Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin irritation / corrosion
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study (OECD 431 / 439)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)
Version / remarks:
(April 13, 2004)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
(July 22, 2010)
Deviations:
no
Principles of method if other than guideline:
In addition, the studies follow the test strategy for determination of a corrosion/irritation property as given in the following guideline: OECD Guideline for Testing of Chemicals No. 404, April 24, 2002 (“Acute Dermal Irritation/Corrosion”).
GLP compliance:
yes (incl. QA statement)
Remarks:
(BASF SE, Experimental Toxicology and Ecology, Ludwigshafen, Germany)

Test material

Constituent 1
Chemical structure
Reference substance name:
Oxirane, [(4-nonylphenoxy)methyl]-, reaction product with ethylene glycol
EC Number:
807-586-4
Cas Number:
634602-80-5
Molecular formula:
Unspecified
IUPAC Name:
Oxirane, [(4-nonylphenoxy)methyl]-, reaction product with ethylene glycol

Test animals

Species:
human
Strain:
other: Epi-200, MatTek In Vitro Life Science Laboratories, Bratislava, Slovakia

Test system

Type of coverage:
other: The use of a nylon mesh as a spreading support was not necessary for the test substance (determined in a pretest).
Preparation of test site:
other: Three dimensional human epidermis model, EpiDerm TM
Vehicle:
unchanged (no vehicle)
Controls:
other: control tissues with: De-ionized water (NC, corrosion), PBS, sterile (NC, irritation), 8-n potassium hydroxide sol. (PC, corrosion) or 5% (w/v) sodium dodecyl sulfate in de-ionized water, sterile (PC, irritation); NC=negative control, PC=positive control;
Amount / concentration applied:
Corrosion test: 50 µL of the undiluted test substance or negative and positive control, respectively.
Irritation test: 30 µL of the undiluted test substance or negative and positive control, respectively.
Duration of treatment / exposure:
Corrossion test: 3 min, 1 h;
Irritation test: 1 h (under the laminar flow hood at room temperature for 25 minutes overall and for 35 minutes in the incubator)
Observation period:
Additional to the exposure period:

Corrosion test:
Pre-incubation period: 1 - 1.5 h. After exposure (duration see above) the tissues were washed with PBS to remove residual test material after exposure. Rinsed tissues were kept in 24-well plates (holding plates) at room temperature on assay medium until all tissues per application time were dosed and rinsed. The assay medium was then replaced by MTT solution and tissues were incubated for 3 hours.
Irritation test:
Preincubation period: 1 h. After exposure (duration see above) the tissues were washed with PBS to remove residual test material after exposure. Rinsed tissues were blotted on sterile absorbent paper and transferred into new 6-well plates, pre-filled with 0.9 mL fresh medium. When all tissues were rinsed, the surface of each tissue was carefully dried with a sterile cotton swab. Subsequently, the tissues were incubated in the incubator at 37°C for 24 ± 2 hours. After the post-incubation period, the assay medium was replaced by 0.3 mL MTT solution and the tissues were incubated in the incubator for 3 hours.
Number of animals:
other:
Number of tissues used in the corrosion test: Two tissues per exposure time and test group (test material, NC and PC; 12 tissues per test) were used.
Number of tissues used in the irritation test: Three tissues were treated with the test substance, the PC and NC, respectively.
Details on study design:
The objective was to assess the potential for corrosive activity and skin irritation of the test material upon first contact with skin. The present test is based on the experience that corrosive and irritant chemicals produce cytotoxicity in human reconstructed epidermis after a short term topical exposure. The test is designed to predict a skin corrosion or irritation potential of a chemical by using the three dimensional human epidermis model EpiDermTM. After application of the test material to the stratum corneum surface of the EpiDermTM tissue the induced cytotoxicity (= loss of viability) is measured by a colorimetric assay. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity. The mitochondrial dehydrogenase reduces the yellow colored water-soluble 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) to the insoluble blue colored formazan. After isopropanol-extraction of the formazan from the tissues, the optical density of the extract is determined spectrophotometrically. Optical density of the extracts of test-substance treated tissues is compared to negative control values from tissues and expressed as relative tissue viability.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 3 min
Score:
100
Remarks on result:
other: Negative control
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 3 min
Score:
112
Remarks on result:
other: Test group
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 3 min
Score:
13
Remarks on result:
other: Positive control
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 1 hour
Score:
100
Remarks on result:
other: Negative control
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 1 h
Score:
91
Remarks on result:
other: Test group
Irritation parameter:
other: Viability (% of negativ control), Corrosion test
Basis:
mean
Remarks:
(2 tissues)
Time point:
other: Exposure: 1 h
Score:
5
Remarks on result:
other: Positive control
Irritation parameter:
other: Viability (% of negativ control), Irritation test
Basis:
mean
Remarks:
(3 tissues)
Time point:
other: Exposure: 1 h
Score:
100
Remarks on result:
other: Negative control
Irritation parameter:
other: Viability (% of negativ control), Irritation test
Basis:
mean
Remarks:
(3 tissues)
Time point:
other: Exposure: 1 h
Score:
3
Remarks on result:
other: Test group
Irritation parameter:
other: Viability (% of negativ control), Irritation test
Basis:
mean
Remarks:
(3 tissues)
Time point:
other: Exposure: 1 h
Score:
3
Remarks on result:
other: Positive control

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information