Registration Dossier

Administrative data

Description of key information

Skin Irritation:

Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data on skin irritation of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is classified for Skin corrosion (Cat. 1B, H314) as a worst case.

WoE - o-cresol (RL2; no guideline, no GLP; rabbit): corrosive

WoE - p-cresol (RL2; no guideline, no GLP; rabbit): irritating

WoE - m-cresol (RL2; no guideline, no GLP; rabbit): irritating

WoE - 2,4-xylenol (RL4; no guideline, no GLP; rat): corrosive

WoE - 2,6-xylenol (RL4; no guideline, no GLP; rat): corrosive

WoE - 3,5-xylenol (RL2; no guideline; no GLP; rabbit): not irritating

Eye Irritation:

Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data on eye irritation of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is classified for Eye Dam. 1 (H318) as a worst case.

WoE - o-cresol. (RL2; no guideline; no GLP; rabbit): highly irritating

WoE - p-cresol. (RL2; no guideline; no GLP; rabbit): highly irritating

WoE - m-cresol. (RL2; no guideline; no GLP; rabbit): highly irritating

WoE - 3,5-xylenol (RL2; CFR/USA 1500.42; no GLP; rabbit): severely irritating

Respiratory irritation:

No data identified

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: sufficient information for evaluation
Qualifier:
no guideline followed
Principles of method if other than guideline:
application of the undiluted substance on shaved intact or abraded skin areas, coverage not mentioned, reading 24, 48, 72 hours
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
no further information
Type of coverage:
not specified
Preparation of test site:
other: shaved : intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
no data
Observation period:
72 hours
Number of animals:
6
Details on study design:
evaluation of erythema and edema
Irritation parameter:
erythema score
Basis:
other: mean score of each animals
Time point:
other: abraded and intact skin: after 72 hours
Score:
ca. 4
Max. score:
4
Reversibility:
not specified
Irritation parameter:
edema score
Basis:
other: mean score of each animal
Time point:
other: abraded and intact skin: after 72 hours
Score:
ca. 4
Max. score:
4
Reversibility:
not specified
Irritation parameter:
overall irritation score
Basis:
other: mean value overall animals
Time point:
other: abraded and intact skin: after 72 hours
Score:
ca. 8
Max. score:
8
Reversibility:
not specified
Irritant / corrosive response data:
no further information
Other effects:
no further information
intact and abraded skin:
total irritation score: 8.00/8.00
Interpretation of results:
other: corrosive (worst case estimation as corrosion could not be excluded)
Conclusions:
Application of 0.5 mL undiluted substance on shaved intact or abraded rabbit skin areas, coverage not mentioned, and reading 24, 48, 72 hours post application yielded mean irritation score 8 of max 8. Reversibility is not reported (Industrial Biotest Laboratories 1969).
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information about strain used and on exposure time, no information on GLP
Qualifier:
no guideline followed
Principles of method if other than guideline:
0.5 mL undiluted TS was applied to the intact and abraded skin, time of observation: 24 and 72 hrs.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
no further data
Type of coverage:
not specified
Preparation of test site:
other: shaved intact skin or shaved and abraded skin
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 mL undiluted
Duration of treatment / exposure:
no data
Observation period:
up to 72 hours
Number of animals:
6 rabbits intact skin and 6 rabbits abraded skin
Details on study design:
reading for erythema and edema
Irritation parameter:
erythema score
Remarks:
(intact skin)
Basis:
mean
Remarks:
(animal 1 - 6)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: No scores for 48 h given. Calculations of the mean for 24, 48 and 72 h done with a worst case estimation of a score of 4 for 48 h (as for 24 and 72 h) for each animal.
Irritation parameter:
edema score
Remarks:
(intact skin)
Basis:
mean
Remarks:
(animal 1 - 6)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: No scores for 48 h given. Calculations of the mean for 24, 48 and 72 h done with a worst case estimation of a score of 4 for 48 h (as for 24 and 72 h) for each animal.
Irritant / corrosive response data:
No tissue destruction and / or necrosis reported
Other effects:
no further data

intact skin:   

erythema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6
oedema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6
abraded skin: 

erythema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6
oedema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6


