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EC number: 202-075-7 | CAS number: 91-53-2
- 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
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- Peer-reviewed assessment report (attached in section 13)
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 81-6 (Skin Sensitisation)
- Version / remarks:
- US EPA FIFRA Guideline §81-6
- Deviations:
- yes
- Remarks:
- Purity of the test compound was not determined by the laboratory prior to conduct of the test.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- not applicable
- GLP compliance:
- yes
- Remarks:
- self-certified to US EPA regulations at 40 CFR Parts 160 and 792
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- Test was conducted for another regulatory purpose, other than and prior to REACH registration.
Test material
- Reference substance name:
- Ethoxyquin
- EC Number:
- 202-075-7
- EC Name:
- Ethoxyquin
- Cas Number:
- 91-53-2
- Molecular formula:
- C14H19NO
- IUPAC Name:
- ethoxyquin
- Details on test material:
- Chemical name
IUPAC: 6-ethoxy-2,2,4-trimethyl-1,2-dihydroquinoline
CAS: 6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- Hartley
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Indianapolis, IN, USA
Study design: in vivo (non-LLNA)
Induction
- Route:
- other: topical
- Vehicle:
- unchanged (no vehicle)
- Day(s)/duration:
- Once per week for three weeks for a total of three induction exposures. The duration of the exposures was six hours.
- Adequacy of induction:
- not specified
Challengeopen allclose all
- No.:
- #1
- Route:
- other: topical
- Vehicle:
- not specified
- Concentration / amount:
- 50%
- Day(s)/duration:
- Two weeks after the last induction exposure
- Adequacy of challenge:
- highest non-irritant concentration
- No.:
- #2
- Route:
- other: topical
- Vehicle:
- not specified
- Concentration / amount:
- 50%
- Day(s)/duration:
- One week after challenge, test group animals were re-challenged to confirm the initial results.
- Adequacy of challenge:
- highest non-irritant concentration
- No. of animals per dose:
- 6
- Details on study design:
- MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures / Exposure period / Test groups / Frequency of applications / Duration: A test group was dosed topically for each 6 hours with the undiluted test material once per week for three weeks for a total of three induction exposures.
- Control group: A positive control group of three male and three female guinea pigs was included to demonstrate the reliability of the test system. The positive control group was induced and challenged on a similar regimen as the test group with dinitrochlorobenzene (DNCB) as the positive control material. Two naive control groups of three male and three female guinea pigs each were dosed only at challenge and re-challenge, respectively, in the same manner as the test group and served as irritation controls.
- Concentrations: neat
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge / Exposure period / Test groups: Two weeks after the last induction exposure, test group animals were challenged for detection of sensitisation by topical application of a concentration of the test material that had been proven to be non-irritating before to previously unexposed areas of skin. One week after challenge, test group animals were re-challenged to confirm the initial results. The test material concentrations used for induction challenge and re-challenge dosing were selected based on the results of range-finding experimentation in the primary irritation phase.
- Control group: see above
- Site: previously unexposed areas of skin
- Concentrations: 50%
- Evaluation (hr after challenge): Reactions to challenge and re-challenge dosing were evaluated at approximately 24 and 48 hours after completion of exposure.
OTHER: Body weights and clinical observations were recorded just prior to initiation of dosing and at termination. - Challenge controls:
- Two naive control groups of three male and three female guinea pigs each were dosed only at challenge and re-challenge, respectively, in the same manner as the test group and served as irritation controls.
- Positive control substance(s):
- yes
- Remarks:
- dinitrochlorobenzene (DNCB)
Results and discussion
- Positive control results:
- Induction phase: For positive control group animals, irritation noted after the first induction dosing with 0.25 % DNCB included five slight (grade 1) erythema reactions and one very slight (grade ±) reaction. Following the second induction, positive control group dermal findings included one severe (grade 3) reaction and five sites with moderate (grade 2) reactions. Eschar was present on five sites following second induction. After the third induction dosing, five animals had slight reactions and one site had a very slight erythema reaction. In addition, eschar was noted on one site following the third induction.
