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EC number: 617-422-1 | CAS number: 82991-48-8
- 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

Endpoint summary
Administrative data
Description of key information
For irritation skin / eye, a read across to reliable GLP studies performed for a chemical analyogue according OECD TG is provided. No irritation was observed in the studies used for the read across.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- Mar 12 - Apr 09, 1997
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 404.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- Principles of method if other than guideline:
- None
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Strain: Albino rabbit, Crl:KBL(NZW), female (f) Source: Charles River Wiga GmbH, KifßleggAge: about 27 weeksInitial Weight: 3,66 kg 3 female rabbits
- Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- other: aqua pro injectione
- Amount / concentration applied:
- 0,5 g
- Duration of treatment / exposure:
- 4 hours
- Observation period:
- 1, 24, 48, 72 hours after removal of patches and then daily up to day 8
- Number of animals:
- 3 (f)
- Details on study design:
- Identification and adaptationThe animal was kept in the experimental room for more than 7 days to allow them to acclimatize.The animal was uniquely identified by a tattoo in the ear displaying the animal number. An individual cage card was affixed to the cage displaying the study number, test material, day of treatment, and animal number.AssignmentOne female rabbit, with the animal number 23, was used for this study. The initial body weight at the start of the experimental part was 3.98 kg. Housing and dietThe rabbit was housed in an air-conditioned room of about 28 m^2 in the Institute of Toxicology. Lighting was controlled by a timer to provide a 12-hour light and a 12-hour dark regime. They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm^2, a shelter with an integrated sitting board of about 1820 cm^2; overall height: 60 cm) with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least three times a week. The cages were cleaned before the start of the study. Temperature and relative humidity were measured using a thermohygrograph. The room temperature varied from 16 to 18°C and the relative humidity from 47 to 67 %. The rabbit received a commercial diet for rabbits, Altromin Standard Diet ad libitum and fresh tap water from Makrolon drinking bottles ad libitum. According to the specifications given by the manufacturer, the diet had been checked by independent laboratories. Analysis included both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. The drinking water was periodically analyzed according to the German regulations for human drinking water.Observations for clinical symptomsThe rabbit was examined for skin alterations, behavior, and general condition 1 hour after removal of the patch, after 24, 48, 72 hours, and then daily up to experimental day 8.Skin changes at the application sites were evaluated according to the DRAIZE-, OECD-and EEC recommendations.Grading scale for evaluation: Erythema and eschar formation Scores--------------------------------------------------No erythema 0Very slight erythema (barely perceptible) 1Well defined erythema 2Moderate to severe erythema 3 Severe erythema (beet redness) to eschar formation preventing grading of erythema 4--------------------------------------------------Maximum possible: 4--------------------------------------------------Edema formation Scores--------------------------------------------------No edema 0Very slight edema (barely perceptible) 1Slight edema (edges of area well defined by definite raising) 2Moderate edema (raised approx. 1 mm) 3 Severe edema (raised more than 1 mm and extending beyond area of exposure) 4--------------------------------------------------Maximum possible: 4--------------------------------------------------Total possible irritation score (maximum): 8Mean score = Mean grading for erythema or edema of all the rabbits per time pointMean cumulative score = Mean grading of all readings for erythema and edema per time pointMean score per animal = Mean grading for each animal of erythema or edema (24, 48, and 72 hours after removal of the patches)
- Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: 24, 48, 72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: 24, 48, 72 h
- Score:
- 0
- Max. score:
- 0
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: other: CLP
- Conclusions:
- According to EU Regulation No. 1272/2008 and CLP the test material must not be classified as an irritant to the skin.
- Executive summary:
Purpose
The purpose of this assay was to identify the skin irritation/corrosion potential of the test material when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions.
This study should provide a rational basis for risk assessment to the irritating potential of the test item in man.
Study Design
To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of aqua pro injectione to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions.
The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for another 7 days.
Results
No signs of irritation were observed after administration.
Day 1(1 hour) 2(24 hours) 3(48 hours) 7(72 hours) edema 0 0 0 0 erythma 0 0 0 0 Conclusion
According to EU Regulation No. 1272/2008 and CLP the test material must not be classified as an irritant to the skin.
Reference
0.5 g of the test material was administered. After a single application to the intact dorsal skin of a rabbit, for 4 hours under semiocclusive conditions, no signs of irritation were observed.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Study period:
- Jul 11 - Sep 24, 2007
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: For this endpoint information from a structural similar compound is available. This study for this similar compound was performed according to GLP and the methods applied are fully compliant with OECD TG 405.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- Principles of method if other than guideline:
- None
- GLP compliance:
- yes (incl. QA statement)
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Strain: Albino rabbit, Crl:KBL(NZW), female (f) Source: Charles River Wiga GmbH, KifßleggAge: about 31-32 weeksMean weight: 4,3 kg
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- 0,1 g
- Observation period (in vivo):
- 1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part.