Summary: irritation score: 8.00/8.00

Interpretation of results:
other: irritating (no tissue destruction and / or necrosis reported)
Conclusions:
Application of 0.5 mL undiluted p-cresol on shaved intact or abraded rabbit skin areas (coverage and exposure time not mentioned) and reading up to 72 hours post application yielded mean irritation score 8 of max. 8. Reversibility is not reported.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: limited documentation; no information on exposure time and conditions
Qualifier:
no guideline followed
Principles of method if other than guideline:
0.5 mL undiluted TS was applied to the intact and to the abraded skin, time of observation: 24 and 72 hours
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
no data
Type of coverage:
not specified
Preparation of test site:
other: partly shaved intact skin, partly shaved and abraded skin
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
no data
Observation period:
up to 72 hours
Number of animals:
6
Details on study design:
evaluation of erythema and edema
Irritation parameter:
erythema score
Basis:
mean
Remarks:
(animal 1 - 6)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: No scores for 48 h given. Calculations of the mean for 24, 48 and 72 h done with a worst case estimation of a score of 4 for 48 h (as for 24 and 72 h) for each animal.
Irritation parameter:
edema score
Basis:
mean
Remarks:
(animal 1 - 6)
Time point:
24/48/72 h
Score:
ca. 4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: No scores for 48 h given. Calculations of the mean for 24, 48 and 72 h done with a worst case estimation of a score of 4 for 48 h (as for 24 and 72 h) for each animal.
Irritant / corrosive response data:
All animals showed erythema (score 4 of max.4) and edema (score 4 of max.4) from the first observtion time point being reported (24h); no tissue destruction and/or necrosis reported.
Other effects:
no data

intact skin,erythema, oedema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6

abraded skin, erythema, oedema: 24 hr: Score 4 in 6/6; 72 hr: Score 4 in 6/6; no further details reported

Summary: irritation score: 8.00/8.00

Interpretation of results:
other: irritating (no tissue destruction and / or necrosis reported)
Conclusions:
Application of 0.5 mL undiluted substance on shaved intact or abraded rabbit skin areas, coverage not mentioned, and reading up to 72 hours post application yielded mean irritation score 8 of max 8. Reversibility is not reported.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: no details on animals / test design given
Principles of method if other than guideline:
No information on principles of methods given.
GLP compliance:
no
Species:
rat
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
No information given
Observation period:
No information given
Number of animals:
No information given
Irritation parameter:
other: necrosis
Time point:
other: no data
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
Undiluted 2,4 xylenol caused necrosis upon application to skin of rats. No further details given.
Interpretation of results:
other: corrosive
Conclusions:
Undiluted 2,4 xylenol caused necrosis upon application to skin of rats. No further details given.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: no details on animals / test design given
Principles of method if other than guideline:
No information on principles of methods given.
GLP compliance:
no
Species:
rat
Strain:
not specified
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
No information given
Observation period:
No information given
Number of animals:
No information given
Irritation parameter:
other: necrosis
Time point:
other: no data
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
Undiluted 2,6 xylenol caused necrosis upon application to skin of rats. No further details given
Interpretation of results:
other: corrosive
Conclusions:
Undiluted 2,6 xylenol caused necrosis upon application to skin of rats. No further details given
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study based on early national standard, well documented, acceptable for assessment due to absence of effects (despite 24 h exposure)
Qualifier:
according to
Guideline:
other: CFR/USA, Title 16, Section 1500.41
Principles of method if other than guideline:
according to the Consumer Product Safety Commission/USA: 24 h exposure

GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: J. Scheele, Werl/Germany
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: mesh metal cage
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Air-conditioned room
- Temperature (°C): 22 ± 1
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
other: shaved intact and abraded
Vehicle:
other: Polyethylene glycol (PEG) 400
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg mixed with 0.5 mL PEG

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
24 h
Observation period:
14 days
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: gauze/mull soaked with the test suspension, fixed with adhesive bandage ("Elastoplast")

SCORING SYSTEM: numerical scoring system of effects according to Draize (erythema, oedema, other lesions such as necrosis)
(ETAD recommendation)

- EVALUATION: Reading after 24 and 72 h and calculation of a "Primary Irritation Index" = Sum of effects (erythema and oedema) at both time points for each animal divided by 24 (4 effect values each, 6 animals).

