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EC number: 606-396-7 | CAS number: 198904-86-8
- 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:
- 1998-12-27 to 1998-11-16
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
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 (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- At the time this study was conducted, an in-vivo maximization test was an acceptable test for determining skin sensitization.
Test material
- Reference substance name:
- tert-butyl 2-{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-2-[4-(pyridin-2-yl)benzyl]hydrazinecarboxylate
- EC Number:
- 606-396-7
- Cas Number:
- 198904-86-8
- Molecular formula:
- C32H42N4O5
- IUPAC Name:
- tert-butyl 2-{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}-2-[4-(pyridin-2-yl)benzyl]hydrazinecarboxylate
- Test material form:
- solid
- Details on test material:
- - Appearance: Off-white powder
- Storage condition of test material: At room temperature protected from light
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor and 002
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Prepared in arachis oil BP/Freund's Complete Adjuvant to the desired concentration based on the type of test
FORM AS APPLIED IN THE TEST (if different from that of starting material)
lntradermal Induction: 5% w/v in arachis oil BP and 5% w/v in a mixture of Freund's Complete Adjuvant plus distilled water (1 :1)
Topical Induction: 50% w/w in arachis oil BP
Topical Challenge: 10% and 5% w/w in arachis oil BP
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Females (if applicable) nulliparous and non-pregnant: not specified
- Microbiological status of animals, when known:
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 361-437 g
- Housing: Singly or in paris in in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): ad libitum (Guinea Pig FD1 Diet, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): ad libtium tap water
- Acclimation period: >5 days
- Indication of any skin lesions: None
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 43-54
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- arachis oil
- Concentration / amount:
- 50% w/w
- Day(s)/duration:
- 2
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- arachis oil
- Concentration / amount:
- 5% w/v
- Day(s)/duration:
- 9
- Adequacy of induction:
- highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
- Route:
- intradermal
- Vehicle:
- other: Freund's Complete Adjuvant plus distilled water (1:1)
- Concentration / amount:
- 5% w/v
- Day(s)/duration:
- 9
- 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:
- arachis oil
- Concentration / amount:
- 10% w/w
- Day(s)/duration:
- 1 d
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- epicutaneous, occlusive
- Vehicle:
- arachis oil
- Concentration / amount:
- 5 w/v %
- Day(s)/duration:
- 1 d
- No. of animals per dose:
- 10 animals for the test concentration
5 animals for the control - Details on study design:
- RANGE FINDING TESTS:
Selection of Concentrations for Main Study (Sighting Tests) The concentrations of test material to be used at each stage of the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test material. The procedures were as follows:
Selection of Concentration for lntradermal Induction
Three concentrations of test material were investigated (1 %, 5% and 10% w/v in arachis oil BP). A total of three guinea pigs were used, each guinea pig receiving four 0.1 ml injections of only one concentration of test material. The degree of erythema at the injection sites was assessed approximately 24, 48 and 72 hours and 7 days after injection according to the Draize scale shown in Appendix X. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that could be intradermally injected and 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 (intradermally injected with Freund's Complete Adjuvant ten days earlier) were treated with four preparations of the test material (50%, 25%, 10% and 5% w/w in arachis oil BP). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
Selection of Concentrations for Topical Challenge
Four preparations of the test material (50%, 25%, 10% and 5% w/w in arachis oil BP) were applied to the clipped flanks of two guinea pigs under occlusive dressings for an exposure period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing 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: 3
- Exposure period: 9 days
- Test groups: 1
- Control group: 1
- Site: Shoulder region
- Frequency of applications: Once on day 0 intradermally, and once on day 7 topically
- Duration: 9 days for the intradermal, and 2 days for topical
- Concentrations: a) Freund's Complete Adjuvant plus distilled water in the ratio 1: 1 (vehicle control)
b) a 5% w/v formulation of the test material in arachis oil BP
c) a 5% w/v formulation of the test material in a 1: 1 preparation of Freund's Complete Adjuvant plus distilled water.
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 1
- Exposure period: 1 day
- Test groups: 1
- Control group: 1
- Site: Shorn right flank and shorn left flank of each animal
- Concentrations: 10% w/w in arachis oil for the right shorn flank, and 5% w/w in arachis oil for the left shorn flank.
- Evaluation (hr after challenge): 24 and 48 hours
- Challenge controls:
- Induction of the Control Animals:
Intradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
a) Freund's Complete Adjuvant plus distilled water in the ratio 1 :1
b) arachis oil BP
c) a 50% w/v formulation of arachis oil BP in Freund's Complete Adjuvant/distilled water 1 :1
Approximately 24 and 48 hours after intradermal injection the degree of erythema at the vehicle injection sites (ie injection site b) was evaluated according to the scale shown in Appendix X. The topical applications followed the same procedure as for the test animals except that the vehicle alone was applied to the filter paper. Skin reactions were quantified as for the test animals. - Positive control substance(s):
- no
Results and discussion
- Positive control results:
- No concurrent positive control was used.
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 10% w/w
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- Animal 9 was found dead on day 9, Cause of animal death not considered substance related. No impact to overall study results
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 5 % w/w
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- Animal 9 was found dead on day 9. Cause of animal death not considered substance related. No impact to overall study results
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 10 % w/w
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- Animal 9 was found dead on day 9. Cause of animal death not considered substance related. No impact to overall study results
- Remarks on result:
- no indication of skin sensitisation
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 5% w/w
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- Animal 9 was found dead on day 9. Cause of animal death not considered substance related. No impact to overall study results
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: No positive control group used
- Group:
- positive control
- Remarks on result:
- not measured/tested
- Reading:
- other: No negitive control goups used
- Group:
- negative control
- Remarks on result:
- not measured/tested
Any other information on results incl. tables
Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 23 were comparable to those observed in the control group animals over the same period.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- This study validly determined that the test substance does not meet the criteria to be classified as a skin sensitizer according to GHS criteria.
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