Registration Dossier

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Administrative data

Description of key information

SKIN
A skin irritation study was performed using methodology similar to that outlined in OECD 404 and identified the test material to be corrosive and irritating to the skin of rabbits.
EYE
An eye irritation study was performed using methodology similar to that outlined in OECD 405 and identified the test material to be irritating to the eyes of rabbits.
RESPIRATORY
A 14 day repeated dose inhalation study was carried out in rats. The NOAEC was deemed to be 200 mg/m³. Signs of upper respiratory tract irritation and ulceration were noted.

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: Study was conducted in methods comparable to OECD guideline 404. However, animals were only observed immediately after patch removal and at 72 hours.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Animals were observed immediately after patch removal and at 72 hours.
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.1 to 2.7 kg.
Type of coverage:
occlusive
Preparation of test site:
other: both intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin areas were used as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: The test substance was moistened with a small amount of water and applied to six one-inch square patches in the amount of 0.5 grams per patch.
Duration of treatment / exposure:
24 hours
Observation period:
The test sites were observed for irritation 24 and 72 hours after application.
Number of animals:
Six animals were divided into two groups, three with intact and the remaining three with abraded skin.
Details on study design:
TEST SITE
- Area of exposure: designated area on the denuded back
- Type of wrap if used: The trunk of each animal was wrapped with rubberized cloth to keep the patches in place and retard any evaporation of the test substance.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: Following an exposure period of 24 hours, the binders and patches were removed.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24
Score:
> 1
Reversibility:
other: not reported
Remarks on result:
other: A necrotizing effect was noted at all time points; no dermal irritation score was reported.
Irritant / corrosive response data:
Necrosis was noted on all of the intact and abraded areas at 24 and 72 hours post exposure. The necrotizing effect of the test substance precluded any accurate readings for erythema; therefore it was not possible to determine the primary irritation index of the test substance. Slight to marked edema was observed in most or all exposed sites at each of the observation intervals.
Interpretation of results:
Category 1 (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single application of 0.5 grams of 2,6-xylenol to the intact and abraded rabbit skin by a 24-hour patch test produced necrosis and edema on all exposed areas at 24 and 72 hours after application. The test substance was considered to be corrosive and irritating to the skin.
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted in methods comparable to OECD guideline 405. However, study was terminated at 72 hours after application. The reversibility of effects after 21 days could not be evaluated.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Study was terminated at 72 hours after application, the reversibility of the effects after 21 days could not be evaluated.
GLP compliance:
no
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.1 to 2.9 kg
- Housing: Throughout the study animals were individually housed in metal cages.
- Diet: Purina rabbit pellets were freely available at all time.
- Water: Water was freely available at all time.
- Other: Prior to application, the left eye of each rabbit was examined with 2.0% sodium fluorescein solution to detect any corneal lesions not otherwise visible, and only those animals with eyes free of irritation and corneal damage were used in this study.

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: A single application of 100 mg of the undiluted test substance was made into the conjunctival sac of the left eye of each animal.
Duration of treatment / exposure:
Single application. The treated eye was held closed for 30 seconds following application.
Observation period (in vivo):
The animals were observed for signs of eye irritation and systemic toxicity at 24, 48, and 72 hours after application.
Number of animals or in vitro replicates:
Six
Details on study design:
SCORING SYSTEM: The signs of eye irritation were graded and recorded according to the numerical scoring system of Draize, J.H., from the Appraisal of the Safety of Chemicals in Foods, Drugs, and Cosmetics, Assn. of Food and Drug Officials of the U.S., Austin, Texas, 1959.

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
mean
Time point:
other: 24, 48 and 72 hours after installation of the test material
Score:
1.8
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Remarks on result:
other: All six animals had mean corneal opacity scores of ≥ 1 following grading at 24, 48 and 72 hours after installation.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours after installation of the test material
Score:
1
Max. score:
2
Reversibility:
not reversible
Remarks:
within 72 hours
Remarks on result:
other: All six animals had mean iris scores of 1 following grading at 24, 48 and 72 hours after installation.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48 and 72 hours after installation of the test material
Score:
2.9
Max. score:
3
Reversibility:
not reversible
Remarks:
within 72 hours
Remarks on result:
other: All six animals had mean conjunctivae redness scores of ≥ 2 following grading at 24, 48 and 72 hours after installation.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours after installation of the test material
Score:
1.8
Max. score:
4
Reversibility:
not reversible
Remarks:
within 72 hours
Remarks on result:
other: Four of six animals had mean chemosis scores of 2 following grading at 24, 48 and 72 hours after installation.
Irritant / corrosive response data:
The irritation was severe and consisted of marked conjunctival irritation, slight iritis, corneal opacity, and corneal sloughing in all treated eyes at 24, 48, and 72 hours after eye installation. The fluorescein examination at 72 hours confirmed the presence of corneal damage in all six animals. The effects were not reversible.
Other effects:
All animals seemed normal in appearance and behavior throughout the study and showed normal body weight gains.
Interpretation of results:
other: Category 2
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A single application of 100 mg of 2,6-xylenol to the eyes of albino rabbits produced severe conjunctival irritation, iritis, corneal opacity, and sloughing in rabbits at 24, 48, and 72 hours after application. The test substance is therefore considered to be an eye irritant based on the results of this study.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin

