Registration Dossier
Registration Dossier
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EC number: 935-756-9 | CAS number: 1344-95-2
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
A screening test for reproductive/developmental toxicity is not required based on the information requirements outlined in the ECHA REACH fact sheet of 15/09/2009 (ref: ECHA-09-FS-05-EN), as three prenatal developmental toxicity studies (rat, mouse and hamster) with amorphous calcium silicates are included. No developmental effects were observed in these studies.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
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
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose appl No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose app No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.lied.ied.
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose appl
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
ied.No adverse effect related to the treatment with hydrated calcium silicate was detected. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 1972
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- For reproductive/developmental toxicity a prenatal developmental toxicity / teratogenicity study (hamster) with amorphous calcium silicates (read across with Crystalline silicic acid, calcium salt) is included. No developmental effects were observed in this study.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- no gross pathological examination of the organ dams other than the urogenital tract; statistical evaluation is missing from the report.
- GLP compliance:
- no
- Remarks:
- Study performed prior to GLP adoption
- Limit test:
- no
- Species:
- hamster, Syrian
- Strain:
- other: outbred
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: young adult
- Housing: individually in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Oral gavage
PREPARATION OF DOSING SOLUTIONS: the substance was given as a water solution
DIET PREPARATION no data
VEHICLE
- Amount of vehicle (if gavage): 1 mL/kwg bw
The sham-exposed group received anhydrous corn oil. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- - Impregnation procedure: mated
-Observation of the vaginal sperm checked on Day 0 of gestation - Duration of treatment / exposure:
- Gestation Day 6 to Day 10 (5 days)
- Frequency of treatment:
- daily
- Duration of test:
- All dams were sacrificed after Cesarian section on gestation Day 14
- No. of animals per sex per dose:
- 21-23
- Control animals:
- yes, sham-exposed
- other: positive control aspirin (given at 250 mg/kg bw)
- Details on study design:
- - Dose selection rationale: no data
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes (appearance, behaviour)
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 8, 10, and 14 of gestation
FOOD CONSUMPTION: Yes, daily
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 14
- Organs examined: urogenital tract examined macroscopically - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - Mortality reported: Yes
- External examinations: Yes, all per litter
- In general congenital abnormalities: Yes, all per litter
- Detailed visceral examinations: Yes, 1/3 per litter
- Skeletal examinations: Yes, 2/3 per litter
- Average fetuses weights and sex were recorded. - Statistics:
- No data
- Indices:
- Not reported
- Historical control data:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No effects observed up to the highest dose applied. - 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
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 600 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No effects observed up to the highest dose applied. - Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Embryotoxic / teratogenic effects:
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Oral administration by gavage of hydrated calium silicate to female pregnant golden hamsters, during gestation days 6-15, did not result to any maternal or developmental toxicity, at doses up to 1600 mg/kg bw.
- Executive summary:
In a developmental toxicity study, hydrated calcium silicate (FDA 71-4, fine white powder) was administered by gavage to groups of female pregnant golden hamsters, during gestation, from Day 6 to Day 15, at dose levels of 16, 74, 350 and 1600 mg/kg bw. Sham-exposed animals were used as negative control and aspirin was given at 150 mg/kg bw to an additional group, as a positive control. Bodyweights were recorded on Days 0, 8, 10 and 14 of gestation. Clinical observations and food consumption were recorded daily. Caesarean sections were performed to all dams on Day 14, and the number of dead, live or resorbed fetuses, sex ratio and number of implantation sites were recorded. All fetuses were weighed and examined for external congenital abnormalities. One-third of the fetuses/litter was examined for visceral malformations, and the other two-thirds for skeletal malformations. The ovaries and uterine content of all dams were examined.
