Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-11-08 to 2011-11-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study conducted in compliance with minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive and done to a valid guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Minor - On occasions during the study, the humidity was recorded out of the target range. The actual range was at the humidity 26-57%. This deviation has no impact on the outcome of the study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Minor - On occasions during the study, the humidity was recorded out of the target range. The actual range was at the humidity 26-57%. This deviation has no impact on the outcome of the study
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
yes
Remarks:
Minor - On occasions during the study, the humidity was recorded out of the target range. The actual range was at the humidity 26-57%. This deviation has no impact on the outcome of the study
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Dark Brown Liquid
Specific details on test material used for the study:
EC Number: 939-946-2

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Number of animals per test: 3 (males)
Age at treatment: ~12 weeks
Identification: The animals were identified by engraved ear tags. The cages were marked with individual identity cards with information about study number, sex, cage number, dose group and individual animal number.
Acclimatization: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study.
Husbandry
Housing: Animals were housed individually in metal cages.
Lighting periods: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature range during the study: 17.0-19.8 °C
Relative humidity during the study: 26-57%
Enrichment: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65x65 cm with height of 45 cm). The cages are of an open wire structure and placed together to allow some social interaction with rabbit(s) in adjoining cages.
Ventilation: 15-20 air exchanges/hour. The environmental parameters were recorded twice daily during the study and the acclimation period.
Diet Animals received Purina Base – Lap gr. diet (Lot number: 0570 0811 and 0580 1011) for rabbits ad libitum.
Water The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. The quality control analysis is performed once every three month, and microbiological assessment is performed. Copies of the relevant Certificates of Analysis are retained in the archives

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL on a surgical guaze (ca. 2.5 cm x 2.5 cm)
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours, 1 and 2 weeks after the end of the exposure
Number of animals:
3
Details on study design:
A volume of 0.5 mL (per animal) was measured with a syringe and applied undiluted as supplied by the Sponsor.
According to EC 2004/73, B.4. and OECD Guidelines 404, a test item does not need to be tested if the pH-value is less than 2 or greater than 11.5, owing to its predictable corrosive properties. The pH of the test item was measured before the study initiation date and was found to be 4.5.
Approximately 24 hours prior to the test the hair was clipped from the back and flanks of the animals with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10cm).
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, 0.5mL was placed on a surgical gauze pad (ca. 2.5 cm x 2.5 cm). This gauze pad was applied to the intact skin of the clipped area and was kept in contact with the skin by a patch with a surrounding adhesive hypoallergenic plaster. The entire trunk of the animals was then wrapped with plastic wrap and held in place with an elastic stocking.
The duration of treatment was 4 hours. The dressing was removed and the skin was flushed with lukewarm tap water to clean the application site. Initially, a single animal was treated. As neither a corrosive effect nor a severe irritant effect were observed after the 1-hour exposure, the test was completed using the 2 remaining animals with an exposure period of 4 hours. The viability/mortality was recorded daily from the day of application of the animals to the termination of test. The clinical signs were recorded daily. The body weights were recorded on the day of application and at termination of observation

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.22
Max. score:
8
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: No corrosive effects were noted on the treated skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: No corrosive effects were noted on the treated skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: No corrosive effects were noted on the treated skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24 and 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 1 week
Remarks on result:
other: No corrosive effects were noted on the treated skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 adn 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No corrosive effects were noted on the treated skin

Any other information on results incl. tables



 Animal Number  Sex  Evaluation Interval  Erythema  Oedema  Cumulative Score  Cumulative Mean
123  M 1 hour  200  211  4.001.001.00  2.00
 123  M  24 hours 200 110   3.001.000.00  1.33
123  M  48 hours  200  110  3.001.001.00  1.33
 123  M  72 hours  200  100  3.000.000.00  1.00
 123  M  1 week  200  100  3.001.001.00  1.00
 123  M  2 weeks  000  000  0.000.000.00  0.00

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The application of the test substance caused signs of skin irritation which persisted for up to one week after application in one animal.
According to the Draize classification criteria the test substance is considered to be a “mild-irritant” to rabbit skin (P.I.I. = 1.22).
The study is considered to be relevant, reliable, adequate for risk assessment, and adequate for classification purposes.
Executive summary:

The primary skin irritation potential was investigated according to the OECD 404 (2002), OPPTS 870.2500 (1998) and EC No 440/2008, B.4 (2008). The animals were treated by topical semi-occlusive application of 0.5 mL to the intact shaved flank of 3 young adult New Zealand White rabbits. The duration of treatment was 4 hours. The scoring of skin reactions was performed 1, 24, 48, 72 hours, 1 and 2 weeks after removal of the dressing. The primary irritation index was calculated by totalling the mean cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points.

Results

The primary irritation index was 1.22. At the 1, 24, 48 and 72 hours observations and one week observation, well-defined erythema (score 2) was noted in one animal. Slight oedema (score 2) was observed in one animal at the 1 hour observation which resolved to very slight oedema (score 1) at the observations 24, 48, 72 hours and 1 week after removal of the dressing. Very slight oedema was observed in the other two animals at the 1 hour interval and then only in one animal, 24 and 48 hours after removal of the dressing. Two weeks after removal of the dressings, all animals had fully recovered and showed no signs of skin irritation. No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred. As no clinical signs were observed 2 weeks after patch removal, the study was terminated after the 2 weeks observation. The body weights of all rabbits were considered to be within the normal range of variability.

Conclusion

The application of the test substance caused signs of skin irritation which persisted for up to one week after application in one animal. According to the Draize classification criteria test item is considered to be a “mild-irritant” to rabbit skin (P.I.I. = 1.22).