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Toxicological information

Eye irritation

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Administrative data

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.

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 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)

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 / tissue source

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.

Test system

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.

Results and discussion

In vivo

Results
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.

Applicant's summary and conclusion

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.