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EC number: 233-190-0 | CAS number: 10058-44-3
- 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
Endpoint summary
Administrative data
Description of key information
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- The study was performed between 21 June 2011 and 13 July 2011
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. The reliability has been amended in accordance with 'practical guide 6: How to report read-across and categories' which states that the maximum reliability for a read-across study is 2. The study is considered to be adequate and reliable for the purpose of registration under REACH (Regulation (EC) No. 1907/2006) and for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Read-across is justified on the basis that the sensitisation potential of tetrairon tris(pyrophosphate) will be determined by the Fe cation. Pyrophosphate itself is not considered to be a sensitiser, in addition, the breakdown product of pyrophosphate (orthophosphate) is a natural component of blood and cellular fluids. As, tetrairon tris(pyrophosphate) has a lower water solubility than iron orthophosphate it is considered to be less bioavailable and therefore iron orthophosphate is considered to be a worst case for sensitisation potential of the Fe cation.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- other: CBA/Ca (CBA/CaOlaHsd)
- Sex:
- female
- Details on test animals and environmental conditions:
- Animals and Animal Husbandry
Female CBA/Ca (CBA/CaOlaHsd) strain mice were supplied by by a reputable supplier. For full details please see Harlan Laboratories Ltd Study number 41101364. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were in the weight range of 15 to 23 g, and were eight to twelve weeks old.
The animals were individually housed in suspended solid floor polypropylene cages furnished with softwood woodflakes. Free access to mains tap water and food was allowed throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 19 to 25°C and 30 to 70%, respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06.00 to 18.00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study. - Vehicle:
- dimethylformamide
- Remarks:
- Please see below for Vehicle Determination Record
- Concentration:
- Groups of mice were treated with the test item at concentrations of 50%, 25% or 10% w/w in dimethyl formamide.
- No. of animals per dose:
- Groups of four mice were treated
- Details on study design:
- Preliminary Screening Test
As no toxicological information was available regarding the systemic toxicity/irritancy potential of the test item, a preliminary screening test was performed using one mouse. The mouse was treated by daily application of 25 µl of the test item at a concentration of 50% w/w in dimethyl formamide, to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The mouse was observed twice daily on Days 1, 2 and 3 and once daily on Days 4, 5 and 6. Local irritation was scored daily according to the scale included as Appendix 5. Any clinical signs of toxicity, if present, were also recorded. The bodyweight was recorded on Day 1 (prior to dosing) and on Day 6.
The thickness of each ear was measured using an Oditest micrometer (Dyer, PA), pre dose on Day 1, post dose on Day 3 and on Day 6. Any changes in the ear thickness were noted. Mean ear thickness changes were calculated between time periods Days 1 and 3 and Days 1 and 6. A mean ear thickness increase of equal to or greater than 25% was considered to indicate excessive irritation and limited biological relevance to the endpoint of sensitisation.
Main Test
Test Item Administration
Groups of four mice were treated with the test item at concentrations of 50%, 25% or 10% w/w in dimethyl formamide. The preliminary screening test suggested that the test item would not produce systemic toxicity or excessive local irritation at the highest suitable concentration. The mice were treated by daily application of 25 µl of the appropriate concentration of the test item to the dorsal surface of each ear for three consecutive days (Days 1, 2, 3). The test item formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
A further group of four mice received the vehicle alone in the same manner.
3H-Methyl Thymidine Administration
Five days following the first topical application of the test item or vehicle (Day 6) all mice were injected via the tail vein with 250 µl of phosphate buffered saline (PBS) containing 3H methyl thymidine (3HTdR: 80 µCi/ml, specific activity 2.0 Ci/mmol, ARC UK Ltd) giving a total of 20 µCi to each mouse.
Observations
Clinical Observations: All animals were observed twice daily on Days 1, 2 and 3 and on a daily basis on Days 4, 5 and 6. Any signs of toxicity or signs of ill health during the test were recorded.
Bodyweights: The bodyweight of each mouse was recorded on Day 1 (prior to dosing) and Day 6 (prior to termination). - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- None provided.
- Positive control results:
- One group of five animals was treated with 50 µl (25 µl per ear) of alpha-Hexylcinnamaldehyde, Tech, 85% as a solution in dimethyl formamide at a concentration of 15% v/v. A further group of five animals was treated with dimethyl formamide alone
The Stimulation Index expressed as the mean radioactive incorporation for the treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows:
Concentration % v/v in acetone/olive oil 4:1 Stimulation Index (SI) Result
15 4.77 Positive
Alpha-Hexylcinnamaldehyde, Tech 85% was considered to be a sensitiser under the conditions of the test. - Parameter:
- SI
- Remarks on result:
- other: A stimulation index of less than 3 was recorded for test material at concentrations of 50% , 25% and 10% v/v in dimethyl formamide. The stimulation index (SI) results are given in Table 4.
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: The radioactive disintegrations per minute (dpm) per lymph node and the stimulation index (SI) are given in Table 4.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test material was considered to be a non-sensitiser under the conditions of the test. This study is considered to be scientifically justified for use as a key study under Regulation (EC) No. 1907/2006 (REACH) and the results are appropriate for the purposes of classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
Reference
Preliminary Screening Test
Clinical observations, bodyweight and mortality data are given in Table 1 and local skin irritation is given in Table 2. The ear thickness measurements and mean ear thickness changes are given in Table 3.
No signs of systemic toxicity, visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted. Off white residual test item on the ears was noted on Days 2 to 6.
Based on this information the dose levels selected for the main test were 50%, 25% and 10% w/w in dimethyl formamide.
