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Administrative data

Description of key information

The test substance was neither irritating to the skin nor to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From August 13, 2012 to August 23, 2012
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
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Principles of method if other than guideline:
Another guideline was also followed: "Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions".
GLP compliance:
yes
Specific details on test material used for the study:
Specific Gravity / Density: 1.14 g/cm3; pH (1% in water, indicative range): 5.5 – 5.5 (determined at WIL Research Europe); Stability at higher temperatures: yes, maximum temperature 40°C.
Species:
rabbit
Strain:
New Zealand White
Remarks:
male
Details on test animals or test system and environmental conditions:
Animals:
Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, Germany. Number of animals: 3 Males. Age and body weight: at least 6 weeks old and at least 1.0 kg. Identification: earmark. Health inspection: performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Conditions:
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study. Accommodation: animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. Diet: pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period. Water: free access to tap water. Diet, water and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures. There were no findings that could interfere with the study.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin of each animal
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4h
Observation period:
1, 24, 48 and 72 hours after exposure
Number of animals:
3
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of skin irritation observed in the first animal.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
Irritation:
Four hours exposure to 0.5 mL of the test substance resulted in very slight erythema in the treated skin areas of the three rabbits on Day 1. No oedema was noted.
Corrosion:
No evidence of a corrosive effect on the skin.
Other effects:
Coloration / Remnants:
No staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the skin on Day 1 and 2.
Toxicity / Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

The results were evaluated according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations and the EC criteria for classification and labelling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Union).

Interpretation of results:
other: CLP criteria not met
Remarks:
- does not have to be classified
Executive summary:

A study was conducted to determine the skin irritation/corrosion potential of the test substance according to OECD Guideline 404, EU Method B.4 and EPA OPPTS 870.2500. Three New Zealand White rabbits were exposed to 0.5 ml test substance by application onto clipped skin (150 cm2 area) for 4 h using a semi-occlusive dressing. The untreated skin of each animal served as the reference control. Four hours after application, the dressing was removed and the skin cleaned of residual test substance using tap water. Skin reactions were assessed 1, 24, 48 and 72 h after exposure. Exposure to 0.5 mL of the test substance resulted in very slight erythema in the treated skin areas of the three rabbits on Day 1. No oedema was noted. No corrosive effects on the skin were observed. Under the study conditions, the test substance was considered as not irritating to skin (van Huygevoort, 2012).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From October 17, 2011 to October 27, 2011
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
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
Additional guideline: "Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions."
GLP compliance:
yes
Specific details on test material used for the study:
Specific Gravity / Density: 1.14 g/cm3; pH (1% in water, indicative range): 5.5 – 5.5 (determined at WIL Research Europe); Stability at higher temperatures: yes, maximum temperature 40°C.
The test substance was instilled undiluted as delivered by the sponsor. For technical reasons, the test substance was heated in a water bath at a maximum temperature of 37ºC for a maximum of 82 minutes.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animals:
Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognized by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, Germany. Number of animals: 3 Males. Age and body weight: at least 6 weeks old and at least 1.0 kg. Identification: earmark. Health inspection: performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.
Conditions:
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0ºC (actual range: 18.8 – 21.2ºC), a relative humidity of 40-70% (actual range: 43 - 77%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity. Accommodation: animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm). Acclimatization period was at least 5 days before start of treatment under laboratory conditions. Diet: pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period. Water: free access to tap water. Results of analysis for diet (nutrients and contaminants) and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.
Vehicle:
unchanged (no vehicle)
Controls:
other: The other eye remained untreated and served as the reference control.
Amount / concentration applied:
instillation of 0.1 mL of the test substance in the conjunctival sac of one of the eyes
Duration of treatment / exposure:
72h
Observation period (in vivo):
1, 24, 48, 72 hours after instillation
Number of animals or in vitro replicates:
3
Details on study design:
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritant / corrosive response data:
Irritation:
Instillation of 0.1 mL of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 48 hours in all 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:
Coloration / Remnants:
Remnants of the test substance were present on the outside of the eyelids on Days 1, 2 and/or 3. No staining of (peri) ocular tissues by the test substance was observed.
Toxicity / Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

The results were evaluated according to: Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007), and Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures.

Interpretation of results:
other: CLP criteria not met
Remarks:
does not have to be classified
Conclusions:
Under the study conditions, 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) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

A study was conducted to determine the eye irritation/corrosion potential of the test substance, according to OECD Guideline 405, EU Method B.5 and EPA OPPTS 870.2400. Single samples of 0.1 ml substance were instilled into one eye of each of three New Zealand White rabbits. The other eye remained untreated and served as control. Observations were made 1, 24, 48 and 72 h after instillation. Exposure resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 48 h in all animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 h after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion. Under the study conditions, the test substance was considered as not irritating to eyes (Stitzinger, 2011).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

A study was conducted to determine the skin irritation/corrosion potential of the test substance according to OECD Guideline 404, EU Method B.4 and EPA OPPTS 870.2500. Three New Zealand White rabbits were exposed to 0.5 ml test substance by application onto clipped skin (150 cm2area) for 4 h using a semi-occlusive dressing. The untreated skin of each animal served as the reference control. Four hours after application, the dressing was removed and the skin cleaned of residual test substance using tap water. Skin reactions were assessed 1, 24, 48 and 72 h after exposure. Exposure to 0.5 mL of the test substance resulted in very slight erythema in the treated skin areas of the three rabbits on Day 1. No oedema was noted. No corrosive effects on the skin were observed. Under the study conditions, the test substance was considered as not irritating to skin (van Huygevoort, 2012).

 

Eye irritation

A study was conducted to determine the eye irritation/corrosion potential of the test substance, according to OECD Guideline 405, EU Method B.5 and EPA OPPTS 870.2400. Single samples of 0.1 ml substance were instilled into one eye of each of three New Zealand White rabbits. The other eye remained untreated and served as control. Observations were made 1, 24, 48 and 72 h after instillation. Exposure resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 48 h in all animals. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 h after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion. Under the study conditions, the test substance was considered as not irritating to eyes (Stitzinger, 2011).

Justification for classification or non-classification

In vivo studies in rabbits showed that the substance is not irritating to skin and eyes. No classification is therefore required according to CLP (1272/2008) criteria.