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EC number: 230-785-7 | CAS number: 7320-34-5
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data

Toxicity to reproduction
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because a pre-natal developmental toxicity study is available
Cross-reference
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Meets generally accepted scientific standards with acceptable restrictions. Deficiencies: Food consumption not reported Uterine weights and corpora lutea 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
(1) The source and target substances are both inorganic salts of a monovalent cation from Group 1A of the periodic table, sodium or potassium, and pyrophosphoric acid. Thus, they all share the Na+ or K+ cation and the P2O74- anion as common functional groups.
(2) All members of the group will ultimately dissociate into the common breakdown products of the Na+ or K+ cations and the P2O74-anion.
(3) The pyrophosphate ion is the simplest form of a condensed phosphate group. A condensed phosphate anion has one or several P-O-P bonds. As the group contains only two phosphate groups, both of the phosphorus ions are classified as “terminal phosphorus”. The pyrophosphate can undergo ionisation with loss of H+ from each of the two –OH groups on each P and therefore can occur in the -1, -2 -3 or -4 state. The degree of ionisation is dependent upon the associated cations and the ambient pH (if in solution). Therefore the above substances have a pyrophosphate anion that is likely to behave in a similar way. In addition, the sodium and potassium cations are key elements in various cellular processes their import and export over cell membranes is regulated via pore systems and usually tightly regulated. As such, the presence of varying quantities of such cations is not expected to have an impact on the genotoxicity of the substances therefore as the both ionic components of the substance are common the results of toxicity studies can be reliably read-across within the group.
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:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- read-across: supporting information
- 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 1.69, 9.24, 42.95 and 169.0 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 was recorded. On Day 20 of gestation all dams underwent Caesarean section. Number of 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
- 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: 214 - 225 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): Not recorded
- Humidity (%): Not recorded
IN-LIFE DATES: No data - 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:
- Table 1 Number of animals dosed
Material Dose (mg/kg) Total
Mated Pregnant
Sham 0.0 25 23
Aspirin 250.0 24 21
FDA 71-61 1.69 25 24
9.24 25 24
42.95 24 24
169.0 25 21 - Control animals:
- yes, sham-exposed
- other: positive control: 250 mg/kg aspirin
- 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: No
- 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
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- Effect level:
- > 169 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects observed
- Abnormalities:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
- Dose descriptor:
- NOAEL
- Effect level:
- > 169 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Under the conditions of the study, the test material administered to pregnant rats for 10 days up to a dose level of 169 mg/kg bw showed no maternal or developmental toxicity. The NOAEL for both maternal and fetotoxicity is > 169 mg/kg bw.