The ranking system of the "Primary Irritation Index" was as follows (based on ETAD recommendation):
0.0 - 0.5 not irritating
0.6 - 3.0 slightly irritating
3.1 - 5.0 moderately irritating
5.1 - 8.0 severely irritating
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Remarks:
(6 animals)
Time point:
other: 24 and 72 h
Score:
0.25
Max. score:
8
Irritant / corrosive response data:
Slight oedema in 3/6 animals (24 h after application), no effects after 72 h, no difference between intact and scarified skin
Interpretation of results:
other: not irritating according to ETAD recommendation
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: sufficient information to evaluate the substance
Principles of method if other than guideline:
Application of 0.1 mL of the undiluted substance into the eye of each of 6 rabbits; reading: 24 hrs, 48 hrs and 72 hrs (cornea, iris, conjunctivae)
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no further information
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
no data
Observation period (in vivo):
up to 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
no data
Irritation parameter:
other: cornea score, iris score, conjunctivae score
Basis:
mean
Time point:
24 h
Score:
ca. 91.3
Max. score:
110
Irritation parameter:
other: cornea score, iris score, conjunctivae score
Basis:
mean
Time point:
48 h
Score:
ca. 86.3
Max. score:
110
Irritation parameter:
other: cornea score, iris score, conjunctivae score
Basis:
mean
Time point:
72 h
Score:
ca. 82.7
Max. score:
110
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 91.3
Max. score:
110
Reversibility:
not reversible
Irritant / corrosive response data:
no further data
Other effects:
none reported
Total irritation score: 91.3/110
Interpretation of results:
other: highly irritating
Conclusions:
Application of 0.1 mL undiluted test substance into the eyes of rabbits and observation for up to 72 hours resulted into a mean score of 97 of max 110. Reversibility is not reported (Industrial Biotest Laboratories 1969).
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: no information on GLP, strain used
Principles of method if other than guideline:
0.1 mL undiluted TS was applied into the eye of rabbits, time of reading: 24, 48, 72 hrs
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
unspecified
Observation period (in vivo):
up to 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
no further data
Irritation parameter:
other: mean score: cornea, iris conjunctivae
Basis:
animal: mean score for all animals
Time point:
24 h
Score:
ca. 84.7
Max. score:
110
Irritation parameter:
other: mean score cornea, iris, conjunctivae
Basis:
animal: mean score of all animals
Time point:
48 h
Score:
ca. 89.7
Max. score:
110
Irritation parameter:
other: mean score cornea, iris, conjunctivae
Basis:
animal: mean score of all animals
Time point:
72 h
Score:
ca. 93
Max. score:
110
Irritation parameter:
overall irritation score
Basis:
animal: mean score of all animals
Time point:
24/48/72 h
Score:
ca. 89
Max. score:
110
Reversibility:
not reversible

24 hours: 

cornea, iris, conjunctivae: 84.7/110 (mean score)
mean score for cornea: 60; 

mean score for iris: 10; 

mean score for  conjunctivae: 14.7

48 hours: 

cornea, iris, conjunctivae: 89.7/110 (mean score)
mean score for cornea: 63.3, 

mean score for iris: 10, 

mean score for  conjunctivae: 16.3

72 hours: 

cornea, iris, conjunctivae: 93.0/110 (mean score)
mean score for cornea: 66.6, 

mean score for iris: 10; 

