doses of 9, 40, 185 and 855 mg/kg bw/day (FDA, 1972).
There were no treatment-related mortalities in any dose group and no effects on body weight development of the dams. For all dose groups, no litter parameters were affected, including the number of corpora lutea, live litters, implant sites, resorptions, live and dead fetuses. At external, visceral and skeletal fetal examination, no treatment-related findings were observed. A positive control group was included into the study design. These animals received Aspirin at a dose of 250 mg/kg bw/day. In this group, clear effects on intrauterine development were observed: decrease in the number of live litters and live fetuses, increase in resorptions as well as skeletal findings when compared to the negative control group.
In conclusion, for maternal and developmental toxicity, the NOAEL was determined to be ≥ 855 mg/kg bw/day.
Justification for classification or non-classification
The available data on reproductive toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.
Additional information
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