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EC number: 953-513-5 | 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
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Endpoint summary
Administrative data
Description of key information
A primary skin irritation test was conducted with rabbits to determine the potential for Dihydronepetalactone to produce irritation after a single topical application. Under the conditions of this study, the test substance is classified as slightly irritating to the skin.
Initially, one rabbit was tested to determine the irritation/corrosion potential of the test substance. Three dose sites, each approximately 6-cm2, were delineated on this animal. Five-tenths of a milliliter of the neat test substance was applied to the skin of each dose site. The pads and entire trunk of the animal were then wrapped with semi-occlusive 3-inch MicroporeTM tape to avoid dislocation of the patches. The patches were removed at the appropriate intervals (3 minutes, 1 hour, and 4 hours). All dose sites were evaluated for skin irritation according to the Draize method of scoring and for corrosion 30-60 minutes after the appropriate patch removal. Subsequent evaluations were performed approximately 24, 48, 72 hours and at 7 days after removal of the 4-hour patch. Since there was no corrosion observed at any of the dose sites for this animal, two additional rabbits were selected for testing and had the test substance applied for 4 hours only. All dose sites were evaluated for skin irritation according to the Draize scoring system at 30-60 minutes, and 24, 48, 72 hours and at 7 days after patch removal.
No visible necrosis (corrosion) of the skin tissue was observed at the 3-minute, 1-hour and 4-hour dose sites during the study.
3-Minute Exposure Site: Within 30-60 minutes of patch removal, very slight erythema was noted at the 3-minute exposure site, which resolved by 24 hours.
1-Hour Exposure Site: Within 30-60 minutes of patch removal, very slight erythema was noted at the 1-hour exposure site. The overall incidence and severity of irritation decreased with time. Dermal irritation cleared from the treated site by 48 hours.
4-Hour Exposure Site: Over the first 72 hours after patch removal, all three treated sites exhibited very slight to well-defined erythema and/or very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by Day 7 (study termination).
The Primary Dermal Irritation Index (PDII) calculated for this test substance was 1.7. The test substance is Mildly irritating according to GHS (8th revised edition).
A primary eye irritation test was conducted with rabbits to determine the potential for Dihydronepetalactone to produce irritation from a single instillation via the ocular route. One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the Draize method of scoring.
Within 24 hours after test substance instillation, two treated eyes exhibited corneal opacity and ‘positive’ conjunctivitis. There was no iritis observed in any treated eye during this study. The overall incidence and severity of irritation decreased gradually with time. Positive irritation cleared from the two treated eyes by Day 4. All animals were free of ocular irritation by Day 7 (study termination).
The Maximum Mean Total Score of Dihydronepetalactone is 14.7. Under the conditions of this study, Dihydronepetalactone is classified as mildly irritating to the eye.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- May 19 to June 3, 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- 2015
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - lot number of test material:
CH-DA-01-18
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Stored refrigerated
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage:
Test substance was expected to be stable for the duration of testing.
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis:
The test substance was applied as received
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium:
The test substance was applied as received
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding):
Mixed well prior to use
- Preliminary purification step (if any):
None - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Robinson Services, Inc.
- Age at study initiation: 14 weeks
- Weight at study initiation: 2584-2870 grams
- Housing:
The animals were singly housed in suspended stainless steel caging, which conforms to the size recommendations in the most recent Guidefor the Care and Use ofLaboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum):
PMI 5326 High Fiber Rabbit Diet. A designated amount of the diet (approximately 150 grams/day) and alfalfa hay cubes (Grainland Select Alfalfa Cubes) were available to each rabbit.
- Water: Filtered tap water was supplied ad libitum
- Acclimation period: 14 or 20 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 49 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not required
- Amount / concentration applied:
- Five-tenths of a millilitre
- Duration of treatment / exposure:
- 3 minutes, 1 hour, and 4 hours
- Observation period:
- All dose sites were evaluated for corrosion 30-60 minutes after patch removal. Subsequent evaluations were performed approximately 24, 48, 72 hours and at 7 days after removal of the four-hour patch.
- Number of animals:
- 3
- Details on study design:
- TEST SITE
- Area of exposure: 6 Cm2
- coverage: 1-inch x 1-inch, 4-ply gauze pad.
