Acetophenone

Endpoint summary

Description of key information

Skin irritation: not irritating (testing procedure being comparable to OECD Guideline 404, skin contact 24 hrs with occlusion): primary irritation score for intact skin 0.5 (Key study: Worstmann, 1980)

Eye irritation potential (testing procedure comparable to OECD Guideline 405): no effects (Key study: Worstmann, 1980; supporting study: Marzin, 1978; Worstmann, 1980)

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:

November 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(more severe exposure conditions: prolonged skin contact of 24 hrs, occlusive dressing, treatment of intact and scarified skin, scoring of skin lesions at 24 and 72 hrs)

Qualifier:

according to guideline

Guideline:

other: Consumer Product Safety Commission of the USA, Code of Federal Regulations, Title 16, Section 1500.41

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: J. Scheele, Büderich/Westfalen, 4760 Werl, Germany
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 1 °C
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Remarks:

shaved, or shaved and scarified

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

24 hrs

Observation period:

24 and 72 hrs after start of exposure

Number of animals:

6

Details on study design:

TEST SITE
- Application: the test substance was dispensed on 2.5 x 2.5 cm2 patches which were then applied to the prepared skin areas and fixed by elastoplast; patches were removed after 24 hrs of skin contact
- Area of exposure: 2.5 x 2.5 cm2
- Type of wrap if used: unpermeable material as e.g. a rubber cloth

SCORING SYSTEM: according to Draize, comparable to OECD Guideline 404 (for details see Table 1)
Calculation of primary dermal irritation index:
sum of the scores of each animal for [(Erythema and eschar formation) + (Oedema formation) from intact skin] + [(Erythema and eschar formation) + (Oedema formation) from scarified skin] divided by 24; maximal achievable value is 8.0
For criteria for classification see Table 2

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 hrs

Score:

0.63

Reversibility:

fully reversible within: 48 hrs after termination of application

Remarks on result:

other: includes reactions both for intact and abraded skin

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs

Score:

0.5

Reversibility:

fully reversible within: 48 hrs after termination of application

Remarks on result:

other: reaction for intact sklin

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 0.17

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Irritant / corrosive response data:

see Table 3

Table 3: Overview on skin reactions after single occlusive application of acetophenone for 24 hrs (scores at the end of the exposure period)

Rabbit No.	Erythema score		Edema score
	intact skin	scarified skin	intact skin	scarified skin
1	1	1	1	1
2	1	1	1	1
3	0	0	1	1
4	0	0	1	1
5	0	2	0	1
6	0	0	0	0

All changes were fully reversible within the following 48 hrs: all scores were 0

Interpretation of results:

GHS criteria not met

Conclusions:

With a primary irritation index of 0.5 after a 24-hr contact with intact skin, the classification would be "not irritating" according to the ETAD criteria.
No classification according to EU criteria is expected as mean irritation scores for erythema or edema were significantly below the critical value of 2.0 even under the conditions of this test with a prolonged contact time of 24 hrs instead of 4 hrs.

Executive summary:

Skin irritation scores according to Draize were assessed on skin sites of six rabbits (both shaved intact skin or shaved scarified skin) following a 24-hr occlusive application of 0.5 mL acetophenone on a patch. Except for the prolonged skin contact the testing procedure was comparable to OECD Guideline 404. Findings at the end of exposure on intact skin were very slight erythema in 2/6 rabbits and very slight oedema in 4/6 rabbits. Abraded skin sites showed very slight erythema in 2/6 and slight erythema in 1/6, and very slight oedema in 5/6 rabbits. All effects were fully reversible within the following 48 hrs. With a primary irritation index (PII) of 0.63 after a 24-hr skin contact, acetophenone was assessed as slightly irritating to rabbit skin according to ETAD criteria (PII of 0.6 -3.0) when the reactions of both intact and scarified skin were considered. With a PII of 0.5 for intact skin acetophenon is non irritating.

No classification according to EU criteria is expected as mean irritation scores for erythema or edema with maximal scores of 1.0 for intact skin were significantly below the critical value of 2.0 even under the conditions of this test with a prolonged contact time of 24 hrs instead of 4 hrs.

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

Study period:

November 1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(no scoring at 1 hr after instillation of test substance)

Qualifier:

according to guideline

Guideline:

other: Consumer Product Safety Commission of the USA, Code of Federal Regulations, Title 16, Section 1500.42

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: J. Scheele, Büderich/Westfalen, 4760 Werl, Germany
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +- 1 °C
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

no washout of test substance

Observation period (in vivo):

24, 48, 72 hrs, 7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to Draize (see Table 1)

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48 and 72 hrs

Score:

0

Max. score:

0

Remarks on result:

other: no effects at any timepoint

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Acetophenone had no irrtitating effect on rabbit eyes.

Executive summary:

The eye irritation potential of 0.1 mL acetophenone was investigated in 6 rabbits following a testing procedure comparable to OECD Guideline 405 (without scoring at 1 hr post instillation). According to the scoring system of Draize there was no adverse reaction at any timepoint from 24 hrs to 7 days post application. Acetophenone had no irrtitating effect on rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

Two skin irritation studies are available that applied test protocols similar to OECD Guideline 404 except for the more severe condition of a 24 hr skin contact under an occlusive dressing and an observation period limited to 72 hrs after the start of exposure (Marzin, 1978; Worstmann, 1980). Based on the slight signs of irritation reported at the end of exposure and the tendency of the skin effects to be reversible within the next 48 hrs, these studies can be used as key studies to make a conclusion on the classification of skin irritation. As, even under these more severe exposure conditions, only 1 from 4 rabbits (Marzin, 1978) or none from 6 rabbits (Worstmann, 1980) had mean irritation scores (mean for 24 -72 hrs) for erythema or oedema > 2.3, no classification results based on the criteria of EU Directive 1272/2008.

Eye irritation

Under test conditions comparable to OECD Guideline 405, acetophenone had no irritating effect on rabbit eyes (Key study: Worstmann, 1980; supporting study: Marzin, 1978). Indications of a possible irritation effect on rabbit eyes were reported in old, insufficiently documented studies (Smyth and Carpenter, 1944; Carpenter and Smyth, 1946), that are not comparable to the guideline conditions of the key studies and are therefore not adequate for classification. The more recent studies leading to no irritation are superseding the old study (quoted as reliability 4 according to Klimisch criteria) having lead to DSD Annex I classification as Xi R36.

Justification for selection of skin irritation / corrosion endpoint:
Comparable to guideline study with acceptable deviations, sufficiently documented; study acceptable as key study ((quoted as reliability 2 according to Klimisch)

Justification for selection of eye irritation endpoint:
Comparable to guideline study with sufficient documentation; study acceptable as key study (quoted as reliability 1 according to Klimisch)

Justification for classification or non-classification

According to EU regulation 1272/2008 no classification for skin irritation is justified, as mean irritation scores for erythema or oedema were significantly below the critical value of 2.3 even with a prolonged contact time of 24 hrs instead of the standard 4 hrs.

According to EU regulation1272/2008 there is no classification for eye irritation as no significant eye changes were observed in the key studies.

However as acetophenone is classified as Eye Irrit. 2 H319 in Annex VI of CLP Regulation, it shall be classified and labelled in accordance with this harmonised classification.