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Endpoint summary
Administrative data
Description of key information
Skin irritation/corrosion
Two studies are available:
1) A primary skin irritation study (Latour, 2015) is available which is key study. This study showed that the test substance is not irritating.
2) An in vitro skin corrosion study (Buskens, 2014) is available which is supporting study. This study showed that the test substance is not corrosive.
Eye irritation
Two studies are available:
1) An acute eye irritation study (Latour, 2015) is available which is key study. This study showed that the test substance is slightly irritating.
2) An in vitro BCOP study (Verspeek-Rip, 2014) is available which is supporting study. This study showed that the test substance is not irritating.
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:
- From 19 to 30 Nov 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Specific details on test material used for the study:
- Purity: 96.6%
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: body weights were at least 1.5 kg
- Housing: labeled cages with perforated floors and shelters
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay and wooden sticks were available during the study period.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle
IN-LIFE DATES: From: To: - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- other: watery ethanol (50% v/v)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams of the test substance
VEHICLE
- Amount(s) applied (volume or weight with unit): 1 mL - Duration of treatment / exposure:
- 4 h
- Observation period:
- 72 hours after the removal of the dressings and test substance
- Number of animals:
- 3 males
- Details on study design:
- TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: The metalline patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the dressing was removed and the skin cleaned of residual test substance using tap water.
- Time after start of exposure: Four hours
OBSERVATION:
-Mortality/Viability: Twice daily.
-Toxicity: At least once daily.
-Body Weight: Day of treatment (prior to application) and after the final observation.
-Necropsy: No necropsy was performed according to protocol.
-Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
SCORING SYSTEM: Draize - Irritation parameter:
- erythema score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- edema score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritant / corrosive response data:
- No skin irritation was caused by 4 hours exposure to the test substance.
- Other effects:
- No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- not classified
- Conclusions:
- Based on these results the test substance does not have to be classified and has no obligatory labelling requirement for skin irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments);
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Reference
Individual skin irritation scores
Animal |
815 |
812 |
816 |
|||
Time after exposure |
Erythema (0-4) |
Oedema (0-4) |
Erythema (0-4) |
Oedema (0-4) |
Erythema (0-4) |
Oedema (0-4) |
1 hour |
0 |
0 |
0 |
0 |
0 |
0 |
24 hours |
0 |
0 |
0 |
0 |
0 |
0 |
48 hours |
0 |
0 |
0 |
0 |
0 |
0 |
72 hours |
0 |
0 |
0 |
0 |
0 |
0 |
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:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From 26 Nov to 17 Dec 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Deviations:
- no
- GLP compliance:
- yes
- Specific details on test material used for the study:
- Purity: 96.6%
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: between 12 and 24 weeks old
- Weight at study initiation: at least 1.5 kg
- Housing: Animals were individually housed in labeled cages with perforated floors and shelters.
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay and wooden sticks were available during the study period.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: at least 5 days before start of treatment
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): a 12-hour light/12-hour dark cycle
IN-LIFE DATES: From 26 Nov to 17 Dec 2014 - Vehicle:
- unchanged (no vehicle)
- Controls:
- no
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): on average, 37.2 mg (range 36.8 - 37.3 mg) - Duration of treatment / exposure:
- 24 hours
- Observation period (in vivo):
- 7 days
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- TREATMENT
Animals were treated by instillation of, on average, 37.2 mg (range 36.8 - 37.3 mg) of the test substance (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage.
Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg were administered by subcutaneous injection.
OBSERVATION
-Mortality/Viability: Twice daily.
-Toxicity: At least once daily.
-Body Weight: Day of treatment (prior to instillation) and after the final observation.
-Necropsy: No necropsy was performed according to protocol.
-Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
SCORING SYSTEM: Draize - Irritation parameter:
- cornea opacity score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- iris score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 0
- Irritation parameter:
- conjunctivae score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- ca. 0.89
- Max. score:
- 2
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- other: fully reversible within 72 hours in one animal and within 7 days in the other two animals.
