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Administrative data

Description of key information

Skin: In a GLP study conducted in rabbits, the data, 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), did not result in the test substance being labeled as a skin irritant.

Eye: Concluding from 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 labeled as an eye irritant based on a GLP study in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
72 hours
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP study done according to OECD 405 test guideline, and having supporting documentation.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Instead of the protocolled 120 g food per day, 100 g was fed to the animals. This is not considered to have adversely affected the outcome of the study
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Animal s and husbandry
Three young adult female rabbits (approximately 7 months old) of the New
Zealand White strain were obtained from The Broekman Institute, Someren,
The Netherlands. Date of arrival at the animal house: September 18, 1985.
From that date on the animals, ear-marked 243, 244 and 245, have been
individually housed in Lurane cages with perforated floors. The
quarantine period was 12 days, the acclimation period another 5 weeks.
Their body weights were measured three days before
dose administration. They were fed standard laboratory animal diet (100
9 per day), obtained from Hope Farms, Woerden (LK-01, pellet diameter 4
mm), and had free access to tap-water. The animal room temperature was
maintained at 19 - 21'C and the relative humidity at 40-75 per cent. The
artificial light sequence was 12 hours light, 12 hours dark.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 ml
Duration of treatment / exposure:
The animals were manually restrained for dose administration. Of the
test substance 0.1 ml was instilled in the conjunctival sac of the right
eye of each animal using a syringe. The lids were then held gently
together for two seconds and released. Immediately after treatment, the
animals were transferred to their cages. The left eye, remaining
untreated, served as a control.
Observation period (in vivo):
up to 72 hours
Number of animals or in vitro replicates:
three
Details on study design:
Administration of the test substance
The animals were manually restrained for dose administration. Of the
test substance 0.1 ml was instilled in the conjunctival sac of the right
eye of each animal using a syringe. The lids were then held gently
together for two seconds and released. Immediately after treatment, the
animals were transferred to their cages. The left eye, remaining
untreated, served as a control.

Observations
Prior to dose administration, both eyes of the animals were inspected in
order to detect any eye defect. Immediately after instillation of the
test substance, the animals were observed and abnormalities were
recorded. In addition, the eyes were examined apprOXimately 1, 24, 48
and 72 hours after instillation of the test substance.

Grading of the ocular lesions
The following scoring system was used for grading of the ocular lesions:
CORNEA:
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity ....................................... 0
Scattered or diffuse areas of opacity
(other than slight dulling of normal lustre),
details of iris clearly visible ................................ 1
Easily discernible translucent areas, details
of iris sl ightly obscured ...................................... 2
Nacreous areas, no details of iris visible, size of
pupil barely discernible ....................................... 3
Opaque cornea, iris not discernible through the opacity ........ 4
IRIS:
Normal ......................................................... 0
Markedly deepened rugae, congestion, swelling,
moderate circumcorneal hyperaemia or injection, any of these
or any combination thereof, iris still reacting to light
(sluggish reaction is positive) ................................. 1
No reaction to light, haemorrhage, gross destruction
(any or all of these) ........................................... 2
CONJ UNCT I V AE:
Redness: (refers to palpebral and bulbar conjunctivae,
excluding cornea and iris).
Blood vessels normal ........................................... 0
Some blood vessels definitely hyperaemic or injected ........... 1
Diffuse, crimson colour, individual vessels not
easily discernible ............................................. 2
Di ffuse beefy red .............................................. 3
Chemosis: lids and/or nictating membranes
No swell i ng .................................................... a
Any swelling above normal (includes nictating membranes) ....... 1
Obvious swelling with partial eversion of lids ...••............ 2
Swelling with lids about half closed ........................... 3
Swelling with lids more than half closed ....................... 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) .
3.4.2 Fluorescein treatment
Approximately twenty-four hours after instill ation of the test substance
(immediately after scoring the corneal opacity and alterations of iris and
conjunctivae), a solution of 2% fluorescein in water (pH adjusted to 7.0)
was applied to both eyes of each animal to examine quantitatively the
potential for corneal injury. The brightly green staining area indicating
epithelial damage was estimated as a percentage of the total corneal area.
Any observed local effects other than those indicated above were recorded.
Irritation parameter:
overall irritation score
Basis:
other: all 3 animals
Time point:
other: 72 hrs
Score:
ca. 1
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: non-irritating to eye
Irritant / corrosive response data:
No effects on the cornea and the iris were observed in any
of the rabbits. Slight conjunctival redness (score 1) was seen for all
animals one hour after instillation, however, this had totally disappeared
24 nours after instillation for animal 245, 48 hours after instillation for
animal 244 and 72 hour after instillation for animal 243. Sl ight
conjunctival swelling (score 1), seen in all three animals one hour after
instillation, had totally disappeared 24 hours after instillation.
Treatment of the eyes with fl uorescein 24 hours after instillation of the
test substance did not reveal any epithelial damage. Slight lacrimation was
observed one hour after instillation for animals 243 and 244. In addition,
animal 243 repeatedly closed its eyes fully or partly during observations
one and 24 hours after instillation. 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 an
irritant to the eyes.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
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 an irritant to the eyes.
Executive summary:

A sample of tert. amylperoxy-2-ethylhexylcarbonate was tested in the rabbit acute eye irritation/corrosion test to determine its possible irritating effects. Of the test substance 0.1 ml was instilled into one of the eyes of three adult female New Zealand White rabbits. Slight conjunctival redness was observed in all three animals one hour after instillation, which however had totally disappeared 72 hours thereafter. Slight conjunctival swelling in all three animals was only seen one hour after instillation. No effects on the cornea and the iris were observed in any of the rabbits. Concluding from 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 an eye irritant.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:

An apparently well conducted GLP study.

Justification for selection of eye irritation endpoint:

An apparently well conducted GLP study.

Justification for classification or non-classification

The in vivo test results from the skin and eye irritation studies were negative. The data are conclusive, and not sufficient for clasification.