No adverse effect related to the treatment with hydrated calcium silicate was detected. Malformations recorded in the fetuses were comparable to sham-exposed controls. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 1972
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- For reproductive/developmental toxicity a prenatal developmental toxicity / teratogenicity study (Mouse) with amorphous calcium silicates (read across with Crystalline silicic acid, calcium salt) is included. No developmental effects were observed in this study.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- different species used: mice; no gross pathological examination of the organ dams other than the urogenital tract; statistical evaluation is missing
- GLP compliance:
- no
- Remarks:
- Study performed prior to GLP adoption
- Limit test:
- no
- Species:
- mouse
- Strain:
- CD-1
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: young adult
- Housing: individually in disposable plastic cages
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled, no other data
- Humidity (%): controlled, no other data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Oral gavage
PREPARATION OF DOSING SOLUTIONS: the substance was given as a water solution
DIET PREPARATION no data
VEHICLE
- Amount of vehicle (if gavage): 1 mL/kwg bw
The sham-exposed group received anhydrous corn oil. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- - Impregnation procedure: mated
- Duration of treatment / exposure:
- Gestation Day 6 to Day 15 (10 days)
- Frequency of treatment:
- daily
- Duration of test:
- All dams were sacrficed after Cesarian section on gestation Day 17
- No. of animals per sex per dose:
- 21-23
- Control animals:
- yes, sham-exposed
- other: positive control aspirin (given at 150 mg/kg bw)
- Details on study design:
- - Dose selection rationale: no data
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes (appearance, behaviour)
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 6, 11, 15 and 17 of gestation
FOOD CONSUMPTION: Yes, daily
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: the urogenital tract was examined macroscopically - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - Mortality reported: Yes
- External examinations: Yes, all per litter
- In general congenital abnormalities: Yes, all per litter
- Detailed visceral examinations: Yes, 1/3 per litter
- Skeletal examinations: Yes, 2/3 per litter
-Average fetuses weights and sex were recorded. - Statistics:
- No data
- Indices:
- Not reported
- Historical control data:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No effects observed up to the highest dose applied. - 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
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 600 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No effects observed up to the highest dose applied. - Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Embryotoxic / teratogenic effects:
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Oral administration by gavage of hydrated calium silicate to female CD 1 mice, during gestation days 6-15, did not result to any maternal or developmental toxicity, at doses up to 1600 mg/kg bw.
- Executive summary:
In a developmental toxicity study, hydrated calcium silicate (FDA 71-4, fine white powder) was administered by gavage to groups of female pregnant albino CD-1 mice, during gestation, from Day 6 to Day 15, at dose levels of 16, 74, 350 and 1600 mg/kg bw. Sham-exposed animals were used as negative control and aspirin was given at 150 mg/kg bw to an additional group, as a positive control. Bodyweights were recorded on Days 0, 6, 11, 15 and 17 of gestation. Clinical observations and food consumption were recorded daily. Caesarean sections were performed to all dams on Day 17, and the number of dead, live or resorbed fetuses, sex ratio and number of implantation sites were recorded. All fetuses were weighed and examined for external congenital abnormalities. One-third of the fetuses/litter was examined for visceral malformations, and the other two-thirds for skeletal malformations. The ovaries and uterine content of all dams were examined.
No adverse effect related to the treatment with hydrated calcium silicate was detected. Malformations recorded in the fetuses were comparable to controls. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity was considered to be 1600 mg/kg bw/day, the highest dose applied.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 1972
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- For reproductive/developmental toxicity a prenatal developmental toxicity / teratogenicity study (rats) with amorphous calcium silicates (read across with Crystalline silicic acid, calcium salt) is included. No developmental effects were observed in this study.
- Reason / purpose for cross-reference:
- reference to other study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- no gross pathological examination of the organ dams other than the urogenital tract; statistical evaluation is missing.
