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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
Study period:
10 days
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP study done according to OECD 404 test guideline, and having supporting documentation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
Chemical name (IUPAC) : Carbonoperoxoic acid, OO-(1,1-dimethylpropyl), O-(2-ethylhexyl)ester
Trade name/code: Tert. amylperoxy-2-ethylhexylcarbonate
- Batch no. 850213/14/18
- Purity: 93.8%; major impurities: 2-ethylhexanol, tert. amylalcohol and di tert. amyl peroxide
- Specific gravity: 925 kg/m3 (20°C)
- Solubility: 10% (W/W) in DMSO at 20'C
- Stabllity: Stable for more than a year at 4°C; recovery from saturated sol utions in DMSO at 20° 95% after 7 days
- Appearance: Colourless, clear liquid
- Storage: At 4°C in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three adult female rabbits (approximately 3 months old) of the New
Zealand White strain, SPF-quality, were obtained from The Broekman
Institute, Someren, The Netherlands.
Date of arrival at the animal house: December 9, 1985.
The animals, marked with ear label nos. 249, 250 and 255, were
individually housed in metal cages with perforated floors. A combined
quarantine/acclimatisation period of 7 days was observed. The body
weights of the animals were measured one day before
dose administration. They were fed standard laboratory animal diet (100
g per day), obtained from Hope Farms, Woerden (LK-OI, pellet diameter 4
mm), and had free access to tap-water. The animal room temperature was
19 - 20°C and the relative humidity 35-80 per cent. The artificial
light sequence was 12 hours light, 12 hours dark. One day before dose
administration, the fur was removed from the central back of the
animals by clipping, exposing an area of the skin of approximately 10
cm x 10 cm. In addition, due to rapid hair growth animal no. 255 was
clipped a second time on day 10.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hrs
Observation period:
72 hours initial ... extended to 10 days
Number of animals:
three
Details on study design:
For each animal the test substance was dosed as such.

Administration of the test substance
Of the test substance 0.5 ml was applied to a 6 cm2 gauze patch, which
was attached with a drop of petrolatum to aluminium foil and mounted on
permeable tape (Micropore ,3M, St. Paul. USA). This was applied to the
right flank of each animal, the left flank being covered with the same
dressing without test substance. Finally, the animals were wrapped in
flexible bandage (Caban, 3M, St. Paul, USA). Exposure duration was 4
hours after which period the remaining test substance was removed,
using a tissue moistened with tap-water.

Observations
The exposed skin areas were examined for signs of erythema and oedema
and the responses were scored at 60 minutes, and approximately 24, 48
and 72 hours after removal of the dreSSing. For reference the control
site on the contralateral flank was used.


Grading of the skin irritation
The following scoring system was used for grading the skin irritation:
Erythema and eschar formation
No erythema ............•....•..........................•.... 0
Very sl ight erythema (barely perceptible). .......•.......... 1
Well-defined erythema .•....•.•••..•..•.......•..•.•........• 2
Moderate to severe erythema .•.....•.•.........•......•...••• 3
Severe erythema (beet redness) to eschar formation
(injuries in depth) ..•••..•.• , ...•••.•...•..•.••..•..•••...• 4
Oedema formation
No oedema .••.•.••......•..•..••....•..•.•••..•..•.•........• 0
Very sl ight oedema (barely perceptible) •.••..........•...•.. 1
Slight oedema (edges of area well defined by
definite raising) .•••.•....•••..•••..••..•.. , ..•.•...••...•• 2
Moderate oedema (raised approximately 1 millimetre) ..•..•..• 3
Severe oedema (ra ised more than 1 mill imetre and
extending beyond area of exposure) •.•......•••..•..••.•..... 4
The test results were evaluated according to the EEC criteria for
classification and labelling of dangerous substances (Annex VI of the EEC
Council Directive 67/548/EEC as amended by Directive 83/467/EEC: Labelling
Guide).

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
other: all 3 animals
Time point:
other: 72 hrs
Score:
< 1
Max. score:
1
Reversibility:
fully reversible within: 10 days
Irritant / corrosive response data:
For all three
animals, very slight oedema was observed one hour after bandage removal.
This was reversible since 24 hours after exposure no more oedema was
observed. Very slight or well-defined erythema was seen in all three animals
one hour after exposure but gradually disappeared in two animals 48 hours
after exposure. For these two animals, designated 249 and 250, no erythema
and very sl ight erythema, respectively, was observed 24 hours after
exposure. In addition, eschar formation was observed 72 hours after
exposure, indicating rapid recovery. The third animal, designated 255,
revealed well-defined erythema 24 hours after exposure and very slight
erythema 48 and 72 hours after exposure. Since this was persistent, the
study was prolonged and on day 10 all animals were examined. No
abnormalities were observed indicating rapid recovery and total
reversibility. Concluding from these experimental results and applying the
EEC criteria for classification and labelling of dangerous substances (Annex
VI of Directive 67/548/EEC as amended by Directive 83/467/EEC: Labelling
GUide), the test substance need not be labelled as a skin irritant.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Per EEC criteria for classification and labelling of dangerous substances (Annex VI of Directive 67/548/EEC as amended by Directive 83/467/EEC: Labelling GUide), the test substance need not be labelled as a skin irritant.
Executive summary:

A sample of tert. amyl peroxy-2-ethyl hexyl carbonate was tested in the rabbit primary skin irritation/corrosion test to determine its possible irritating or corrosive effects. The flank skin of 3 female rabbits of the New Zealand White strain was exposed to the test substance for 4 hours using semi-occlusive dressing. For all three animal s, very sl ight oedema was observed one hour after bandage removal; this was reversible since 24 hours after exposure no more oedema was observed. Very slight or well-defined erythema was seen in all three animals one hour after exposure but gradually disappeared in two animals 48 hours after exposure. The third animal revealed very slight erythema 48 and 72 hours after exposure, however, showed total recovery 10 days after exposure. The primary skin irritation Index amounted to 0.7. According to the criteria laid down in Annex VI of the EEC Council Directive 67/548/EEC as amended by Directive 83/467/EEC (Labelling Guide), the test substance need not be labelled as a skin irritant.