- Type of wrap if used: semi-occlusive 3-inch Micropore tape
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 3% soap solution followed by tap water and a clean paper towel
- Time after start of exposure: 3 minutes, 1 hour, and 4 hours
OBSERVATION TIME POINTS
30-60 minutes; 24, 48, 72 hours and at 7 days
SCORING SYSTEM:
- Method of calculation: Draize scoring system - Irritation parameter:
- primary dermal irritation index (PDII)
- Basis:
- mean
- Remarks:
- Average values for three rabbits.
- Time point:
- other: 30-60 minutes; 24, 48 and 72 hours
- Score:
- 1.7
- Reversibility:
- fully reversible
- Remarks:
- All animals were free of dermal irritation by Day 7 (study termination).
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- No visible necrosis (corrosion) of the skin tissue was observed at the 3-minute, 1-hour and 4-hour
dose sites during the study. In the 3-minute exposure site, within 30-60 minutes of patch removal, very slight erythema was noted at the 3-minute exposure site, which resolved by 24 hours.
In 1 hour exposure site, within 30-60 minutes of patch removal, very slight erythema was noted at the 1-hour exposure site. The overall incidence and severity of irritation decreased with time. Dermal irritation cleared from the treated site by 48 hours.
In 4 hours exposure sites, over the first 72 hours after patch removal, all three treated sites exhibited very slight to well-defined erythema and/or very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by Day 7 (study termination).
The Primary Dermal Irritation Index for Dihydronepetalactone was 1.7. - Interpretation of results:
- Category 3 (mild irritant) based on GHS criteria
- Conclusions:
- Mildly irritating according to GHS (8th revised edition)
- Executive summary:
A primary skin irritation test was conducted with rabbits to determine the potential for Dihydronepetalactone to produce irritation after a single topical application. Under the conditions of this study, the test substance is classified as slightly irritating to the skin.
Initially, one rabbit was tested to determine the irritation/corrosion potential of the test substance. Three dose sites, each approximately 6-cm2, were delineated on this animal. Five-tenths of a milliliter of the neat test substance was applied to the skin of each dose site. The pads and entire trunk of the animal were then wrapped with semi-occlusive 3-inch MicroporeTM tape to avoid dislocation of the patches. The patches were removed at the appropriate intervals (3 minutes, 1 hour, and 4 hours). All dose sites were evaluated for skin irritation according to the Draize method of scoring (Draize et al., 1944; see Table 6) and for corrosion 30-60 minutes after the appropriate patch removal. Subsequent evaluations were performed approximately 24, 48, 72 hours and at 7 days after removal of the 4-hour patch. Since there was no corrosion observed at any of the dose sites for this animal, two additional rabbits were selected for testing and had the test substance applied for 4 hours only. All dose sites were evaluated for skin irritation according to the Draize scoring system at 30-60 minutes, and 24, 48, 72 hours and at 7 days after patch removal.
No visible necrosis (corrosion) of the skin tissue was observed at the 3-minute, 1-hour and 4-hour dose sites during the study.
3-Minute Exposure Site: Within 30-60 minutes of patch removal, very slight erythema was noted at the 3-minute exposure site, which resolved by 24 hours.
1-Hour Exposure Site: Within 30-60 minutes of patch removal, very slight erythema was noted at the 1-hour exposure site. The overall incidence and severity of irritation decreased with time. Dermal irritation cleared from the treated site by 48 hours.
4-Hour Exposure Site: Over the first 72 hours after patch removal, all three treated sites exhibited very slight to well-defined erythema and/or very slight edema. The overall incidence and severity of irritation decreased gradually with time. All animals were free of dermal irritation by Day 7 (study termination).
The Primary Dermal Irritation Index (PDII) calculated for this test substance was 1.7. The test substance is Mildly irritating according to GHS (8th revised edition).
