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EC number: 941-049-6 | CAS number: -
- 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:
- 15 September - 23 October 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP - 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)
- Deviations:
- yes
- Remarks:
- : The deviations did not, in any case, influence the development and the results of the study. (for details see "any other information on materials and methods incl. tables")
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- yes
- Remarks:
- : The deviations did not, in any case, influence the development and the results of the study. (for details see "any other information on materials and methods incl. tables")
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
Test material
- Reference substance name:
- 2-methylbutyl pyridine-3-carboxylate; pentyl pyridine-3-carboxylate
- Molecular formula:
- Multi constituent substance
- IUPAC Name:
- 2-methylbutyl pyridine-3-carboxylate; pentyl pyridine-3-carboxylate
- Reference substance name:
- Nikotinsäurepentylester
- IUPAC Name:
- Nikotinsäurepentylester
- Test material form:
- other: liquid
- Details on test material:
- - Name of test material (as cited in study report) : Nicotinsäurepentylester HF
- Substance type : organic
- Physical state : pale yellow liquid
- Analytical purity : 99,9%
- Purity test date : not stated
- Lot/batch No. : 03030417/005
- Storage condition of test material : room temperature
Constituent 1
Constituent 2
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Dunkin-Hartley
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source : Centre de Production animale (F-45160 Olivet)
- Age at study initiation : not stated
- Weight at study initiation : 238g - 318g
- Housing : not stated
- Diet (e.g. ad libitum) : guinea pig breeding diet , feeding frequency not stated
- Water (e.g. ad libitum) : not stated
- Acclimation period : 5 days
ENVIRONMENTAL CONDITIONS
- Temperature : 18°C - 22°C
- Humidity : 39% - 79%
- Air changes (per hr) : not stated
- Photoperiod (hrs dark / hrs light) : not stated
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- other: intradermal injection and topical application
- Vehicle:
- other: Preliminary studies : olive oil and paraffin oil ; Main study induction phase : olive oil and physiological saline solution ; Main study challenge phase : paraffin oil
- Concentration / amount:
- Preliminary studies
Maximum Non Necrotizing Concentration (M.N.N.C.) determination :
- The test item was injected by intradermal route at the following concentrations: 100%, 50%, 25%, 12.5%, 6.25% and 3.125% diluted in olive oil.
Pre -Maximum Non Irritant Concentration (M.N.I.C.) determination :
- The item was applied under an occlusive dressing during 24 hours, at the following concentrations pure (100%) and diluted 50%, 25% and 12.5% in paraffin oil.
Maximum Non Irritant Concentration (M.N.I.C.) determination :
- After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 17-days rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations diluted 50%, 25%, 12.5% and 6.25% in paraffin oil.
Main study
1st induction:
- 2 intradermal injections of the item diluted at 12.5% in olive oil.
- 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50% in a physiological saline solution.
- 2 intradermal injections of a mixture with equal volumes - Freund’s Complete Adjuvant at 50% and the item diluted at 25% in olive oil.
2nd induction:
- topical application, on the same zone, with the item at 100% , 24 hours after brushing with 0.5 ml of a solution of Sodium lauryl sulfate at 10%.
Challenge phase :
- topical application under occlusive dressing at the following concentrations : 25% & 12.5%.
Challengeopen allclose all
- Route:
- other: topical application under occlusive dressing
- Vehicle:
- other: Preliminary studies : olive oil and paraffin oil ; Main study induction phase : olive oil and physiological saline solution ; Main study challenge phase : paraffin oil
- Concentration / amount:
- Preliminary studies
Maximum Non Necrotizing Concentration (M.N.N.C.) determination :
- The test item was injected by intradermal route at the following concentrations: 100%, 50%, 25%, 12.5%, 6.25% and 3.125% diluted in olive oil.
Pre -Maximum Non Irritant Concentration (M.N.I.C.) determination :
- The item was applied under an occlusive dressing during 24 hours, at the following concentrations pure (100%) and diluted 50%, 25% and 12.5% in paraffin oil.
