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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 928-842-2 | CAS number: 1184648-08-5
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- 1995-08-21 to 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. The fact that the study is used for read-across purposes triggers reliability rating 2.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guidelineopen allclose all
- 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:
- At the time of test execution the guinea pig maximisation test was considered a valid test option. The ginea pig maximisation test used to cover this end point has been used within the read-across approach.
Test material
- Reference substance name:
- (R)-2-(4-Hydroxyphenoxy)propanoic acid
- IUPAC Name:
- (R)-2-(4-Hydroxyphenoxy)propanoic acid
- Reference substance name:
- Propanoic acid, 2-(4-hydroxyphenoxy)-, (2R)-
- IUPAC Name:
- Propanoic acid, 2-(4-hydroxyphenoxy)-, (2R)-
- Reference substance name:
- 94050-90-5
- Cas Number:
- 94050-90-5
- IUPAC Name:
- 94050-90-5
- Reference substance name:
- (R)-2-(4-hydroxyphenoxy)propanoic acid
- EC Number:
- 407-960-3
- EC Name:
- (R)-2-(4-hydroxyphenoxy)propanoic acid
- IUPAC Name:
- 407-960-3
- Details on test material:
- - Substance type: Pure test substance
- Physical state: Solid
Constituent 1
Constituent 2
Constituent 3
Constituent 4
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Pirbright-Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- 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
- 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
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- 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
Challengeopen allclose all
- 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:
- 6 guinea pigs (3 males, 3 females) received 2 pairs of consecutive intradermal injections of adjuvant/ saline (50:50) in the neck. 7 days later, 2 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: 1 intradermal (day 0), 1 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
Results and discussion
- 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.
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 10%
- No. with + reactions:
- 16
- Total no. in group:
- 20
- Clinical observations:
- none reported
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 10%
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Clinical observations:
- none reported
- Remarks on result:
- positive indication of skin sensitisation
- 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:
- no indication of skin sensitisation
- 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:
- no indication of skin sensitisation
- 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:
- no indication of skin sensitisation
- 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:
- no indication of skin sensitisation
Any other information on results incl. tables
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.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Conclusions:
- Potassium (R)-2-(4-hydroxy-phenoxy)-propionate is not expected to be sensitising derived from read-across.
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.
