Acetophenone

Endpoint summary

Description of key information

Skin sensitisation: not considered as sensitising (based on a weight of evidence approach with test results from a modified Draize test and a Human Repeated Insult Patch Test).

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: peer reviewed database

Principles of method if other than guideline:

peer reviewed database, method not reported

GLP compliance:

not specified

Type of study:

other: not specified

Justification for non-LLNA method:

The data was available before the validation of the LLNA method.

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Remarks on result:

no indication of skin sensitisation

/LABORATORY ANIMALS: ... No skin- sensitizing potential was demonstrated. when solutions of acetophenone were tested on guinea-pigs. [BIBRA working group; TA:Toxicity profile. BIBRA Toxicology International: 4 (1991) ]**PEER REVIEWED**

Reference 2

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study meets generally accepted scientific principles as a modification of a standard Draize test procedure, selection of test concentrations based on preliminary irritation tests both for intradermal injection and topical application, suffcient description of test protocol; minor restrictions: only qualitative test result presented in a table, no data on sensitisation scores for the test group or individual test animals; limited number of 10 test animals, no replicate study; study acceptable as supporting information

Principles of method if other than guideline:

Draize test with modified protocol for induction

GLP compliance:

no

Type of study:

Draize test

Justification for non-LLNA method:

The study was carried out in 1978, before the validation of the LLNA method.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: inbred from own colony
- Weight at study initiation: 350 g
- Housing: in pairs
- Diet: ad libitum
- Water: ad libitum

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

2.5 x ICC (ICC: 0.25%)

Day(s)/duration:

4 injections on Day 0

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

no data

Concentration / amount:

intradermal: ICC = 0.25%
epicutaneous: ACC = 20%

Day(s)/duration:

Day 14 (24h duration for epicutaneous application)

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10

Details on study design:

- Induction treatment:
0.1 ml aliquots of the test substance at 2.5 times the injection challenge concentration were administered on one occasion as 4 intradermal injections at 4 sites which overlie the 2 auxilary and 2 inguinal lymph nodes. Induction time was 14 days.

- Challenge treatment:
intradermal injection in one flank and topical application on the other flank by spreading 0.1 ml of the test substance onto the shaved flank in a small circular area which was not covered.

- Scoring of reactions:
24 hrs later
Apparent sensitization reactions were confirmed 7 days later by a second challenge.
In the absence of sensitisation reactions at first challenge, the induction and challenge procedures were repeated, but htis time a confirmatory challenge with controls was included.

- Controls:
At each challenge 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC, respectively.

- Scoring:
Injection reaction: total score based on size, erythema and oedema.
Positive reaction: total score of individual reaction significantly greater than the total average score for control reactions.
Application reaction: 0 to +++ scale
Positive reaction: (a) scoring >= + and (b) no erythema reactions in controls

Positive control substance(s):

yes

Remarks:

other test substances that yielded positive test results

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.25% intradermal (ICC) and 20% epicutaneous (ACC)

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Remarks:

No. with + reaction not available but conclusion is "Non-sensitizer"

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.25% intradermal (ICC) and 20% epicutaneous (ACC)

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Remarks:

No. with + reaction not available

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

positive indication of skin sensitisation

Remarks:

in the same publication positive results were obtained with several other substances used as positive controls.

Negative (no details of test results reported)

Interpretation of results:

GHS criteria not met

Conclusions:

Acetophenone was assessed as non-sensitiser in a modified Draize test with Hartley guinea pigs.

Executive summary:

Acetophenone was tested in a modified Draize test with groups of 10 male and female Hartley guinea pigs. For induction treatment, 0.1 ml aliquots of the test substance at 2.5 times the injection challenge concentration (ICC) were administered on one occasion as 4 intradermal injections at 4 sites which overlied the 2 auxilary and 2 inguinal lymph nodes. After an induction time of 14 days, the challenge treatment consisted of an intradermal injection in one flank and topical application (uncovered) on the other flank with an application challenge concentration (ACC) of 20 %. Reactions were scored 24 hrs later. In the absence of sensitization reactions at first challenge, the induction and challenge procedures were repeated, but this time a confirmatory challenge with controls was included. At each challenge 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC, respectively. Acetophenone was assessed as non-sensitiser (no details on test results available).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

An evaluation of the sensitizing potential of acetophenone is possible based on a weight of evidence approach with test results from a modified Draize test and a Human Repeated Insult Patch Test.

 

Acetophenone was assessed as non-sensitizer in a modified Draize test (no guideline study) with 10 Hartley guinea pigs at challenge concentrations of 0.25% for injection and 20% for topical application. The selection of test concentrations was based on preliminary irritation tests both for intradermal injection and topical application (Sharp et al., 1978). No information is available on sensitisation scores or other details of test results.

 

In a Human Repeated Insult Patch Test, 2% acetophenone in petrolatum did not provoke a sensitizing response in human volunteers (number not specified). The test protocol consisted of pretreatment of the skin test site with a mild irritant, five 48-hour closed patches during a 10-day induction period followed by 10-14 days without treatment, and a final 48-hour closed patch for challenge (Kligman, 1971, cited from BIBRA, 1987).

Migrated from Short description of key information:
A modified Draize test with Hartley guinea pigs (no guideline study) revealed that acetophenone is a no sensitizer. In a peer reviewed database acetophenone is reported to be not sensitizing.
Human Repeated Insult Patch Test: test result negative

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on a weight of evidence approach with test results from a modified Draize test and a Human Repeated Insult Patch Test, showing negative responses, no classification of acetophenone for skin sensitisation is required.