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Description of key information

In an in vivo skin irritation study performed according to OECD/EC guideline and GLP principles, the substance was not irritating.
In an in vivo eye irritation study performed according to OECD/EC guideline and GLP principles, the substance was not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31-Oct-2011 to 04-Nov-2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
other: Guideline no. 431: In Vitro Skin Corrosion: Human Skin Model Test
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EU method B.40 BIS: "In Vitro Skin Corrosion: Human Skin Model Test
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg, moistened with 25 µl water

NEGATIVE CONTOL:
- Amount(s) applied (volume or weight with unit): 50 µl Milli-Q water

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 50 µl KOH
- Concentration (if solution): 8 N
Duration of treatment / exposure:
Exposure:3 minutes and 1 hour
Details on study design:
TEST SITE
- Area of exposure: human skin model
- % coverage: 0.6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): phosphate buffered saline
- Time after start of exposure: 3 minutes and 1 hour


SCORING SYSTEM:
- Percentage viability: After treatment, the medium was replaced by 300 µl MTT-medium and tissues were incubated for
3 hours at 37 °C in air containing 5 % CO2. After incubation the tissues were washed with PBS and formazan was extracted with 2 ml isopropanol over night at room temperature. The amount of extracted formazan was determined spectrophotometrically at 540 nm.
Irritation / corrosion parameter:
other: other: percentage viability
Value:
98
Remarks on result:
other:
Remarks:
Basis: other: percentage of control. Time point: 3 minutes. (migrated information)
Irritation / corrosion parameter:
other: other: percentage viability
Value:
111
Remarks on result:
other:
Remarks:
Basis: other: percentage of control. Time point: 1 hour. (migrated information)
Interpretation of results:
other: not corrosive
Conclusions:
The in vitro skin irritation test was conducted according to OECD 431 guideline and GLP principles. It is concluded that this test is valid and that FAT 41043/A is not corrosive in the in vitro skin irritation test.
Executive summary:

Skin corrosion is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with FAT 41043/A compared to the negative control tissues was 98 % and 111 %, respectively. Because the mean relative tissue viability for FAT 41043/A was not below 50 % after the 3-minute treatment and not below 15 % after the 1-hour treatment FAT 41043/A is considered to be not corrosive. The positive and negative controls induced appropriate responses.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22-Nov-2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to guideline
Guideline:
other: OECD guideline 437 “Bovine corneal opacity and permeability (BCOP) test method for identifying ocular corrosives and severe irritants”
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EU Method B.47 “Bovine corneal opacity and permeability method for identifying ocular corrosives and severe irritants
Deviations:
no
GLP compliance:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 300 mg per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 20 % (w/v) Imidazole
Duration of treatment / exposure:
240 minutes
Details on study design:
TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 240 minutes

SCORING SYSTEM:
- After exposure the cornea is thoroughly rinsed to remove the test substance followed by immediate opacity measurement and permeability evaluation of the cornea.
- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).

TOOL USED TO ASSESS SCORE:
- Opacitymeter and microplate reader

DATA EVALUATION:
A test substance that induces an IVIS ≥55.1 is defined as a corrosive or severe irritant
Irritation parameter:
other: In vitro irritancy score (IVIS)
Run / experiment:
mean
Value:
0.1
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: 240 min
Interpretation of results:
other: not severe irritant or corrosive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
FAT 41043/A is not irritant or corrosive in the Bovine Corneal Opacity and Permeability test

Executive summary:

The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical rangeindicating that the negative control did not induce irritancy on the corneas.The mean in vitro irritancy score of the positive control (20 % (w/v) Imidazole) was 98 and within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. FAT 41043/A did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of 0.1 after 240 minutes of treatment.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion


In an in vitro skin corrosion test performed according to OECD 431 and GLP principles, the substance was not corrosive. In the subsequently performed in vivo skin irritation test in rabbits performed according to OECD 404 and GLP principles, the substance was not irritating.


 


Eye irritation/corrosion


In the Bovine Corneal Opacity and Permeability test performed according to OECD/EC guideline, the substance showed a mean irritancy score of 0.1 after 240 minutes of treatment, which means the substance is not an ocular irritant in this test. In the subsequently performed in vivo eye irritation test in rabbits performed according to OECD/EC guideline, instillation of the substance in the eye resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The irritation has completely resolved within 48 hours and the substance was considered to be slightly irritating to the eyes.



Justification for selection of skin irritation / corrosion endpoint:
Reliable in vivo study performed according to guideline (Klimisch code 1).

Justification for selection of eye irritation endpoint:
Reliable in vivo study performed according to guideline (klimisch code 1).

Justification for classification or non-classification

Based on these results the substance does not have to be classified and has no obligatory labelling requirement for skin and eye irritation according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.