2-tert-butylhydroquinone

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of test chemical was assessed in various experimental studies conducted on rabbits and guinea pigs for test and its structurally similar read across chemical. The predicted data using Danish QSAR database has also been compared with the experimental data. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is able to cause skin irritation and thus considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

 

Eye irritation

An ocular irritation potential of target chemical was assessed in various experimental studies conducted on rabbits for test and its structurally similar read across chemical. Based on the available data for the key and supporting studies, it can be concluded that the test chemical is able to cause eye damage and thus can be considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

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:

guideline study

Justification for type of information:

Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation study was condcuted to determine the skin irritation potential of test chemical.

GLP compliance:

not specified

Species:

guinea pig

Strain:

not specified

Type of coverage:

other: rubber dam cuff

Preparation of test site:

not specified

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

0.25-1.00 g/kg

Duration of treatment / exposure:

48 hrs

Observation period:

2 weeks

Number of animals:

Not specified

Details on study design:

Not specified

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 hr and 48 hrs

Reversibility:

no data

Remarks on result:

other: Dose : 0.25 - 1.0 g/kg, moderate skin irritant

Irritant / corrosive response data:

No escars or scarring were present at 2 weeks , superficial necrosis occurred during the period of exposure . No evidence of percutaneous absorption.

SUMMARY
DOSE	MAXIMUM EFFECT			WEIGHT CHANGE
g/Kg	SKIN 24/48 Hrs	SKIN 2 WEEKS	SYSTEMIC	1 WEEK	2WEEK
0.25	Mod ery/edema	Normal		+32	+67
0.50	Slt necrosis	Normal		+2	+33
1.00	Mod necrosis	Normal		+16	+43
1.00	Slt necrosis	Normal		+17	+59
1.00	Slt necrosis	Normal		-4	+47

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The test substance when applied at 0.25-1.0 g/kg concentration to guinea pig skin showed moderate irritation . Hence the test chemical was considered as irritating to the skin.

Executive summary:

The skin irritation study was conducted on guinea pigs to assess the skin irritation potential of test chemical.

The test chemical was applied on each guinea pig at concentration of 0.25-1.0 g/kg by using rubber dam cuff.

Although no escars or scarring were present at 2 weeks, superficial necrosis occurred during the period of exposure. No evidence of percutaneous absorption.

Thus the test chemical can be considered as moderately irritating to the skin of treated guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental study reports

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

An eye irritation study was conducted to determine the eye irritating effects caused by the chemical.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

14 days

Observation period (in vivo):

1 hr,24 hr,48 hr,7 days and 14 days

Number of animals or in vitro replicates:

3

Irritation parameter:

other: Hair around eye disc red

Basis:

mean

Time point:

other: 1 hr

Score:

3

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: Slight irritation observed for unwashed eye

Irritation parameter:

other: cornea appears dry,possible area of necrosis ~ 4mm diameter on conjunctiva

Basis:

mean

Time point:

other: 1 hr

Score:

1

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: for unwashed eye

Irritation parameter:

other: watery discharge

Basis:

mean

Time point:

other: 1 hr

Score:

1

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: showed slight irritation for unwashed and washed eye.

Irritation parameter:

other: purulent discharge

Basis:

mean

Time point:

other: 24 hrs. and 48 hrs.

Score:

2

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: slight irritation observed ; unwashed eye

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 7 days and 14 days

Score:

1

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: for unwashed eye

Irritant / corrosive response data:

Residual corneal damage and notched lids present at 14 days.

Summary	3 Unwashed
	Immed	1Hr	24 Hr	48Hr	Day 7	Day 14
Initial	Slight
Conjuctiva		Mod	Strong	Mod	Slight
Lids		Slight	Slight	Slight	Slight
Nict. Membrane		Slight	Mod	Slight
Corneal capacity			Mod	Mod	Slight	Slight
Iris
Adnexa stain			3/3
Corneal stain			3/3
Number normal	0/3	0/3*	0/3**	0/3***	2/3	2/3

Remarks:

* 1hr. – hair around eye disc red – 3/3 slight.

Cornea appears dry, possible area of necrosis ~4mmdiameter on conjuctive -1/3.

Water discharge – 1/3 slight.

 

** 24 hr. – purulent dischg – 2/3 slight.

*** 48hr. – purulent dischg – 2/3 slight.

7 days – pannus, lids notched – 1/3.

14 hays – pannus, lids notched - /3.

3 Washed
Immed	1Hr	24Hr	48Hr	Day 7	Day 14
	Slight	Slight
		Slight
	Slight	Slight	Slight
		2/3
		0/3
3/3	1/3*	1/3	2/3	3/3	3/3

Remarks:

*1 hr – watery dischg – 1/3.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test substance when applied at 1.0 ml concentration to rabbit eye showed moderate to strong eye irritation.

Executive summary:

The eye irritation study was conducted to determine the adverse eye effects caused by the chemicals.

About 0.1 ml of undiluted test chemical was instilled into the eyes of each rabbit and the eyes were scored at 1 hr,24 hr,48 hr,7 days and 14 days.

