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EC number: 443-520-7 | CAS number: -
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2002-05-30 - 2002-08-08
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 002
- Report date:
- 2002
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- 2000-04-26
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- An appropriate guinea pig maximisation test is available which would not justify conducting an additional LLNA due to animal welfare
Test material
- Reference substance name:
- -
- EC Number:
- 443-520-7
- EC Name:
- -
- Cas Number:
- 33016-77-2
- Molecular formula:
- C2H4Na4O6P2
- IUPAC Name:
- tetrasodium (1-phosphonatoethenyl)phosphonate
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- - Synonyms: ITC 908, vinylidenephosphonic acid tetrasodium salt (VDPA tetrasodium salt)
- Lot/batch No.of test material: 562CH/646
- Purity: 87.33%
- Storage condition of test material: Room temperature, in the dark
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK (interdermal and topical induction sighting studies) and Harlan UK Limited, Bicester, Oxon, UK (rest of the study)
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 281 - 336g
- Housing: The animals were housed singly or in pairs in solid-floor polypropylene cages furnished with woodflakes.
- Diet: Certified Guinea Pig Diet supplied by PMI Nutrition International, Nottingham, UK and IPS Product Supplies Limited, Wellingborough, Northants, UK, ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days
- Indication of any skin lesions:
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal
- Vehicle:
- water
- Concentration / amount:
- 1%
- Day(s)/duration:
- 7
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- 50%
- Day(s)/duration:
- 2
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- 5 and 10%
- Day(s)/duration:
- 1
- Adequacy of challenge:
- other: 10%: highest non-irritant concentration; 5%: verification of the use of the maximum non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- water
- Concentration / amount:
- 2 and 5%
- Day(s)/duration:
- 1
- No. of animals per dose:
- 10
- Details on study design:
- RANGE FINDING TESTS:
Selection of concentration for intradermal induction: Intradermal injections (0.1 ml/injection site) were made with two guinea pigs, using concentrations of 1% and 5% w/w in distilled water. The degree of erythema at the injection sites was assessed approximately 24, 48, 72 hours and 7 days after injection. The degree of oedema was not evaluated. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.
Selection of concentration for topical induction: Two guinea pigs were treated with four preparations of the test material (50%, 25%, 10% and 5% w/w in distilled water). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was assessed approximately 1, 24 and 48 hours after removal.The highest concentration that caused only mild to moderate skin irritation was selected for the topical induction stage of the main study.
Selection of concentration for topical challenge: Four preparations of the test material (25%, 10%, 5% and 2% w/w in distilled water) were applied to two guinea pigs under occlusive dressings for an exposure period of 24 hours. The degree of erythema and oedema was assessed approximately 1, 24 and 48 hours after removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 7 days (intradermal), 48 hours (topical)
- Test groups: 1
- Control group: 1
- Site: Should region
- Frequency of applications: 2
- Duration: 21 days
- Concentrations: 1% (intradermal), 50% (topical)
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24h
- Test groups: 1
- Control group: 1
- Site: flanks
- Concentrations: 10% (right flank), 5% (left flank)
- Evaluation (hr after challenge): 24 and 48 hours
C. RECHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 32
- Exposure period: 24h
- Test groups: 1
- Control group: 1 (not previously exposed)
- Site: previously untreated areas
- Concentrations: 2% and 5%
- Evaluation (hr after challenge): 24 and 48 hours
OTHER: - Positive control substance(s):
- yes
- Remarks:
- 2-Mercaptobenzothiazole
Results and discussion
- Positive control results:
- 80% Incidence of sensitisation
(Induction intradermal 5%, topical 50%, Challenge 50 and 25%).
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 5
- Total no. in group:
- 10
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 4
- Total no. in group:
- 10
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 2%
- No. with + reactions:
- 8
- Total no. in group:
- 10
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 2%
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5%
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 3
- Total no. in group:
- 5
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 1
- Total no. in group:
- 5
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 5
- Total no. in group:
- 5
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 10%
- No. with + reactions:
- 5
- Total no. in group:
- 5
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 2%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 2%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 5%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Reading:
- other: Not specified
- Group:
- positive control
- Dose level:
- 50%
- No. with + reactions:
- 8
- Total no. in group:
- 10
Applicant's summary and conclusion
- Interpretation of results:
- Category 1A (indication of significant skin sensitising potential) based on GHS criteria
- Conclusions:
- The test material produced a 70% sensitisation rate after an intradermal induction at 1% indicating that it is a strong sensitiser.
- Executive summary:
In a GLP-compliant OECD TG 406 skin sensitisation study according to Magnusson-Kligmann (guinea pig - maximisation test, GPMT), 10 test guinea pigs and 5 control animals were treated with the test material using water as a vehicle.
Based on the results of the pretests, a test substance concentration of 1% was used for intradermal induction (0.1 ml), followed by a 50% concentratio at epidermal induction. Challenge was performed using two concentrations, 5 and 10%. A rechallenge was also performed using 2 and 5% concentrations.
After challenge treatment, skin reactions were observed in 2 to 5 animals after 24 hours and 0 to 4 animals after 48 hours. After rechallenge, skin reactions were observed in 7 to 8 animals after 24 hours and 7 out of 10 animals after 48 hours.
Under the experimental conditions of this study, the test material is considered as a skin sensitiser.
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