4-(α,α-dimethylbenzyl)phenol

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

in vivo study in the rabbit. The existing in vivo data is considered to fulfil the in vitro eye irritation requirement.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-January-12 to 1998-February-2

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Examinations were not made on days 7 and 14 after application as outlined by the guideline. Alternatively examinations were conducted on days 6, 8, 10, 13, and 17. This deviation did not negatively affect the validity of the test.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-(α,α-dimethylbenzyl)phenol

EC Number:

209-968-0

EC Name:

4-(α,α-dimethylbenzyl)phenol

Cas Number:

599-64-4

Molecular formula:

C15H16O

IUPAC Name:

4-(α,α-dimethylbenzyl)phenol

Details on test material:

- Name of test material: p-Cumylphenol
- Substance type: organic
- Physical state: solid white flakes
- Analytical purity: 99%
- Impurities: <1% phenol, <1% o-Cumylphenol, <1% 2,4-di-Cumylphenol
- Storage condition of test material: under protective gas in a humidity-free environment

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Fa. Dr. Karl Thomae GmbH
- Weight at study initiation: 2.4 to 2.5 kg
- Housing: individually in cages
- Diet: fed K4 Alleindiaet for rabbits, Ssniff Special Feed GmbH (4770 Soest), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 1 °C
- Humidity: 60 ±5 %
- Air changes: 15/hour
- Photoperiod: 12 hours of light/12 hours of darkness

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount: The eyelid was lifted and 0.1 g of the test substance was applied to the conjunctival sac of the right eye. (The left eye was treated in one animal.)

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

The eyes were examined at 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days after the application.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Seventy-two hours after the application the treated eyes were rinsed with a sodium fluorescein solution to examine corneal damage and were rinsed with a warm physiological saline (sodium chloride) solution.
- Time after start of exposure: 72

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: eye lamp and fluorescein

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

41.1

Max. score:

110

Reversibility:

not reversible

Remarks on result:

other: The effects of the test substance on the eye increased over the 21 day observation period, particularly in the cornea.

Any other information on results incl. tables

Individual Irritation Scores
Corneal Assessment
	1 hour		24 hour		48 hours		72 hours		6 days		8 days		10 days		13 days		17 days		21 days
	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5	A,B	AxBx5
Animal 1	1,4	20	1,4	20	1,4	20	1,4	20	2,3	30	2,3	30	2,3	30	2,3	30	2,3	30	2,3	30
Animal 2	1,4	20	2,4	40	2,3	30	2,3	30	2,3	30	2,3	30	2,3	30	2,3	30	2,3	30	3,3	45
Animal 3	1,4	20	1,4	20	2,4	40	2,4	40	2,4	40	2,4	40	2,4	40	2,4	40	2,4	40	3,4	60
Mean		20.00		26.67		30.00		30.00		33.33		33.33		33.33		33.33		33.33		45.00
A Opacity B Area of opacity
Iris Assessment
	1 hour		24 hour		48 hours		72 hours		6 days		8 days		10 days		13 days		17 days		21 days
	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5	A	Ax5
Animal 1	0	0	1*	5	0	0	0	0	c1	5	c1	5	stc1	5	stc1	5	stc1	5	stc1	5
Animal 2	0	0	1*	5	1*	5	1*	5	xc1	5	c1	5	stc1	5	stc1	5	stc1	5	stc1	5
Animal 3	0	0	1*	5	1*	5	1*	5	xc1	5	c1		stc1	5	stc1	5	stc1	5		5
Mean		0.00		5.00		3.33		3.33		5.00		5.00		5.00		5.00		5.00		5.00
A Iris Score * Reddened x Partially reddened c Circumcorneal injection: enlargement of the ciliary and conjunctival blood vessels near the margin of the cornea with reduction in size peripherally st Strong
Conjunctiva Assessment
	1 hour		24 hour		48 hours		72 hours		6 days		8 days		10 days		13 days		17 days		21 days
	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2	A,B,C	A+B+Cx2
Animal 1	2,1,2	10	3,2,2	14	!3,1,2	12	!3,1,2	12	2,1,0	6	2,1,0	6	2,1,0	6	2,1,0	6	2,1,0	6	2,1,0	6
Animal 2	2,1,2	10	3,2,2	14	!3,2,2	14	!3,1,2	12	#3,1,0	8	3,1,2	12	2,1,0	6	2,1,0	10	2,1,2	10	2,1,0	6
Animal 3	2,1,2	10	3,2,2	14	!3,1,2	12	!3,1,2	12	#3,1,0	8	3,1,1	10	2,1,0	6	2,1,1	6	2,1,0	6	2,1,0	6
Mean		10.00		14.00		12.67		12.00		7.33		9.33		6.00		7.33		7.33		6.00
A Redness B Chemois C Discharge ! White secretions (pus) # Mucous membrane partially bloody

 

The average of the maximum values for all experimental animals is reported as X(bar) The average for all assessment time points was corresponded to the irritation index, which was compared to the following classification scheme:

0-10 not irritating

11-25 slightly irritating

26-56 moderately irritating

57-110 severely irritating

Per Annex VI of 79/831/EEC, the average scores for cornea, iris and conjunctivae at 24, 48 and 72 hour were determined.

Results according to Annex VI:

Cornea: X(bar) = 1.56

Iris: X(bar) = 0.78

Conjunctiva:

Redness: X(bar) = 3.00

Chemosis: X(bar) = 1.44

Applicant's summary and conclusion

Interpretation of results:

other: Category 1 (irreversible effects on the eye) in accordance with EU criteria

Conclusions:

Under the conditions of this study, PCP is considered to cause irreversible effects to the eye of Russian rabbits.

Executive summary:

The eye irritation potential was investigated in a study performed per OECD Test Guideline 405 under GLP conditions

Three Russian rabbits were dosed with 0.1 g of the neat test substance and the eyes were examined at 1, 24, 48 and 72 hours and 6, 8, 10, 13, 17 and 21 days after the application.

Under the conditions of this study, PCP is considered to cause irreversible effects to the eye. The effects of the test substance on the eye increased over the 21 day observation period, particularly in the cornea.