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Diss Factsheets

Administrative data

Description of key information

All control sites of all animals were without positive skin reaction

In both control groups all test substance treated sites were normal after challenge exposure.

According to the scheme of Magnusson and Klingman, atest substance is graded as "weakly sensitising" in the guinea pig maximisation test if 0-8% of the treated animals show a positive effect.

Therefore the test substance is classified as weakly sensitising agent when applied as a 5% solution for intradermal induction exposure and undiluted (100%) for epicutaneous induction and challenge exposure.

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:
July 1992-December 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
and under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
LLNA study was adopted at a later stage
Specific details on test material used for the study:
50% aqueous solution of N-methyl-N-ethyl-Pyrollidinium-Bromid
CAS # 69227-51-6
Batch # 0691
pH 6-9
Contents of quaternary compounds 49.9%
Supplier Chemson, Polymer-additive Gesellschaft m.b.H A-9601 Arnolstein
Storage at approx. 5°C in the dark
colorless liquid

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
Supplier Charles river Wiga GmbH, D-8741 Sulzfeld
Number in preliminary study 3 females
Number in main study 40 females
Body weight (gr): Control group mean 306 (-1 day) 453 (24 day); test substance group mean 306 (-1) 473 (24 day)
Animal maintenance:
Hygiene: improved hygienic condition.
Room number B3-10
Room temperature; average of 22°C
Relative humidity: average of 55%
Air exchange: 12/h
Light: artificial light from 6 a.m to 6 p.m
Cages: Makrolon cages type III (23 cm x 39 cm x 15 cm) with wire mesh lids, single caging.
Feed: Altromin standard Diet No. 3022, ad libitum.
Bedding material: wood chips (aspen) from Finn Tapvei Ky, SF-73600 Kaavi.
Water: Tap water, acidified to pH 3 with HCl, offered in Makrolon bottles with stainless steel canules, ad libitum.
Identification of animals: numbers tattooed in the pinna of the right ear.
Acclimatisation: ca. one week

Route:
intradermal
Vehicle:
physiological saline
Remarks:
for induction exposure of all groups
Concentration / amount:
5% solution in physiological saline for intradermal induction exposure
Adequacy of induction:
not specified
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% undiluted
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100% undiluted
No. of animals per dose:
to find out the appropriate concentrations for the main study 3 female guinea pigs were used. 4 different concentrations of the test substance were administered epicutaneously in the lumbar region and 4 different concentrations were applied intradermally in the interscapular region.
Intradermal injuction:
Test substance concentration: 5%, 1%, 0.1% and 0.01% in physiological saline. No lesions in the skin were noted at anyconcentration noted. therefore the highest concentration, 5% was used for the intradermal induction in the main study.
Epicutanous application:
Test substance concentrations were 100%, 30% 10% and 1%in distilled water. No adverse skin reactions could be detected at any concentration. therefore it was decided to use highest concentration (undilluted test substance) for the epicutaneous induction exposure and for challenge exposure in the main study.

main study


Details on study design:
First induction exposure: intradermal injuctions of the test substance, of FCA (to enhance a possible sensitisation) and of the test substance diluted with FCA. Application site was an area of approx. 2 cm X 4 cm in the interscapular region.
Second induction exposure: epicutaneous application of the test substance to the sites of the intradermal injuctions.
Challenge exposure: epicutaneous application of the test substance to the left flanks and application of the vehicle to the right flanks of all animals.
Skin reactions of the challenge exposure were recorded. Positive skin reactions of the test substance treated sites indicate a sensitising effect of the test substance, if the scores are higher than those of the vehicle treated sites and if the rate of those-positively reacting-animals is higher than the corresponding percentage of animals in the negative control group.

main test: 20 females, intradermal exposure, test substance 5% in physiological saline; epicutaneous exposure, test substance undiluted (100%); Challenge exposure, left flank , test substance, undiluted (100%), right flank distilled water.
Challenge controls:
negative control, left flank test substance, undiluted (100%); right flank distilled water 20 females
Positive control substance(s):
yes
Remarks:
1,4-phenylenediamine
Reading:
other: mortality
Group:
other: all animals
Dose level:
all doses
Clinical observations:
all animals survived till end of the study
Remarks on result:
other: no mortality
Reading:
other: Body weight
Group:
other: all animals
Dose level:
all doses
Clinical observations:
Body weight gain was within normal range in all groups.
Remarks on result:
other: no effect on body gain
Reading:
other: General observations
Group:
other: epicutaneous exposure (induction, challenge)
Clinical observations:
immediately after the begining of all epicutaneous exposures (induction, challenge) the motor activities of all animals were increased. this is due to the dressings which restrict the freedom of movement. Soon afterwards the behaviour was regular again.
Remarks on result:
other: motor activity was back to normal
Key result
Reading:
other: skin reaction after intradermal induction exposure
Group:
test chemical
Clinical observations:
local irritations observed in all animals begining on the day after injections. local erythema, became more severe and led to ulcerations. lesions did not heal until the end of the study. these are effects of freunds adjuvant.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: Skin reaction after epicutaneous induction exposure
Group:
test chemical
Clinical observations:
All animals of all groups had severe erythema and oedema in the interscapular region, which were attributed to the adjuvant
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: after challenge exposures
Group:
other: control
Clinical observations:
control sites were normal
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: after challenge exposure
Group:
negative control
Clinical observations:
no positive reactions were noted 24 and 48 hr after challenge exposure
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: after challenge exposure
Group:
test chemical
Clinical observations:
no positive reactions were noted
Remarks on result:
no indication of skin sensitisation
Reading:
other: intradermal induction, epicutanous induction exposure, epicotinous challenge exposure
Group:
positive control
Dose level:
0.5% in physiological saline for intradermal induction; 25% in white petrolium for epicutanous induction exposure, 10% in w. petrolium for epicotinous challenge exposure
Clinical observations:
cotrol group 100% positive reaction (oedema), the treated sites were regarded as sensitized 24 and 48 hr after challenge. No positive reactions occured in control and test substance treated area of negative control
Remarks on result:
positive indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
All control sites of all animals were without positive skin reaction
In both control groups all test substance treated sites were normal after challenge exposure.
According to the scheme of Magnusson and Klingman, atest substance is graded as "weakly sensitising" in the guinea pig maximisation test if 0-8% of the treated animals show a positive effect.
Therefore the test substance is classified as weakly sensitising agent when applied as a 5% solution for intradermal induction exposure and undiluted (100%) for epicutaneous induction and challenge exposure.
Executive summary:

Maximisation test according to Magnusson and kligman (OECD 406) was conducted on guinea pigs in order to reveal a possible sensitising potential of 50% aqueous solution of N-Methyl-N-Ethyl-Pyrollidinium-Bromid (MEP).

20 female guinea pigs were used as test substance group and 20 as negative controls.

there were 2 induction exposures (intradermally and epicutaneously) and one epicutaneous challenge exposure. The test substance concentrations were 5% in physiological saline for intradermal induction and 100% (undiluted) for epicutaneous induction and challenge exposures.

Application of Freunds adjuvant was included in the intradermal exposure of both groups to enhance possible sensitisation.

All animals survived till the end of the study. Intradermal injections of Freunds adjuvant caused severe local reactions in all animals (a known effect of the adjuvant). Sensitisation exccluded, no other adverse effects were noted.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Justification for classification or non-classification