Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 232-088-3 | CAS number: 7785-84-4
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27/09/1974 - 29/10/1974
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with national standard methods with acceptable restrictions
- Remarks:
- Meets generally accepted scientific standards with acceptable restrictions. Deficiencies: Food consumption not reported, Uterine weights not determined, One third used for visceral examination; should be 50%, Test substance identification (Batch etc) missing, No details on housing conditions/source of animals, Administration only during periods of organogenesis, not until day before pregnancy.
- Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
1. a common functional group
2. the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
3. a constant pattern in the changing of the potency of the properties across the category
In this instance, the substance similarities are as follows:
1. The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table; sodium and phosphate anion(s).
2. Both substances will ultimately dissociate into the common breakdown products; Na+ cations and PO43- anions. In biological systems, the metaphosphate will undergo hydrolysis (increased in acidic solutions) to form shorter phosphate chains and ultimately phosphate (PO43- anions).
3. Both substances have similar physicochemical and toxicological profiles. The ionic components of both the source and the target compounds are essential micronutrients and their uptake is tightly regulated.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.
The similarities may be based on:
1. a common functional group
2. the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
3. a constant pattern in the changing of the potency of the properties across the category
In this instance, the substance similarities are as follows:
1. The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table; sodium and phosphate anion(s).
2. Both substances will ultimately dissociate into the common breakdown products; Na+ cations and PO43- anions. In biological systems, the metaphosphate will undergo hydrolysis (increased in acidic solutions) to form shorter phosphate chains and ultimately phosphate (PO43- anions).
3. Both substances have similar physicochemical and toxicological profiles. The ionic components of both the source and the target compounds are essential micronutrients and their uptake is tightly regulated.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.
3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.
4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’. - Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- read-across source
- Reason / purpose for cross-reference:
- read-across: supporting information
- Vehicle:
- water
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 370 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects noted
- Key result
- Abnormalities:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 370 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects noted
- Key result
- Abnormalities:
- no effects observed
- Key result
- Developmental effects observed:
- no
- Conclusions:
- Under the conditions of the study, the test material administered to pregnant mice for 10 days up to a dose level of 370 mg/kg bw showed no maternal or developmental toxicity. The NOAEL for both maternal and fetoxicity is > 370 mg/kg bw.
Table 2 Reproduction data
Dose (mg/kg) |
Sham |
Aspirin |
3.7 |
17.2 |
79.7 |
370.0 |
Pregnancies |
|
|
|
|
|
|
Total No. |
21 |
20 |
22 |
19 |
20 |
22 |
Died or aborted (before Day 17) |
0 |
0 |
0 |
0 |
0 |
0 |
To term (on Day 17) |
21 |
20 |
22 |
19 |
20 |
22 |
Corpora Lutea |
|
|
|
|
|
|
Total no. |
275 |
233 |
255 |
233 |
251 |
279 |
Average/dam mated |
11.0 |
8.63 |
10.2 |
9.32 |
10.0 |
11.2 |
Live litters |
|
|
|
|
|
|
Total No.* |
21 |
20 |
22 |
19 |
20 |
22 |
Implant Sites |
|
|
|
|
|
|
Total No. |
259 |
218 |
240 |
224 |
236 |
255 |
