N-(1,1-dimethyl-3-oxobutyl)acrylamide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

EC Number:

220-713-2

EC Name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

Cas Number:

2873-97-4

Molecular formula:

C9H15NO2

IUPAC Name:

N-(1,1-dimethyl-3-oxobutyl)acrylamide

Constituent 2

Reference substance name:

diacetone acrylamide

IUPAC Name:

diacetone acrylamide

Details on test material:

Appearance: White powder. Batch No.: SSHD 044Conditions of storage: In the dark, may be used under light. Stability in solution: Stable.

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Strain: Mice, CBA/CaOlaHsd. Supplier: Harlan Winkelman GmbH, D-33176 Borchen.Sex, specification: Females, healthy young adult nulliparous animals.Age of the animals: About 8 weeks at the first administration.Weight range of the animals at the first application: 16.9 - 22.3 g.Hygiene: Optimal hygienic conditions.Room temperature: Average of 22.0 °C (continuous monitoring and recording).Relative humidity: Average of 46.1 % (continuous monitoring and recording).Light: Only artificial light from 6.00 a.m. to 6.00 p.m.Cages: Single caging. Makrolon cages type II, (22 cm x 16,5 cm ground area, 15 cm high).Feed: Altromin maintenance diet for rats and mice, item No. 1324forte, ad libitum.Random samples of the feed are analysed for contaminants.Water: Tap water offered in Makrolon-bottles with stainless steel canules, ad libitum.Bedding material: Wood chips (aspen) Fa. ABEDD Dominik Mayr KEG, A 8580 Köflach. Reduction of microorganisms by autoclaving.Acclimatisation: 6 days.Identification of the animals: By shearing a defined fur region on the back of the animal.

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

Group Substances concentrationstotal amount of substance applied/animal A (low dose)25 % test substance37.5 mgB (mid dose)50 % test substance75 mgC (high dose)62.1 % test substance93.2 mgK (negative control) DMF 150 mgP (positive control) 25 % HCA in AOO (v/v)37.5 mgHCA: Hexyl cinnamic aldehyde.AOO: Acetone:olive oil (4:1, v/v).

No. of animals per dose:

Number of animals: 5 animals/group:3 test substance groups,negative control group, positive control group.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Results are presented as test/control ratio (Stimulation index, SI), calculated as dpm test group/dpm negative control group.(dpm = disintegrations per minute, corrected by the subtraction of the background)A substance is regarded as a sensitizer in the LLNA if the test substance induces a 3-fold or greater increase in 3HTdR incorporation into lymph node cells of test lymph nodes relative to that recorded for control lymph nodes, as indicated by the SI, together with the consideration of dose response.

Results and discussion

Positive control results:

Application of 25 % HCA in AOO resulted in an Stimulation Index (SI) of 5. This result proves the sensitivity of the strain of animals used and the reliability of the experimental technique.HCA: Hexyl cinnamic aldehyde.AOO: Acetone:olive oil (4:1, v/v).

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The SIs of the test substance groups were between 0.8 and 1.7.

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

Group dpm SInegative control 1964 1low dose 2602 1.3mid dose 1556 0.8high dose 3387 1.7positive control 49834 25.4

Any other information on results incl. tables

No abnormal behaviour or clinical signs were detected during the experiment in the animals.

No local irritations were observed at the application sites of all animals of all test substance groups and the negative control group throughout the whole study.

On Days 3-5 all animals of the positive control group had slight erythema at the application sites indicating slight irritative skin reactions.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Diacetone acrylamide is regarded as a non sensitizer in the LLNA according to the OECD-Guideline 429, "Skin Sensitisation: Local Lymph Node Assay", since the SIs of all examined test substance concentrations were clearly below 3.

Executive summary:

The Local Lymph Node Assay was performed to evaluate a possible skin sensitising potential of diacetone acrylamide according to the OECD-Guideline 429.

The stimulation indexes SIs of the tested test substance concentrations were 1.3 (low dose), 0.8 (mid dose) and 1.7 (high dose). The positive control substance led to a stimulation index of 25.4, thus demonstrating the validity of the experiment.

According to the OECD-Guideline 429, "Skin Sensitisation": Local Lymph Node Assay", diacetone acrylamide is not regarded as a skin sensitier in the LLNA.