Challenge phase: In the positive control group, there was one slight and five moderate (grade 2) reactions). Eschar was observed for one animal at 24 hours post-dose. By 48 hours, slight and moderate erythema was noted for three animals each. Focal eschar and eschar were present on one site each at 48 hours post-challenge.
Re-challenge phase: Four and five very slight reactions were observed at the 24- and 48-hour observations, respectively, for naïve control II group guinea pigs dosed with 50 % ethoxyquin.
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50% ethoxyquin
- No. with + reactions:
- 10
- Total no. in group:
- 12
- Clinical observations:
- The 50 % concentration of ethoxyquin induced ten very slight (grade ±) reactions at 24 hours for test group animals following challenge dosing.
- Remarks on result:
- other:
- Remarks:
- result similar to control
- Reading:
- 1st reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50% ethoxyquin
- No. with + reactions:
- 10
- Total no. in group:
- 12
- Clinical observations:
- By 48 hours, irritation included nine sites with very slight reactions and one with a slight (grade 1) reaction.
- Reading:
- rechallenge
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 50% ethoxyquin
- No. with + reactions:
- 12
- Total no. in group:
- 12
- Clinical observations:
- There were 12 very slight (grade ±) reactions noted for test group animals re-challenged with 50 % ethoxyquin. Focal eschar was noted for one site at both 24 and 48 hours.
- Reading:
- rechallenge
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 50% ethoxyquin
- No. with + reactions:
- 12
- Total no. in group:
- 12
- Clinical observations:
- By 48 hours, dermal irritation included 11 very slight reactions and one site with a slight (grade 1) reaction. Focal eschar was noted for one site at both 24 and 48 hours. At 48 hours post-dose, four animals had desquamation.
Any other information on results incl. tables
Findings
General: There were no deaths, clinical findings, or remarkable changes in body weights observed during the study.
Primary irritation phase
One very slight (regarded as “grade ±” by the study author) reaction was noted for sites dosed with 50 % ethoxyquin at the 24 and 48 hour observations. The undiluted (100 %) concentrate of ethoxyquin induced one slight (grade 1) and one very slight erythema at the 48-hour scoring. Based on these results, undiluted ethoxyquin was considered to be appropriate for induction and was used in order to maximise the potential for systemic exposure. The 50 % concentration of ethoxyquin in acetone was considered to be the maximal, essentially nonirritating concentration and was therefore appropriate for challenge and re-challenge dosing.
Induction phase
Undiluted ethoxyquin induced seven very slight (grade ±) reactions in the test group following both the first and second induction dosings. Six sites had very slight reactions and one site had a slight (grade 1) reaction after the third induction dose. For positive control group animals, irritation noted after the first induction dosing with 0.25 % DNCB included five slight (grade 1) erythema reactions and one very slight (grade ±) reaction. Following the second induction, positive control group dermal findings included one severe (grade 3) reaction and five sites with moderate (grade 2) reactions. Eschar was present on five sites following second induction. After the third induction dosing, five animals had slight reactions and one site had a very slight erythema reaction. In addition, eschar was noted on one site following the third induction.
Challenge phase
The 50 % concentration of ethoxyquin induced ten very slight (grade ±) reactions at 24 hours for test group animals following challenge dosing. By 48 hours, irritation included nine sites with very slight reactions and one with a slight (grade 1) reaction. Five very slight reactions were observed at both 24 and 48 hours for naïve control I group animals dosed with 50 % ethoxyquin. In addition, focal eschar was noted for one animal at both 24 and 48 hours. In the positive control group, there was one slight and five moderate (grade 2) reactions). Eschar was observed for one animal at 24 hours post-dose. By 48 hours, slight and moderate erythema was noted for three animals each. Focal eschar and eschar were present on one site each at 48 hours post-challenge.