Reference
INDIVIDUAL SKIN IRRITATION SCORES
3-MINUTE EXPOSURE
Animal No | Sex | Time after removal of patch | ||||
Minute | Hours | Days | ||||
30 - 60 | 24 | 48 | 72 | 7 | ||
3501 | F | 1/0 | 0/0 | 0/0 | 0/0 | 0/0 |
1-HOUR EXPOSURE
Animal No | Sex | Time after removal of patch | ||||
Minute | Hours | Days | ||||
30 - 60 | 24 | 48 | 72 | 7 | ||
3501 | F | 1/0 | 1/0 | 0/0 | 0/0 | 0/0 |
4-HOUR EXPOSURE
Animal No | Sex | Time after removal of patch | ||||
Minute | Hours | Days | ||||
30 - 60 | 24 | 48 | 72 | 7 | ||
3501 | F | 1/0 | 2/0 | 2/0 | 2/0 | 0/0 |
3502 | F | 1/0 | 2/0 | 1/0 | 1/0 | 0/0 |
3503 | F | 1/1 | 2/1 | 1/1 | 1/1 | 0/0 |
Total | 3/1 | 6/1 | 4/1 | 4/1 | 0/0 | |
Mean | 1.0/0.3 | 2.0/0.3 | 1.3/0.3 | 1.3/0.3 | 0/0 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- June 1 - June 8, 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- 2017
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- - lot number of test material:
CH-DA-01-18
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
Stored refrigerated
- Stability and homogeneity of the test material in the vehicle/solvent under test conditions (e.g. in the exposure medium) and during storage:
Test substance was expected to be stable for the duration of testing.
- Stability in the medium, i.e. sensitivity of the test material to hydrolysis and/or photolysis:
The test substance was applied as received
- Solubility and stability of the test material in the solvent/vehicle and the exposure medium:
The test substance was applied as received
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding):
Mixed well prior to use
- Preliminary purification step (if any):
None - Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Robinson Services, Inc.
- Age at study initiation: 15 - 16 weeks
- Weight at study initiation: 2965 - 3478 grams
- Housing:
The animals were singly housed in suspended stainless steel caging, which conforms to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Enrichment (e.g., toy) was placed in each cage. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum):
PMI 5326 High Fiber Rabbit Diet. A designated amount of the diet (approximately 150 grams/day) and alfalfa hay cubes (Grainland Select Alfalfa Cubes) were available to each rabbit.
- Water: Filtered tap water was supplied ad libitum
- Acclimation period: 19 or 33 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24
- Humidity (%): 49 - 68
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: The other eye of each rabbit remained untreated with the test substance and served as a control.
- Amount / concentration applied:
- One-tenth of a milliliter of the test substance.
- Duration of treatment / exposure:
- The upper and lower lids were gently held together after instillation for about one second before releasing to minimize loss of the test substance.
- Observation period (in vivo):
- 1, 24, 48, and 72 hours and at 4 and 7 days post-instillation.
- Number of animals or in vitro replicates:
- 3
- Details on study design:
- REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Ocular irritation was evaluated using Draize method of scoring at 1, 24, 48, and 72 hours and at 4 and 7 days post-instillation. The fluorescein dye evaluation procedure (which involves rinsing with physiological saline) was used in the treated eye at 24 hours and as needed at subsequent scoring intervals
SCORING SYSTEM: Draize method
TOOL USED TO ASSESS SCORE: fluorescein - Irritation parameter:
- maximum mean total score (MMTS)
- Basis:
- mean
- Remarks:
- The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits was used to classify the test substance by the system of Kay and Calandra
- Time point:
- 24 h
- Score:
- 14.7
- Reversibility:
- fully reversible within: 96 hours
- Remarks on result:
- probability of mild irritation
- Irritant / corrosive response data:
- Within 24 hours after test substance instillation, two treated eyes exhibited corneal opacity and
‘positive’ conjunctivitis. There was no iritis observed in any treated eye during this study. The
overall incidence and severity of irritation decreased gradually with time. Positive irritation
cleared from the two treated eyes by Day 4. All animals were free of ocular irritation by Day 7
(study termination).
