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EC number: 609-496-9 | CAS number: 379685-94-6
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 13 August 2002 to 11 April 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- 17th July 1992
- Deviations:
- yes
- Remarks:
- the vehicule used for epicutaneous induction is different from the vehicle used for challenge
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Version / remarks:
- 30 July 1996
- Deviations:
- yes
- Remarks:
- the vehicule used for epicutaneous induction is different from the vehicle used for challenge
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Test performed before the implementation of the new requirements.
Test material
- Reference substance name:
- Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester
- EC Number:
- 609-496-9
- Cas Number:
- 379685-94-6
- Molecular formula:
- C18H23F3N2O4
- IUPAC Name:
- Glycine, N-acetyl-N-[3-(trifluoromethyl)phenyl]valyl-, ethyl ester
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Other: ochre fine powder
Constituent 1
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: room temperature
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Remarks:
- Crl: (HA) BR, Caesarian obtained, Barrier sustained - Virus Antibody Free (COBS-VAF)
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS- Source: Charles River Laboratories, L'ArbresIe, France. - Females nulliparous and non-pregnant: yes- Age at study initiation: 1-2 months old- Weight at study initiation: 427 ± 27 g for the males and 390 ± 34 g for the females. - Housing: Animals were housed individually in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm) equipped with a polypropylene bottle. Each cage contained autoclaved sawdust (SICSA, Alfortville, France). Sawdust was analysed by the supplier for composition and contaminant levels. - Diet: ad libitum to 106 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France). Diet is regularly analysed by the supplier for composition and contaminant levels. The diet formula was presented in the study report. - Water: ad libitum to drinking water filtered by a FG Millipore membrane (0.22 micron). Bacteriological and chemical analyses of water were performed regularly by extemal laboratories ( include detection of possible contaminants (pesticides, heavy metals and nitrosamines)).- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 2- Humidity (%): 30 to 70%- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air- Photoperiod (hrs dark / hrs light): 12 /12
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal
- Vehicle:
- corn oil
- Concentration / amount:
- 0.1%
- Adequacy of induction:
- highest technically applicable concentration used
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: 80/20 (w/w) mixture of ethanol and purified water
- Concentration / amount:
- 50%
- Adequacy of induction:
- other: highest technically applicable concentration used non-irritant substance, but skin pre-treated with 10% SDS
Challenge
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: acetone
- Concentration / amount:
- 50%
- Adequacy of challenge:
- other: highest technically applicable concentration used highest non-irritant concentration
- No. of animals per dose:
- Preliminary test: 2 males and 2 females Main test: 15 males and 15 females (20 animals for the test group and 10 animals for the control group)
- Details on study design:
- CRITERIA FOR THE CHOICE OF VEHCILE AND DOSAGE PREPARATIONS:- The choice of the vehicle was based on tests to check the homogeneity (visual check) of the preparation (for cutaneous application and intradermal injections) and its free passage through a needle (for intradermal injections). The highest concentrations which satisfied these criteria were called the maximal practicable concentrations.- Test item was finely pulverised before being incorporated in the vehicle. All dosage form preparations were made freshly on the morning of administration and any unused material was discarded that same day.PREPARATION OF ANIMALS FOR BOTH THE RANGE FINDING AND THE MAIN TEST:The application sites of all animals were: - clipped before intradermal injections (inter-scapular region 4 cm x 3 cm), - clipped before topical applications of the induction phase (same region), - clipped and shaved before topical applications of the challenge phase (each flank 3 cm x 3 cm)- shaved before the 48h reading of the challenge phase and after the 24h reading of the induction phase (range finding test).RANGE FINDING TESTS:A. INTRADERMAL INJECTION TOLERANCE TEST- Test group: 2 males- Intradermal application: each site of the inter-scapular region was injected with 0.1 ml of a single concentration of the test item (Day1).- Concentrations: only 0.1% (w/w)- Observations: approximately 24, 48 hours and 6 days after the injectionsB. TOPICAL APPLICATION TOLERANCE TESTB.1. Under the conditions of the induction phase:- Test group: 1 male and 1 female- Dosing: a filter paper (approximately 8 cm2) was fully-loaded with a dosage form preparation and was then applied to the clipped area of the skin. The filter paper was held in place by means of an occlusive dressing for 48 h.