Maximum Non Irritant Concentration (M.N.I.C.) determination :
- After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 17-days rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations diluted 50%, 25%, 12.5% and 6.25% in paraffin oil.
Main study
1st induction:
- 2 intradermal injections of the item diluted at 12.5% in olive oil.
- 2 intradermal injections of Freund’s Complete Adjuvant diluted at 50% in a physiological saline solution.
- 2 intradermal injections of a mixture with equal volumes - Freund’s Complete Adjuvant at 50% and the item diluted at 25% in olive oil.
2nd induction:
- topical application, on the same zone, with the item at 100% , 24 hours after brushing with 0.5 ml of a solution of Sodium lauryl sulfate at 10%.
Challenge phase :
- topical application under occlusive dressing at the following concentrations : 25% & 12.5%.
- No. of animals per dose:
- Negative control group : 5
Treated group : 10 - Details on study design:
- PRELIMINARY STUDIES
Maximum Non Necrotizing Concentration (M.N.N.C.) determination : 2 female guinea pigs identified C8584 & C8585 were used.
-The test item was injected by intradermal route at the following concentrations: 100%, 50%, 25%, 12.5%, 6.25% and 3.125% diluted in olive oil.
Pre -Maximum Non Irritant Concentration (M.N.I.C.) determination : 2 female guinea pigs identified C8584 & C8585 were used.
-The item was applied under an occlusive dressing during 24 hours, at the following concentrations pure (100%) and diluted 50%, 25% and 12.5% in paraffin oil.
Maximum Non Irritant Concentration (M.N.I.C.) determination : 3 female guinea pigs identified C8605 to C8507 were used.
-After induction by intradermal injection with olive oil and by topical application with paraffin oil and a 17-days rest phase, the challenge phase under occlusive dressing for 24 hours consists in a single topical application of the test item at the following concentrations diluted 50%, 25%, 12.5% and 6.25% in paraffin oil.
MAIN STUDY
GROUP 1 (negative control) : 5 female guinea pigs identified n° C8635 to C8639;
GROUP 2 (treated) : 10 female guinea pigs identified n° C8640 to C8649;
Note : The results of the 3 latest positive group (Reference substance : neomycin sulfate Test 6 and benzocaine Test 4 and 5) carried out as method sensibility, were presented in "any other information on results incl. tables"
CHALLENGE PHASE
-topical application under occlusive dressing at the following concentrations : 25% & 12.5%.
- Evaluation (hr after challenge) : 24h and 48h - Positive control substance(s):
- yes
- Remarks:
- The results of the 3 latest positive group (Reference substance : neomycin sulfate Test 6 and benzocaine Test 4 and 5) carried out as method sensibility, were presented in "any other information on results incl. tables"
Results and discussion
- Positive control results:
- See "any other information on results incl. tables"
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- Concentration : 25%
- No. with + reactions:
- 4
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Concentration : 25%. No with. + reactions: 4.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- Concentration : 25%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Concentration : 25%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Concentration : 25%
- No. with + reactions:
- 1
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Concentration : 25%. No with. + reactions: 1.0. Total no. in groups: 5.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Concentration : 25%
- No. with + reactions:
- 1
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Concentration : 25%. No with. + reactions: 1.0. Total no. in groups: 5.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- Concentration : 12.5%
- No. with + reactions:
- 4
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Concentration : 12.5%. No with. + reactions: 4.0. Total no. in groups: 10.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- Concentration : 12.5%