mean score for  conjunctivae: 16.3


summary: irritation score: 89.0/110

Interpretation of results:
other: highly irritating
Conclusions:
The application of 0.1 mL undiluted p-cresol into the eyes of rabbits followed by an observation period of up to 72 hours resulted in a mean irritation score 89 of max 110. Reversibility is not reported.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: observation time should be longer to evaluate reversibility
Principles of method if other than guideline:
0.1 mL undiluted test substance was applied into the eye of rabbits, time of reading: 24, 48 and 72 hours
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
no data
Vehicle:
unchanged (no vehicle)
Controls:
other: the second eye served as control
Amount / concentration applied:
undiluted
Amount applied: 0.1 mL
Duration of treatment / exposure:
unspecified
Observation period (in vivo):
up to 72 hours
Number of animals or in vitro replicates:
6
Details on study design:
no data
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 87.3
Max. score:
110
Reversibility:
not reversible
Irritation parameter:
other: score cornea, iris, conjunctivae
Basis:
animal: mean score of all animals
Time point:
24 h
Score:
ca. 87.3
Max. score:
110
Irritation parameter:
other: mean score: cornea, iris, conjunctivae
Basis:
animal: mean score of all animals
Time point:
48 h
Score:
ca. 87.3
Max. score:
110
Irritation parameter:
other: mean score: cornea, iris, conjunctivae
Basis:
animal: mean score of all animals
Time point:
72 h
Score:
ca. 87.3
Max. score:
110
Irritant / corrosive response data:
From beginning of the observation all animals showed irritational effects in the cornea (score 60), iris (score 10) and concunctivae (score 16-18) of the eye which did not change during the observation period of 72 hours.
Other effects:
no data

after 24 hrs: cornea, iris, conjunctivae: 87.3 (mean score); mean score for cornea: 60; mean score for iris: 10; mean score for conjunctivae: 18

after 48 hrs: cornea, iris, conjunctivae: 87.3 (mean score); mean score for cornea: 60; mean score for iris: 10; mean score for conjunctivae: 18

after 72 hrs: cornea, iris, conjunctivae: 87.3 (mean score); mean score for cornea: 60; mean score for iris: 10; mean score for conjunctivae: 18
summary: irritation score: 87.3/110

Interpretation of results:
other: highly irritating
Conclusions:
Application of 0.1 mL into the eye of rabbits and observation up to 72 hours post application resulted in mean irritation score 87.3 of max 110. Reversibility was not reported.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study in compliance with specific test guidelines, well documented, acceptable for assessment
Qualifier:
according to
Guideline:
other: CFR/USA, Title 16, Section 1500.42
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: J. Scheele, Werl/Germany
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: mesh metal cage
- Diet: ad libitum
- Water: ad libitum


ENVIRONMENTAL CONDITIONS
- Air-conditioned room
- Temperature (°C): 22 +-1 °C
- Photoperiod (hrs dark / hrs light): 12 / 12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 100 mg

TEST MATERIAL
- Amount(s) applied: 100 mg


TEST MATERIAL
- Amount(s) applied: 100 mg
Duration of treatment / exposure:
not rinsed
Observation period (in vivo):
24 h, 48 h, 72 h and 7 d after instillation
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize numerical scores (recommendation of the Food and Drug Officials of USA 1959)
- Cornea: opacity (A), area affected (B) => basis of calculation A x B x 5 (Draize Score 1)
- Iris: irritation effect, response to light (A) => basis of calculation A x 5 (Draize Score 2)
- Conjunctivae: erythema (A), oedema/chemosis (B), discharge (C): => basis of calculation (A + B + C) x 2 (Draize Score 3)

- EVALUATION: Reading after 24, 48, and 72 h and
calculation of an "Irritation Score" = Sum of "Draize Scores" at the three time points for each animal
divided by 18 ( 3 time points, 6 animals).

