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EC number: 605-140-1 | CAS number: 158237-07-1
- 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:
- 14 Feb - 10 Mar 1995
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- adopted 17 July 1992
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The test was performed in 1995 before the alternative OECD guidelines (LLNA and in vitro test methods) were set into force.
Test material
- Reference substance name:
- 4-(2-chlorophenyl)-N-cyclohexyl-N-ethyl-5-oxo-4,5-dihydro-1H-1,2,3,4-tetrazole-1-carboxamide
- EC Number:
- 605-140-1
- Cas Number:
- 158237-07-1
- Molecular formula:
- C16H20ClN5O2
- IUPAC Name:
- 4-(2-chlorophenyl)-N-cyclohexyl-N-ethyl-5-oxo-4,5-dihydro-1H-1,2,3,4-tetrazole-1-carboxamide
1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- other: Hsd/Win:DH
- Sex:
- male
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Females nulliparous and non-pregnant: yes (females only used in range-finding study to determine induction concentration)
- Microbiological status of animals, when known: SPF-bred, Healthy animals exhibiting no clinical signs of illness were used for the study. one animal showd symptoms like emaciation, sunken flanks and labored breathing and temporary breathing sounds.
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 259 - 382 g
- Housing: in groups of five during the adaptation period and groups of two or three per cage throughout the study period type IV makrolon cages
- Diet: Altromin®3020 - Maintenance Diet for Guinea Pigs supplied by Altromin Gmb, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 1,5
- Humidity (%): 40 -70
- Air changes (per hr): 12 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Study design: in vivo (non-LLNA)
Induction
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: sterile physiological saline solution containing 2% Cremophor EL® (v/v)
- Concentration / amount:
- intradermal induction: 5%
epicutaneous induction: 40% (maximum achievable concentration) - Day(s)/duration:
- 48 h (epicutaneous)
- Adequacy of induction:
- other: induction doses based on dose range-finding test; after intradermal injection, concentrations of 2.5% - 5% induced local skin reactions; topical application up to 40% did not induce local reactions, thus, the skin was pre-treated with 10% SDS
Challenge
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: physiological saline solution containing with 2% Cremophor EL® (v/v)
- Concentration / amount:
- 40% and 25% (w/v), 0.5 mL
- Day(s)/duration:
- 24 h
- Adequacy of challenge:
- other: the dose for challenge was selected based on the results of the dose range-finding test; concentrations up to 40% (maximum achievable concentration) did not induce local reactions; thus, the highest achievable concentration was selected
- No. of animals per dose:
- 20 (in test groups), 10 (controls)
- Details on study design:
- RANGE FINDING TESTS:
Dose-range finding study for intradermal induction:
One guinea pig was given intradermal injections twice, in each case, with 0.1 mL of the following test substance concentrations: 0%; 1%; 2.5%; 5%
The injection sites were evaluated after 24 and 48 h:
Scoring after 24 h: 0%: no reaction, 2.5% - 5%: reddish wheal
Scoring after 48 h: 0% - 1%: no reaction, 2.5% - 5%: wheal
Dose range-finding study for topical induction:
In each case, 4 concentrations were tested on 4 guinea pigs. 4 patches each saturated with 0.5 mL of test substance formulation were applied to each animal under occlusive conditions for 24 h. At the end of the exposure period, the remaining test substance was removed with physiological saline solution and 21 h later the treated areas were shorn. The skin reactions were evaluated 48 h and 72 h after the start of the application.
Dose range-finding study for challenge:
One week prior to the challenge, the challenge concentrations were determined on 5 guinea pigs that were treated in the same manner as the control animals during the inductions. 4 patches each saturated with 0.5 mL test substance formulation were applied to each animal under occlusive conditions for 24 h. At the end of the exposure period, the remaining test substance was removed with physiological saline solution and 21 h later the treated areas were shorn. The skin reactions were evaluated 48 h and 72 h after the start of the application.
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 mixture complete Freund's adjuvant (Difco) and physiological NaCl solution
Injection 2: 5% test substance in physiological NaCl solution containing 2% v/v Cremophor El®
Injection 3: 5% test substance in a 1:1 mixture physiological NaCl solution containing 2% v/v Cremophor El® and complete Freund's adjuvant (Difco)
Epicutaneous: 0.5 mL test substance 40%
- Control group:
Intradermal (3 pairs of injections):
Injection 1: 1:1 mixture complete Freund's adjuvant (Difco) and physiological NaCl solution
Injection 2: physiological NaCl solution containing 2% v/v Cremophor El®
Injection 3: physiological NaCl solution containing 2% v/v Cremophor El® and complete Freund's adjuvant (Difco)
Epicutaneous: 0.5 mL physiological NaCl solution containing 2% v/v Cremophor El®
- Site: cranial, medial and caudal bilateral
- Frequency of applications: every 7 days, topical induction was performed one week after the intradermal induction
- Duration: Days 0-8
- Concentrations: intradermal 5%, epicutaneous 40%
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 3 weeks after intradermal induction
- Exposure period: 24 h
- Test groups: 40% and 25% test substance and vehicle
- Control group: vehicle and test substance
- Site: dorsal region and the flanks
- Concentrations: 40% and 25%
- Evaluation (hr after challenge): 48 and 72 h
- Challenge controls:
- The control group is actually a challenge control
- Positive control substance(s):
- yes
- Remarks:
- 2-mercaptobenzothiazole
Results and discussion
- Positive control results:
- Challenge with 2-mercaptobenzothiazole formulated with physiological NaCl at 40% and 25%, exhibited in 80% and 65% of the test animals dermal alterations after the first challenge. After the 2nd challenge both with 12% and 6% test substance formulations 80% and 75% of the test animals developed dermal signs. There was no reddening of the skin to be observed on control group animals. In another test series performed with female animals, 70% of the treated animals showed positive reactions after the 1st challenge. Thus, sensitivity as well as reliability of the experimental technique is confirmed in both studies.
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- induction: 5% intradermal, 40% epicutaneous, challenge: 40% and 25%
- No. with + reactions:
- 1
- Total no. in group:
- 20
- Clinical observations:
- One animal showed symptoms like emaciation, sunken flanks and beside on day 5 labored breathing and temporary breathing sounds. From day 15 up to the end of the study it showed only labored breathing.
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- challenge: 40% and 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- test chemical
- Dose level:
- induction: 5% intradermal, 40% epicutaneous, challenge: 40% and 25%
- No. with + reactions:
- 0
- Total no. in group:
- 20
- Key result
- Reading:
- 2nd reading
- Hours after challenge:
- 72
- Group:
- negative control
- Dose level:
- challenge: 40% and 25%
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- After the 2nd induction on Day 10, encrustations at the treatment areas were observed in 3 animals, which lasted latest until Day 22.
- Reading:
- 1st reading
- Group:
- positive control
- Dose level:
- induction: 2,5% intradermal, 40% epicutaneous, challenge with 25 and 40%
- Clinical observations:
- in respective control animals, no reddening was observed
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- test performed in males (for further information, please refer to "Positive control results")
- Reading:
- 1st reading
- Group:
- positive control
- Dose level:
- induction: 2,5% intradermal, 40% epicutaneous, challenge with 25 and 40%
- Clinical observations:
- in respective control group, no reddening was observed
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- test performed in females (for further information, please refer to "Positive control results")
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:
- Challenge with up to 40% test substance formulation (maximum achievable concentration) induced skin redness in only 1 animal at the first reading time point. As no skin redness was observed at the later time point and in none of the remaining animals, the test substance is not considered to exhibit skin sensitising properties.
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