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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride
EC Number:
303-085-5
EC Name:
2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride
Cas Number:
94158-14-2
Molecular formula:
C9H11NO3.ClH
IUPAC Name:
2-(1,3-benzodioxol-5-ylamino)ethanol hydrochloride
Test material form:
solid: particulate/powder
Details on test material:
beige, cryst. powder

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/J
Sex:
female

Study design: in vivo (LLNA)

Vehicle:
other: DMSO and in aqua/acetone (1:1) / olive oil (4:1)
Concentration:
0.5, 1.5, 5.0 and 10.0 % (w/v)
No. of animals per dose:
5
Positive control substance(s):
other: p-phenylenediamine (PPD) at 1 % in DMSO

Results and discussion

Positive control results:
The positive control (PPD, 1 % in DMSO) caused a stimulation index of 12.5, which demonstrated the sensitivity of the test system used.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Value:
6.4
Test group / Remarks:
0.5 % test material in DMSO
Parameter:
SI
Value:
5
Test group / Remarks:
1.5 % test material in DMSO
Parameter:
SI
Value:
8
Test group / Remarks:
5 % test material in DMSO
Parameter:
SI
Value:
12.4
Test group / Remarks:
10 % test material in DMSO
Parameter:
EC3
Value:
< 0.5
Test group / Remarks:
DMSO as vehicle
Remarks on result:
other: since all stimulation indices were above 3, an EC3 value < 0.5 % can be deduced from these findings.
Parameter:
SI
Value:
4.3
Test group / Remarks:
0.5 % test material in aqua/acetone/olive oil
Parameter:
SI
Value:
3.6
Test group / Remarks:
1.5 % test material in aqua/acetone/olive oil
Parameter:
SI
Value:
3.3
Test group / Remarks:
5 % test material in aqua/acetone/olive oil
Parameter:
SI
Value:
4.4
Test group / Remarks:
10 % test material in aqua/acetone/olive oil
Parameter:
EC3
Value:
< 0.5
Test group / Remarks:
aqua/acetone/olive oil as vehicle
Remarks on result:
other: since all stimulation indices were above 3, an EC3 value < 0.5 % can be deduced from these findings.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL induced a biologically relevant immune response in local lymph nodes after dermal application to the mouse ear with both vehicles tested. HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL is evaluated to be a skin-sensitiser under the described test conditions in DMSO and acetone/water (1:1) mixed with olive oil (4:1), with an EC3 value below 0.5 %.
The responses noted in both groups are considered positive and indicates a strong skin sensitising potency of HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL.
Executive summary:

The skin sensitising potential of HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL was investigated in female CBA/J mice by measuring the cell proliferation in the draining lymph nodes after topical application on the ear.

25 μl of 0 (vehicles only), 0.5, 1.5, 5 and 10 % of HYDROXYETHYL-3,4-METHYLENEDIOXY-ANILINE HCL in DMSO or in a mixture of aqua/acetone (1:1) and olive oil (4:1) (equal to the maximum solubility) were applied to the surface of the ear of five female CBA/J mice per group for three consecutive days. After application, the ears were dried by means of a hair dryer for about 5 minutes. A positive control, p-phenylenediamine (PPD) at 1 % in DMSO, was investigated in parallel under identical test conditions.

Animals were checked for morbidity/mortality at least once daily. Observation for clinical signs was done daily before and at least once after dosing. Body weight was determined at day -1 and at day 5. At day 5, the mice received an intravenous injection of 250 μl phosphate buffered saline containing 23.5 μCi of [H3] methyl thymidine. Approximately five hours later, the mice were sacrificed by CO2-inhalation and the draining auricular lymph nodes were removed and weighed. After preparing a single cell suspension for each mouse, cells were precipitated by TCA and the radioactivity was determined (incorporation of [H3] methyl thymidine in the pellets) by means of liquid scintillation counting as disintegration per minute (dpm). The mean dpm per treated group was determined and the stimulation index (test item compared to the concurrent vehicle control) was calculated. The responses noted in both groups are considered positive and indicates a strong skin sensitising potency of HYDROXYETHYL-3,4-METHYLENEDIOXYANILINE HCL.

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