The ranking system of the "Irritation Score" was as follows
(based on ETAD recommendation):
0 - 10 not irritating
11 - 25 slightly irritating
26 - 56 moderately irritating
57 - 110 severely irritating

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein (not specified)
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
(6 animals)
Time point:
24/48/72 h
Score:
58.4
Max. score:
110
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Cornea with diffuse and partly opalescent areas (6/6 animals);
iris with reduced response to light, increased injection of blood vessels (2/6 animals);
conjunctivae and eyelids swollen, erythematous, nictitating membrane covered with blebs, increased discharge (6/6 animals).
No significant reversibility of effects during the observation period.
Interpretation of results:
other: severely irritating according to Code of Federal Regulations, Title 16 Section 1500.42
Conclusions:
The average irritation index was 58.4 and the substance was evaluated as severely irritating in accordance with the recommendations of ETAD.
Executive summary:

The eye irritancy of 3,5 xylenol was studied in 6 New Zealand white rabbits using the method of the US consumer product safety commission (Code of Federal Regulations, Title 16 Section 1500.42). The animals were given a single instillation of 100 mg into the conjunctival sac of one eye and the effects were assessed at 24, 48 and 72 hrs after instillation. The effects were evaluated using the Draize scoring system in accordance with the recommendations of ETAD. In all rabbits, irritation of the conjunctivae with reddening, chemosis and ocular dishcarge were present at all time points as was corneal clouding, the effects being only slightly reversible during the 3 -day observation period. The iris showed injected vessels. The average irritation index was 58.4 and the substance was evaluated as severely irritating in accordance with the recommendations of ETAD.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

There are no data for irritation/corrosion available for Tar acids, Xylenol fraction (CAS 84989-06-0). In order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.1 and 8.2, read-across from appropriate substances is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5.

According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.

Tar acids, Xylenol fraction (CAS 84989-06-0) is an UVCB substance comprised of the main constituents xylenols (all isomers in total > 60%; 2,4- and 2,5 -xylenol > 40%), ethyl phenols (< 30%) and cresols (< 25%). The read-across approach is therefore based on the main constituents of Tar acids, Xylenol fraction (CAS 84989-06-0), given common functional groups, common precursors and the likelihood of common breakdown products via biological processes. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

For skin irritation read-across from reliable data on the analogue substances cresol isomers (m- (CAS 108-39-4), p- (CAS 106-44 5) and o-cresol (CAS 95-48-7)) and on the analogue substances 2,4-xylenol (CAS 100-67-9), 2,6-xylenol (CAS 576-26-1) and 3,5-xylenol (CAS 108-68-9) was conducted. For eye irritation data are available on the cresol isomers (m- (CAS 108-39-4), p- (CAS 106-44 5) and o-cresol (CAS 95-48-7)) and on the analogue substance 3,5-xylenol (CAS 108-68-9). Nevertheless, the data base is very limited and does not allow a final conclusion. Further testing is, however, not required, because Tar acids, Xylenol fraction (CAS 84989-06-0) is evaluated as corrosive in a worst-case approach and classified / labelled accordingly. This is in accordance with the specific rules (Column 2) of Annex VII, No. 8.1 of Regulation (EC) No. 1907/2006 (REACH): skin irritation/corrosion studies do not generally need to be conducted if the substance is classified as corrosive to the skin.

Skin irritation

o-cresol (CAS 95-48-7)

The skin irritation potential of o-cresol (CAS 95-48-7) was determined by an in vivo skin irritation test in rabbits (no guideline followed, no GLP) (IBTL, 1969a). A dose of 0.5 mL of undiluted test substance was applied to the shaved intact or shaved abraded skin of six rabbits. No information about coverage was given. After an unknown exposure period the skin sites were evaluated for erythema and edema at 24, 48 and 72 h reading time points. Severe erythema (grade 4) and edema (grade 4) was observed on abraded and intact skin, respectively, and yielded in overall irritation mean scores of 8.0 of 8.0 [max]. No information about reversibility was reported. Based on the results, the test substance was considered corrosive to the skin (worst case estimation as corrosion could not be excluded) under the conditions of the test.

p-cresol (CAS 106-44-5)