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Concentration : 12.5%. No with. + reactions: 1.0. Total no. in groups: 10.0.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Concentration : 12.5%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Concentration : 12.5%. No with. + reactions: 0.0. Total no. in groups: 5.0.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Concentration : 12.5%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Concentration : 12.5%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Any other information on results incl. tables
Positive control results :
Test substances :
-Benzocaine (5thtest)
-Neomycin sulfate (6th& 7thtest)
Application date (test 5) : 02/20/01 ; Animals : 10
Application date (test 6) : 01/15/02 ; Animals : 10
Application date (test 7) : 03/25/03 ; Animals : 9
Overall
results
Macroscopic
evaluations (reading at 24 and 48 hours) of cutaneous reactions
Test | Reading Time | Concentrations | Quotations | % of Positive Responses | |||
0 | 1 | 2 | 3 | ||||
Treated Group Test 5 | 24 h | 12,5% | 1 | 5 | 4 | 0 | 40% |
48 h | 12,5% | 2 | 3 | 5 | 0 | 50% | |
24 h | 6,25% | 1 | 5 | 4 | 0 | 40% | |
48 h | 6,25% | 2 | 3 | 5 | 0 | 50% | |
Treated Group Test 6 | 24 h | 75% | 4 | 2 | 4 | 0 | 40% |
48 h | 75% | 5 | 1 | 4 | 0 | 40% | |
24 h | 38% | 4 | 3 | 3 | 0 | 30% | |
48 h | 38% | 4 | 2 | 4 | 0 | 40% | |
Treated Group Test 7 | 24 h | 75% | 3 | 1 | 4 | 0 | 50% |
48 h | 75% | 4 | 1 | 3 | 0 | 38% | |
24 h | 38% | 4 | 2 | 2 | 0 | 25% | |
48 h | 38% | 4 | 1 | 3 | 0 | 38% |
In conclusion, in view of these results, under these experimental conditions, the substances NEOMYCIN SULFATE and BENZOCAINE :
must be classified R 43 "may sause sensitization by skin contact" in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C.Directives 67/548, 2001/59 and 99/45.These products must be characterised by the symbol "Xi" and the warning label "Irritant".
PRELIMINARY STUDIES :
MNNC determination :
No necrosis has been observed since the concentrations of 12.5%, the first induction has been carried out by intradermal injection at the same concentration. Macroscopic evaluation of cutaneous reaction
Injection | No. of animals | Concentrations | |||||
100% | 50% | 25% | 12.5% | 6.25% | 3.125% | ||
Intradermic injection | C8584 | Ne | Ne | Ne | 0 | 0 | 0 |
Intradermic injection | C8585 | Ne | Ne | Ne | 0 | 0 | 0 |
Ne : necrosis
Maximal Non Necrotizing Concentration (MNNC) = 12.5%
Pre-MNIC determination :
24 hours after the removal of the occlusive dressings, it was recorded a slight erythema on the treated area at 100% in one animal. In view of these results, the concentrations selected were pure (100%) for the 2nd induction of the main study and the MNIC began at the concentration of 50%. Macroscopic evaluation of cutaneous reactionsApplication | No. of animals | Concentrations | |||||
100% | 50% | 25% | 12,5% | ||||
Topical application under occlusive dressing | C8584 | 1(E) | 0 | 0 | 0 | ||
Topical application under occlusive dressing | C8585 | 0 | 0 | 0 | 0 |
E = Erythema
MNIC deterrnination :
24 hours after removal of the occlusive dressings, it was recorded a slight erythema on the treated area at 50% in two animals. In view of this result, the concentrations selected were 25% (MNIC) and 12.5% (1/2 MNIC) for the challenge phase.Application | No. of animals | Concentrations | |||||
50% | 25% | 12.5% | 6.25% | ||||
Topical application under occlusive dressing | C8605 | 0 | 0 | 0 | 0 | ||
Topical application under occlusive dressing | C8606 | 1(E) | 0 | 0 | 0 | ||
Topical application under occlusive dressing | C8607 | 1(E) | 0 | 0 | 0 |
E = Erythema
Maximal Non Irritant Concentration (MNIC) = 25%
MAIN STUDY :
Induction phase :
The induction phase was performed by intradermal injection at D0 with the test item diluted at 12.5% and by topical application at D7 with the test item at 100% .
Challenge phase :
The test item has been used diluted at 25% and diluted at 12.5% in paraffin oil (1/2 MNIC).
