[[(2-ethylhexyl)oxy]methyl]oxirane

Endpoint summary

Description of key information

It can be concluded that test substance possesses a cumulative skin irritation potential in albino rabbits.

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:

from October 1, 1984 to October 18, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

well documented under GLP principle

Principles of method if other than guideline:

An area of about 6 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 mL/application of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. The patches were covered with an occlusive membrane and held in place for 6 hours by an adhesive tape. The treatment was repeated for 5 consecutive days. The skin reactions were evaluated 24 hours after each application.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animal Strain: New Zealand white rabbits (KFM-NZW)
Breeder: Kleintierfarm Maedorin AG, CH-4414 Fuellinsdorf
Acclimatization period: 5 days
Group Size and Husbandry: The test was performed on 3 male rabbits , checked for normal skin conditions, weighing between 2 to 3 kg (approx. 12 - 14 weeks old) . The animals were housed individually in metal cages, identified with individually numbered ear tags, kept at a constant room temperature of 20 ±3 °C, at a relative humidity of 30 - 70% and on a 12 hours light cycle per day.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral flank

Amount / concentration applied:

0.5 mL/application of test substance

Duration of treatment / exposure:

held in place for 6 hours, repeated for 5 consecutive days

Observation period:

the observation period was extended to 17 days.

Number of animals:

3 males

Details on study design:

An area of about 6 cm² was shaved on both flanks of the animals approximately 24 hours before treatment. A gauze patch bearing 0.5 mL/application of the test substance was applied to the flank. A control gauze patch was applied to the contralateral flank. The patches were covered with an occlusive membrane and held in place for 6 hours by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg). The treatment was repeated for 5 consecutive days. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 24 hours after each application according to the OECD scoring system.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean value

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean value

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean value

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean value

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean value

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean value

Time point:

24/48/72 h

Score:

ca. 1.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

see Table 1 and Table 2

Other effects:

No abnormal body weight gain was observed during the treatment period.

Table 1 Erythema

Animal No./sex	28 M		29M		30M
	CF	TF	CF	TF	CF	TF
After 1 days	0	1	0	1	0	1
After 2 days	0	2	0	2	0	2
After 3 days	0	3	0	3	0	3
Mean 1-3 days	0	2	0	2	0	2
After 4 days	0	4	0	4	0	4
After 5 days	0	4	0	4	0	4
Mean 1-5 days	0	2.8	0	2.8	0	2.8
After 7 days	0	2	0	3	0	3
After 10 days	0	1	0	1	0	2
After 14 days	0	0	0	0	0	0
After 17 days	0	0	0	0	0	0

Table 2 Edema

Animal No./sex	28 M		29M		30M
	CF	TF	CF	TF	CF	TF
After 1 days	0	0	0	0	0	0
After 2 days	0	2	0	1	0	2
After 3 days	0	2	0	2	0	3
Mean 1-3 days	0	1.3	0	1	0	1.66
After 4 days	0	3	0	3	0	3
After 5 days	0	3	0	2	0	3
Mean 1-5 days	0	2	0	1.3	0	2.2
After 7 days	0	2	0	3	0	3
After 10 days	0	1	0	1	0	2
After 14 days	0	0	0	0	0	0
After 17 days	0	0	0	0	0	0

Interpretation of results:

Category 2 (irritant)

Remarks:

Criteria used for interpretation of results: EU CLP

Conclusions:

It can be concluded that test substance possess a cumulative skin irritation potential in albino rabbits.

Executive summary:

A 5-day skin irritation/corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of test substance on the albino rabbit skin. Under the experimental conditions employed, test substance induced weak erythema reactions after 1 treatment and strong erythema and edema reactions after repeated application comparing with control treatment. The skin reactions were reversible until the end of the observation period on day 17. Therefore, test substance can be classified as category 2 of skin irritation in the rats according to CLP (Regulation EC No. 1272/2008).

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:

from September 29, 1983 to October 10, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Experimental animals:
Rationale
The albino rabbit has been selected as being a recognized species for the conduct of acute eye irritation studies.
Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
Initial age range: 12 - 14 weeks
Initial body weight range: 2000 - 2310 g
Individual identification: numbered ear tags; The cages were marked with sex, animal No., GU-Project No. and the company code of the
test article.
Husbandry: Animals were housed individually in metal cages. The animal room was air conditioned: temperature 20 ±3 ° C, relative humidity 30 - 70%; 12 hours light/day, approximately 15 air changes/h.
Diet and water: Rabbit food, NAFAG, No. 814 Tox, NAFAG AG, Gossau, SG (Switzerland), and water were provided ad libitum.
Euthanasia: At the end of the observation period, the animals were killed by the intravenous injection of hypnotic T61 (Hoechst).

