Registration Dossier

Administrative data

Description of key information

- Skin: corrosive (GHS corrosive category 1B)
- Eye: highly irritating (GHS category 1 of irreversible effects to the eye)

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:
From 16 February 1987 to 27 May 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a recognised guideline and under GLP conditions. However, the purity of the test substance is not specified.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: Hybrid Albino New-Zealand
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Hybrid Albino New-Zealand
- Sex: males
- Sources: *Charles River: Saint Aubin Les Elbeuf - 76410 Cléon - France
*E.G.A.V: Saint Mars d'Egrenne - 61350 Passais La Conception - France
*E.S.D: Roman - 01400 Châtillon sur Chalaronne - France
- Age at study initiation: no data
- Weight at study initiation: 2.5 +/- 0.2 kg
- Housing: individual housing, in polystyrene cages, of internal dimensions 560x355x315 mm, with a perforated floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: 30 to 70%
- Air changes: no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: 3 March 1987 To: 17 March 1987
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Concentration: 0.5 mL undiluted
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: a surface of about 6 cm2
- % coverage: no data
- Type of wrap: a Codex hydrophilic eight layer gauze pad


REMOVAL OF TEST SUBSTANCE
- Washing: the bandages were removed and if necessary excess test substance which had not penetrated was wiped away with a gauze pad moistened with distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: based on erythema and oedema formation, according to directive OECD 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: aspect of burn on all the zone of application
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
3.34
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: see table of results
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 14 days

Erythema:

 animal

mean 24/48/72 hours 

 n°1 4.00 
 n°2 4.00
 n°3 4.00
 n°4 4.00
 n°5 4.00
 n°6 4.00
mean  4.00

After 14 days: mean = 4.00 for all animals + presence of eschars on all the zone of application

Oedema:

 animal

mean 24/48/72 hours 

 n°1 3.67 
 n°2 2.67
 n°3 3.67
 n°4 3.67
 n°5 3.00
 n°6 3.33
mean  3.34

After 14 days: mean = 0.00 for all animals

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
4-tert-butylpyrocatechol 85% in water is classified as :
- Skin corrosive category 1B according to UN/EU GHS classification criteria
Executive summary:

In a dermal irritation study (Hazleton, 1987), hybrid albino New-Zealand White rabbits (6 males) were dermally exposed to 0.5 mL of 4 -tert-butylpyrocatechol 85% in water on a 6 cm2 body surface area. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 14 days. Irritation was scored by the method of directive OECD 404.

After 1 hour of exposure, severe erythema and moderate (1/6 rabbits) or severe (5/6 rabbits) oedema were observed in all treated animals. Severe erythema was not reversible after 14 days and oedema was fully reversible within 14 days. In this study, 4 -tert-butylpyrocatechol 85% in water was corrosive to the skin based on the observed skin reactions.

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:
From 16 February 1987 to 27 May 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a recognised guideline and under GLP conditions. However, the purity of the test substance is not specified.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
other: Hybrid Albino New-Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: Hybrid Albino New-Zealand
- Sex: males
- Sources: *Charles River: Saint Aubin Les Elbeuf - 76410 Cléon - France
*E.G.A.V: Saint Mars d'Egrenne - 61350 Passais La Conception - France
*E.S.D: Roman - 01400 Châtillon sur Chalaronne - France
- Age at study initiation: no data
- Weight at study initiation: 2.5 +/- 0.2 kg
- Housing: individual housing, in polystyrene cages, of internal dimensions 560x355x315 mm, with a perforated floor
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: 30 to 70%
- Air changes: no data
- Photoperiod: 12 hrs dark / 12 hours light
Vehicle:
other: no
Controls:
yes
Amount / concentration applied:
Amount applied: 0.1 ml
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
no washing

SCORING SYSTEM: based on changes in cornea, iris, conjunctivae and chemosis, according to guideline OECD 405

TOOL USED TO ASSESS SCORE: Heine's ophthalmoscope / fluorescein

Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.51
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: see table of results
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.6
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3.6
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.6
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: see table of results
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.6
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.6
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: see table of results
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: see table of results
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible

Irritant/corrosive response data for each animal at each observation time

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

4/4/4/4/4/4

 2/2/2/2/2/2

 1/1/1/1/1/1

3/4/3/3/4/3

24 h

4/4/4/4/4/4

 2/2/2/2/2/2

 1/1/2/2/2/1

 3/3/3/4/4/3

48 h

4/4/4/4/4/4

 2/2/2/2/2/2

 2/1/2/2/1/1

 3/3/4/4/3/3

72 h

4/4/4/4/4/4

 2/2/a/2/2/2

 2/2/2/2/2/2

 4/4/4/4/4/4

Average 24h, 48h, 72h

4/4/4/4/4/4

 2/2/2/2/2/2

 1.6/1.3/2/2/1.6/1.3

 3.3/3.3/3.6/4/3.6/3.3

Reversibility*)

 n.

n. 

n. 

n. 

