Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin: Rabbit. No irritation. EPA OPP 81 -5 Reliability = 1

Eye: Rabbit. Slight irritation resolved in 24hrs. EPA OPP 81 -4 Reliability = 1

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
R Enantiomer of XRD-453 Methyl Ester
Lot # AGR 259823
Purity: 95.7%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, Pennsylvania
- Weight: 2.1 to 2.4 kg
- Housing: Individually
- Diet: Purina Certified Rabbit Chow # 5322 (Ralston Purina Co., St. Louis, Missouri), ad libitum
- Water: Tap water ad libitum
- Acclimation period: At least two weeks

ENVIRONMENTAL CONDITIONS
- Animal room was designed to maintain adequate environmental conditions concerning temperature and humidity
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
6 (2M + 4F)
Details on study design:
TEST SITE
- Area of exposure: Approximately 2.5 x 2.5 cm
- Type of wrap if used: Gauze patch held in place with non-irritating tape. The gauze patch was covered with a flannel bandage taped to the rabbit

REMOVAL OF TEST SUBSTANCE
- Washing: The wrapping and gauze patch were removed after four hours and the back was wiped with a damp disposable towel to remove any residual test substance
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
- The application sites were graded for erythema and edema within thirty minutes and 24, 48 and 72 hours after patch removal.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
There were no signs of dermal irritation at any time post-treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
There were no signs of dermal irritation in the rabbits at any time post-treatment.
Executive summary:

The primary dermal irritation study was conducted on New Zealand White rabbits according to the guideline EPA OPP 81-5. Aliquots of 0.5 ml of undiluted test substance were applied for four hours to the intact skin on the back of six New Zealand White rabbits. There were no signs of dermal irritation at any time post-treatment.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
R Enantiomer of XRD-453 Methyl Ester
Lot #: AGR 259823
Purity: 98.6%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Dutchland, Inc., Denver, Pennsylvania
- Weight: 2.3 to 2.7 kg
- Housing: Iindividually
- Diet: Purina Certified Rabbit Chow # 5322 (Ralston Purina Co., St. Louis, Missouri), ad libitum
- Water: Tap water ad libitum
- Acclimation period: At least two weeks

ENVIRONMENTAL CONDITIONS
- Animal room was designed to maintain adequate environmental conditions concerning temperature and humidity.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration: Undiluted
Duration of treatment / exposure:
The eyes of all rabbits remained unwashed
Observation period (in vivo):
Approximately 1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
6 (2M + 4F)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- The eyes of all rabbits remained unwashed

TOOL USED TO ASSESS SCORE: Penlight
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
redness and discharge
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Slight discomfort was observed in two rabbits immediately post-instillation; the remaining four rabbits had no response upon instillation of the test substance. Examination of the eyes one hour post-treatment revealed slight to moderate redness in all rabbits; five animals had discharge from the treated eye. All signs of ocular irritation were resolved by 24 hours post-treatment; there were no other signs of ocular irritation present in any animals throughout the remainder of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating in rabbits
Executive summary:

The study was conducted according to EPA guideline 81-4. The potential of the test substance to cause ocular irritation was assessed by instillation of a 0.1 mL aliquot into the conjunctival sac of the right eye of six New Zealand White rabbits. Examination of the eyes one hour post-treatment revealed slight to moderate redness in all rabbits; five animals had discharge from the treated eye. All signs of ocular irritation were resolved by 24 hours post-treatment; there were no other signs of ocular irritation present in any animals throughout the remainder of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The primary dermal irritation study was conducted on New Zealand White rabbits according to the guideline EPA OPP 81-5. Aliquots of 0.5 ml of undiluted test substance were applied for four hours to the intact skin on the back of six New Zealand White rabbits. There were no signs of dermal irritation at any time post-treatment.

Eye irritation study was conducted according to EPA guideline 81-4. The potential of the test substance to cause ocular irritation was assessed by instillation of a 0.1 mL aliquot into the conjunctival sac of the right eye of six New Zealand White rabbits. Examination of the eyes one hour post-treatment revealed slight to moderate redness in all rabbits; five animals had discharge from the treated eye. All signs of ocular irritation were resolved by 24 hours post-treatment; there were no other signs of ocular irritation present in any animals throughout the remainder of the study.

Justification for classification or non-classification

The test substance produced no skin irritation and, therefore, does not need to be classified for skin irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. 

The test substance produced slight eye irritation in all rabbits as evidenced by slight to moderate reddness which is resolved by 24 hours, respectively.Therefore, the substance does not need to be classified according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.