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Description of key information

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
Study period:
1985
Reliability:
2 (reliable with restrictions)
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
3 male rabbits, weighing 2 - 3 kg (12 - 14 weeks old), were individually housed in metal cages, identified with ear tags, and kept at constant temperature of 20 +/- 3 °C, a relative humidity of 30-70% and at a 12 hour dark/light cycle. m They received diet and water ad libitum Body weight was recorded on days 0, 3, and 7 of the test.
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 grams per flank of 6 cm2
Duration of treatment / exposure:
4 hours with a semi-occlusive bandage
Observation period:
Observation was daily.
Skin reactions and signs of toxicity were recorded at 1 hour, 24, 48, 72 hours , and daily afterwards,
Number of animals:
three male rabbits
Details on study design:
Irritation / corrosion was classified according to EEC guideline 83/467/1983 (Appendix 2).
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
> 0.3 - < 0.4
Max. score:
4
Reversibility:
fully reversible within: after 7 days
Remarks on result:
other: max. score = 4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
> 0.3 - < 0.4
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: max. score = 4
Irritant / corrosive response data:
The resposnses were mild and the average from 3 animals was lower than minimum for classification and labelling
Other effects:
Body weight development was not adversely affected by the treatment
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Although there was erythema in 2/3 animals and oedema in 1/3 animals with a minimum score of 1, the mean value was below the threshold for classificaiton and labelling
Executive summary:

Although there was erythema in 2/3 animals and oedema in 1/3 animals with a minimum score of 1, the mean value was below the threshold for classification and labelling; the product TK 10884/1 is minimally irritating to skin

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was conducted between 26 October 2016 and 08 NOvember 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
02 October 2012
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
EC 440/20082
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW strain
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Leicestershire, UK.
- Age at study initiation: 12-52 weeks
- Weight at study initiation: 2.88 - 4.49 kg
- Housing: Envigo RMS (UK) Limited, Leicestershire, UK.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:>5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23”C
- Humidity (%): 30 - 70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 October 2016 To: 08 November 2016
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released.
Duration of treatment / exposure:
72h
Observation period (in vivo):
7 d
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre dose anesthesia of ocular anesthetic (two drops of 0.5% proxymetacaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Table 1.
Eight hours after test item application, a subcutaneous injection of post dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.
After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Any clinical signs of toxicity, if present, were also recorded.
An additional observation was made in one treated eye on Day 7 to assess the reversibility of the ocular effects.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
cornea opacity score
Remarks:
No irritation observed
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
cornea opacity score
Remarks:
No irritation observed
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
iris score
Remarks:
No irritation observed
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
iris score
Remarks:
No irritation observed
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
conjunctivae score
Remarks:
No irritation observed
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
conjunctivae score
Remarks:
No irritation observed
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
overall irritation score
Remarks:
No irritation observed
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
overall irritation score
Remarks:
No irritation observed
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
10
Reversibility:
fully reversible
Remarks on result:
other: No irritation observed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.5
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.751
Max. score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
Individual Total Scores and Group Mean Scores for Ocular Irritation
Rabbit Number
and Sex Individual Total Scores At:
1 Hour 24 Hours 48 Hours 72 Hours 7 Days
75597 Female 8 4 2 0 -
75630 Female 10 6 6 4 0
Group Total 18 10 8 4 0
Group Mean Score 9.0 5.0 4.0 2.0 0.0

Ocular Reactions

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in both treated eyes 1 hour after treatment.  Minimal conjunctival irritation was noted in both treated eyes at the 24 and 48 Hour observations and in one treated eye at the 72 Hour observation.

An area of fur loss on the lower eyelid of the test eye was noted in one animal at the 24, 48, 72 Hour and 7 Day observations.

One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 7 Day observation.

Body Weight

Both animals showed expected gain in body weight during the study.

Table: Individual Total Scores and Group Mean Scores for Ocular Irritation

 Rabbit No and Sex  Individual Total Scores            
   1h  24h  45h  72h  7Days
 75597 Female  8  4  2  0  -
 75630 Female  10  6  6  4  0
 Group Total  18  10  8  4  0
 Group Mean Score  9.0  5.0  4.0  2.0  0.0
Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
The test item does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals
Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

Results

A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation.  An area of fur loss on the lower eyelid of the test eye was noted in one animal. One treated eye appeared normal at the 72 Hour observation and the other treated eye appeared normal at the 7 Day observation.

Conclusion

The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance is a multifunctional epoxide and thus prone to be irritant. However, due to its relatively large molecular weight the irritation potential is only slight for skin and mild irritant for eyes.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: Mild irritant to the rabbit eye according to a modified Kay and Calandra classification system. The test item does not meet the criteria foe classification according to the Globally Harmonized System of Classification and Labelling of Chemicals.

Justification for classification or non-classification

The degree of skin and eye irritation was insufficient for classification and labelling (below threshold-value) and thus no classification is proposed for irritation.