4-(α,α-dimethylbenzyl)phenol

Endpoint summary

Description of key information

In a skin irritation study performed per OECD Test Guideline 404 and EPA OPPTS 870.2500 the substance was non-irritating in the rabbit. 
In an eye irritation study performed per OECD Test Guideline 405 the substance caused irreversible cornea, iris and conjunctival effects on the eye in the rabbit. 

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted per OECD Test Guideline 404 and EPA OPPTS 870.2500 following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA 40 CFR, Part 792 and OCED GLPs, 1996

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits, at least 10 weeks of age, weighing 2.15 to 2.21 kg were obtained from Millbrook Breeding Labs. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages with hardwood chip bedding. They were provided rabbit diet and tap water ad libitum. Room temperature was 68+/-5 degrees F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Three rabbits were dosed with 0.5 g of PCP on a small area, approximately 6 cm², of skin on the shaved trunk. A gauze patch was placed over the area and secured with non-irritating tape.

Duration of treatment / exposure:

The exposure time was four hours.

Observation period:

Dermal scores were recorded at 1, 24, 48 and 72 hours after the end of the contact period. Daily clinical observations included all toxicologic and pharmacologic signs.

Number of animals:

Three

Irritation parameter:

other: erythema and edmea score

Basis:

mean

Time point:

other: all

Score:

0

Max. score:

8

Remarks on result:

other: No erythema or edema observed

Irritant / corrosive response data:

No erythema/edema was observed for any animal at any time period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, PCP is considered to be a non-irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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:

1988-January-12 to 1998-February-2

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted according to OECD method 405

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

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 - 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 degrees C
- Humidity: 60% ±5%
- Air changes: 15/hour
- Photoperiod: 12 hours light/12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye of each animal served as control

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

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.

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

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential was investigated in a study performed per OECD Test Guideline 404 and EPA OPPTS 870.2500 under GLP conditions (Toxikon Corporation, 2002).

Three New Zealand White rabbits were dosed with 0.5 g of the neat test substance under semi-occlusive conditions for 4 hours.

Under the conditions of this study, PCP is considered to be a non-irritant.

 

Eye irritation

The key study was conducted according to OECD method 405 (Hüls, 1988).

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.

 

The supporting study was conducted per OECD 405 and EPA OPPTS 870.2400 under GLP conditions (Toxikon Corporation, 2002).

Three New Zealand White rabbits were dosed with 0.1 mL of PCP per eye. Eye irritation scores were recorded at 1, 24, 48 and 72 hours post-dose. Following the 24-hour observation, the treated eyes were rinsed.

Under the conditions of this study, PCP is considered to be a non-irritant to rabbit eyes.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Two studies are available. The study which resulted in classification was selected as key.

Effects on eye irritation: corrosive

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin irritation.

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does require classification with respect to eye irritation as Category 1 (H318: Causes serious eye damage).