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye remained untreated and served as the control

Amount / concentration applied:

0.1 mL of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test material.

Duration of treatment / exposure:

1 second

Observation period (in vivo):

The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period.

Number of animals or in vitro replicates:

3 females

Details on study design:

The ocular irritation scores were evaluated according to the scoring system.
The irritating and/or corrosive potential of the test article (theoretical range: non irritant - extremely irritant) was assessed on the basis of the maximum irritant effect observed
- in one or several of the ocular tissues (conjunctiva, iris, cornea), observed over the range of observation time
- in one or more animals and taking into account the reversibility of the effect.
Symptoms: daily (a.m. and p.m. on working days, once daily on weekends and holidays).
Body weight: At begin of the acclimatisation and end of test
Mortality: Daily (a.m. and p.m. on working days, once daily on weekends and holidays).

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean value

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 48hrs

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean value

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

3

Reversibility:

fully reversible within: 48hrs

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean value

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritant / corrosive response data:

The reaction scores of treated eyes are summarized in the table 1 and table 2 below.

Other effects:

The animals showed a normal body weight development.
No other reactions to treatment were recorded during the whole observation period.

Table 1 individual eye scores

Animal No./Sex	54/F	55/F	56/F	Evaluation
After 1 h	0	0	0	0= non irritant 1= slightly irritant 2= irritant 3-4 = severely irritant += corrosion Cornea
After 24 h	0	0	0
After 48 h	0	0	0
After 72 h	0	0	0
After 7 days	0	0	0
After 1 h	0	0	0	0= non irritant 1= irritant 2= severely irritant += corrosion Iris
After 24 h	0	0	0
After 48 h	0	0	0
After 72 h	0	0	0
After 7 days	0	0	0
After 1 h	1	2	2	0= non irritant 1= slightly irritant 2= irritant 3= severely irritant += corrosion Conjuctival(redness)
After 24 h	0	1	1
After 48 h	0	0	0
After 72 h	0	0	0
After 7 days	0	0	0
After 1 h	1	1	1	0= no swelling 1= slightly swelling 2= swelling 3-4 = severe swelling Chemosis(swelling)
After 24 h	0	0	0
After 48 h	0	0	0
After 72 h	0	0	0
After 7 days	0	0	0

Table 2 Mean value of 24 -72 hrs

	Cornea	Iris	conjuctiva	chemosis
54/F	0	0	0	0
55/F	0	0	0.33	0
56/F	0	0	0.33	0

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU CLP

Conclusions:

It can be concluded that test substance is slightly irritant and not corrosive when applied to the rabbit eye mucosa; there was a clear tendency of recovery towards the end of the observation period.

Executive summary:

Acute eye irritation study was established to assess the potential of eye irritation of test substance. 0.1 mL of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period. The animals showed a normal body weight development. No other reactions to treatment were recorded during the whole observation period. Because the mean values of the readings 24 to 72 hours after instillation of test substance are below the threshold of significance, and there was a clear tendency of recovery towards the end of the observation period the test substance does not require classification for eye effects in accordance with CLP (Regulation EC No. 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The eye irritation study (1997) was established to assess the irritation potential of test substance in the rabbit eyes. 0.1 mL of the test article was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The ocular reactions were examined 1, 24, 48, and 72 hours after substance instillation and again during the following observation period. No other reactions to treatment were recorded during the whole observation period. There was a clear tendency of recovery towards the end of the observation period.

 

A 5-day skin irritation/corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of test substance on the albino rabbit skin. Under the experimental conditions employed, test substance induced weak erythema reactions after the first treatment and strong erythema and edema reactions after repeated application comparing with control treatment. The skin reactions were reversible until the end of the observation period on day 17. It can be concluded that test substance possess a cumulative skin irritation potential in albino rabbits. Therefore, test substance can be classified as category 2 of skin irritation in the rats according to CLP (Regulation No. 1272/2008).

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The mean values of the readings 24 to 72 hours after instillation of test substance are below the threshold of significance in the eye irritation test, and there was a clear tendency of recovery towards the end of the observation period. Therefore, the test substance does not require classification for eye irritation in accordance with CLP (Regulation No. 1272/2008). However, based on the available result of a skin irritation study, the test substance can be classified as skin irritation category 2 under CLP.