Average/dam* |
12.3 |
10.9 |
10.9 |
11.8 |
11.8 |
11.6 |
Resorptions |
|
|
|
|
|
|
Total No* |
8 |
8 |
5 |
9 |
10 |
13 |
Dams with 1 or more sites resorbed |
8 |
6 |
5 |
4 |
9 |
11 |
Dams with all sites resorbed |
-- |
-- |
-- |
-- |
-- |
-- |
Per cent partial resorptions |
38.1 |
30.0 |
22.7 |
21.1 |
45.0 |
50.0 |
Per cent complete resorptions |
-- |
-- |
-- |
-- |
-- |
-- |
Live foetuses |
|
|
|
215 |
|
|
Total No |
248 |
208 |
233 |
11.3 |
224 |
240 |
Average/dam* |
11.8 |
10.4 |
10.6 |
1.01 |
11.2 |
10.9 |
Sex ratio (M/F) |
1.04 |
0.84 |
0.82 |
|
0.84 |
1.07 |
Dead Foetuses |
|
|
|
-- |
|
|
Total No.* |
3 |
2 |
2 |
-- |
2 |
2 |
Dams with 1 or more dead |
3 |
1 |
2 |
-- |
2 |
2 |
Dams with all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Per cent partial dead |
14.3 |
5.00 |
9.09 |
-- |
10.0 |
9.09 |
Per cent all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average foetus weight (g) |
0.8 |
0.85 |
0.85 |
0.92 |
0.93 |
0.86 |
* Includes only those dams examined at term
** Positive control: 150 mg/kg
Table 3 Summary of skeletal findings
Findings |
Dose (mg/kg) |
|||||
Sham |
Aspirin |
3.7 |
17.2 |
79.7 |
370.0 |
|
Live foetuses examined (at term) |
173/21 |
144/20 |
165/22 |
148/149 |
156/20 |
167/22 |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
60/19 |
65/19 |
32/14 |
51/16 |
13/5 |
81/19 |
Scrambled |
|
|
|
|
|
|
Bipartite |
|
1/1 |
|
3/2 |
|
3/2 |
Fused |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Missing |
39/12 |
36/11 |
19/9 |
13/7 |
2/2 |
20/12 |
Other |
|
|
|
|
|
|
Ribs |
|
|
|
|
|
|
Incomplete oss. |
|
|
|
|
|
|
Fused/split |
|
|
|
1/1 |
|
|
Wavy |
|
|
|
|
|
|
Less than 12 |
|
|
|
|
|
|
More than 13 |
23/10 |
32/14 |
23/12 |
25/10 |
30/16 |
25/15 |
Other |
|
|
|
|
|
|
Vertebrae |
|
|
|
|
|
|
Incomplete oss. |
4/2 |
11/5 |
4/3 |
1/1 |
|
|
Scrambled |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. oss. |
|
|
|
|
|
|
Scoliosis |
|
|
|
|
|
|
Tail defects |
|
|
|
|
|
|
Other |
|
|
|
|
|
|
Skull |
|
|
|
|
|
|
Incomplete closure |
2/2 |
|
|
|
|
|
Missing |
|
|
|
|
|
|
Craniostosis |
|
|
|
|
|
|
Other |
|
|
|
|
|
|
Extremities |
|
|
|
|
|
|
Incomplete oss. |
6/4 |
15/5 |
2/2 |
1/1 |
|
1/1 |
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Miscellaneous |
|
|
|
|
|
|
Hyoid; missing |
30/12 |
60/16 |
24/12 |
26/11 |
27/11 |
43/15 |
Hyoid; reduced |
26/12 |
18/13 |
22/13 |
26/16 |
19/10 |
22/14 |
* Numerator = Number of foetuses affected; Denominator = Number of litters affected
** Positive control: 150 mg/kg
Summary of soft tissue abnormalities: 1 pup from a litter where the dam was dosed with 3.7 mg/kg test material showed exophthalmos and encephalmeningocele.
- Reason / purpose for cross-reference:
- read-across: supporting information
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 975
- Report date:
- 1975
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: no data
- Deviations:
- not specified
- Principles of method if other than guideline:
- Adult female albino (Wistar derived stock) rats were mated with young adult males. Observation of a vaginal sperm plug was considered as Day 0 of gestation. Dosing by oral intubation with a control (Vehicle at level equivalent to group receiving the highest dose or aspirin at 250 mg/kg) or test article in a water suspension at 4.1, 19.0, 88.3 or 410.0 mg/kg was carried out daily on Days 6 to 15 of gestation. Observations of body weight, appearence, behaviour, and food consumption were performed. Daily room temperature and humidity were recorded. On Day 20 of gestation all dams underwent Caesarean section. Sex, number of corpora lutea, implantation sites, resorption sites and live/dead foetuses recorded. Body weights of live pups recorded. Urogenital tract of each dam examined for anatomical normality. All foetuses examined grossly for presence of external congenital abnormalities. One third foetuses of each litter underwent detailed visceral examination and the remaining two thirds were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects.