The skin irritation potential of p-cresol (CAS 106-44-5) was determined by an in vivo skin irritation test in rabbits (no guideline followed, no GLP) (IBTL, 1969b). A dose of 0.5 mL of undiluted test substance was applied to the shaved intact or shaved abraded skin of six rabbits each. No information about coverage was given. After an unknown exposure period the skin sites were evaluated for erythema and edema at 24 and 72 h reading time points. Severe erythema (grade 4) and edema (grade 4) was observed in 6/6 animals on abraded and intact skin, respectively, after 24 and 72 h. Overall mean score after 24, 48 (worst case estimation) and 72 h for erythema and edema was 4.0 in all animals. No tissue destruction and/or necrosis were reported and no information about reversibility was given. Based on the results, the test substance was irritating to the skin under the conditions of the test.

m-cresol (CAS 108-39-4)

The skin irritation potential of m-cresol (CAS 108-39-4) was determined by an in vivo skin irritation test in rabbits (no guideline followed, no GLP) (IBTL, 1969c). A dose of 0.5 mL of undiluted test substance was applied to the shaved intact or shaved abraded skin of six rabbits each. No information about coverage was given. After an unknown exposure period the skin sites were evaluated for erythema and edema at 24 and 72 h reading time points. Severe erythema (grade 4) and edema (grade 4) was observed in 6/6 animals on abraded and intact skin, respectively, after 24 and 72 h. Overall mean score after 24, 48 (worst case estimation)and 72 h for erythema and edema was 4.0 in all animals. No tissue destruction and/or necrosis were reported and no information about reversibility was given. Based on the results, the test substance was irritating to the skin under the conditions of the test.

2,4-xylenol (CAS 100-67-9)

The skin irritation potential of 2,4-xylenol (CAS 100-67-9) was determined by an in vivo skin irritation test in rats (no guideline followed, no GLP) (Uschdavini, 1974). Application of the undiluted test substance caused necrosis upon the skin. No further details are given in the study report. Based on the results, the test substance was considered corrosive to the skin under the conditions of the test.

2,6-xylenol (CAS 576-26-1)

The skin irritation potential of 2,6-xylenol (CAS 576-26-1) was determined by an in vivo skin irritation test in rats (no guideline followed, no GLP) (Uschdavini, 1974). Application of the undiluted test substance caused necrosis upon the skin. No further details are given in the study report. Based on the results, the test substance was considered corrosive to the skin under the conditions of the test.

3,5-xylenol (CAS 108-68-9)

The skin irritation potential of 3,5-xylenol (CAS 108-68-9) was determined by an in vivo skin irritation test in rabbits according to a protocol of US consumer product safety commission (Code of Federal Regulations, Title 16, Section 1500.41; no GLP) (Rütgers, 1981d). A dose of 0.5 g test substance diluted in 0.5 mL polyethylene glycol was applied to the shaved intact or shaved abraded skin of six rabbits each under occlusive conditions. After an exposure period of 24 h, the skin sites were evaluated for erythema and edema at 24 and 72 h reading time points. The observation period was 14 days in total. Slight edema was observed at intact and abraded skin sites in 3/6 animals 24 h after application, reversible within 72 h. The primary dermal irritation index (PDII) was calculated to be 0.25 of 8.0[max] for all animals. Based on the results, the test substance was not irritating to the skin under the conditions of the test.

In addition, in the public toxicological evaluation of 3,5-xylenol (CAS 108-68-9) of BG Chemie (No. 139, last updated 02/2005) it was stated that the effect of 3,5-xylenol on the skin of rabbits is described as severely irritant in older studies which do not fulfil the requirements of current guidelines. Modern studies, however, have concluded that 3,5-dimethylphenol is not irritating to the rabbit skin (like Rütgers, 1981d) but also that a 1-percent solution in Lutrol E 400 has an irritant effect.

Conclusion:

Available data on source substances show inconsistent results on skin irritation properties. For the three cresol isomers severe skin irritation (score 4) was observed in all test animals. 2,4- and 2,6-xylenol showed corrosive properties, whereas 3,5-xylenol was not irritating under conditions of the test. Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data regarding the skin irritation potential of Tar acids, Xylenol fraction (CAS 84989-06-0), the substance is classified for Skin Corr. 1B in a worst case assumption.