- Irritation parameter:
- chemosis score
- Basis:
- mean
- Time point:
- other: Mean of 24, 48 and 72 hours
- Score:
- 0
- Max. score:
- 1
- Reversibility:
- fully reversible within: 24 hours
- Remarks on result:
- other: fully reversible within 24 hours in all three animals.
- Irritant / corrosive response data:
- Irritation:
Instillation of approximately 37 mg of test substance (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation had completely resolved within 72 hours in one animal and within 7 days in the other two animals.
No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
Corrosion:
There was no evidence of ocular corrosion. - Other effects:
- Remnants of the test substance were present on the outside of the eyelids of all animals on Day 1.
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred. - Interpretation of results:
- GHS criteria not met
- Remarks:
- lts
- Conclusions:
- Based on these results, the test substance does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments);
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).
Reference
Individual eye irritation scores
Animal |
Time after dosing |
Cornea opacity |
Iris |
Conjunctivae redness |
Conjunctivae Chemosis |
813 |
1 hour |
0 |
0 |
2 |
1 |
24 hours |
0 |
0 |
1 |
0 |
|
48 hours |
0 |
0 |
1 |
0 |
|
72 hours |
0 |
0 |
1 |
0 |
|
7 days |
0 |
0 |
0 |
0 |
|
818 |
1 hour |
0 |
0 |
2 |
1 |
24 hours |
0 |
0 |
1 |
0 |
|
48 hours |
0 |
0 |
1 |
0 |
|
72 hours |
0 |
0 |
1 |
0 |
|
7 days |
0 |
0 |
0 |
0 |
|
824 |
1 hour |
0 |
0 |
2 |
1 |
24 hours |
0 |
0 |
1 |
0 |
|
48 hours |
0 |
0 |
1 |
0 |
|
72 hours |
0 |
0 |
0 |
0 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
Skin irritation/corrosion
Two studies are available:
1) A primary skin irritation study was conducted according to OECD 404 using rabbits (Latour, 2015). Key study.
This study showed that the test substance is not irritating.
2) An in vitro skin corrosion study was conducted according to OECD 431 using a human skin model (Buskens, 2014). Supporting study.
In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, a human skin model test was performed. This study showed that the test substance is not corrosive. Based on this, in vivo skin irritation study in rabbit was performed to establish the possible skin irritating properties of the test substance.
Eye irritation
Two studies are available:
1) An acute eye irritation study was conducted according to OECD 405 using rabbits (Latour, 2015). Key study.
This study showed that the test substance is slightly irritating.
2) An in vitro BCOP study was conducted according to OECD 437 using bovine cornea (Verspeek-Rip, 2014). Supporting study.
In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, an in vitro BCOP test was performed. This study showed that the test substance is not irritating. Based on this, in vivo eye irritation study in rabbit was performed to establish the possible eye irritating properties of the test substance.
Justification for selection of skin irritation / corrosion endpoint:
This study was conducted according to OECD 404 using rabbits.
Justification for selection of eye irritation endpoint:
This study was conducted according to OECD 405 using rabbits.
Effects on eye irritation: slightly irritating
Justification for classification or non-classification
Skin irritation/corrosion: Mean scores at 24, 48 & 72 hours for erythema were < 2.3 (actual value 0) for oedema were < 2.3 (actual value 0). In addition all reactions were fully reversible within the observation period.
Serious eye damage/eye irritation: Mean scores at 24, 48 & 72 hours for corneal opacity were < 1 (actual value 0), for iritis were < 1 (actual value 0), for conjunctival redness were < 2 (actual value 0.89) and for conjunctival oedema were < 1 (actual value 0).
Therefore in accordance with Regulation (EC) No. 1272/2008 Tables 3.2.2 & 3.3.2 the substance is not classified for the skin corrosion/irritation and serious eye damage/eye irritation endpoint.
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