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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
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).
Reason / purpose:
read-across source
Reference
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.
Reason / purpose:
read-across source
Reference
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.
Reason / purpose:
read-across source
Reference
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.
Reason / purpose:
read-across source
Reference
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
Reason / purpose:
read-across source
Reference
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

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vivo

Results
Irritation parameter:
other: necrosis
Time point:
other: no data
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
Source: CAS 2,4-xylenol, Uschdavini, 1974, rat
Irritant / corrosive response data:
In the result table above the most critical value of the weight of evidence approach is given. In the following, the results are shown for the other source substances of this weight of evidence approach:
Source CAS 95 -48 -7: o-cresol: erythema and edema score for mean score of each animal after 72 hours on abraded and intact skin: 4.0, reversibility was not specified; IBTL, 1969
Source CAS 106-44-5: p-cresol: erythema and edema score as mean score of all six animal at 24/4872 hours on intact skin: 4.0, reversibility was not specified (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.); IBTL, 1969
Source CAS 108 -39 -4: m-cresol:erythema and edema score as mean score of all six animal at 24/4872 hours on intact skin: 4.0, reversibility was not specified (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.); IBTL, 1969
Source CAS 576-26-1: 2,6-xylenol: necrosis was observed; Uschdavini, 1974
Source CAS 108 -68 -9: 3,5-xylenols: primary dermal irritation index (PDII) mean out of six animals at 24 and 72 h: 0.25 of 8.0; Rütgers, 1981

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 1B (H314) according to Regulation (EC) No 1272/2008
Conclusions:
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.
Executive summary:

Available data on source substances show inhomogenous results on skin irritation properties. For the three cresol isomers severe skin irritation (score 4) was observed in all test animals. Xylenol isomers 2,4 -xylenol and 2,6 -xylenol showed corrosive properties, whereas 3,5 -xylenol was not irritating under conditions of the test. However, as there are no skin irritation data available for Tar acids, Xylenol fraction (CAS 84989-06-0) a worst-case approach was conducted taking into account all available data on the source substances and Tar acids, Xylenol fraction (CAS 84989-06-0) was therefore classified as Skin Corr. 1B (H314) according to Regulation (EC) No 1272/2008.