(3E)-dec-3-en-2-one

Endpoint summary

Description of key information

The potential of (3E)-dec-3-en-2-one (target substance) to induce skin irritation was evaluated in one suitable in vivo acute dermal irritation study conducted in accordance to OECD test guideline 404. Based on the results, the target substance can be considered as irritant to the skin. Therefore, classification as Skin Irrit. 2, H315 is warranted in accordance with the CLP Regulation 1272/2008.

The potential of the target substance to induce eye irritation was assessed by using data from an in vivo acute eye irritation study performed in accordance to OECD test guideline 405. Based on the results, the target substance can be considered as non-irritant to the eye and no classification is warranted in accordance with the CLP Regulation 1272/2008.

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:

2009-04-16 to 2009-07-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. Clemmons, NC on April 22, 2009
- Age at study initiation: Young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 40-66
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

The animals were observed and scored for skin irritation according to Draize at 30-60 minutes, 24, 48 and 72 hours and at 7, 10 and 14 days after patch removal.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- % coverage: semi-occlusive
- Type of wrap if used: Micropore tape

REMOVAL OF TEST SUBSTANCE
- Washing: yes, ffter 4 hours of exposure to the test substance, the pads and the collars were removed and the test sites were gently cleansed of any residual test substance.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
30-60 minutes, 24, 48 and 72 hours and 7, 10 and 14 days after patch removal.

SCORING SYSTEM:
- Method of calculation: According to Draize [J. Pharmacol. Exp. Ther. 1944, 82: 377-390]. The classification of irritancy was obtained by adding the average erythema and edema scores for the 30-60 minutes, 24, 48, and 72-hour scoring intervals and dividing by the number of evaluation intervals. The resulting Primary Dermal Irritation Index (PDII) was classified as follows:
PDII: 0 = non irritating
PDII >0 - 2.0 = slightly irritating
PDII 2.1 - 5.0 = Moderately irritating
PDII > 5.0 Severly irritating

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Apart from one male exhibiting small feces on Day I, the animals appeared active and healthy during the study. One hour after patch removal, all three treated sites exhibited well-defined to severe erythema and moderate edema. At 48 hours through 72 hours, irritation increased to severe erythema for one animal. The overall incidence and severity of irritation decreased gradually thereafter. Although hyperkeratosis and desquamation were noted for all three animals between Days 7 and 14, they were free of erythema and edema by Day 14 (study termination). The Primary Dermal Irritation Index for the test substance is 5.5.
For detailed results please refer to table 1 and table 2 in box "Any other information on results incl. tables".

Table 1: Individual skin irritation score

Animal No	Sex	Time after patch removal
		30 -60 min	24 hrs	48 hrs	72 hrs	Day 7	Day 10	Day 14
3501	M	2/3	2/2	3/2	3/2	2/1^a	1/0^a,b	0/0^b,c
3502	M	3/3	3/3	3/2^d	3/2^d	2/1^a	0/0^a,b	0/0^b,c
3503	M	4/3^e	4/2^e	4/2^f	4/2^f	3/1^a,d	1/0^a,b	0/0^b,c

a Hyperkeratosis

b New skin

c Desquamation

d Small dark red areas in dose site.

e Dark red areas in dose site.

f Small black areas in dose site.

Table 2 : Summary of primary skin irritation scores*

	Time after patch removal
	30 -60 min	24 hrs	48 hrs	72 hrs	Day 7	Day 10	Day 14
Erythema	3.0	3.0	3.3	3.3	2.3	0.7	0
Edema	3.0	2.3	2.0	2.0	1.0	0	0
TOTAL (PDI)**	6.0	5.3	5.3	5.3	3.3	0.7	0

* Average values for three rabbits.

** PDI = Average Erythema + Average Edema

Primary Dennal Irritation Index (PDII): (PDI for 30-60 minutes, 24,48 and 72 hours) /4 = 5.5

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

In conclusion, the test item is severly irritating to the skin of rabbits when applied for 4 h under semi-occlusive conditions.

Executive summary:

In a primary dermal irritation study conducted according to OECD 404 three albino New Zealand White rabbits were dermally exposed to 0.5 mL the test item for 4 hours under semi-occlusive conditions. Animals then were observed for 14 days. Irritation was scored by the method of Draize. In this study, the test item is severely irritation to the skin based on the observation made. One hour after patch removal, all three treated sites exhibited well-defined to severe erythema and moderate edema. At 48 hours through 72 hours, irritation increased to severe erythema for one animal. The overall incidence and severity of irritation decreased gradually thereafter. Although hyperkeratosis and desquamation were noted for all three animals between Days 7 and 14, they were free of erythema and edema by Day 14. Based on these findings, the test item is considered to be irritant to the skin and in accordance with CLP Regulation 1272/2008 classification as Skin Irrit. 2 (H315) is warranted.

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:

2009-04-16 to 2009-07-24

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:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: New Zealand albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Received from Robinson Services, Inc. Clemmons, NC on April 29 and May 20, 2009.
- Age at study initiation: Young adult.
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Pelleted Purina Rabbit Chow #5326
- Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 12 or 19 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 36-70
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye used as control

Amount / concentration applied:

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

Duration of treatment / exposure:

0.1 mL of the test substance was instilled into the conjunctival sac of the right eye of the first rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimize loss of the test substance.

