Registration Dossier

Administrative data

Description of key information

The substance showed no effect on intact skin after exposure for 4 hours, moistened and semi-occlusive, according to OECD 405. This is confirmed by a study in which abraded and  intact skin was exposed to the subsatnce for 24 hours, the substance was also moistened in this case but there is no information on how the substance was kept in contact with the skin.

A animals were exposed to 0.1 grams test substance on their eye in 2 goups. In one group the eyes were washed 30 seconds after exposure. Slight effects were observed in both groups. These findings are confirmed by another eye irritation/corrosion study.

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:
key study
Study period:
21 June 2011 - 24 June 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has some deviations and some information in the report is incomplete. However the study was conducted in accordance with current guidelines and the report includes a QA certification statement.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The study has some deviations and some information in the report is incomplete. However, it appears the study was conducted in accordance with current guidelines.
- The laboratory has no GLP accreditation. However the report includes a QA certification and guideline compliance statement.
- It is not mentioned if water/diet is analyzed for contaminants.
- The animals should be observed up to 14 days after removal of the patches, the total observation period was 72 hours.
GLP compliance:
no
Remarks:
The study was conducted in China for a Chinese registration. The laboratory has no GLP accreditation. However the report includes a QA certification and guideline compliance statement.
Species:
rabbit
Strain:
other: Japanese white
Details on test animals and environmental conditions:
Four healthy male albino rabbits, 2.1-2.2kg, were supplied by Beijing
KeYu Expenerimental Animals Products Center (Certificate No:
SCXK(Jing)2007 -0003).

Animals were kept in animal room in Institute of Laboratory Animal
Sciences, CAMS (normal environment, Certificate No.: SYXK(Jing)
2010-0030). Environmental conditions for animal husbandry are
maintained with the 12-h light/dark cycle, the temperature of 20-23°C,
and the relative humidity of 40-70%. All animals had free access to
sterilized drinking water and irradiation sterilized commercial pellet diets
except during exposure (Beijing HFK Bio-technology Co., Ltd.
Certificate No.: SCXK(Jing) 2009- 0008). The tap water was of drinking
water quality (Sterile water for reverse osmosis).Animals were
acclimatized to the laboratory conditions for at least 5d prior to the test.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
water
Controls:
other: The right flank was treated with 0.5 ml distilled water as control
Amount / concentration applied:
0.5 grams
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
4
Details on study design:
24 hours before the test, the fur on the bilateral dorsal sides (3 X 3 cm2) of rabbits was removed by clipping, respectively.
It was treated with 0.5 g
substance (moistened with distilled water) on the left skin area evenly at
the second day, and covered with one layer of sulfate paper and two
layers of surgical bandages, and fixed with non-irritation tapes, The right
free fur area was treated with 0.5 ml distilled water as control, the
covering was same as the left, The exposure duration was 4 hours.
Afterwards, the dressing was removed and the residual test substance was
cleaned with detergent and warm water.
The test areas were evaluated for both erythema and edema, and
compared with the control areas, Scores were given at 24, 48 and 72h
following removal of the dressing. The irritation intensity of the test
substance was recorded according to the criteria in "The Guidelines for
the Testing of Chemicals".



Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24-48-72 hours
Score:
0
Remarks on result:
other: No effects observed
Irritant / corrosive response data:
No erythema was observed on the treated skin area of any rabbit. There
was no erythema on the control area of the rabbits. The average score of
skin responses was zero.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not irritating to skin
Executive summary:

