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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye 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:
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).
Reason / purpose:
read-across source
Reference
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.
Reason / purpose:
read-across source
Reference
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.
Reason / purpose:
read-across source
Reference
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.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vivo

Results
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
for all animals
Time point:
24/48/72 h
Score:
ca. 91.3
Max. score:
110
Reversibility:
not reversible
Remarks on result:
other: Source: CAS 95-48-7, o-cresol, IBTL, 1969, rabbit
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 106-44-5: p-cresol: overall irritation score: mean for all animals: 24/48/72 h: 89.0 of 110; IBTL, 1969
Source CAS 108 -39 -4: m-cresol:overall irritation score: mean for all animals: 24/48/72 h: 87.3 of 110; IBTL, 1969
Source CAS 108 -68 -9: 3,5-xylenols: overall irritation score: mean for all animals: 24/48/72 h: 58.4 of 110; Rütgers, 1981

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS Category 1 (H318) 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 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.
Executive summary:

All three cresol isomers as well as 3,5-xylenol show severe eye irritating properties towards cornea, iris and cunjunctivae, not reversible within 72 h. However, as there are no eye 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 Eye Dam. 1 (H318) according to Regulation (EC) No 1272/2008.