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Administrative data

Description of key information

Guaiacol is officially classified as Eye Irrit. and Skin Irrit. Category 2 (H319: Causes serious eye irritation - H315: Causes skin irritation) according to the Regulation (EC) n° 1272/2008 annex VI table 3.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The purity of the test substance was known: 99.4%. The authors argued that the in vivo data were generated in studies carried out since 1981 according to OECD Test Guideline 404 and following the principles of Good Laboratory Practice.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The heating equipment failed during the acclimatisation period, resulting in the low temperatures recorded. Temperature was typically greater than 14°C.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS:
- Source: from Gorseside Rabbits, Northchurch, Berkhamsted, Herfordshire, and delivered by road transport
- Age at study initiation: 10-12 weeks
- Weight at study initiation: approximatively 2 kg
- Housing: individually in grid bottomed metal cages
- Diet: ad libitum, a commercially available antibiotic free rabbit diet (SQC standard rabbit pellets produced by special Diets Services, Witham, Essex)
- Water: ad libitum, mains drinking water via automatic nozzles
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 17-23°C
- Humidity (%): 37-68%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h light/ 12h dark

IN-LIFE DATES: from 8th november to 15th november 1988
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
Amount applied: 0.5 ml, undiluted
Duration of treatment / exposure:
4 hour(s)
Observation period:
7 days
Number of animals:
4
Details on study design:
TEST SITE:
- Area of exposure: over a 2.5 cm square (approximately 6 square cm)
- % coverage: no data
- Type of wrap if used: "Elastoplast" elastic adhesive bandage 10 cm wide.

REMOVAL OF TEST SUBSTANCE:
- Washing: The treated site was cleansed by gentle swabbing with cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: The treated area was scored for erythema and oedema using a numerical system based on that described by Draize et al. (1944) and the primary dermal irritation index (PDII) was calculated.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.8
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual data
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.6
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Reversibility:
other: No individual data
Remarks on result:
other: No individual score
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
24/48/72 h
Score:
2.38
Irritant / corrosive response data:
The publication is old. Therefore individual scores are not available.
Other effects:
none

Remark: 

The primary irritation index (PII = PDII) = ((SUM erythema  24/48/72 hr)+ (SUM oedema 24/48/72 hr)) / (3 x Number of animals). Since no scale was 

identified in the OECD protocol, the AFNOR scale was used to interpret the results as following: PDII below 0.5, non-irritant; 0.5-3,  slightly irritant; 

3-5, moderately irritant; 5.8, severely irritant.
The numerical scores obtained were summed and a mean was calculated. When the mean value obtained for either erythema or oedema equalled 

or exceeded 2, the test substance was considered as irritant.
The scores were determmined from the numerical values given to the irritation observed at the 24, 48 and 72 hour. The corresponding PDII was  

2.38 and guaiacol was determined as "slightly irritant".

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Based on CLP criteria the substance is not classified as irritant. Only slight irritation was observed. However, erythema is not fully reversible within 7 days (observation period). Therefore in a conservative approach the substance is classified Skin. Irrit. Cat. 2, H315.
Executive summary:

In a dermal irritation study (Haynes for RIFM, 1988), four New-Zealand White female rabbits were dermally exposed to 0.5 ml of guaiacol for 4 hours to left flank (6 cm square).  Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days.  Irritation was scored by the method of Draize.
In this study, guaiacol is slightly irritating to the skin. However, erythema is not fully reversible within 7 days (observation period). Therefore in a conservative approach the substance is classified Skin. Irrit. Cat. 2, H315.

Guaiacol is officialy classified as Skin Irrit. Category 2 (H315: Causes skin irritation) according to the Regulation (EC) n° 1272/2008 annex VI table 3.

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
Study period:
from 01 jun 2006 to 16 jan 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Age and body weights of animals are not the same as those described in protocol
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: female
- Source: CEGAV breeding establishment - Les Hautes Noës, St Mars d'Egrenne, 61350 Passais la Conception (France).
- Age at study initiation: between 19 and 22 weeks old
- Weight at study initiation: between 3.9 and 4.1 kg
- Housing: individually in cages of standard size (635*435*335 mm).
- Diet: SDS/DIETEX STANRAB (P) SQC feed distruted daily at fixed time
- Water: drinking water (analysed every 6 months with a certificate), ad libitum
- Acclimation period: at least 5 days before the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 45-65%
- Air changes: 10 times per hours
- Photoperiod (hrs dark / hrs light): 12/12 (light on at 7.30 a.m.)

