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EC number: 619-490-8 | CAS number: 303186-36-9
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:
- April 17, 2009 - September 11, 2009
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- The study was performed in compliance with the Good Laboratory Practice (GLP) regulations (revised in 1997, ENV/MC/CHEM(98)17). The method followed that described in the OECD Guidelines for Testing of Chemicals, Updated Guideline No 406 Skin Sensitisation (adopted 17 Julyl 1992).
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 009
- Report date:
- 2009
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted on July 1992
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- Council Regulation (EC) No. 440/2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and the council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
- Deviations:
- no
- Principles of method if other than guideline:
- None
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The data have been generated before teh OECD 429 protocol was mandatory for REACH.
Test material
- Reference substance name:
- 4-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-3-fluoro-4'-propyl-1,1'-biphenyl
- EC Number:
- 619-490-8
- Cas Number:
- 303186-36-9
- Molecular formula:
- C27H22F8O2
- IUPAC Name:
- 4-{4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3,5-difluorophenyl}-3-fluoro-4'-propyl-1,1'-biphenyl
- Test material form:
- solid: bulk
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- other: HsdPoc:DH
- Sex:
- female
- Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen
- Females (if applicable) nulliparous and non-pregnant:yes
- Microbiological status of animals, when known: no data
- Age at study initiation: about 5 weeks
- Weight at study initiation: 362 g (range from 321 to 394 g)
- Housing: Five guinea pigs were housed in type GM/5 (EBECO) Makrolon cages with a shelter and placed on mobile racks. The animals were kept on conventional softwood granulate as bedding. The bedding was changed twice per week. The softwood granulate was analytically checked by independent laboratories.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days
- Indication of any skin lesions: no
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 25 °C
- Humidity (%): 46 to 63 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light – 12 hour dark regime
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- paraffin oil
- Concentration / amount:
- see details on study design
Challengeopen allclose all
- Route:
- epicutaneous, semiocclusive
- Vehicle:
- polyethylene glycol
- Concentration / amount:
- see details on study design
- No. of animals per dose:
- Total: 20 females Pre-test: 5 females Control group: 5 females Test group 10 females
- Details on study design:
- RANGE FINDING TESTS:
To determine the concentrations suitable for the main study, a pretest with intradermal or topical administrations of the vehicles and of Art. 281385 preparations were performed. 6 intradermal (i.d.) injections with different concentrations were given to one animal. Four further animals were used to determine the topical concentrations for the main study. Two of the guinea pigs were exposed for 48 hours without pretreatment to 4 different concentrations to determine the slightly irritating concentration for the dermal induction. The other two animals were treated according to the control group including intradermal injections with FCA. One week after topical induction the two animals of the pretest group were exposed for 24 hours to 4 different test material concentrations to find out the non irritating challenge concentration. In the pretest the following concentrations were used:
Art. 281385 with liquid paraffin as vehicle:
without pretreatment: intradermal injection: 50, 25, 10, 5, 1, and 0 g/L
Art. 281385 with polyethylene glycol 400 as vehicle:
without pretreatment: topical exposure (48 hours): 400, 200, 100, and 50 g/L
pretreatment with FCA: topical exposure (24 hours): 200, 100, 50, and 10 g/L
MAIN STUDY
A. INDUCTION STAGE 1 (intradermal injection)
After shaving of the shoulder region, six intradermal injections were given (three on each side of the spinal column in a total area of 2 x 4 cm). The guinea pigs received the following injections:
Group 1 (negative control group)
cranial: 0.1 ml Freund's complete adjuvant + sodium chloride solution
medial: 0.1 ml Liquid paraffin
caudal: 0.1 ml Freund's complete adjuvant + sodium chloride solution
Group 2 (test material group)
cranial: 0.1 ml Freund's complete adjuvant + sodium chloride solution
medial: 0.1 ml Art. 281385 (10 g/L ad liquid paraffin)
caudal: 0.1 ml Freund's complete adjuvant with Art. 281385
+ sodium chloride solution
(10 g test material/L preparation)
A. INDUCTION STAGE 2 (topical application)
One week after the intradermal injections, the shoulder area of the guinea pigs was shaven again and the injection sites were covered with a filter paper patch of about 8 cm², fully soaked with 1 ml of the test material preparation or the vehicle. The patches were attached for 48 hours under occlusive conditions by a self adhesive fabric (Fixomull® stretch, Beiersdorf).
Group 1: Polyethylene glycol 400
Group 2: Art. 281385 (200 g/L ad polyethylene glycol 400)
B. CHALLENGE EXPOSURE
Two weeks after topical induction the challenge was performed on the shaven right site of the animal by fixing two filter papers of about 4 cm2, one fully loaded with 0.5 ml of the Art. 281385 preparation and one soaked with 0.5 ml polyethylene glycol 400.
Group 1: Topical induction: Polyethylene glycol 400 (undiluted)
Challenge: Polyethylene glycol 400 (undiluted)
Primary irritation: Art. 281385 (100 g/L ad polyethylene glycol 400)
Group 2: Topical induction: Art. 281385 (200 g/L ad polyethylene glycol 400)
Challenge: Art. 281385 (100 g/L ad polyethylene glycol 400)
Challenge: Polyethylene glycol 400 (undiluted)
The patches were fixed for 24 hours under occlusive conditions by a self-adhesive fabric. - Positive control substance(s):
- yes
- Remarks:
- Hexylcinnamaldehyde
Results and discussion
- Positive control results:
- Under the given experimental conditions and with respect to the evaluation criteria, the test material alpha-Hexylcinnamaldehyde exhibits a skin-sensitization potential.
Positive reactions were observed in more than 30 % of the animals after the challenge. This study confirms the sensitivity and reliability of the GPMT performed at the Institute of Toxicology, Merck KGaA, with the guinea pig strain: HsdPoc:DH under the conditions used (Hübler, 2009).
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10 g/L (intradermal induction I), 200 g/L (topical induction II), 100 g/L (topical challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no signs of toxicity
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 10 g/L (intradermal induction I), 200 g/L (topical induction II), 100 g/L (topical challenge)
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no signs of toxicity
- Remarks on result:
- no indication of skin sensitisation
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the given experimental conditions, the test material induced no reactions.
- Executive summary:
Conclusion
Under the given experimental conditions, the test material Art. induced no reactions.
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