Assessment of the sensitising potential :
Overall results (Erythema & Oedema)
Macroscopic evaluation (readings at 24 and 48 hours) of cutaneous reactions
Groups | Reading Time | Concentrations | Quotations | % of Positive Responses | |||
0 | 1 | 2 | 3 or > | ||||
Negative control group | 24 h | 25% | 3 | 1 | 0 | 0 | 0% |
48 h | 25% | 3 | 1 | 0 | 0 | 0% | |
24 h | 12.5% | 4 | 0 | 0 | 0 | 0% | |
48 h | 12.5% | 4 | 0 | 0 | 0 | 0% | |
Treated group | 24 h | 25% | 5 | 4 | 0 | 0 | 0% |
48 h | 25% | 8 | 1 | 0 | 0 | 0% | |
24 h | 12.5% | 5 | 4 | 0 | 0 | 0% | |
48 h | 12.5% | 8 | 1 | 0 | 0 | 0% |
Note : The animals which died during the test are not counted
Grading scales :
Erythema
0 = No visible modification
1 = Slight or patches of erythema
2 = Moderate confluent erythema
3 = Internal erythema and swelling
Oedema
0 = No visible modification
1 = Slight oedema
2 = Moderate oedema
3 = Important oedema
Individual results
Macroscopic evaluation (readings at 24 and 48 hours) of cutaneous reactions
N° of animals | MNIC (25%) | 1/2 MNIC (12.5%) | ||||||
24 hours | 48 hours | 24 hours | 48 hours | |||||
Er | Oe | Er | Oe | Er | Oe | Er | Oe | |
Negative control group (Distilled water) | ||||||||
N° C8635 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8636 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8637 F | ||||||||
N° C8638 F | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8639 F | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Treated group (Test item) | Er | Oe | Er | Oe | Er | Oe | Er | Oe |
N° C8640 F | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
N° C8641 F | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
N° C8642 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8643 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8644 F | ||||||||
N° C8645 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8646 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8647 F | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
N° C8648 F | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
N° C8649 F | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Er = Erythema ; Oe = Oedema ; F = Female
C8637 & C8644 : died at D7 (this mortality is not attributable to the test item administration)
No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item .
No cutaneous intolerance reactions was recorded in animals from the negative control group .
Weight evolution
No abnormality was recorded in the weight growth of the negative control group and the treated group .
Applicant's summary and conclusion
- Interpretation of results:
- other: not classified
- Remarks:
- Criteria used for interpretation of results: EU
- Conclusions:
- The study was performed according to the Magnusson and Kligman method (J. Invest. Dermatol. 1969. 52, 268-276) and in accordance with O.E.C.D. Guideline N° 406 of July 17th, 1992, and the test method B.6 of the 96/54 E.E.C. Directive and therefore considered to be of the highest quality (reliability Klimisch 1).
In conclusion, in view of the results, under these experimental conditions, the item Nicotinsäurepentylester HF, in accordance with the criteria for classification, packaging and labelling of dangerous substances of the E.E.C. Directives 67/548, 2001/59 and 99/45, must not be classified. - Executive summary:
After induction (intradermic injection and topical application) of 10 Guinea Pigs (female) of treated group with the test item Nicotinsäurepentylester HF and a 18 -days rest phase, the challenge phase, under occlusive dressing for 24 hours, consisted to a single topical application of the test item diluted at 25% and 12.5% in paraffin oil, according to the experimental protocol established from the O.E.C.D. guideline n°406 dated July 17th, 1992 and the method B.6 of the E.E.C. n°96/54 dated July 30th,1996.
No macroscopic cutaneous reactions attributable to allergy was recorded during the examination following the removal of the occlusive dressing (challenge phase) from the animals of the treated group with the test item. No cutaneous intolerance reaction was recorded in animals from the negative control group.
In conclusion, in view of these results, under these experimental conditions, the item Nicotinsäurepentylester HF, in accordance with the criteria for classification, packaging and labelling of dangerous substances and preparations of the E.E.C. Directives 67/548, 2001/59 and 99/45, must not be classified.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.