IN-LIFE DATES: From: 05 jun 2006 To: 26 jun 2006
Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye served as control
Amount / concentration applied:
TEST SYSTEM:
- Amount/concentration applied: 0.1 ml
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
Comment: not rinsed
- Scoring system: in accordance with the OECD guideline 405
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Reversibility:
fully reversible within: 1 hour
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 15 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.66
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.33
Reversibility:
fully reversible within: 15 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.55
Max. score:
4
Reversibility:
fully reversible within: 15 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Reversibility:
fully reversible within: 15 days
Other effects:
After instillation, all animals presented obvious swelling with partial eversion of the lids, added to a lacrimation with the moistening of the eyelids and of fur around eyelids. At this time, some blood vessels definitely hyperaemic (injected) was noted in any animals.

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

1/1/1 

 2/2/2

24 h

0/0/0

0/0/0

 2/1/2

 2/1/2

48 h

0/0/0

0/0/0

 1/1/3

1/1/4 

72 h

0/0/0

0/0/0

 0/1/2

 0/1/2

Average 24h, 48h, 72h

0/0/0 

 0/0/0

 1.66/1/2.33

 1/1/2.67

Reversibility*)

 -

-

 c (15 days)

 c (15 days)

 

*) Reversibility: c. = completely reversible.

Interpretation of results:
Category 2B (mildly irritating to eyes) based on GHS criteria
Conclusions:
Based on this test, the substance is slightly irritating and not classified according to GHS EU criteria.





Executive summary:

In a primary eye irritation study (CERB, 2006), 0.1 ml of gaiacol (99.6% of purity) was instilled into the conjunctival sac of left eye of adult New Zealand White rabbits (female). Eyes were not rinsed and the other eye served as control.
Animals then were observed for 14 days.
  Irritation was scored by the method in accordance with EU and OECD guidelines.
In this study, gaiacol is slightly irritating.

However, guaiacol is officialy classified as Eye irritation category 2 (H319: Causes serious eye irritation) according to annex VI table 3 of the Regulation (EC) n°1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

three studies performed on animals and one on human volunteers were available. Only one was performed on rabbits was considered as reliable (reliability 2 according to Klimish ranking) and was selected as a key study. In this study (Haynes, 1988), four New-Zealand White female rabbits were dermally exposed to 0.5 ml of guaiacol for 4 hours to left flank (6 cm square). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days. Irritation was scored by the method of Draize. In this study, guaiacol was slightly irritating.

Moreover, guaiacol was tested in a international prevalidation study (Fentem et al.,1998) on in vitro tests forreplacing the in vivo rabbit test  for skin corrosivity conducted during 1996 and 1997 under the auspices of European Centre for the Validation of Alternative Methods (ECVAM) (see section 7.12).

Eye irritation:

Two studies were available. Only one was considered as reliable (Reliability 1according to Klimish) and was considered as a key study.

In this study (CERB, 2006), 0.1 ml of gaiacol (99.6% of purity) was instilled into the conjunctival sac of left eye of adult New Zealand White rabbits (female). Eyes were not rinsed and the other eye served as control.
Animals then were observed for 14 days. Irritation was scored by the method in accordance with EU and OECD guidelines, and results gave "slightly irritating" and should not be classified as irritating.

Respiratory irritation:

No data available.


Justification for classification or non-classification

The available studies selected as key studies showed that guaiacol is slightly irritating for skin and eye rabbits and should not be classified for these endpoints based on the calculated scores and according to the Regulation (EC) n°1272/2008 annex I.

However, guaiacol is officially classified as Eye Irrit. and Skin Irrit. Category 2 (H319: Causes serious eye irritation - H315: Causes skin irritation) according to the Regulation (EC) n° 1272/2008 annex VI table 3.