Table 2 Reproduction data
Dose (mg/kg) |
Sham |
Aspirin |
1.69 |
9.24 |
42.95 |
169.0 |
Pregnancies |
|
|
|
|
|
|
Total No. |
23 |
21 |
24 |
24 |
24 |
21 |
Died or aborted (before Day 20) |
0 |
1 |
0 |
0 |
0 |
0 |
To term (on Day 20) |
23 |
20 |
24 |
24 |
24 |
21 |
Live litters |
|
|
|
|
|
|
Total No.* |
23 |
18 |
24 |
24 |
24 |
21 |
Implant Sites |
|
|
293 |
|
|
|
Total No. |
283 |
234 |
12.2 |
284 |
287 |
254 |
Average/dam* |
12.3 |
11.7 |
|
11.8 |
12.0 |
12.1 |
Resorptions |
|
|
|
|
|
|
Total No* |
4 |
35 |
4 |
4 |
4 |
-- |
Dams with 1 or more sites resorbed |
2 |
5 |
4 |
4 |
3 |
-- |
Dams with all sites resorbed |
-- |
2 |
-- |
-- |
-- |
-- |
Per cent partial resorptions |
8.70 |
25.0 |
16.7 |
16.7 |
12.5 |
-- |
Per cent complete resorptions |
-- |
10.0 |
-- |
-- |
-- |
-- |
Live foetuses |
|
|
|
|
|
|
Total No |
279 |
197 |
288 |
280 |
283 |
254 |
Average/dam* |
12.1 |
9.85 |
12.0 |
11.7 |
11.8 |
12.1 |
Sex ratio (M/F) |
1.08 |
0.80 |
1.27 |
1.00 |
0.98 |
1.03 |
Dead Foetuses |
|
|
|
|
|
|
Total No.* |
-- |
2 |
1 |
-- |
-- |
-- |
Dams with 1 or more dead |
-- |
2 |
1 |
-- |
-- |
-- |
Dams with all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Per cent partial dead |
-- |
10.0 |
4.17 |
-- |
-- |
-- |
Per cent all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average foetus weight (g) |
3.65 |
2.41 |
3.71 |
3.78 |
3.78 |
3.75 |
* Includes only those dams examined at term
** Positive control: 250 mg/kg
Table 3 Summary of skeletal findings
Findings |
Dose (mg/kg) |
|||||
Sham |
Aspirin |
1.69 |
9.24 |
42.95 |
169.0 |
|
Live foetuses examined (at term) |
191/23 |
137/18 |
198/24 |
193/24 |
196/24 |
176/21 |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
71/20 |
86/16 |
83/19 |
54/19 |
61/16 |
47/17 |
Scrambled |
|
|
|
|
|
|
Bipartite |
|
7/5 |
|
|
2/2 |
4/3 |
Fused |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Missing |
7/6 |
117/7 |
9/7 |
15/8 |
1/1 |
5/4 |
Other |
|
|
|
|
|
|
Ribs |
|
|
|
|
|
|
Incomplete oss. |
1/1 |
3/2 |
3/2 |
|
|
1/1 |
Fused/split |
|
14/4 |
|
|
|
|
Wavy |
14/8 |
54/14 |
34/9 |
12/7 |
15/8 |
13/8 |
Less than 12 |
|
|
|
|
|
|
More than 13 |
1/1 |
89/15 |
6/5 |
3/3 |
|
6/5 |
Other |
|
|
|
|
|
|
Vertebrae |
|
|
|
|
|
|
Incomplete oss. |
6/5 |
120/17 |
12/4 |
21/11 |
5/4 |
10/8 |
Scrambled |
|
1/1 |
|
|
|
|
Fused |
|
|
1/1 |
|
|
|
Extra ctrs. oss. |
|
|
|
|
|
|
Scoliosis |
|
3/3 |
|
|
|
|
Tail defects |
|
1/1 |
|
|
|
|
Other |
|
|
|
|
|
|
Skull |
|
|
|
|
|
|
Incomplete closure |
23/10 |
60/13 |
50/16 |
31/12 |
25/13 |
20/11 |
Missing |
|
9/4 |
|
|
|
|
Craniostosis |
|
|
|
|
|
|
Other |
|
1/1 |
|
|
|
|
Extremities |
|
|
|
|
|
|
Incomplete oss. |
|
4/3 |
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Miscellaneous |
|
|
|
|
|
|
Hyoid; missing |
19/11 |
69/17 |
37/15 |
14/9 |
26/13 |
7/6 |
Hyoid; reduced |
7/5 |
20/8 |
38/14 |
27/12 |
35/16 |
28/12 |
* Numerator = Number of foetuses affected; Denominator = Number of litters affected
** Positive control: 250 mg/kg
Table 4 Summary of soft tissue abnormalities
Material |
Dose level (mg/kg) |
Dam |
Number of pups |
Description |
Aspirin |
250.0 |
A 4910 |
1 |
Encepalomyelocele |
|
|
A 4913 |
1 |
Exencephaly; exophthalmos |
|
|
A 4917 |
1 |
Renal agenesis |
|
|
A 4921 |
1 |
Encephalomyelocele; gastroschisis |
|
|
A 4923 |
3 |
Encephalomyelocele |
|
|
|
1 |
Exophthalmos; gastroschisis |
|
|
A 4925 |
2 |
Encepalomyelocele |
FDA 71-61 |
42.95 |
M 4076 |
1 |
Gastroschisis |
Data source
Materials and methods
Results and discussion
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
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.