- Concentrations: 25 and 50% (w/w) in 80/20 (w/w) mixture of ethanol and purified water - Observations: 24 and 48 hours after removal of the dressingB.2. Under the conditions of the challenge phase:- Test group: 1 male and 1 female- Dosing: the filter paper of a chamber (Finn Chamber®) was fully-loaded with a dosage form preparation. The chamber was then applied to the clipped area of the skin (one concentration per flank). The chamber was held in place by means of an occlusive dressing for 24 hours.- Concentrations: 25 and 50% (w/w) in acetone- Observations: 24 and 48 hours after removal of the dressing- On removal of the dressing, any residual test item was removed by means of a moistened cotton pad.MAIN STUDY:A. INDUCTION EXPOSURE- Test group: 10 males and 10 females- Control group: 5 males and 5 femalesA1. INTRADERMAL INDUCTION (Day 1)- Dosing: 3 pairs of intradermal injections were made at the prepared skin site of each animal. - Treatment of the Test group:* Anterior site: 0.1mL of FCA at 50% (v/v) in 0.9% NaCl * Median site: 0.1mL of test item at 0.1% (w/w) in corn oil* Posterior site: 0.1mL of test item at 0.1% (w/w) in the mixture FCA/0.9% NaCl (50/50, v/v) - Treatment of the Control group:* Anterior site: 0.1mL of 0.1mL of FCA at 50% (v/v) in 0.9% NaCl * Median site: 0.1mL of the vehicle (corn oil)* Posterior site: 0.1mL of the vehicle at 50% in the mixture FCA/0.9% NaCl (50/50, v/v)A2. TOPICAL INDUCTION (Day 8)- Preparation of the site: As the test item was shown to be non-irritant during the preliminary test, animals of both groups were treated on day 7 with 0.5 mL of sodium lauryl sulfate at the concentration of 10% (w/w) in vaseline, in order to induce local irritation. - Dosing: on Day 8, a pad of filter paper (approximately 8 cm2) was fully-loaded with the test item at the concentration of 50% (w/w) and was then applied to the inter-scapular region of the animals of the treated group. Animals of the control group received an application of the vehicle alone under the same experimental conditions. The pad was held in place for 48 h by means of an adhesive hypoallergenic dressing and an adhesive anallergenic waterproof plaster. - On removal of the dressing (Day 10), no residual test item was observed. - A local irritation was recorded in all animals of the control and treated groups.B. CHALLENGE EXPOSURE (Day 22)- Dosing: animals of treated and control groups received an application o fthe test item and vehicle. The filter paper of a chamber (Finn Chamber®) was fully-loaded with the test item at the concentration of 50% (w/w) and was then applied to a clipped area of the skin of the posterior right flank of all animals. The vehicle was applied under the same experimental conditions to the skin of the posterior left flank. The chambers were held in contact with the skin for 24 hours by means of an adhesive anallergenic waterproof plaster. - On removal of the dressing, any residual test item was removed by means of a moistened cotton pad.SCORING OF THE CUTANEOUS REACTIONS24 and 48 h after removal of the dressing of the challenge application, both flanks of the treated and control animals were observed in order to evaluate cutaneous reactions, according to the following scale: . no visible change.................................................................................................................. 0 . discrète or patchy erythema.................................................................................................. 1 . moderate and confluent erythema........................................................................................ 2 . intense erythema................................................................................................................... 3 Any observed oedema was recorded. Any other lesions were noted. OTHER 1: IN VIVO OBSERVATIONS- Mortality and morbidity: animals were observed at least once a day during the study in order to check for clinical signs and mortality. - Body weight: animals were weighed individually on the day of allocation into the groups, on the first day of the study (Day 1) and on the last day of the study (Day 25).OTHER 2: TERMINAL STUDIES- Termination and euthanasia method: At the end of the study, all the surviving animals were killed by carbon dioxide asphyxiation.- Necropsy: not performed.- Skin samples: no skin samples were takenOTHER3 : RELIABILITY CHECKThe sensitivity of the experimental technique is regularly assessed using a known moderate sensitizer, MERCAPTOBENZOTHIAZOLE. In a recent study (June 2002) performed under the testing laboratory experimental conditions, the strain of guinea pigs used showed a satisfactory sensitization response in 100% animals (results were presented in the study report).
- Challenge controls:
- no
- Positive control substance(s):
- no
- Remarks:
- no concomittent positive control performed but a reliability check with MERCAPTOBENZOTHIAZOLE was presented in the study report
Results and discussion
- Positive control results:
- In a recent study performed with MERCAPTOBENZOTHIAZOLE, under the testing laboratory experimental conditions, the strain of guinea pigs used showed a satisfactory sensitization response in 100% animals (results were presented in the study report).