- GLP compliance:
- no
- Remarks:
- Study predates GLP
- Limit test:
- no
Test material
- Reference substance name:
- Sodium dihydrogenorthophosphate
- EC Number:
- 231-449-2
- EC Name:
- Sodium dihydrogenorthophosphate
- Cas Number:
- 7558-80-7
- Molecular formula:
- H3O4P.Na
- IUPAC Name:
- sodium dihydrogen phosphate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): FDA 73-2 (Monosodium phosphate, anhydrous)
- Physical state: Fine white powdered material
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Outbred
- Age at study initiation: No data
- Weight at study initiation: 223 - 237 g
- Fasting period before study: No data
- Housing: Individual housing in mesh bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 28
- Humidity (%): 42 - 74%
IN-LIFE DATES: From: 27/09/1974 To: 29/10/1974
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE: Water
- Amount of vehicle (if gavage): 1 mL/kg bw at doses equal to or below 250 mg/kg bw and 2 mL/kg at doses up to 500 mg/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: No data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy - Duration of treatment / exposure:
- 10 days (Day 6 to Day 15 of gestation)
- Frequency of treatment:
- Daily
- Duration of test:
- 20 days
- No. of animals per sex per dose:
- Test material and vehicle control: 20 females / dose level
- Control animals:
- yes, sham-exposed
- other: positive control: 250 mg/kg aspirin
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Appearence, behaviour, food consumption and weight observed daily.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights recorded on days 0, 6, 11, 15 and 20.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: uterus and urogenital tract - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes: one third per litter
- Soft tissue examinations: Yes: one third per litter
- Skeletal examinations: Yes: two thirds per litter
- Head examinations: Yes: two thirds per litter - Statistics:
- No data
- Indices:
- No data
- Historical control data:
- No
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:
- > 410 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects noted
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- > 410 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects noted
Fetal abnormalities
- Abnormalities:
- no effects observed
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Table 1 Reproduction data
Dose (mg/kg) |
Sham |
Aspirin |
4.1 |
19.0 |
88.3 |
410.0 |
Pregnancies |
|
|
|
|
|
|
Total No. |
20 |
20 |
20 |
20 |
20 |
20 |
Died or aborted (before Day 20) |
0 |
0 |
0 |
0 |
0 |
0 |
To term (on Day 20) |
20 |
20 |
20 |
20 |
20 |
20 |
Corpora Lutea |
|
|
|
|
|
|
Total no. |
267 |
263 |
263 |
252 |
264 |
267 |
Average/dam mated |
12.7 |
12.5 |
12.5 |
12.0 |
12.6 |
13.4 |
Live litters |
|
|
|
|
|
|
Total No.* |
20 |
19 |
20 |
20 |
20 |
20 |
Implant Sites |
|
|
|
|
|
|
Total No. |
262 |
238 |
240 |
251 |
239 |
244 |
Average/dam* |
13.1 |
11.9 |
12.0 |
12.6 |
12.0 |
12.2 |
Resorptions |
|
|
|
|
|
|
Total No* |
-- |
35 |
1 |
5 |
1 |
2 |