- GLP compliance:
- no
- Remarks:
- Study performed prior to GLP adoption
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: young adult
- Housing: individually in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- Oral gavage
PREPARATION OF DOSING SOLUTIONS: the substance was given as a water solution
DIET PREPARATION no data
VEHICLE
- Amount of vehicle (if gavage): 1 mL/kwg bw
The sham-exposed group received anhydrous corn oil. - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Details on mating procedure:
- - Impregnation procedure: mated
-Observation of the vaginal sperm checked on Day 0 of gestation - Duration of treatment / exposure:
- Gestation Day 6 to Day 15
- Frequency of treatment:
- daily
- Duration of test:
- All dams were sacrificed after Cesarian section on gestation Day 17
- No. of animals per sex per dose:
- 21-23
- Control animals:
- yes, sham-exposed
- other: positive control aspirin (given at 250 mg/kg bw)
- Details on study design:
- - Dose selection rationale: no data
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes (appearance, behaviour)
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0, 6, 11, 15 and 17 of gestation
FOOD CONSUMPTION: Yes, daily
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- Organs examined: urogenital tract examined macroscopically - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - Mortality reported: Yes
- External examinations: Yes, all per litter
- In general congenital abnormalities: Yes, all per litter
- Detailed visceral examinations: Yes, 1/3 per litter
- Skeletal examinations: Yes, 2/3 per litter
- Average fetuses weights and sex were recorded. - Statistics:
- No data
- Indices:
- Not reported
- Historical control data:
- No data
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
No effects observed up to the highest dose applied. - 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
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 600 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No effects observed up to the highest dose applied. - Dose descriptor:
- NOAEL
- Effect level:
- 1 600 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Embryotoxic / teratogenic effects:
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Oral administration by gavage of hydrated calium silicate to female Wistar rats, during gestation days 6-15, did not result to any maternal or developmental toxicity, at doses up to 1600 mg/kg bw.
- Executive summary:
In a developmental toxicity study, hydrated calcium silicate (FDA 71-4, fine white powder) was administered by gavage to groups of female pregnant Wistar rats, during gestation, from Day 6 to Day 15, at dose levels of 16, 74, 350 and 1600 mg/kg bw. Sham-exposed animals were used as negative control and aspirin was given at 150 mg/kg bw to an additional group, as a positive control. Bodyweights were recorded on Days 0, 6, 11, 15 and 17 of gestation. Clinical observations and food consumption were recorded daily. Caesarean sections were performed to all dams on Day 17, and the number of dead, live or resorbed fetuses, sex ratio and number of implantation sites were recorded. All fetuses were weighed and examined for external congenital abnormalities. One-third of the fetuses/litter was examined for visceral malformations, and the other two-thirds for skeletal malformations. The ovaries and uterine content of all dams were examined.