Table 1 Clinical Observations, Bodyweight and Mortality Data – Preliminary Screening Test
Concentration (%w/w) in |
Animal Number |
Bodyweight (g) |
Day |
|||||||||
1 |
2 |
3 |
4 |
5 |
6 |
|||||||
Day 1 |
Day 6 |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
50 |
S-1 |
17 |
18 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0Rt |
0Rt |
0Rt |
0= No signs of systemic toxicity
Rt = Off white residual test item on the ears
Table 2 Local Skin Irritation – Preliminary Screening Test
Concentration |
Animal Number |
Local Skin Irritation |
|||||||||||
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
||||||||
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
left |
right |
||
50 |
S-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Table 3 Measurement of Ear Thicknessand Mean Ear Thickness Changes – Preliminary Screening Test
Concentration |
Animal Number |
Ear Thickness Measurement (mm) |
|||||
Day 1 |
Day 3 |
Day 6 |
|||||
pre‑dose |
post dose |
||||||
left |
right |
left |
right |
left |
right |
||
50 |
S-1 |
0.240 |
0.250 |
0.265 |
0.270 |
0.260 |
0.270 |
overall mean (mm) |
0.245 |
0.268 |
0.265 |
||||
overall mean ear thickness change (%) |
na |
9.184 |
8.163 |
na= Not applicable
Main Test
Estimation of the Proliferative Response of Lymph Node Cells
The radioactive disintegrations per minute per lymph node and the stimulation index are given in Table 4.
Table 4 Disintegrations per Minute, Disintegrations per Minute/Node and Stimulation Index
Concentration |
dpm |
dpm/Nodea |
Stimulation Indexb |
Result |
Vehicle |
10037.10 |
1254.64 |
na |
na |
10 |
14799.04 |
1849.88 |
1.47 |
Negative |
25 |
14840.58 |
1855.07 |
1.48 |
Negative |
50 |
20102.10 |
2512.76 |
2.00 |
Negative |
dpm= Disintegrations per minut
a= Disintegrations per minute/node obtained by dividing the disintegrations per minute value by 8 (total number of lymph nodes)
b= Stimulation Index of 3.0 or greater indicates a positive result
na = Not appl
Clinical Observations and Mortality Data
Individual clinical observations and mortality data for test and control animals are given in Table 5.
There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Off white residual test item on the ears was noted in animals treated with the test item at concentrations of 50% or 25% w/w in dimethyl formamide.
Table 5 Individual Clinical Observations and Mortality Data
Concentration |
Animal Number |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
|||
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
Pre-Dose |
Post Dose |
|||||
Vehicle |
1-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
1-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
10 |
2-1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
2-2 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-3 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
2-4 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
25 |
3-1 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0 |
3-2 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0 |
|
3-3 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0 |
|
3-4 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0 |
|
50 |
4-1 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0Rt |
4-2 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0Rt |
|
4-3 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0Rt |
|
4-4 |
0 |
0 |
0 |
0 |
0 |
0Rt |
0Rt |
0Rt |
0Rt |
0= No signs of systemic toxicity
Rt = Off white residual test item on the ears
Bodyweight
Individual bodyweights and bodyweight changes for test and control animals are given in Table 6.
Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.Table 6 Individual Bodyweights and Bodyweight Changes
Concentration |
Animal Number |
Bodyweight (g) |
Bodyweight Change (g) |
|
Day 1 |
Day 6 |
|||
Vehicle |
1-1 |
18 |
19 |
1 |
1-2 |
18 |
20 |
2 |
|
1-3 |
19 |
19 |
0 |
|
1-4 |
22 |
21 |
-1 |
|
10 |
2-1 |
20 |
22 |
2 |
2-2 |
18 |
18 |
0 |
|
2-3 |
19 |
20 |
1 |
|
2-4 |
18 |
19 |
1 |
|
25 |
3-1 |
18 |
18 |
0 |
3-2 |
19 |
20 |
1 |
|
3-3 |
20 |
20 |
0 |
|
3-4 |
18 |
20 |
2 |
|
50 |
4-1 |
19 |
19 |
0 |
4-2 |
17 |
19 |
2 |
|
4-3 |
19 |
19 |
0 |
|
4-4 |
18 |
19 |
1 |
Appendix4 Scale for Erythema
Observation |
Score |
No erythema................................................................................................................. |
0 |
Very slight erythema (barely perceptible).................................................................. |
1 |
Well-defined erythema................................................................................................. |
2 |
Moderate to severe erythema..................................................................................... |
3 |
Severe erythema (beef redness) to eschar formation preventing grading of erythema....................................................................................................................... |
4 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
- Migrated from Short description of key information:
One key study is available (Bradshaw J, 2011) for the skin sensitisation endpoint. The reliability has been amended in accordance with 'practical guide 6: How to report read-across and categories' which states that the maximum reliability for a read-across study is 2. The study is considered to be adequate and reliable for the purpose of registration under REACH (Regulation (EC) No. 1907/2006) and for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
Read-across is justified on the basis that the sensitisation potential of tetrairon tris(pyrophosphate) will be determined by the Fe cation. Pyrophosphate itself is not considered to be a sensitiser, in addition, the breakdown product of pyrophosphate (orthophosphate) is a natural component of blood and cellular fluids. As, tetrairon tris(pyrophosphate) has a lower water solubility than iron orthophosphate it is considered to be less bioavailable and therefore iron orthophosphate is considered to be a worst case for sensitisation potential of the Fe cation. The study reports that iron orthophosphate is a non-sensitiser under the conditions of the study.
Justification for selection of skin sensitisation endpoint:
Study conducted according to an appropriate guideline (OECD 429) and under the conditions of GLP.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
On the basis of a read-across approach tetrairon tris(pyrophosphate) is not considered to be classified for skin sensitisation in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The key study is considered to be adequate and reliable for the purpose of classification and therefore further testing is not scientifically justified.
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