4-methylpent-3-en-2-one

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The Magnussion and Kligman test was perfomed before the implementation of the LLNA guideline.

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Centre d'Elevage Lebeau, 78950 Gambais, France
- Age at study initiation: approximately 3 months old
- Weight at study initiation: mean body weight ± standard deviation of 340 ± 22 g for males and 326 ± 15 g for females
- Housing: individually in polycarbonate cages
- Diet (ad libitum): 106 pelleted diet available ad libitum
- Water (ad libitum): filtered by a F.g. Millipore membrane and provided ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): 12 cycles/hr
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal and epicutaneous

Vehicle:

paraffin oil

Concentration / amount:

0.1 ml of 10% (w/w) of test substance in vehicle for intradermal injections and 0.5 mL of the test substance in original form for cutaneous route

Route:

intradermal

Vehicle:

paraffin oil

Concentration / amount:

0.1 ml of 10% (w/w) of test substance in vehicle for intradermal injections and 0.5 mL of the test substance in original form for cutaneous route

No. of animals per dose:

5 animals/sex for control and 10 animals/sex for treated group

Details on study design:

- Induction phase by intradermal and cutaneous routes
. Intradermal route
On day 1, six injections were made deep into the dermis of a clipped area (4 cm x 2 cm) in the dorsal region between the shoulders, using a needle mounted on a 1 ml glass syringe.

Three injections of 0.1 ml were made into each side of this shoulder region, as follows:
Injection sites* Treated group Control group
Anterior l: FCA diluted at 50% (v/v) with 0.9% NaCI 1: FCA diluted at 50% (v/v) with 0.9% NaCI
Middle 2: test substance at 10% (w/w) in paraffin oil 2: vehicle
Posterior 3: mixture of 50150 (w/v) of 1 and 2 3: mixture of 50150 (w/v) of 1 and 2

* : three pairs of sites
FCA: Freund's complete adjuvant

. Cutaneous route
On day 7, the scapular area was clipped. As the test substance was shown to be non-irritant during the preliminary tests, the animals were treated with 0.5 ml of sodium lauryl sulfate (10% w/w) in vaseline in order to induce local irritation.
On day 8, a topical application to the region of the intradermal injections (4 cm x 2 cm) was performed.
Control group
. application of 0.5 ml of the vehicle.
Treated Loup
. application of 0.5 ml of the test substance in its original form.

The test substance and the vehicle were prepared on a dry gauze pad, which was then applied to the dorsal region between the shoulders and held in place for 48 hours by means of an adhesive hypoallergenic dressing and an adhesive anallergenic waterproof plaster.
No residual test substance was observed after removal of the dressing.
Cutaneous reactions were recorded one hour after removal of the occlusive dressing.

- Challenge phase
On day 22, the animals from both groups received an application of 0.5 ml of the test substance in its original form to the posterior right flank, and 0.5 ml of the vehicle to the posterior left flank. This application was performed using a 1 ml plastic syringe . The test substance and the vehicle were prepared on a dry gauze pad , then applied to a 4 cm2 (2 cm x 2 cm) clipped area of the skin. The gauze pad was held in contact with the skin for 24 hours by means of an occlusive, hypoallergenic dressing and an adhesive anallergenic waterproof plaster.
No residual test substance was observed after removal of the dressing.

Positive control substance(s):

yes

Remarks:

2,4-Dinitrochlorobenzene (DNCB)

Positive control results:

According to the Magnusson and Kligman method, the test substance 2,4-DINITRO CHLOROBENZENE at a concentration of 0.5% (w/w) induced positive skin sensitization reactions in 50% of the guinea-pigs

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0.5 mL of the test substance in original form

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.5 mL of the test substance in original form. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0.5 mL of the test substance in original form

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.5 mL of the test substance in original form. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.5 mL of the test substance in original form

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.5 mL of the test substance in original form. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.5 mL of the test substance in original form

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5 mL of the test substance in original form. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.

- Clinical examinations

No mortalities were observed during the study.

Hypoactivity and piloerection were observed in one animal (female No. 258 of the treated group), from days 15 to 23.

The body weight gain of the treated animals was normal when compared to that of the control animals.