No adverse effect related to the treatment with hydrated calcium silicate was detected. Malformations recorded in the fetuses were comparable to sham-exposed controls. Treatment with the teratogen aspirin resulted in several malformations of the pups. Under the conditions of this test, the NOAEL for both maternal and developmental toxicity for the test item was considered to be 1600 mg/kg bw/day, the highest dose applied.
Referenceopen allclose all
Table 1. Reproduction data
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin 250 |
16 |
74 |
350 |
1600 |
|
PREGNANCIES |
|
|||||
Total No |
21 |
23 |
21 |
22 |
19 |
21 |
Died or aborted |
0 |
0 |
1 |
0 |
0 |
0 |
To termination |
21 |
23 |
20 |
22 |
19 |
21 |
CORPORA LUTEA |
|
|||||
Total No |
330 |
345 |
297 |
319 |
289 |
291 |
Average/dam mated |
15.0 |
13.3 |
14.1 |
14.5 |
13.1 |
13.2 |
LIVE LITTERS |
|
|||||
Total No* |
21 |
22 |
20 |
22 |
19 |
21 |
IMPLANTATION SITES |
|
|||||
Total No |
267 |
273 |
232 |
256 |
229 |
250 |
Average/dam* |
12.7 |
11.9 |
11.6 |
11.6 |
12.1 |
11.9 |
RESORPTIONS |
|
|||||
Total No* |
8 |
25 |
10 |
12 |
6 |
6 |
Dams with ≥1 resorption sites |
7 |
10 |
7 |
10 |
5 |
4 |
Dams with all sites resorbed |
- |
- |
- |
- |
- |
- |
% partial resorptions |
33.3 |
43.5 |
35.0 |
45.5 |
26.3 |
19.0 |
% complete resorptions |
- |
- |
- |
- |
- |
- |
LIVE FETUSES |
|
|||||
Total No* |
259 |
237 |
221 |
242 |
221 |
243 |
Average/dam* |
12.3 |
10.3 |
11.1 |
11.0 |
11.6 |
11.6 |
Sex ratio M/F |
0.53 |
0.51 |
0.63 |
0.56 |
0.47 |
0.66 |
DEAD FETUSES |
|
|
|
|
|
|
Total No* |
- |
11 |
1 |
2 |
2 |
1 |
Dams with ≥1 dead fetuses |
- |
3 |
1 |
2 |
2 |
1 |
Dams with all dead fetuses |
- |
- |
- |
- |
- |
- |
% partial dead |
- |
13.0 |
5.0 |
9.09 |
10.5 |
4.76 |
% all dead |
- |
- |
- |
- |
- |
- |
AVERAGE FETUS WEIGHT (g) |
1.77 |
1.63 |
1.81 |
1.76 |
1.80 |
1.80 |
*Includes only dams examined at termination
Table 2. Skeletal findings
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin 250 |
16 |
74 |
350 |
1600 |
|
Live Fetuses examined |
182/21 |
165/22 |
155/20 |
169/22 |
155/19 |
175/21 |
STERNEBRAE |
|
|||||
Incomplete Oss. |
117/20 |
114/21 |
95/20 |
99/22 |
89/17 |
96/21 |
Scrambled |
|
|
|
|
|
|
Bipartite |
16/9 |
17/11 |
22/6 |
21/12 |
15/9 |
12/7 |
Fused |
|
|
1/1 |
1/1 |
|
1/1 |
Extra |
|
|
|
|
|
3/2 |
Missing |
17/10 |
29/14 |
12/7 |
20/14 |
14/7 |
14/7 |
RIBS |
|
|||||
Incomplete Oss. |
|
|
|
|
|
|
Fused/split |
|
|
|
|
|
|
Wavy |
|
|
|
|
|
|
Less than 12 |
|
|
1/1 |
|
|
|
More than 13 |
14/10 |
41/6 |
37/19 |
20/11 |
17/12 |
30/17 |
VERTEBRAE |
|
|||||
Incomplete Oss. |
|
1/1 |
|
|
1/1 |
|
Scrambled |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. Oss. |
|
|
|
|
|
|
Scoliosis |
|
|
|
|
|
|
Tail defects |
|
|
|
|
|
|
SKULL |
|
|||||
Incomplete closure |
|
|
