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EC number: 603-758-6 | CAS number: 133647-88-8
- 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 (non-LLNA)
- Type of information:
- read-across from similar mixture/product
- Adequacy of study:
- key study
- Study period:
- 1995-08-21 until 1995-09-14
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP study on structural analogue (free acid) according to OECD guideline 406. The fact that the study is used for read-across purposes triggers reliability rating 2.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- An appropriate guinea pig maximization test is available which would not justify conducting an additional LLNA due to animal welfare.
- Species:
- guinea pig
- Strain:
- Pirbright-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Ciba-Geigy Ltd, Animal Production, CH-4332 Stein, Switzerland
- Strain: Pirbright White Strain (Tif: DHP)
- Age at study initiation: no data
- Weight at study initiation: 332 - 412 g
- Housing: individually in Macrolon cages (Type 3)
- Diet: standard guinea pig pellets NAFAG 845 ad libitum (NAFAG, Gossau, Switzerland)
- Water: fresh drinking water ad libitum
- Acclimation period: 5 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12
IN-LIFE DATES: From: 1995-08-21 To: 1995-09-14 - Route:
- intradermal and epicutaneous
- Vehicle:
- physiological saline
- Concentration / amount:
- Pretest: 1, 5, 10, 20, 30 and 50% w/v
Intradermal induction: 5% (in saline and saline/adjuvant), 0.1 mL per injection
Epidermal induction: 50% in saline
Challenge: 1% in saline - Route:
- epicutaneous, occlusive
- Vehicle:
- physiological saline
- Concentration / amount:
- Pretest: 1, 5, 10, 20, 30 and 50% w/v
Intradermal induction: 5% (in saline and saline/adjuvant), 0.1 mL per injection
Epidermal induction: 50% in saline
Challenge: 1% in saline - No. of animals per dose:
- Pretest: 2 (1 male, 1 female, with two doses applied on each animal)
Main study: 10 males, 10 females in test group; 5 males, 5 females in control group - Details on study design:
- RANGE FINDING TESTS:
- Six guinea pigs (3 males, 3 females) received two pairs of consecutive intradermal injections of adjuvant/ saline (50:50) in the neck. Seven days later, two different concentrations of the test substance were tested simultaneously (left and right flank, Hilltop chamber, occlusive) for 24 hours, to assess the primary irritation potential, scored 24 and 48 hours after removal of dressing.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: one intradermal (day 0), one epicutaneous (day 8)
- Exposure period: epicutaneous 48 hours
- Test groups: 1 (10 males + 10 females): intradermal: adjuvant/saline 1:1, test substance in saline, test substance in adjuvant/saline; epicutaneous: test substance in saline
- Control group: 1 (5 males + 5 females): intradermal: saline, adjuvant/saline 1:1; epicutaneous: saline
- Site: injections and epicutaneous application: shaved neck
- Frequency of applications: Day 0 + 8
- Concentrations: injection 5% (0.1 mL), epicutaneos 50% (approx. 0.4 g on a filter paper patch 2x4 cm, occlusive dressing)
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 22
- Exposure period: epicutaneous 24 hours
- Test groups: 1% test substance in saline on one flank, saline on the other (epicutaneous, Hilltop chamber)
- Control group: 1% test substance in saline on one flank, saline on the other (epicutaneous, Hilltop chamber)
- Site: flanks
- Concentrations: 1% (approx. 0.35 mL per Hilltop chamber)
- Evaluation (hr after challenge): 24 and 48 hours after removal of dressing - Positive control substance(s):
- yes
- Remarks:
- 2-mercaptobenzothiazole
- Positive control results:
- 2-mercaptobenzothiazole (intradermal induction: 5% in oleum arachidis, epidermal induction: 50% in vaseline, challenge: 10% in vaseline) caused 16/20 positive animals after 24 hours, 19/20 after 48 hours, with no irritation in the control.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 10% in vaseline
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 10% in Vaseline
- No. with + reactions:
- 16
- Total no. in group:
- 20
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- no irritant skin reactions, no other findings
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no irritant skin reactions, no other findings.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 1%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Clinical observations:
- no irritant skin reactions, no other findings
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no irritant skin reactions, no other findings.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 1%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no irritant skin reactions, no other findings
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no irritant skin reactions, no other findings.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 1%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no irritant skin reactions, no other findings
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 1%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no irritant skin reactions, no other findings.