- Number of animals or in vitro replicates:
- 3 female rabbits
- Details on study design:
- -- Identification and adaptationHealthy rabbits were allocated to the study group. The animals were kept in the experimental room for more than 7 days to allow for acclimatization. Each animal was uniquely identified by a tattoo in the ear displaying the animal number. Individual cage cards were affixed to each cage displaying the study number, test material, day of treatment, and animal number.-- Assignment3 female rabbits were used for this study.-- Housing and dietAll rabbits were housed in an air-conditioned room of about 28 m^2 in the test facility. Lighting was controlled by a timer to provide a 12-hour light and a 12-hour dark regime.They were kept separately in special rabbit cages (manufacturer: Becker; type K99/30 KU, floor area about 5400 cm^2, a shelter with an integrated sitting board of about 1820 cm^2; overall height: 60 cm) with plastic grids placed on mobile racks. The collection pans underneath the cages were cleaned at least three times a week. The cages were cleaned before the start of the study.Temperature and relative humidity were measured using a thermohygrograph. The room temperature varied from 20 to 22 °C and the relative humidity from 50 to 64 %. The rabbits received diet for rabbits Provimi Kliba 3418.0 and sniff K snack ad libitum, and fresh tap water from Makrolon drinking bottles at least three times a week.The diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.The drinking water is periodically analyzed according to the German regulations for human drinking water.-- PreparationBefore the application, the test material was ground in a mortar using a pestle.–- Administration and dose levelTo ensure that only rabbits with normal eyes were included in the study, approximately 24 hours before treatment ophthalmological examinations were performed after instillation of a 0.15 % fluorescein solution (Dr. Thilo & Co.) using an ophthalmoscope. Animals with eye defects, injury or irritation were excluded.0.1 g test material was instilled into the conjunctival sac of the left eye of each animal by gently pulling the lower lid away from the eyeball to form a cup into which the test material was placed. The right eye remained untreated and served as control. After instillation, the eyelids were closed for about 30 seconds.-- Observation for clinical symptomsThe rabbits were examined for eye irritation and for changes in behavior and general condition 1 hour after treatment, after 24, 48, and 72 hours, then daily up to day 8 of the experimental part.Eye changes were evaluated according to the DRAIZE- , OECD- and EEC recommendations.-- Evaluation of eye reactions- Cornea ScoresA) Opacity-degree of density (area most dense taken for reading)No ulceration or opacity 0Scattered or diffuse areas of opacity (other than slight dullingof normal lustre), details of iris clearly visible 1Easily discernible translucent area, details of iris slightly obscured 2Nacrous area, no details of iris visible, size of pupil barely discernible 3Opaque cornea, iris not discernible through the opacity 4B) Area of cornea involved not evaluated (Rating according to the DRAIZE method)- IrisA) Normal 0 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1 No reaction to light, hemorrhage, gross destruction (any or all of these) 2 - Conjunctivae ScoresA) Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)Blood vessels normal 0Some blood vessels definitely hyperemic (injected) 1Diffuse, crimson color, individual vessels not easily discernible 2Diffuse beefy red 3B) Chemosis: lids and/or nictating membranesNo swelling 0Any swelling above normal (includes nictating membranes) 1Obvious swelling with partial eversion of lids 2Swelling with lids about half closed 3Swelling with lids more than half closed 4C) Discharge (Rating according to the DRAIZE method ) No discharge 0 Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1Discharge with moistening of the lids and hairs just adjacent to lids 2Discharge with moistening of the lids and hairs, and of a considerable area around the eye 3Mean score of all animals = Mean grading for irritations of cornea, iris, and conjunctivae per time pointMean score per animal = Mean grading for each animal of irritations of cornea, iris, and conjunctivae (1, 24, 48, and 72 hours after application)Maximum value = Maximum grading of a sign of irritation within a period
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- other: 24, 48, 72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- other: 24, 48, 72 h
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- other: 24, 48, 72 h
- Score:
- 0
- Max. score:
- 0
- Interpretation of results:
- not irritating
- Remarks:
- Migrated informationCriteria used for interpretation of results: other: CLP
- Conclusions:
- No eye irritating potential could be detected, thus the test material should not be classified as eye irritant according to EU Regulation No. 1272/2008 (CLP).
- Executive summary:
Purpose
The purpose of this primary eye irritation assay was to provide information on possible health hazards in case of acute eye contact with a test material and serve as a rational basis for risk assessment to the eye irritating potential of the test item in man.