Dams with 1 or more sites resorbed |
-- |
7 |
1 |
3 |
1 |
1 |
Dams with all sites resorbed |
-- |
1 |
-- |
-- |
-- |
-- |
Per cent partial resorptions |
-- |
35.0 |
5.00 |
15.0 |
5.00 |
5.00 |
Per cent complete resorptions |
-- |
5.00 |
-- |
-- |
-- |
-- |
Live foetuses |
|
|
|
|
|
|
Total No |
262 |
203 |
239 |
246 |
238 |
242 |
Average/dam* |
13.1 |
10.2 |
12.0 |
12.3 |
11.9 |
12.1 |
Sex ratio (M/F) |
1.06 |
0.92 |
1.03 |
0.95 |
1.00 |
1.12 |
Dead Foetuses |
|
|
|
|
|
|
Total No.* |
-- |
-- |
-- |
-- |
-- |
-- |
Dams with 1 or more dead |
-- |
-- |
-- |
-- |
-- |
-- |
Dams with all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Per cent partial dead |
-- |
-- |
-- |
-- |
-- |
-- |
Per cent all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average foetus weight (g) |
3.93 |
2.92 |
3.84 |
3.91 |
4.00 |
3.85 |
* Includes only those dams examined at term
** Positive control: 250 mg/kg
Table 2 Summary of skeletal findings
Findings |
Dose (mg/kg) |
|||||
Sham |
Aspirin |
4.1 |
19.0 |
88.3 |
410.0 |
|
Live foetuses examined (at term) |
179/20 |
143/19 |
166/20 |
171/20 |
168/20 |
170/20 |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
37/16 |
89/19 |
42/17 |
82/18 |
49/15 |
45/11 |
Scrambled |
|
8/6 |
1/1 |
|
|
1/1 |
Bipartite |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Missing |
3/3 |
70/15 |
4/3 |
10/7 |
|
7/6 |
Other |
|
|
|
|
|
|
Ribs |
|
|
|
|
|
|
Incomplete oss. |
2/2 |
15/8 |
7/2 |
|
|
1/1 |
Fused/split |
|
5/2 |
|
|
|
|
Wavy |
23/8 |
60/17 |
19/8 |
23/11 |
11/6 |
13/5 |
Less than 12 |
|
|
|
|
|
|
More than 13 |
2/2 |
59/15 |
|
4/4 |
|
1/1 |
Other |
|
|
|
|
|
|
Vertebrae |
|
|
|
|
|
|
Incomplete oss. |
4/4 |
68/18 |
2/1 |
1/1 |
9/6 |
10/4 |
Scrambled |
|
|
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. oss. |
|
1/1 |
|
|
|
|
Scoliosis |
|
|
|
|
|
|
Tail defects |
|
|
|
|
|
|
Other |
|
|
|
|
|
|
Skull |
|
|
|
|
|
|
Incomplete closure |
38/13 |
88/19 |
33/14 |
30/12 |
37/11 |
40/11 |
Missing |
|
|
|
|
|
|
Craniostosis |
|
|
|
|
|
|
Other |
|
|
|
|
|
|
Extremities |
|
|
|
|
|
|
Incomplete oss. |
|
3/3 |
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Miscellaneous |
|
|
|
|
|
|
Hyoid; missing |
21/10 |
54/16 |
21/12 |
19/10 |
12/8 |
20/11 |
Hyoid; reduced |
26/13 |
21/10 |
33/14 |
28/11 |
41/14 |
47/14 |
* Numerator = Number of foetuses affected; Denominator = Number of litters affected
** Positive control: 250 mg/kg
Table 3 Summary of soft tissue abnormalities
Material |
Dose level (mg/kg) |
Dam |
Number of pups |
Description |
Aspirin |
250.0 |
44235 |
1 |
Hydrocephalus |
|
|
44240 |
1 |
Hydrocephalus; Encephalomeningocele |
|
|
44246 |
2 |
Hydrocephalus |
|
|
44252 |
1 |
Spina bifida; Encephalomeningocele |
|
|
44255 |
1 |
Hydrocephalus |
FDA 73-2 |
88.3 |
44337 |
1 |
Umbilical hernia |
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the study, the test material administered to pregnant rats for 10 days up to a dose level of 410 mg/kg bw showed no maternal or developmental toxicity. The NOAEL for both maternal and fetoxicity is > 410 mg/kg bw.
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.