The potential of the test material to cause skin corrosion or irritation was assessed in a study conducted using methodology comparable to that outlined in the standardised guideline OECD 404. The study was awarded a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997).

The test material was applied to the intact and abraded skin of albino rabbits in an occlusive fashion for 24 hours. Three animals were exposed on intact skin and three on abraded skin. The test material was moistened with a small amount of water and applied to six one-inch square patches in the amount of 0.5 grams per patch. The test sites were observed for irritation 24 and 72 hours after application.

Necrosis was noted on all of the intact and abraded areas at 24 and 72 hours post exposure. The necrotizing effect of the test material precluded any accurate readings for erythema; therefore it was not possible to determine the primary irritation index of the test material. Slight to marked edema was observed in most or all exposed sites at each of the observation intervals.

Under the conditions of the study, the test material was determined to be corrosive o the skin of albino rabbits.

Eye

The potential of the test material to cause corrosion or irritation to the eye was assessed in a study conducted using methodology comparable to that outlined in the standardised guideline OECD 405. The study was awarded a reliability score of 2 in accordance with the principles for assessing data quality set forth by Klimisch et al. (1997).

A single application of 100 mg of the undiluted test material was made into the conjunctival sac of the left eye of 6 albino rabbits. The treated eye was held closed for 30 seconds following application. The animals were observed for signs of eye irritation and systemic toxicity at 24, 48, and 72 hours after application.

The irritation was severe and consisted of marked conjunctival irritation, slight iritis, corneal opacity and corneal sloughing in all treated eyes at 24, 48, and 72 hours after installation into the eyes. The fluorescein examination at 72 hours confirmed the presence of corneal damage in all six animals. The effects were not reversible.

All animals seemed normal in appearance and behavior throughout the study and showed normal body weight gains.

Under the conditions of this study, the test material was determined to be corrosive to the eye of albino rabbits.

Respiratory

Further information is available in the form of a repeated dose inhalation study. The report is summarised in the repeated dose section of the dossier; it is however considered that the effects noted in this study were relevant to irritation and that the effects would potentially be seen after a single exposure.

The toxicity of the test material via the inhalation route was investigated in a well-documented, non-guideline study performed under GLP conditions. The study was awarded a reliability score of 2 in accordance with the criteria for assessing data quality set forth by Klimisch et al. (1997).

Male and female Fischer 344 rats were exposed to dose levels of 67, 200 and 670 mg/m³ (10 rats per sex per dose) in a 14 day inhalation study with exposure 5 days per week. The test material was administered as an aerosol in air. The rats were subjected to the test material 6 hours a day using a whole body exposure technique.

Clinical signs of toxicity were confined to rats in the high dose group. A red nasal discharge was observed in all animals, noted to be a sign of upper respiratory tract irritation and ulceration. No gross pathology findings were noted. Lesions considered to be related to the treatment were confined to the nasal cavity of the high dose males and females and were present in the same anatomical location and at essentially the same degree of severity from both sexes. Histopathologically, the lesions involving the nasal cavities seen in the high dose animals were not present in the low and mid dose rats.

Under the conditions of this study the NOEL for rats of both sexes was determined to be 200 mg/m³. The LOEC was determined to be 670 mg/m³.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Justification for classification or non-classification

In accordance with Annex VI, Regulation (EC) No. 1272/2008, the substance is classified as corrosive to skin Category 1B (H314: Causes severe skin burns and eye damage).

 

With regard to the data available, in accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance would require classification as corrosive to eyes Category 1 (H318: Causes serious eye damage) and corrosive to skin Category 1 (H314: Causes severe skin burns and eye damage).

 

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance requires classification for specific target organ toxicity as STOT SE 3 (H335: May cause respiratory irritation).

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