Study Design
To test for eye irritation a test according to the OECD-Guidelines for Testing of Chemicals No. 405, the annex to Directive 92/69 EEC, and the recommendations of DRAIZE (1959) was performed.
Results
All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous.
No signs of clinical toxicity were detected. No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. Furthermore, a yellowish discoloration of the hairs around the eyes was seen in all treated animals up to day 6 and 7 of the experimental part. No abnormalities were detected in the untreated eyes.
Conclusion
No eye irritating potential could be detected, thus the test material should not be classified as eye irritant according to EU Regulation No. 1272/2008 (CLP).
Reference
All animals survived the observation period. Body weight development of the treated rabbits was inconspicuous.
No signs of clinical toxicity were detected. No signs of irritation were observed at the cornea or iris. All animals showed discharge (score 1) one hour after instillation of the test material. Furthermore, a yellowish discoloration of the hairs around the eyes was seen in all treated animals up to day 6 and 7 of the experimental part. No abnormalities were detected in the untreated eyes.
Eve irritation of all animals (mean score):
24 h | 48 h | 72 h | |
Cornea (mean /max) | 0/0 | 0/0 | 0/0 |
Iris (mean / max) | 0/0 | 0/0 | 0/0 |
Conjunctivae (mean / max) | 0/0 | 0/0 | 0/0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Justification for read
across
Endpoint:
Irritation
Type of read
across:one-to-one
Test Compound (with data):CAS: 174350-05-1
Dossier Compound (without data):CAS:82991-48-8
The read acrossis basedon the following similarity measures:
(1) Chemical similarity
The test compound (CAS: 174350-05-1) provides the main chemical features present in the dossier compound (CAS: 82991-48-8). Both substances share typical structural features for liquid crystals, i.e. one phenyl ring coupled via single bond to a cyclohexyl ring.
The phenyl ring of the test compound shows a flour substitution (n=2) that is not present in the dossier compound. The cylohexyl ring of both compounds shows a para alkyl substitution of different chain length (dossier cpd.: n=5; test cpd.: n=3). The phenyl ring of the dossier compound shows an ethyl substitution while the test compound exhibits a methoxy substituent at the para position.
(2) Physicochemical
similarity
Thehigh
chemical similarity yields almost identical physicochemical key
parameters relevant for bioavailability as listed in the table below.
(3)
Similar Effects in Biological Systems
Both
compounds have been tested in biological assays for the acute oral
toxicity and for mutagenicity in bacteria. The studies were performed
according to GLP and the methods applied were fully compliant with the
OECD TG.
The LD50 of both compounds exceeds 2000 mg/kg bw/day. Both compounds
were not mutagenic in the OECD 471 studies.
Assay |
Test Compound |
Dossier Compound |
Cyclohexylphenyl core |
yes |
yes |
Terminal substitution at thecyclohexylring |
alkyl (n=3) |
alkyl (n=5) |
Terminal substitution at the phenyl ring |
alkoxy(n=1) |
alkyl (n=2) |
Liquid crystalline properties |
yes |
yes |
FluoroSubstitution at the phenyl ring |
yes (n=2) |
no |
Water solubility |
130 µg/L (EU A.6) |
46 µg/L (EU A.6) |
logP |
> 5.7 (OECD 117, EU A.8) |
> 6.5 (OECD 117, EU A.8) |
Acute OralToxiciytin Rats |
LD50 > 2000 mg/kgbw/d (OECD 423) |
LD50 > 5000 mg/kgbw/d (OECD 401) |
in vitro Genotoxicity |
negative (OECD 471) |
negative (OECD 471) |
Eye irritation in vivo |
negative (OECD 405) |
negative (Read Across) |
Skin irritation in vivo |
negative (OECD 404) |
negative (Read Across) |
Conclusion
The Dossier Compound shows
a data gap for Skin and Eye irritation, however a chemical analogue
provides data for these endpoints. Both the Dossier Compouond and the
Test Compound show chemical similarity and almost identical
physicochemical parameters leading to similar bioavailability. The
response in biological assays was comparable; i.e. the LD50 exceeds
2000 mg/kg bw/d and negative data on mutagenicity in vitro.
Based on these finding it is justified to use the data from the chemical
analogue (Skin irritation in vivo: negative (GLP, OECD TG 404); Eye
irritation in vivo (GLP, OECD TG 405)) to fill the data gap for the
dossier compound.
Justification for selection of skin irritation / corrosion
endpoint:
This study was performed according to GLP and the methods applied
are fully compliant with OECD TG 404.
Justification for selection of eye irritation endpoint:
This study was performed according to GLP and the methods applied
are fully compliant with OECD TG 405.
Justification for classification or non-classification
According to the results of the irritation tests, a classification and labelling is not required for this substance.
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.

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