Observation period (in vivo):

1, 24, 48 and 72 hours and day 4, 7 and 10 after instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: not applicable

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with Draize et al.. The fluorescein dye evaluation was used in the treated eye at 24 hours to verify the absence of corneal damage.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

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:

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:

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:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

10 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

4 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

4 days

Irritant / corrosive response data:

One hour after test substance instillation, all three treated eyes exhibited corneal opacity and 'positive' conjunctivitis and two treated eyes exhibited iritis. The overall incide\}ce and severity of irritation decreased gradually with time. All animals were free of ocular irritation by Day 10. For detailed results please refer to table 1 in box "Any other information on results incl. tables".

Other effects:

All animals appeared active and healthy during the study. Apart from the eye irritation noted in Table 1 below there were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.

Table 1 : Eye irritation score

Animal No	Effect	Time after administration
		Hours				Days
		1	24	48	72	4	7	10
3401	Redness	2	2	1	1	1	1	0
	Chemosis	1	0	0	0	0	0	0
	Discharge	2	1	1	1	1	1	0
	Iritis	0	0	0	0	0	0	0
	Opacity	1	1*	0	0	0	0	0
	Area	2	1	4	4	4	4	4
3402	Redness	2	2	2	1	0	0	-
	Chemosis	2	0	0	0	0	0	-
	Discharge	3	2	2	1	0	0	-
	Iritis	1	0	0	0	0	0	-
	Opacity	1	0*	0	0	0	0	-
	Area	2	4	4	4	4	4	-
3403	Redness	2	2	1	1	0	0	-
	Chemosis	2	0	0	0	0	0	-
	Discharge	3	2	2	1	1	0	-
	Iritis	1	0	0	0	0	0	-
	Opacity	1	0*	0	0	0	0	-
	Area	1	4	4	4	4	4	-

* 2% ophthalmic fluorescein sodium used to verify the absence of corneal opacity.

Interpretation of results:

GHS criteria not met

Conclusions:

(3E)-dec-3-en-2-one caused irritation when applied to rabbit eyes, but does not warrant classification as an eye irritant in accordance to CLP regulation 1272/2008.

Executive summary:

In a primary eye irritation study conducted in accordance to OECD guideline 404, 0.1 mL of the test item was instilled into the conjunctival sac of the right eye of three young adult female New Zealand albino rabbits.  Animals then were observed for 10 days. Irritation was scored by the method of Draize. All animals appeared active and healthy during the study. There were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour. One hour after test substance instillation, all three treated eyes exhibited corneal opacity and 'positive' conjunctivitis and two treated eyes exhibited iritis. The overall incidence and severity of irritation decreased gradually with time. All animals were free of ocular irritation by Day 10. Based on the results, no classification for eye irritation is warranted in accordance to CLP regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin and eye irritating potential of the target substance (3E)-dec-3-en-2-one were assessed in twoin vivostudies conducted according to OECD test guideline 404 and 405, respectively.

In a primary dermal irritation study conducted according to OECD 404 three albino New Zealand White rabbits were dermally exposed to 0.5 mL the test item for 4 hours under semi-occlusive conditions. Animals then were observed for 14 days. Irritation was scored by the method of Draize. In this study, the test item is severely irritating to the skin based on the observation made. One hour after patch removal, all three treated sites exhibited well-defined to severe erythema and moderate oedema. At 48 hours through 72 hours, irritation increased to severe erythema for one animal. The overall incidence and severity of irritation decreased gradually thereafter. Although hyperkeratosis and desquamation were noted for all three animals between Days 7 and 14, they were free of erythema and oedema by Day 14. Based on these findings, the test item is considered to be irritant to the skin and in accordance with CLP Regulation 1272/2008 classification as Skin Irrit. 2 (H315) is warranted.

In a primary eye irritation study conducted in accordance to OECD guideline 405, 0.1 mL of the test item was instilled into the conjunctival sac of the right eye of three young adult female New Zealand albino rabbits. Animals then were observed for 10 days. Irritation was scored by the method of Draize. All animals appeared active and healthy during the study. There were no other signs of gross toxicity, adverse pharmacologic effects, or abnormal behaviour. One hour after test substance instillation, all three treated eyes exhibited corneal opacity and 'positive' conjunctivitis and two treated eyes exhibited iritis. The overall incidence and severity of irritation decreased gradually with time. All animals were free of ocular irritation by Day 10. Based on the results, no classification for eye irritation is warranted in accordance to CLP regulation 1272/2008.

Justification for classification or non-classification

Based on the results from thein vivoacute dermal irritation study conducted in accordance to OECD test guideline 404, classification as Skin Irrit. 2 (H315) is warranted in accordance with CLP Regulation 1272/2008.

Based on the results obtained from the in vivo acute eye irritation study which was conducted in accordance with OECD test guideline 405, the target substance can be considered as non-irritant to the eye and no classification is warranted in accordance with CLP Regulation 1272/2008.