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
EXTERMITIES |
|
|||||
Incomplete Oss. |
|
1/1 |
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
MISCELLANEOUS |
|
|||||
Hyoid; missing |
|
1/1 |
|
|
|
|
Hyoid; reduced |
1/1 |
1/1 |
|
1/1 |
1/1 |
|
-nominator: No of fetuses affected, denominator: No of litters affected
No soft tissue abnoramilites were seen in any of the animals.
Table 1. Reproduction data
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin |
16 |
74 |
350 |
1600 |
|
PREGNANCIES |
|
|||||
Total No |
22 |
22 |
23 |
22 |
21 |
21 |
Died or aborted |
1 |
1 |
0 |
0 |
0 |
1 |
To termination |
21 |
21 |
23 |
22 |
21 |
20 |
CORPORA LUTEA |
|
|||||
Total No |
329 |
321 |
376 |
346 |
350 |
355 |
Average/dam mated |
13.7 |
14 |
13.9 |
13.3 |
12.1 |
12.57 |
LIVE LITTERS |
|
|||||
Total No* |
21 |
20 |
23 |
22 |
21 |
19 |
IMPLANTATION SITES |
|
|||||
Total No |
235 |
244 |
287 |
268 |
255 |
232 |
Average/dam* |
11.2 |
11.6 |
12.5 |
12.2 |
12.1 |
11.6 |
RESORPTIONS |
|
|||||
Total No* |
11 |
20 |
12 |
28 |
9 |
20 |
Dams with ≥1 resorption sites |
9 |
8 |
9 |
11 |
8 |
11 |
Dams with all sites resorbed |
- |
1 |
- |
- |
- |
1 |
% partial resorptions |
42.9 |
38.1 |
39.1 |
50 |
38.1 |
55 |
% complete resorptions |
- |
4.76 |
- |
- |
- |
5 |
LIVE FETUSES |
|
|||||
Total No* |
220 |
221 |
268 |
237 |
246 |
207 |
Average/dam* |
10.5 |
10.5 |
11.7 |
10.8 |
11.7 |
10.4 |
Sex ratio M/F |
0.9 |
0.92 |
0.85 |
0.81. |
0.61 |
0.93 |
DEAD FETUSES |
|
|
|
|
|
|
Total No* |
4 |
3 |
7 |
3 |
0 |
5 |
Dams with ≥1 dead fetuses |
4 |
3 |
7 |
2 |
- |
5 |
Dams with all dead fetuses |
- |
- |
- |
- |
- |
- |
% partial dead |
19 |
14.3 |
30.4 |
9.09 |
- |
25 |
% all dead |
- |
- |
- |
- |
- |
- |
AVERAGE FETUS WEIGHT (g) |
0.89 |
0.79 |
0.84 |
0.81 |
0.77 |
0.86 |
*Includes only dams examined at termination
Table 2. Skeletal findings
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin |
16 |
74 |
350 |
1600 |
|
Live Fetuses examined |
156/21 |
155/20 |
187/23 |
166/22 |
169/21 |
147/19 |
STERNEBRAE |
|
|||||
Incomplete Oss. |
64/19 |
86/18 |
102/22 |
110/22 |
96/20 |
84/19 |
Scrambled |
|
|
|
|
|
|
Bipartite |
4/3 |
2/2 |
3/3 |
1/1 |
1/1 |
2/2 |
Fused |
|
1/1 |
|
|
|
|
Extra |
|
4/1 |
|
|
|
|
Missing |
24/9 |
53/14 |
36/12 |
37/14 |
61/17 |
31/12 |
RIBS |
|
|||||
Incomplete Oss. |
|
|
|
|
5/1 |
|
Fused/split |
|
|
|
|
|
|
Wavy |
|
|
|
|
|
|
Less than 12 |
|
|
|
|
|
|
More than 13 |
32/12 |
24/10 |
8/6 |
1/1 |
|
3/3 |
VERTEBRAE |
|
|||||
Incomplete Oss. |
|
|
|
2/2 |
|
1/1 |
Scrambled |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. Oss. |
|
|
|
|
|
|
Scoliosis |
|
|
|
|
|
|
Tail defects |
|
|
|
|
|
|
SKULL |
|
|||||
Incomplete closure |
|
|
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
EXTERMITIES |
|
|||||
Incomplete Oss. |
1/1 |
5/4 |
1/1 |
2/2 |
8/1 |
2/2 |
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
MISCELLANEOUS |
|
|||||
Hyoid; missing |
42/14 |
68/16 |
34/13 |
36/17 |
47/18 |
31/10 |
Hyoid; reduced |
18/12 |
11/9 |
25/12 |
18/12 |
10/7 |
11/8 |
-nominator: No of fetuses affected, denominator: No of litters affected
No soft tissue abnormalities were detected.
