2-(1,1-dimethylpropyl)phenol

Endpoint summary

Description of key information

One acute dermal irriation study: Safepharm 1992
Two acute dermal irritation studies on a read across substance: Safepharm 1991 and Hazleton 1981 
One eye irritation study on a read across substance: Hazleton 1981

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:

07-07-1992 to 23-07-1992

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: 12-16 weeks
- Weight at study initiation: 2.77 - 3.18 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): 19 - 23°C
- Humidity (%): 53 - 68%.
- 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 and 3 minutes

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:
Moderate to severe erythema and severe oedema were noted at all treated skin sites one hour after patch removal. Evaluation of the erythema and oedema was not possible at the 72-hour and 7 day observations due to the presence of other adverse dermal reactions. These were haemorrhage of the dermal capillaries, brown discolouration of the epidermis (possible necrosis), loss of skin elasticity and flexibility, thickening of the skin, reduced re-growth of fur and scabbing. Well-defined or moderate erythema occasionally surrounded the scabs, with oedema occasionally extending beyond the sites of application during the study. These reactions were considered to be indicative of corrosion.

3 minute exposure:
Well-defined erythema and slight to moderate oedema were noted at all treated skin sites one hour after patch removal. Well-defined erythema and and slight to severe oedema at 24, 48 and 72 hour observations. Other adverse dermal reactions noted at one treated skin site at the 72-hour observation were loss of skin elasticity and flexibility and thickening of the skin. The reaction extended beyond this treated skin site at the 24 to 72-hour observations. Crust formation or desquamation was noted at all treated skin sites seven days after treatment.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

o-tert amylphenol is corrosive when applied as a neat liquid to the clipped dorsal skin of New Zealand white rabbits, for 4 hours or 3 minutes.

Executive summary:

In an OECD guideline study, o-tert amylphenol 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:

2 (reliable with restrictions)

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 an acute dermal irritation study performed to OECD guidelines, o-tert-amylphenol was considered corrosive to skin when 0.5 ml was applied for 4 hours or 3 minutes. In addtion, two acute dermal irritation studies, performed to OECD guidelines, on the read across substance, 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.

There are no eye irritation studies available for o-tert-amylphenol. However, in an eye irritation study performed to an internationally accepted guideline, the read across substance o-tert butylphenol 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 2) conducted on read across substance

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Corrosive to skin

Corrosive to the eye