Eye irritation

o-cresol (CAS 95-48-7)

The eye irritation potential of o-cresol (CAS 95-48-7) was investigated in six albino rabbits (no guideline followed, no GLP) (IBTL, 1969a). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye. The other eye remained untreated and served as control. Eyes were evaluated for cornea, iris and conjunctivae scores at 24, 48 and 72 h after application. Mean irritation scores for cornea, iris and conjunctivae were 91.3, 86.3 and 82.7 of 110.0 [max] at the 24, 48 and 72 h readings, respectively. The overall irritation score was 91.3 of 110.0 [max] without reversibility of effects. Based on the results of this study, the test substance is considered to be severely irritating to the eyes.

p-cresol (CAS 106-44-5)

The eye irritation potential of p-cresol (CAS 106-44-5) was investigated in six albino rabbits (no guideline followed, no GLP) (IBTL, 1969b). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye. The other eye remained untreated and served as control. Eyes were evaluated for cornea, iris and conjunctivae scores at 24, 48 and 72 h after application. Mean irritation scores for cornea, iris and conjunctivae were 84.7, 89.7 and 93.0 of 110.0 [max] at the 24, 48 and 72 h readings, respectively. The overall irritation score was 89.0 of 110.0 [max] without reversibility of effects. Based on the results of this study, the test substance is considered to be severely irritating to the eyes.

m-cresol (CAS 108-39-4)

The eye irritation potential of m-cresol (CAS 108-39-4) was investigated in six albino rabbits (no guideline followed, no GLP) (IBTL, 1969c). 0.1 mL of the undiluted test substance was instilled into the conjunctival sac of one eye. The other eye remained untreated and served as control. Eyes were evaluated for cornea, iris and conjunctivae scores at 24, 48 and 72 h after application. Mean irritation scores for cornea, iris and conjunctivae were all 87.3 of 110.0 [max] at the 24, 48 and 72 h readings, respectively. The overall irritation score was 87.3 of 110.0 [max] without reversibility of effects. Based on the results of this study, the test substance is considered to be severely irritating to the eyes.

3,5-xylenol (CAS 108-68-9)

The eye irritation potential of 3,5-xylenol (CAS 108-68-9) was investigated in six albino rabbits according to a protocol of US consumer product safety commission (Code of Federal Regulations, Title 16, Section 1500.42; no GLP) (Rütgers, 1981e). 100 mg of the undiluted test substance was instilled into the conjunctival sac of one eye. Eyes remained unwashed and were evaluated for cornea, iris and conjunctivae scores at 24, 48 and 72 h after application according to Draize. In all rabbits, irritation of the conjunctivae with reddening, chemosis and ocular discharge as well as corneal clouding were present at all time points. Iris with reduced response to light and increased injection of blood vessels was observed in 2 of 6 animals. The average irritation index was 58.4 and the substance was evaluated as severely irritating in accordance with the recommendations of ETAD.

Conclusion:

All three cresol isomers as well as 3,5-xylenol show severe eye irritating properties towards cornea, iris and conjunctivae, not reversible within 72 h. Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data regarding eye irritation potential of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is classified for Eye Damage 1 as a worst case.

Respiratory irritation

As identified above, no studies with Tar acids, Xylenol fraction (CAS 84989-06-0) are available which address this endpoint adequately. However, cresols and xylenols (and potentially also ethylphenols) are considered to be highly irritating / corrosive to skin and eyes. Therefore, it is reasonable to assume that these substances also cause respiratory irritation in the form of mists, vapors or inhalable aerosols.

References:

BG Chemie 2005: Toxicological evaluation of 3,5-Dimethylphenol (CAS No. 108-68-9), No. 139, last updated: 02/2005.

Justification for classification or non-classification

Based on all available information (weight-of-evidence), following an analogue read-across approach and in the absence of data regarding skin and eye irritation potential of Tar acids, Xylenol fraction (CAS 84989-06-0), Tar acids, Xylenol fraction (CAS 84989-06-0) is classified for Skin Corr. 1B and Eye Dam. 1 as a worst case.