Table 1. Reproduction data
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin 250 |
16 |
74 |
350 |
1600 |
|
PREGNANCIES |
|
|||||
Total No |
21 |
25 |
21 |
21 |
20 |
22 |
Died or aborted |
0 |
0 |
1 |
0 |
0 |
0 |
To termination |
21 |
25 |
20 |
21 |
20 |
22 |
CORPORA LUTEA |
|
|||||
Total No |
271 |
284 |
324 |
269 |
283 |
292 |
Average/dam mated |
11.8 |
10.1 |
11.6 |
11.7 |
12.9 |
12.2 |
LIVE LITTERS |
|
|||||
Total No* |
21 |
21 |
20 |
21 |
20 |
21 |
IMPLANTATION SITES |
|
|||||
Total No |
214 |
249 |
234 |
216 |
230 |
251 |
Average/dam* |
10.2 |
9.96 |
11.7 |
10.3 |
11.5 |
11.4 |
RESORPTIONS |
|
|||||
Total No* |
4 |
62 |
3 |
3 |
1 |
13 |
Dams with ≥1 resorption sites |
4 |
14 |
3 |
2 |
1 |
2 |
Dams with all sites resorbed |
0 |
3 |
0 |
0 |
0 |
1 |
% partial resorptions |
19.0 |
56.0 |
15.0 |
9.52 |
5.0 |
9.09 |
% complete resorptions |
- |
12.0 |
- |
- |
- |
4.55 |
LIVE FETUSES |
|
|||||
Total No* |
210 |
175 |
231 |
212 |
229 |
238 |
Average/dam* |
10.0 |
7.0 |
11.6 |
10.1 |
11.5 |
10.8 |
Sex ratio M/F |
1.08 |
1.22 |
1.14 |
1.12 |
0.88 |
1.14 |
DEAD FETUSES |
|
|
|
|
|
|
Total No* |
- |
12 |
- |
1 |
- |
- |
Dams with ≥1 dead fetuses |
- |
7 |
- |
1 |
- |
- |
Dams with all dead fetuses |
- |
0 |
- |
0 |
- |
- |
% partial dead |
- |
28.0 |
- |
4.7 |
- |
- |
% all dead |
- |
- |
- |
- |
- |
- |
AVERAGE FETUS WEIGHT (g) |
3.77 |
2.38 |
4.04 |
4.01 |
3.90 |
4.06 |
*Includes only dams examined at termination
Table 2. Skeletal findings
|
Dose mg/kg bw/day |
|||||
Sham-exposed |
Aspirin |
16 |
74 |
350 |
1600 |
|
Live Fetuses examined |
146/21 |
127/21 |
157/20 |
149/21 |
158/20 |
166/21 |
STERNEBRAE |
|
|||||
Incomplete Oss. |
39/16 |
89/21 |
38/14 |
37/15 |
36/11 |
43/15 |
Scrambled |
|
|
|
|
|
|
Bipartite |
1/1 |
23/14 |
|
|
|
|
Fused |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Missing |
2/2 |
119/21 |
16/5 |
2/2 |
12/6 |
10/6 |
RIBS |
|
|||||
Incomplete Oss. |
|
|
|
|
|
|
Fused/split |
|
|
|
|
|
|
Wavy |
3/1 |
10/5 |
11/7 |
11/9 |
16/5 |
5/5 |
Less than 12 |
|
|
|
|
|
|
More than 13 |
6/4 |
24/11 |
5/5 |
10/7 |
8/4 |
|
VERTEBRAE |
|
|||||
Incomplete Oss. |
|
99/20 |
4/2 |
1/1 |
5/2 |
3/2 |
Scrambled |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. Oss. |
|
|
|
|
|
|
Scoliosis |
|
|
|
|
|
|
Tail defects |
|
|
|
|
|
|
SKULL |
|
|||||
Incomplete closure |
4/2 |
53/14 |
16/8 |
3/2 |
16/12 |
25/13 |
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
EXTERMITIES |
|
|||||
Incomplete Oss. |
|
2/2 |
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
MISCELLANEOUS |
|
|||||
Hyoid; missing |
1/1 |
17/7 |
15/8 |
9/8 |
19/8 |
15/8 |
Hyoid; reduced |
9/2 |
12/5 |
23/13 |
7/4 |
21/9 |
45/13 |
-nominator: No of fetuses affected, denominator: No of litters affected
Soft tissue abnoramilites such as exncephaly. spina bifida, and umbilical hernia were seen in several pups from dams treated with the positive control aspirin. No soft tissue abnormalities were seen in the sham exposed controls or in the test item treated animals.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 600 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- High. There is one recent non-GLP full OECD 414 comparable study available in rats, mice and hamsters showing no teratogenic effects at toxic dose levels of hydrated calcium silicate.
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
No adverse effect related to the treatment with hydrated calcium silicate was detected in rats, hamsters and mice.
Justification for classification or non-classification
Toxicity to reproduction has been sufficiently evaluated in studies addressing Developmental toxicity / teratogenicity. Available studies for the evaluation with amorphous calcium silicate (hydrated silicic acid, calcium salt) for these endponts indicated no concerns with respect to hazards related to reproduction, and thus no classification is required.
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