The test chemical caused moderate to strong eye irritation, residual corneal damage and notched lid at 14 days. Thus the chemical can be considered as irritating to the eyes of treated rabbits.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Various studieshas been investigated for the test chemical to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in-vivo experiments conducted for target chemicaland its structurally similar read across substance on guinea pigs and rabbits.The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below;

 

The skin irritation study was conducted on guinea pigs to assess the skin irritation potential of test chemical. The test chemical was applied on each guinea pig at concentration of 0.25-1.0 g/kg by using rubber dam cuff. Although no escars or scarring were present at 2 weeks, superficial necrosis occurred during the period of exposure. No evidence of percutaneous absorption. Thus the test chemical can be considered as moderately irritating to the skin of treated guinea pigs.

 

In the next dermal irritation study, the test chemical was applied at 1.0 g/kg concentration to guinea pig skin. Slight edema, staining and blister like spots. Scattered light eschars, sparse hair and some erythema at 1 wk. Light scars at 2 wks. Since the test chemical can cause skin irritation, it was considered as skin irritating to the skin.

 

Another skin irritation study was conducted on five guinea pigs to assess the skin irritation potential of test chemical. About 50 % of test chemical was applied on each guinea pig with total nine application for 11 days. The test chemical caused slight erythema, moderate eschar and strong staining. Hence the test chemical can be considered as irritating to the skin.

 

According to Danish QSAR database, skin irritating effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, known skin irritating effects were observed when test chemical was exposed to rabbits’ skin. Hence, the test chemical can be considered as skin irritant.

 

The above results were further supported by a dermal irritation study conducted on New Zealand white rabbits in accordance with OECD 404 to assess the irritation parameter of the test chemical. In the initial test one healthy rabbit of body weight 2.00 kg was selected for the study after acclimatization. The test compound in the amount of 0.5 gm was applied at the different sites on the shaven back skin of animal. The hairs of back sides were removed (approximately 6 cm2) one day earlier before the treatment. The test substance in the amount of 0.5 gm was applied to a small area (approximately 6 cm2) of skin and covered with a gauze patch, which was held in place with non-irritating tape. The first patch was applied on the shaven back skin of rabbit and removed after three minutes. No serious reaction was observed at the site of application. The second patch was applied on the different shaven back side and removed after one hour. There were no signs of skin reaction observed at this site of application. Finally, a third patch was applied at a different site and was removed after four hour. Slight redness was observed at the site of application of test compound after four hour patch removal. This condition was recovered after 24 hours. Finally, the animal was observed for 14 days, for any irritation and corrosion. Because no corrosive effect observed in the initial test, a confirmatory test was done in order to confirm the irritant or negative response of the test substance by using two additional animals. In the confirmatory test the test compound in the amount of 0.5 gm was applied on the shaven back skin of two animals, each with one patch, for an exposure period of four hours. After four hours the patch was removed and the skin reactions were graded according to Draize’s method. The test compound produced slightly redness after four hour patch removal upto 24 hours. There were no other clinical signs and symptoms recorded during the entire observation period. The dermal irritation index of the test chemical in New Zealand white rabbits was calculated as 0.42 and test compound can be classified under "Slight irritant ".

 

Based on the available data for key and supporting studies, it can be concluded that test chemical is able to cause skin irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

 

Eye irritation:

In different studies, the test chemical has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits for target chemical that have been summarized as below;

 

 

The eye irritation study was conducted to determine the adverse eye effects caused by the chemicals. About 0.1 ml of undiluted test chemical was instilled into the eyes of each rabbit and the eyes were scored at 1 hr,24 hr,48 hr,7 days and 14 days. The test chemical caused moderate to strong eye irritation, residual corneal damage and notched lid at 14 days. Thus the chemical can be considered as irritating to the eyes of treated rabbits.

 

In next ocular study, the instillation of 10 mg of the test substance entailed strong conjunctivitis, iritis and moderate corneal turbidity that nearly subsided only after 21 days. When the eye was rinsed following treatment, the injuries subsided with 14 days. Although the effects were subsided but on the basis of observed effects the test chemical can be considered as irritating to the eyes. 

 

Another eye irritation study was conducted on rabbits to determine its eye irritation potential. When 0.1 ml of test chemical was instilled into the eyes of rabbits, it triggered moderate irritation in rabbit’s eye. Hence the test chemical was considered as irritating to the eyes of treated rabbits.

 

The above results were further supported by the eye-irritating ability of a face powder containing 0.2 percent test chemical was studied in six albino New Zealand rabbits. The test material was instilled into one eye of each animal in a single 0.1 ml dose; the untreated eye of each rabbit served as control. Average eye irritation scores 24 and 48 hours following exposure to the face powder were 2 and 0, respectively (the maximum possible score per observation was 110). The author concluded the test chemical as minimal irritating to the eye of treated albino rabbits.

 

Based on the available data for key and supporting studies, it can be concluded that test chemical is able to cause eye irritation and considered as irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Category 2”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemical were observed in various studies. The results obtained from these studies indicates that the chemical is able to cause skin and eye irritation. Hence the test chemical can be classified under the category “Category 2” for skin and eye as per CLP.