2,5-Furandione, dihydro-, mono-C15-20-alkenyl derivs.

Endpoint summary

Description of key information

Skin: not corrosive and not irritating (OECD 439 and 431 combined report)
Eyes: not irritating (OECD 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Remarks:

a skin corrosion test was included in the test design

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP- and guideline compliant

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Qualifier:

according to guideline

Guideline:

other: OECD 431 Commission Regulation (EC) No 440/2008 OECD Draft for corrosion test

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Cell type:

non-transformed keratinocytes

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL (corrosion test), 30 µL (irritation test)
- Concentration (if solution): 100%

Duration of treatment / exposure:

1 hour

Observation period:

2 days

Number of animals:

not applicable

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

corrosion 3 min exposure

Value:

101

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

no indication of corrosion

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

corrosion 1 hour exposure

Value:

86

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Remarks:

no indication of corrosion

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

irritation 1 hour exposure

Value:

110

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

1. Corrosion test

 

		Exposure: 3 min				Exposure: 1 hour
Test article		tissue 1	tissue 2	KC	mean
NC	mean OD570	1.7627	1.7522	0.2267	1.7574	1.7657	1.6962	0.1762	1.7309
	viability[% of NC]	100.3	99.7	-	100	102.0	98.0	-	100
ASA	mean OD570	1.8112	1.7222	0.2012	1.7667	1.3892	1.6027	0.1867	1.4959
	viability[% of NC]	103.1	98.0	-	101	80.3	92.6	-	86
PC	mean OD570	0.4438	0.3498	-	0.3968	0.1597	0.1867	-	0.1732
	viability[% of NC]	25.3	19.9	-	23	9.2	10.8	-	10

 

Due to the ability of the test substance to reduce MTT directly, a KC was applied in parallel.

However, the result of the KC did not indicate an increased MTT reduction (difference to KC

of NC is not greater than 0.1; see section 3.6.4). Thus the KC was not used for viability

calculation.

 

2. Irritation test

 

Test article		tissue 1	tissue 2	tissue 3	mean	SD
NC	mean OD570	1.6795	1.6125	1.5725	1.6215
	viability[% of NC]	103.6	99.4	97.0	100	3.33
ASA	mean OD570	1.7575	1.7070	1.8980	1.7875
	viability[% of NC]	108.4	105.3	117.1	110	6.10
PC	mean OD570	0.1165	0.1320	0.1215	0.1233
	viability[% of NC]	7.2	8.1	7.5	8	0.49

Interpretation of results:

GHS criteria not met

Remarks:

substance is not corrosive and not irritating to the skin

Conclusions:

Based on the observed results and applying the evaluation criteria it is concluded, that substance does not show a skin irritation potential in the EpiDerm ™ skin corrosion/irritation test under the test conditions chosen.

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:

other: GLP- and guideline compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Stolzenseeweg 32 – 36, 88353 Kisslegg
- Age at study initiation: 9 weeks
- Weight at study initiation: 2.1 kg – 2.2 kg
- Housing:Single housing; Terulan cages, Ehret GmbH, A-3430 Tulln, 73 cm x 73 cm bottom area, 50 cm height.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period:for at least 5 days before application


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3 °C
- Humidity (%): 30 – 70%
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

Approx. 1, 24, 48 and 72 h after application.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): About 24 hours after application of the test item the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe
- Time after start of exposure: About 24 hours after application of the test item


SCORING SYSTEM: Draize

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 48 h

Score:

0.3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Irritant / corrosive response data:

The cornea and the iris were not affected in any animal at any examination term. Slight conjunctival redness (grade 1) was noted in one animal only 1 hour after application, in one animal 1 and 24 hours after application. In the third animal no conjunctival redness was observed.
Slight conjunctival chemosis was noted in all three animals only 1 hour after application. Slight discharge (grade 1) was noted in two animals only 1 h our after application.

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, ASA is not irritating to eyes under the test conditions chosen.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The potential of the substance to cause dermal corrosion/irritation was assessed by a single topical application of 50 μL (corrosion test) or 30 μL (irritation test) of the test substance to a reconstructed three dimensional human epidermis model (EpiDerm™) in accordance with OECD 431 and GLP. Based on the observed results it was concluded, that the substance does not show a skin irritation potential.

Eye irritation was evaluated in study in accordance with OECD 405 and GLP, where 0.1mL of the substance was instilled into the eyes of three New Zealand rabbits. The only observed effects were slight conjunctival effects noted after 48 h, so that it was concluded that substance is not irritating to eyes.

 

The potential of the substance to cause serious damage to the eyes/mucous membranes was assessed by a single topical application of 0.3 mL of the undiluted test substance and 0.3 mL of a 10% test-substance solution in olive oil to the chorioallantoic membrane of fertilized and incubated hen eggs. Based on the absence of haemorrhagia and coagulation, after the 90 or 160 sec observation period, the substance was not found to produce changes indicative for serious eye damage.

Justification for selection of skin irritation / corrosion endpoint:
Guideline study according to GLP

Justification for selection of eye irritation endpoint:
Guideline study according to GLP

Justification for classification or non-classification

The available data are conclusive but not sufficient data for classification with regard to irritation / corrosion in accordance with the CLP Regulation (EC) No 1272/2008.