Re-challenge phase
There were 12 very slight (grade ±) reactions noted for test group animals re-challenged with 50 % ethoxyquin. By 48 hours, dermal irritation included 11 very slight reactions and one site with a slight (grade 1) reaction. Focal eschar was noted for one site at both 24 and 48 hours. At 48 hours post-dose, four animals had desquamation. Four and five very slight reactions were observed at the 24- and 48-hour observations, respectively, for naïve control II group guinea pigs dosed with 50 % ethoxyquin.
Incidence and severity indices
The “Sensitisation Incidence Index” was calculated to be 1/12 (8 %) for the test group following challenge dosing with ethoxyquin. The Irritation Severity Indices were 0.4 and 0.5 at 24 and 48 hours, respectively, for the test group and 0.4 at both 24 and 48 hours postdosing for the naïve control I group. In contrast, the Sensitisation Incidence Index was calculated to be 6/6 (100 %) for the positive control group following challenge dosing with 0.1 % DNCB. The Irritation Severity Indices were 1.8 and 1.5 at 24 and 48 hours, respectively.
Table Skin sensitisation study with ethoxyquin in albino guinea pigs. Incidence of dermal responses at challenge.
Group |
Test material |
Interval |
0 |
± |
1 |
2 |
3 |
No. of animals |
Irritation severity index |
Test |
50% ethoxyquin |
24h |
2 |
10 |
0 |
0 |
0 |
12 |
0.4 |
Test |
50% ethoxyquin |
48h |
2 |
9 |
1 |
0 |
0 |
12 |
0.5 |
Control-I |
50% ethoxyquin |
24h |
1 |
2 |
0 |
0 |
0 |
6 |
0.4 |
Control-I |
50% ethoxyquin |
48h |
1 |
2 |
0 |
0 |
0 |
6 |
0.4 |
Positive Control |
0.1% DNBC |
24h |
0 |
0 |
1 |
5 |
0 |
6 |
1.8 |
Positive Control |
0.1% DNBC |
48h |
0 |
0 |
3 |
3 |
0 |
6 |
1.5 |
DNCB = dinitrochlorobenzene
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- As information was provided via a peer-reviewed assessment report, it can be considered as sufficiently reliable to assess the sensitizing potential of ethoxyquin in guinea pigs. There were no deaths, clinical findings, or remarkable body weight changes.
The positive control material (DNCB) was demonstrated to be an extreme sensitising agent under the conditions of this study based on the Sensitisation Incidence Index of 100 %, thereby demonstrating the reliability of the test system.
Based on a Sensitisation Incidence Index of 8 % (1/12) following both initial challenge and re-challenge dosing with ethoxyquin, the test material may be considered to have a very weak sensitising potential in albino guinea pigs.
As however the irritation response is largely similar to control, this can be also considered as a biological, non-treatment-related variance, so classification as a skin sensitizer is not triggered. For the classification as skin sensitizer Cat. 1B, in the Bühler assay, ≥ 15 % of the animals must be responding at > 20 % topical induction dose. There is no evidence for a response of the animals over control. - Executive summary:
In a modified Buehler method dermal sensitization study (US EPA FIFRA Guideline §81-6, equivalent to OECD 406) with ethoxyquin, six male and six female Hartley albino guinea pigs were tested. Dinitrochlorobenzene servesd as positive control.
There were no deaths, clinical findings, or remarkable changes in body weights observed during the study.
Undiluted ethoxyquin induced seven very slight (grade ±) reactions in the test group following both the first and second induction dosings. Six sites had very slight reactions and one site had a slight (grade 1) reaction after the third induction dose.
The 50 % concentration of ethoxyquin induced ten very slight (grade ±) reactions at 24 hours for test group animals following challenge dosing. By 48 hours, irritation included nine sites with very slight reactions and one with a slight (grade 1) reaction.
There were 12 very slight (grade ±) reactions noted for test group animals re-challenged with 50 % ethoxyquin. By 48 hours, dermal irritation included 11 very slight reactions and one site with a slight (grade 1) reaction. Focal eschar was noted for one site at both 24 and 48 hours.
At 48 hours post-dose, four animals had desquamation.
In this study, ethoxyquin is not a dermal sensitizer.
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