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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study is an OECD guideline study conducted under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Heptan-2-one
EC Number:
203-767-1
EC Name:
Heptan-2-one
Cas Number:
110-43-0
Molecular formula:
C7H14O
IUPAC Name:
heptan-2-one
Constituent 2
Reference substance name:
Methyl n-amyl ketone
IUPAC Name:
Methyl n-amyl ketone
Details on test material:
Description pale yellow liquid
Batch number TD-9024390
Purity 99.63%
Date received 01 November 2010
Expiry date 01 November 2011
Storage conditions room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories U.K. Ltd., Loughborough, UK. At the start of the study the animals weighed 2.21 or 2.49 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected thepurpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. A quantity of 0.5 ml of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period. One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test item was removed by gentle swabbing with cotton wool soaked in distilled water. After consideration of the skin reactions produced in the first animal, an additional two animals were treated with 0.5 ml of test item. One patch was applied to the back of each rabbit and was allowed to remain in contact with the skin for a period of four hours. Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours on the initial animal, followed by 4 hours on the remaining animals
Observation period:
72 hours after patch removal
Number of animals:
3
Details on study design:
Animals were treated with the test article under a semi-occlusive patch for 4 hours. At the end of the exposure period, the treatement sites were washed with distilled water and observed for irritation for 72 hours.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 4 hours
Score:
ca. 3.7
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.6
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Reversibility:
fully reversible

Any other information on results incl. tables

Skin Reaction Observation Time (following patch removal) Individual Scores - Rabbit Number and Sex
69775 Male
3-Minute Exposure 1-Hour Exposure
Erythema/Eschar
Formation
Immediately
1 Hour
24 Hours
48 Hours
72 Hours
7 Days
14 Days
0
0
2
2
2
0D 0D
2
2
2Br
2BrLe
2BrLe
0D 0D
Oedema Formation Immediately
1 Hour
24 Hours
48 Hours
72 Hours
7 Days
14 Days
0
0
1
1
1
0
0
1
1
1
1
1
0
0
D= Slight desquamation, Br = Light brown discoloration of the epimermis, Le = Loss of skin elasticity      

 Individual Skin Reactions Following 4-Hour Exposure       
Skin Reaction Observation Time (following patch removal) Individual Scores- Rabbit Number and Sex Total
69775 Male 69835 Male 70023 Male
Erythema/Eschar
Formation
Immediately
1 Hour
24 Hours
48 Hours
72 Hours
7 Days
14 Days
2
2
2BrLe
2BrLe
2BrLelf
?eCf
OD
0
0
2
2
2
OD
-
0
0
2
2
2
OD
-
( 2 )
( 2)
6
( 6 )
6
( 0-4)
 ( 0 )
Oedema
Formation
Immediately
1 Hour
24 Hours
48 Hours
72 Hours
7 Days
14 Days
2
2
2
2
2
?od
0
0
0
1
2
2
0
-
0
0
2
1
1
0
-
( 2 )
( 2 )
5
( 5 )
5
( 0-4)
( 0 )
Sum of 24 and 72-hour Readings (S)                   22
Primary Irritation Index (S/6)                                 22/6 = 3.7
Classification                                                       MODERATE IRRITANT
( ) = total values not for calculation of primary irritation index, Lf - loss of skin flexability, Cf = crust formation, 
D = slight desquamation, ?e = adverse reactions prevented accurate evaluation of erythema, 
?od = adverse reactions prevented accurate evaluation of edema, -= observation not required 

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.
Executive summary:

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit. The method was designed to be compatible with OECD and EU commission guidelines. Test animals had 0.5 ml aliquots of stock test article applied to shorn patches of skin and covered with an occlusive dressing for 4 hours. After treatment , the test article was washed away and the animals were observed for 72 hours. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced well-defined erythema and slight oedema. Other signs of skin irritation noted were light brown discolouration of the epidermis, loss of skin flexibility and/or elasticity, crust formation and slight desquamation. The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.