Four healthy Japanese white rabbits were taken for the test. 0.5g test substance was applied to an area of shaved skin on left of back of four healthy rabbits and the application site was covered with a semi-occlusive dressing for four hours. Following exposure, dermal irritation was evaluated by the method in the "The Guidelines for the Testing of Chemicals" at 24, 48 and 72h after removal of the dressing. No erythema was observed on the treated skin area of any rabbit. There was no erythema on the control area of the rabbits. The average score of skin responses was 0. According to "The Guidelines for the Hazard Evaluation of New Chemical Substances", a,a,a',a'-tetramethyl-m-xylene-a,a'-diol belongs to non-irritation for rabbits' skin.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 June 2011 - 24 June 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study has some deviations and the information in the report is limited. However the study was conducted in accordance with current guidelines and the report includes a QA certification statement.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
The study has some deviations and some information in the report is incomplete. However, it appears the study was conducted in accordance with current guidelines.
- The laboratory has no GLP accreditation. However the study was conducted in accordance with current guidelines and the report includes a QA certification statement.
- It is not mentioned if water/diet is analyzed for contaminants.
- No details on the scoring method "The Index of Acute Ocular Irritation (I.A.O.I.) "
GLP compliance:
no
Remarks:
The study was conducted in China for a Chinese registration. The laboratory has no GLP accreditation. However the study was conducted in accordance with current guidelines and the report includes a QA certification statement.
Species:
rabbit
Strain:
other: Japanese white
Details on test animals or tissues and environmental conditions:
Four healthy male albino rabbits, 2.1-2.3kg, were supplied by Beijing
KeYu Expenerimental Animals Products Center (Certificate No:
SCXK(Jing)2007 -0003).

Animals were kept in animal room in Institute of Laboratory Animal
Sciences, CAMS (normal environment, Certificate No.: SYXK(Jing)
2010-0030), Environmental conditions for animal husbandry are
maintained with the 12-h light/dark cycle, the temperature of 20-23 'C ,
and the relative humidity of 40-70%. All animals had free access to
sterilized drinking water and irradiation sterilized commercial pellet diets
except during exposure (Beijing HFK Bio-technology Co., Ltd.
Certificate No,: SCXK(Jing) 2009- 0008). The tap water was of drinking
water quality (Sterile water for reverse osmosis). Animals were
acclimatized to the laboratory conditions for at least 5d prior to the test.
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye was used as the control and treated with 0.1 ml saline
Amount / concentration applied:
0.1 gram
Duration of treatment / exposure:
0.1 g was put in the left eye of the rabbits at the start of the study
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
4
Details on study design:
Animals were examined ophthalmoscopically and evaluated with
sodium fluorescein prior to the exposure to assure that they were free of
ocular defects, lesions, or irritation that may have interfered with the
goals ofthe test.
0.lg test substance was put into the conjunctival sac of the left eye of
each test rabbit (4 rabbits). The eye-lids were then gently keep closed.
The eyes were not washed within 24 hours after exposure. The right eye
treated with 0.1 ml normal saline and served as control.
The eye reactions, including those of cornea, iris, and conjunctiva,
were evaluated at 1, 24, 48 and 72h after exposure, respectively. One drop
of 5% sodium fluorescein solution was instilled into both eyes of each
rabbit for evaluation areas of the cornea opacity. At the same time, all
scorings were taken. The irritation intensity of test substance was
recorded according to the criteria in "The Guidelines for the Testing of
Chemicals"
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1-24-48-72 hours
Score:
0
Remarks on result:
other: No effects were observed
Irritant / corrosive response data:
No eye reactions occurred after exposure until 72h. The Index of Acute
Ocular Irritation (I.A.O.I.) was "0", which was classified to non-irritation.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Not irritating to the eye
Executive summary:

Four healthy Japanese white rabbits were taken for the test. An eye irritation test was conducted with rabbits to determine the potential ability to produce irritation and corrosion of test substance. O.lg test substance was put into the left eye of four healthy rabbits. The right eye was treated with 0.1 ml normal saline served as control. Eye irritation was evaluated by the methods in "The Guidelines for the Testing of Chemicals" after exposure. No eye reactions occurred after exposure until the 72 h. The Index of Acute Ocular Irritation (I.A.O.I.) was "0". According to "The Guidelines for the Hazard Evaluation of New Chemical Substances", a,a,a',a'-tetramethyl-m-xylene-a,a'-diol belongs to non-irritation for rabbits' eyes.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:

The 2012 was selected as the key study and is valid with restrictions due to some deficencies (see endpoint study record).  However, it was apparentlyconducted in accordance with current guidelines and includes a QA certification.

An older study is available, which deviates from the current guideline, and has limited details but supports the conclusion of the more current study.

Justification for selection of eye irritation endpoint:

The 2012 was selected as the key study and is valid with restrictions due to some deficencies (see endpoint study record).  However, it was conducted in accordance with current guidelines and includes a QA certification statement.

An older study is available, which deviates from the current guideline, and has limited details but supports the conclusion of the more current study.

Justification for classification or non-classification

Based on the available information the substance is not classified.