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Administrative data

Description of key information

Two acute dermal irritation studies:  Tufnell 1991 study and  Taupin 1981 study. 
One eye irritation study: Taupin 1981 study

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09-01-1991 to 12-02-1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline 404 study, performed to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 2.33 - 2.57 kg
- Housing: individually housed in suspended metal cages
- Diet (ad libitum): Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol
- Mains drinking Water (ad libitum):
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 21°C
- Humidity (%): 45 - 61%.
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 ml neat liquid applied under a 2.5 x 2.5 cm gauze semiocclusive dressing.
Duration of treatment / exposure:
4 hours or
3 mins
Observation period:
Approximately one hour following removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary
irritation and scored according to the Draize method.
Number of animals:
n=3 rabbits (4 hour exposure)
n=3 rabbits (3 minutes exposure)
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm

- Type of wrap if used: gauze patch secured in position with a strip of surgical adhesive tape (BLENOERM: approximate size 2.5 cm x 4.0 cm), the trunk of each
rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether
Irritation parameter:
erythema score
Time point:
other: 4 hours
Remarks on result:
other: Erythema could not be scored due to corrosive burns on the site of application
Irritation parameter:
erythema score
Time point:
other: 3 minutes
Remarks on result:
other: The material was corrosive
Irritant / corrosive response data:
4-Hour Exposure Period
Severe erythema, haemorrhage of the dermal capillaries and oedema were noted at all treated skin sites one hour after patch removal. Evaluation
of the erythema and oedema was not possible at the 24, 48, 72-hour and 7 day observations due to the presence of other adverse dermal
reactions. These were blanching, hardened dark brown/blackcoloured or undulating scabs and dried blood. Well-defined erythema
surrounded the scabs, with erythema extending up to 8cm beyond the sites of application during the study. These reactions were considered
to be indicative of corrosion.

3 minutes exposure:
Well-defined or moderate to severe erythema was noted at all treated skin sites one and 24-hours after patch removal and at two treated skin sites at the 48-hour observation. Well-defined erythema continued to be noted at one treated skin site at the 72-hour observation.
Moderate to severe oedema was noted at all treated skin sites one and 24 hours after patch removal. Moderate oedema was noted at
two treatment sites at the 48-hour observation. Slight oedema was noted at one treatment site at the 72-hour observation. The reaction
extended up to 5 cm beyond the treatment sites of all animals during the study.
Evaluation of the erythema and oedema was not possible at one treatment site at the 48-hour observation, at two treatment sites at the
72-hour observation and at all treatment sites at the 7-day observation due to other adverse brown/black-coloured scabs,
dermis, thickening of the surrounding the scabs, crust reactions. These included hardened dark light brown discolouration of the episkin,
moderate or well-defined erythema formation, hardened light brown-coloured scabs, reduced regrowth of fur, desquamation, glossy skin and small
superficial scattered scabs.
Interpretation of results:
Category 1B (corrosive)
Conclusions:
o-tert butyl phenol is corrosive when applied as a neat liquid to the clipped dorsal skin of New Zealand white rabbits, for 4 hours or 3 mins.
Executive summary:

In an OECD guideline study, o-tert butyl phenol is corrosive when applied as 0.5ml of a neat liquid to the clipped dorsal skin of New Zealand white rabbits (area 2.5 x 2.5cm), for both 4 hours or 3 minutes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September and October 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to internationally accepted testing guideline, well documented
Qualifier:
according to guideline
Guideline:
other: Guideline, USA Interagency Regulatory Liaison Group (IRLG, January 1981)
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: H. Fortkamp, Lengerich, Germany
- Age at study initiation: 11-17 weeks
- Weight at study initiation: 2.52-2.87 kg
- Housing: conventional, singly in stainless steel cages
- Diet (e.g. ad libitum): K complete feed for rabbits ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
Administration of the undiluted test substance as obtained, pH of test substance was determined as pH 5 (litmuspaper). During exposure the second animal showed severe pain, both eyes of the following 4 animals were therefore treated with a local anaesthetic ("Ophtaine", 0.5 % Proxymetacaine hydrochloride solution) several minutes before the application.
Observation period (in vivo):
2 hours, and 1, 2, 3, 4 and 7 days after application
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not rinsed

SCORING SYSTEM: modified Draize scoring system ("The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", 1959, The Association of Food and Drug Officials of the U.S.)

TOOL USED TO ASSESS SCORE: not mentioned
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
93
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: iris score of days 1 and 7 not accounted
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: 3.00
- Iris: could not be evaluated on days 1 and 7 due to the severe chemosis
- Conjuntivae (Redness): 2.56
- Conjuntivae (Chemosis): 3.78
Other effects:
2 hours after treatment all animals showed redness of conjuctivae (1-3), evident chemosis (3-4) and excessive discharge. 4/6 animals showed opaque corneas. Due to the severe chemosis the cornea could not be evaluated at 2 animals and the iris could not be evaluated at all animals. Increased chemosis was seen at the following examinations, the conjuctivae were fleshy red. One animal had a conjunctival bleeding at day 3 and 4. After 7 days chemosis slighty decreased. At the beginning of the observation period the discharge was clear and liquid, later on it was more viscous and of a yellowish creamy consistence. The animals where the iris could be evaluated showed a sluggish reaction to light up to hemorrhage of the iris.
All animals showed cornea pannus after 7 days, additionally 2 animals showed damage of the corneal epithelium.

Table #: Mean irritant/corrosive response data for each animal at each observation time of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Overall

Max. score: 80

mean

Max. score: 10

mean

Max. score: 20

mean

Max. score: 110

2 h

40

0 *

16.33

56.33

1 d

60

0 *

13.66

73.66

2 d

60

9.16

17.33

86.50

3 d

60

5.83

18.33

84.16

4 d

60

7.50

18.66

86.16

7 d

 76.60

 0 *

16.33

93.00 **

 * = could not be evaluated; ** = iris score of days 1 and 7 not accounted

 

Interpretation of results:
Category 1 (irreversible effects on the eye)
Conclusions:
All animals showed cornea pannus after 7 days, additionally 2 animals showed damage of the corneal epithelium.
Executive summary:

In an acute eye irritation study according to USA Interagency Regulatory Liaison Group (IRLG, January 1981) Guideline, 0.1 ml of o-tert.-Butylphenol was instilled into the left eye of six male albino rabbits (New Zealand White strain). Eyes were not washed afterwards. Animals then were observed after 2 hours as well as after 1, 2, 3, 4, and 7 days. Irritation was scored by the method Draize (modified) and Kay & Calandra.

Under the experimental conditions employed, all animals showed cornea pannus after 7 days, additionally 2 animals showed damage of the corneal epithelium. Therefore, the test substance is considered to causes serious eye damage.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In two acute dermal irritation studies, performed to OECD guidelines, o-tert butyl phenol was corrosive to skin, when applied undiluted for 4 hours or 3 minutes to (n= 3 male, n-=3 female) New Zealand White rabbits.

In an eye irritation study performed to an internationally accepted guideline, o-tert butyl was corrosive to the eye in New Zealand white rabbits.


Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, performed to GLP and well documented

Justification for selection of eye irritation endpoint:
single study (Klimisch 1)

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Corrosive to skin

Corrosive to the eye