- Scoring of cutaneous reactions

. End of the induction period

On day 10, after topical application of the induction period, signs of irritation were observed at the test site (dorsal region between shoulders) in the control and treated groups.

. Challenge application

No cutaneous reactions were observed.

No residual test substance was observed after removal of the dressing.

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

According to the maximization method of Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of Mesityl oxide were observed in guinea-pigs.

Executive summary:

The skin sensitization potential of mesityl oxide was assessed in a study performed according to OECD Guidelines 406 and in compliance with GLP in male and female Dunkin Hartley guinea pigs (de Jouffrey, 1997). In the main study, 10 animals comprised the mesityl oxide test group and 5 animals comprised the vehicle control group. The intracutaneous induction was carried out with 0.1 ml of 10% (w/w) of mesityl oxide in vehicle (paraffin oil), and dermal induction was performed with 0.5 mL of undiluted mesityl oxide to the dorsal area under occlusive conditions. The challenge exposure also was conducted with 0.5 mL of undiluted mesityl oxide. Additionally, all animals were dermally exposed to 0.5 mL of 10% w/w sodium lauryl sulphate (SDS) in vaseline 24 hours prior to topical sensitization of the skin area in order to induce local irritation (mesityl oxide was shown to be non-irritating in the preliminary test). Skin reactions were observed and recorded 1 hour after dermal induction and 24 and 48 hours after the challenge exposure, all according to the grading scale by Magnusson and Kligman. Test and control animals displayed normal body weight gain throughout the investigation and no mortalities were observed. Clinical signs included hypoactivity and piloerection in one female of the treated group from Days 15 to 23. On Day 10, following dermal induction, signs of irritation were observed at the site of application in both control and treated groups. Following the challenge exposure, no incidences of erythema or oedema were observed, either at 24 or 48 hours, in all animals. Under the experimental conditions and according to the maximization method of Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of mesityl oxide were observed in guinea-pigs. Therefore, the results of this study demonstrated that mesityl oxide showed no evidence of contact skin sensitization in guinea pigs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitization potential of mesityl oxide was assessed in a maximization study performed according to OECD Guidelines 406 and in compliance with GLP in male and female Dunkin Hartley guinea pigs (de Jouffrey, 1997). In the main study, 10 animals comprised the mesityl oxide test group and 5 animals comprised the vehicle control group. The intracutaneous induction was carried out with 0.1 ml of 10% (w/w) of mesityl oxide in vehicle (paraffin oil), and dermal induction was performed with 0.5 mL of undiluted mesityl oxide to the dorsal area under occlusive conditions. The challenge exposure also was conducted with 0.5 mL of undiluted mesityl oxide. Additionally, all animals were dermally exposed to 0.5 mL of 10% w/w sodium lauryl sulphate (SDS) in vaseline 24 hours prior to topical sensitization of the skin area in order to induce local irritation (mesityl oxide was shown to be non-irritating in the preliminary test). Skin reactions were observed and recorded 1 hour after dermal induction and 24 and 48 hours after the challenge exposure, all according to the grading scale by Magnusson and Kligman. Test and control animals displayed normal body weight gain throughout the investigation and no mortalities were observed. Clinical signs included hypoactivity and piloerection in one female of the treated group from Days 15 to 23. On Day 10, following dermal induction, signs of irritation were observed at the site of application in both control and treated groups. Following the challenge exposure, no incidences of erythema or oedema were observed, either at 24 or 48 hours, in all animals. Under the experimental conditions and according to the maximization method of Magnusson and Kligman, no cutaneous reactions attributable to the sensitization potential of mesityl oxide were observed in guinea-pigs. Therefore, the results of this study demonstrated that mesityl oxide showed no evidence of contact skin sensitization in guinea pigs

Migrated from Short description of key information:
According to a Magnusson and Kligman maximization test (OECD 406), no cutaneous reactions attributable to the sensitization potential of Mesityl oxide were observed in guinea-pigs.

Justification for selection of skin sensitisation endpoint:
GLP guideline study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

This information is not available.

Justification for classification or non-classification

No classification is warranted for skin sensitization according to Regulation no. 1272-2008 and Directive 67/548/EEC.