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EC number: 442-450-4 | CAS number: -
Toxicological information
Skin sensitisation
Currently viewing:
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09 Oct - 08 Dec 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- adopted in 1996
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- adopted in 2008
- Deviations:
- yes
- Remarks:
- environmental condition for animals: the temperature was outside the recommended range (24 ± 2 °C instead of 20 ± 3 °C)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted in1992
- Deviations:
- yes
- Remarks:
- environmental condition for animals: the temperature was outside the recommended range (24 ± 2 °C instead of 20 ± 3 °C)
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Test material
- Reference substance name:
- -
- EC Number:
- 442-450-4
- EC Name:
- -
- Cas Number:
- 203255-81-6
- Molecular formula:
- C42H61O4P
- IUPAC Name:
- 6-(3-(3-tert-Butyl-4-hydroxy-5-methylphenyl)propoxy)-2,4,8,1 0-tetra-tert-butyldibenz(d,f)(1,3,2)dioxaphosphepin
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Co., Ltd. (Kanagawa, Japan)
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 4 weeks
- Weight at study initiation: 351 - 460 g
- Housing: 5/sex in aluminium cages (W450 x D550 x H350 mm)
- Diet: GC-4 (Oriental Yeast Co., Ltd., Tokyo, Japan), ad libitum)
- Water: filtered tap water, ad libitum
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 2
- Humidity (%): 50 ± 20
- Air changes (per hr): > 10
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Induction
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: intradermal induction: corn oil; epicutaneous induction: acetone
- Concentration / amount:
- intradermal induction on Day 0: 5%
epicutaneous induction on Day 7: 50% - Day(s)/duration:
- intradermal induction: single treatment; epicutaneous induction: 48 h
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
- No.:
- #1
- Route:
- epicutaneous, semiocclusive
- Vehicle:
- other: acetone
- Concentration / amount:
- 5%
- Day(s)/duration:
- 24 h
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 10 (controls), 20 (in test groups)
- Details on study design:
- RANGE FINDING TESTS:
A dose-finding study was conducted in order to select suitable concentrations for sensitisation and challenge.
For intradermal injection, concentrations in the range of 0.1 - 5% of the test substance in corn oil were applied. 6 test item concentrations and vehicle control were injected at a volume of 0.1 mL into 3 guinea pigs (7 doses/body). For epicutaneous exposure, concentrations in the range of 5 - 50% of the test substance in acetone were applied for 24 h. 4 test item concentrations were applied to the skin of 6 guinea pigs (2 doses/body). Skin reactions were evaluated 24 and 48 h post application. Concentrations for the main experiment were chosen to cause mild irritation after intradermal and epicutaneous induction. Concentrations for the main experiment challenge were chosen to represent the highest non-irritating concentration.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 1:1 (v/v) mixture complete Freund's adjuvant (FCA) and water (water in oil emulsion)
Injection 2: 5% test substance in corn oil
Injection 3: 5% test substance in a 1:1 mixture of complete Freund's adjuvant (FCA) and distilled water
Epicutaneous: 0.4 mL test substance 50%
- Control group:
Intradermal (3 pairs of injections):
Injection 1: 1:1 (v/v) mixture complete Freund's adjuvant (FCA) and water (water in oil emulsion)
Injection 2: corn oil
Injection 3: 5% corn oil in a 1:1 mixture of complete Freund's adjuvant (FCA) and distilled water
Epicutaneous: 0.4 mL acetone
- Site: dorsal skin in the scapular region
- Frequency of applications: topical induction was performed 1 week after the intradermal induction
- Duration: Days 0 - 7
- Concentrations: intradermal 5%, epicutaneous 50%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Days of challenge: 3 weeks after intradermal induction
- Exposure period: 24 h
- Test groups: test substance and vehicle
- Control group: test substance and vehicle
- Site: left flank (test item) and right flank (vehicle)
- Concentrations: 5%
- Evaluation (hr after challenge): 24 and 48 h after patch removal
OTHER:
All animals were observed for clinical signs of toxicity and body weight development during the course of the study. - Challenge controls:
- The control group is actually a challenge control
- Positive control substance(s):
- yes
- Remarks:
- a-hexylcinnamaldehyde (HCA)
Results and discussion
- Positive control results:
- The positive control substance (a-hexylcinnamaldehyde in acetone, 5% for intradermal induction, 100% for epicutaneous induction and 10% for epicutaneous treatment at challenge) induced positive reactions in 4/5 animals (80%), thus meeting the reliability criteria for the GPMT test (≥ 30% positive response).
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- challenge 5% epicutaneous
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- induction: 5% intradermal, 50% epicutaneous; challenge 5% epicutaneous
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- induction: 5% intradermal, 100% epicutaneous; challenge 10% epicutaneous
- No. with + reactions:
- 4
- Total no. in group:
- 5
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- challenge 5% epicutaneous
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- induction: 5% intradermal, 50% epicutaneous; challenge 5% epicutaneous
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- induction: 5% intradermal, 100% epicutaneous; challenge 10%
- No. with + reactions:
- 4
- Total no. in group:
- 5
Any other information on results incl. tables
No clinical signs of systemic toxicity were observed for any animal. In addition, the body weights of all animals increased similarly during the study period.
Applicant's summary and conclusion
- Interpretation of results:
- other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
- Conclusions:
- CLP: not classified
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