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- Sodium (2R)-2-(4-hydroxyphenoxy)propanoate is not expected to be sensitising derived from read-across.
Reference
Pretest:
Primary Skin Irritation Potential, Erythema score
Concentration | 24-hour |
score | 48-hour | score |
% | M | F | M | F |
50 | + | - | + | + |
30 | + | - | - | - |
20 | + | + | + | + |
10 | + | - | - | - |
5 | - | + | - | - |
1 | - | - | - | - |
No signs of edema were seen at any concentration.
Main Test:
On day 10 (after removal of the occlusive dressing used for epidermal induction), irritation of the application site was observed in all animals treated with the test substance (concentration 50% in saline). The body weight was not affected by the treatment.
Read-across: No signs of skin sensitisation were observed with the source substance, the free acid (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5).
The sensitisation potential of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) (CAS 1184648-08-5) is determined by read-across from the maximisation test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the K+ counterion), and that they form a pH-dependent equilibrium. Upon intradermal induction in the maximisation test, the free acid is neutralized to the Na+ salt (due to the buffer capacity of body fluids), whereas the K+counterion of the salt is exchanged to Na+(due to the sodium excess in body fluids), which makes the two forms indistinguishable. In the subsequent epidermal induction, the acid is more likely than the K+ salt to permeate the stratum corneum, so it is assumed to evoke a stronger effect, if any.
No signs of skin sensitisation were observed with the acid. As a conclusion, the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) is also unlikely to be a skin sensitiser.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
Skin sensitisation of sodium (2R)-2-(4-hydroxyphenoxy)propanoate, (CAS 133647-88-8) was determined by read-across from a skin sensitisation study conducted with the free acid, namely (R)-2-(4-hydroxyphenoxy)propanoic acid (CAS 94050-90 -5).
Only a single skin sensitisation study conducted according to guideline OECD 406 and under GLP is available for the source substance, the free acid (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5). The study is considered to be complete, reliable and adequate for the purposes of risk assessment, classification and labelling. The maximisation study in guinea pigs elicited no positive responses in any animal after 24 and 48 hours.
The sensitisation potential of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) (CAS 133647-88-8) is determined by read-across from the maximisation test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the K+ counterion), and they form a pH-dependent equilibrium. Upon intradermal induction in the maximisation test, the free acid is neutralized to the Na+ salt (due to the buffer capacity of body fluids), which makes the two forms indistinguishable. In the subsequent epidermal induction, the acid is more likely than the Na+ salt to permeate the stratum corneum, so it is assumed to evoke a stronger effect, if any. No signs of skin sensitisation were observed with the source (free acid).
As a conclusion, the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) is also unlikely to be a skin sensitiser.
Migrated from Short description of key information:
Skin sensitisation: [(R)-2-(4-hydroxyphenoxy)-propanoic acid]: Not sensitising, OECD 406, Winkler 1995
Justification for selection of skin sensitisation endpoint:
Only one study was available, which was carried out according to guidelines and under GLP.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Skin sensitisation:
The results from Skin Sensitisation Test in the Guinea Pig, Maximisation test (OECD 406) indicate that the substance is not a skin sensitiser. As a result the substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, Part 3, 3.4.2.2.
The conclusion given above only takes into consideration the properties of the constituent in this mono constituent substance. As indicated in the composition under section 1.2 one of the impurities is relevant for C&L of the substance. This is finally included in the Classification and Labelling section 2 where necessary based on the typical concentration value given and the harmonized classification and labelling that is available for this impurity both under CLP/GHS and DSD-DPD.
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