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 0% Test item
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- 0% Test item
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 0.1% (intrademal injection)
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Clinical observations:
- a discrete erythema (grade 1) was noted in 2/19 animals
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- 0.1% (intradermal injection)
- No. with + reactions:
- 0
- Total no. in group:
- 19
- Clinical observations:
- cutaneous reactions obsereved at the 48h observation time point have dully reversed
Any other information on results incl. tables
CHOICE 0F THE VEHICLE
- The test item was not soluble in 0.9% NaCl: two phases were observed.
- The vehicle chosen for intradermal injections was com oil: the dosage form preparation which could pass through a needle and into the dermis had a maximum concentration of 0.1% (w/w).
- For topical applications, the vehicles used were a mixture ethanol/water (80/20) for the induction phase and acetone for the challenge application: a homogeneous dosage form preparation was obtained at the maximum concentration of 50% (w/w).
RANGE FINDING STUDY
- Administration by intradermal route: As the concentration of 0.1% was well-tolerated systemically and locally, it was retained for the main study.
- Administration by topical route: In order to respect the criteria for the sélection of concentrations (the concentrations should be well-tolerated systemically and locally, cutaneous application for the induction should cause at most weak or moderate skin reactions or be the maximal practicable concentration, cutaneous application for the challenge phase should be the highest concentration which does not cause irritant effect), concentration chosen for the topical application of the induction phase (Day 8) and for the challenge application (Day 22) was 50% (w/w).
MAIN STUDY
- Clinical examinations: One animal of the treated group (male) was found dead on Day 6. No clinical signs were observed prior to death. As such spontaneous mortality is sometimes observed in this species, it
was not attributed to treatment with the test item. Important local reactions (ulceration) at the intradermal injection sites were recorded from Day 12 in 11/19 animals of the treated group and 2/10 animals of the control group
- Body weight: body weight gain of the treated animals was similar to that of controls (detailed results are presented in the study report).
- Challenge phase reactions: No cutaneous reactions were observed in the animais of the control group. In the treated group, a discrete erythema (grade 1) was noted in 2/19 animals, at the 48 h post challenge (24h post dressing removal) reading only. No other cutaneous reactions were recorded.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the experimental conditions of this study, the test material did not elicit a skin sensitisation response in the guinea pig. The test material is not classified for skin sensitisation according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
- Executive summary:
This GLP-compliant study was performed to assess the potential of the test material to induce and elicit delayed dermal sensitization according to the guinea pig maximization test of Magnusson and Kligman described in OECD Guideline 406 (dated July 17th, 1992) and EU Method B.6 of the E.E.C. directive n° 96/54 (dated July 30st, 1996).
Material and methods
Concentrations of the test material used in the main study were determined by performing range finding tests. The suitable concentrations were: 0.1% in corn oil for the intradermal injection, 50 % in a mixture ethanol/water (80/20) for the induction topical application and 50% in acetone for the challenge topical application (highest technically applicable concentrations conforming with guideline requirements for each phase of the test).
The main study was undertaken using 30 male and female guinea pigs (20 in the test group and 10 in the control group).
Test animals were intradermally injected with FCA at 50% (v/v) in 0.9% NaCl (anterior sites), the test material at 0.1% corn oil (middle sites), and the test material at 0.1% in FCA at 50% (v/v) in 0.9% NaCl (posterior sites). One week later, animals were treated by topical application of Sodium Lauryl Sulfate at 10% (w/w) in Vaseline in order to induce a local irritation, and then boosted by topical application of the test material at 50 % in a mixture ethanol/water (80/20) under an occlusive dressing for 48h. Control animals were treated in the same manner but using the selected vehicle instead of the test material.
Two weeks after the second induction stage, animals of both groups were challenged by topical application -under occlusive dressing for 24h- of both the vehicle and the test material at 50% in acetone (to the left and the right flanks respectively).
Skin reactions were evaluated 24 and 48 h after removal of the dressing.
Results
No systemic clinical signs and no deaths related to treatment were noted during the study.
No well-defined cutaneous reactions were observed after the challenge application.
Conclusion
Under the experimental conditions of this study, the test material did not elicit a skin sensitisation response in the guinea pig. The test material is not classified for skin sensitisation according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) and the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) criteria.
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