Average time (unit) for reversion

> 21 days 

> 21 days  

> 21 days  

> 21 days  

 

*) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

a: the degree and the surface of the corneal opacification returned the impossible interpretation.

NB: a total necrosis of the eye was observed in 2 out of the 6 rabbits examined on day 14, on day 21, a necrosis area located on a quarter of the corneal surface was noted in the 3 surviving rabbits and the absence of direct photomotor reflex was still noted in 2 of them (the 2 rabbits showing a necrosis on day 14 were sacrified after the reading and another animal was found dead on day 20).

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
4-tert-butylpyrocatechol 85% in water is classified as:
- Category 1 for irreversible effects on the eye according to UN/EU GHS classification
Executive summary:

In an eye irritation study (Hazleton, 1987), 0.1 mL 4 -tert-butylpyrocatechol 85% in water was instilled into the conjunctival sac of the right eye of hybrid Albino New-Zealand White rabbits (6 males) (no rinsing). Animals were then observed for 21 days. Ocular irritation was scored by the method of directive OECD 405.

After 1 hour of exposure, severe corneal opacity and iris lesions, moderate (4/6 rabbits) or severe (2/6 rabbits) chemosis and slight conjunctival redness were observed in all treated animals. These ocular irritation signs were not reversible after 21 days. In this study, 4 -tert-butylpyrocatechol 85% in water was highly irritating to the eye or causing irreversible effects on the eye based on the observed ocular reactions.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

4-tert-butylpyrocatechol, as a 85% solution in water, was tested for its skin and eye irritation properties in New Zealand White rabbits following dermal application or ocular conjunctival instillation during the same study (Hazleton study No. 705411).

4 -tert-butylpyrocatechol was also tested for its skin irritation properties in New Zealand White rabbits following dermal application (HRC study No. 91607D/DIC 207/SE).

Both studies were considered of reliability 2 according to Klimisch cotation criteria.

For skin irritation, of the two studies available, the first one (Hazleton, 1987) was selected as a key study, based on the higher number of animals used (6 rabbits), the longer exposure time (up to 4 hours) and the larger body surface (6 cm²) used for dermal application. The other study (HRC, 1991), using a 3 -minute application in 3 rabbits, was used as a supporting study. For eye irritation, the available study was used as a key study, of reliability 2 (Hazleton, 1987). Another data for in vivo eye irritation (reliability 2) was available from a reference handbook (1996).

All in vivo results were consistent with a risk of serious skin or eye damage:

- After three minutes of dermal exposure, necrosis with very slight oedema was evident at all treatment sites. These reactions persisted and were still visible at several sites of application on day 14. Following one hour of dermal exposure of a 85% aqueous solution, severe skin erythema and moderate to severe edema were observed (score 4). Skin erythema and edema were not reversible after 14 days of observation. Edema was fully reversible within 14 days.

- After one hour of ocular exposure to a 85% aqueous solution, severe corneal opacity and iritis, moderate to severe chemosis and slight conjunctival redness were observed. None of these findings was reversible after 21 days of observation.

The test substance was therefore classified as corrosive to the skin (or corrosive category 1B) and highly irritating to the eye (or category 1 of irreversible effects to the eye).

 


Justification for selection of skin irritation / corrosion endpoint:
The study was conducted according to a recognised guideline and under GLP conditions.

Justification for selection of eye irritation endpoint:
The study was conducted according to a recognised guideline and under GLP conditions.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the severity (necrotic findings) and absence of recovery of the changes observed in both skin and eye tissues (for up to 21 days of observation), 4-tert-butylpyrocatechol was classified as following: corrosive category 1B, H314: causes severe skin burns and eye damage and Eye damage category 1, H318: causes serious eye damage based on the criteria of UN/EU GHS.