The Maximum Mean Total Score of Dihydronepetalactone is 14.7. - Interpretation of results:
- Category 2B (mildly irritating to eyes) based on GHS criteria
- Conclusions:
- Under the conditions of this study, Dihydronepetalactone is classified as mildly irritating to the
eye. - Executive summary:
A primary eye irritation test was conducted with rabbits to determine the potential for Dihydronepetalactone to produce irritation from a single instillation via the ocular route. One-tenth of a milliliter of the test substance was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the Draize method of scoring.Within 24 hours after test substance instillation, two treated eyes exhibited corneal opacity and ‘positive’ conjunctivitis. There was no iritis observed in any treated eye during this study. The overall incidence and severity of irritation decreased gradually with time. Positive irritation cleared from the two treated eyes by Day 4. All animals were free of ocular irritation by Day 7 (study termination).
The Maximum Mean Total Score of Dihydronepetalactone is 14.7. Under the conditions of this study, Dihydronepetalactone is classified as mildly irritating to the eye.
Reference
INDIVIDUAL SCORES FOR OCULAR IRRITATION
| Rabbit No.: 3401 (Female) | |||||
Hours | Days | |||||
1 | 24 | 48 | 72 | 4 | 7 | |
I. Cornea | ||||||
A. Opacity | 0 | 2 | 2 | 1 | 0 | 0 |
B.Area | 4 | 1 | 1 | 1 | 4 | 4 |
(AxB)x5 | 0 | 10 | 10 | 5 | 0 | 0 |
II. Iris | ||||||
A.Values | 0 | 0 | 0 | 0 | 0 | 0 |
Ax5 | 0 | 0 | 0 | 0 | 0 | 0 |
III. Conjunctivae | ||||||
A.Redness | 1 | 2 | 2 | 2 | 1 | 0 |
B. Chemosis | 2 | 1 | 1 | 0 | 0 | 0 |
C. Discharge | 3 | 1 | 0 | 0 | 0 | 0 |
(A+B+C)x2 | 12 | 8 | 6 | 4 | 2 | 0 |
Total | 12 | 18 | 16 | 9 | 2 | 0 |
| Rabbit No.: 3402 (Female) | |||||
Hours | Days | |||||
1 | 24 | 48 | 72 | 4 | 7 | |
I. Cornea | ||||||
A. Opacity | 0 | 2 | 2 | 1 | 0 | 0 |
B.Area | 4 | 1 | 1 | 1 | 4 | 4 |
(AxB)x5 | 0 | 10 | 10 | 5 | 0 | 0 |
II. Iris | ||||||
A.Values | 0 | 0 | 0 | 0 | 0 | 0 |
Ax5 | 0 | 0 | 0 | 0 | 0 | 0 |
III. Conjunctivae | ||||||
A.Redness | 1 | 2 | 2 | 2 | 1 | 0 |
B. Chemosis | 2 | 2 | 1 | 0 | 0 | 0 |
C. Discharge | 3 | 2 | 0 | 0 | 0 | 0 |
(A+B+C)x2 | 12 | 12 | 6 | 4 | 2 | 0 |
Total | 12 | 22 | 16 | 9 | 2 | 0 |
| Rabbit No.: 3403 (Female) | |||||
Hours | Days | |||||
1 | 24 | 48 | 72 | 4 | 7 | |
I. Cornea | ||||||
A. Opacity | 0 | 0 | 0 | 0 | 0 | 0 |
B.Area | 4 | 4 | 4 | 4 | 4 | 4 |
(AxB)x5 | 0 | 0 | 0 | 0 | 0 | 0 |
II. Iris | ||||||
A.Values | 0 | 0 | 0 | 0 | 0 | 0 |
Ax5 | 0 | 0 | 0 | 0 | 0 | 0 |
III. Conjunctivae | ||||||
A.Redness | 1 | 1 | 0 | 0 | 0 | 0 |
B. Chemosis | 1 | 1 | 0 | 0 | 0 | 0 |
C. Discharge | 2 | 0 | 0 | 0 | 0 | 0 |
(A+B+C)x2 | 8 | 4 | 0 | 0 | 0 | 0 |
Total | 8 | 4 | 0 | 0 | 0 | 0 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
Justification for classification or non-classification
Adverse effects are observed for the substance Dihydronepetalactone in both the skin irritation and eye irritation studies. The skin irritation effects were classified as Category 3 under GHS and it does not meet the criteria for classification according to Regulation (EC) No 1272/2008. The eye irritation effects were classified as category 2 according to Regulation (EC) No 1272/2008 and category 2B under GHS.
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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