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Description of key information

Owing to a sensitization rate below 30%, classification of PBS 856 DS according to Council Directive 67/548/EEC, Commission Directive 93/21/EEC for Classification, Labelling and Packaging of Dangerous Substances, is not required.

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:
Sep 1995 - Nov 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The procedure of Magnusson and Kligman for adjuvant tests was followed.
Species:
guinea pig
Strain:
other: Pirbright White (Tif:DHP)
Sex:
male/female
Details on test animals and environmental conditions:
The test was performed on a total of 10 male and 10 female guinea pigs in the test group and 5 males and 5 females in the control
group, respectively, initially weighing between 338 to 430 g. The animals were housed individually in Macrolon cages (Type 3), randomly assigned to the different groups , identified by individual ear tags, kept at a constant room temperature of 22 ± 3°C, at a relative humidity of 30 to 70% and a 12 hours light cycle day. The animals received ad libitum standard guinea pig pellets - NAFAG 845, NAFAG, GossaujSG, Switzerland - and fresh water.
All batches of the diet are assayed for nutritive ingredients and contamination level by the manufacturer. Analytical results are available at the animal supply office. The drinking water quality fulfilled the critical parameters in the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972). The results of the routine chemical examination of water at source (Grundwasserfassung Stein) as conducted periodically by the water authority (Baudepartement des Kantons Aargau, Abteilung Gewasserschutz) are available to CIBA-GEIGY Limited, as well as the results of inhouse chemical analysis by the analytical laboratories of the Pharmaceutical Division, CIBA-GEIGY Limited.
Route:
intradermal and epicutaneous
Vehicle:
other: peanut oil, vaseline
Concentration / amount:
1% test substance in peanut oil (intradermal) and 50% test substance in vaseline (epicutaneous)
Route:
epicutaneous, occlusive
Vehicle:
other: peanut oil, vaseline
Concentration / amount:
1% test substance in peanut oil (intradermal) and 50% test substance in vaseline (epicutaneous)
No. of animals per dose:
test group: 10 males and 10 females
control group: 5 males and 5 females
Details on study design:
Intradermal Induction
The vehicle, peanut oil, was selected with respect to the solubility of the test article and lack of sensitising properties. The concentration for intradermal injections was selected on account of the solubility of the test article in standard vehicles, the local irritant potency and the systemic tolerability of the
test article in a pretest. The following concentrations of PBS 856 DS were examined in pretest animals in duplicate:
1, 3 and 5% (w/v) in peanut oil.
Local reactions at the injection sites were examined 48 hours after duplicate intradermal injections.
Epidermal Applications (induction and challenqe)
The concentration for the epidermal applications was selected on account of the primary irritation potential of the test article. The following concentrations of PBS 856 DS were examined in pretest animals in duplicate to determine the maximum subirritant concentration:
10, 30 and 50% (w/v) in vaseline.
At least 7 days before application of PBS 856 DS, two pairs of consecutive
intradermal injections of an adjuvant/saline mixture 1:1
(v/v; 0.1 ml per injection) were applied to the shaved neck of 2 guinea pigs. On each animal, 2 different concentrations of PBS 856 OS were tested simultaneously on the left and right flank using Hilltop chambers. Accordingly, each concentration was tested in duplicate. Naive skin site served as control (not reported). Occlu-sive dressing was applied for 24 hours. Skin responses were scored 24 and 48 hours after removal of the dressing according to the Draize scale.
Positive control substance(s):
yes
Remarks:
mercaptobenzothiazole, hexyl cinnamic aldehyde or potassiumdichromate
Positive control results:
Control group:
after 24 hours after 48 hours
vehicle control 0/10 0/10
test article 0/10 0/10

Test group:
vehicle control 0/20 0/20
test article 16/20 19/20


The reliability check resulted in positive response in 19 (9 males and 10 females) of 20 challenged guinea pigs after 48 hours, corresponding
to a sensitisation rate of 95%. There were no irritant skin reactions in control groups.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
1% test substance in vaseline
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
1% test substance in vaseline
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
1% test solution in vaseline
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
1% test solution in vaseline
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% 2-Mercaptobenzothiazole
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5% 2-Mercaptobenzothiazole
No. with + reactions:
19
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation

After removal of the occlusive dressing on Day 10 after epidermal induction, irritation at the application site was seen in all 20 guinea pigs of the test group.

Epidermal challenge of 10 male and 10 female guinea pigs (test group) resulted in positive responses in 1 female after 24 h and in 2 females after 48 h, corresponding to a sensitisation rate of 10%. No skin reactions were recorded for control animals.

Body weights were not affected by treatment with the test substance.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified

A guinea pig maximisation test was initiated to determine sensitising properties of PBS 856 DS after challenge exposure by skin contact. The procedure of Magnusson and Kligman for adjuvant tests was followed.
Epidermal challenge of 10 male and 10 female guinea pigs (test groups) resulted in positive responses in 1 female after 24 hours and in 2 females after 48 hours, corresponding to a sensitisation rate of 10%. No irritant skin reactions were recorded for control animals.
Body weights were unaffected by the treatment.
PBS 856 DS was graded as a mild sensitiser according to the Magnusson and Kligman maximisation scale.

Owing to a sensitization rate below 30%, classification of PBS 856 DS according to Council Directive 67/548/EEC, Commission Directive 93/21/EEC for Classification, Labelling and Packaging of Dangerous Substances, is not required.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

A guinea pig maximisation test was initiated to determine sensitising properties of PBS 856 DS after challenge exposure by skin contact. The procedure of Magnusson and Kligman for adjuvant tests was followed.

Epidermal challenge of 10 male and 10 female guinea pigs (test groups) resulted in positive responses in 1 female after 24 hours and in 2 females after 48 hours, corresponding to a sensitisation rate of 10%. No irritant skin reactions were recorded for control animals.

Body weights were unaffected by the treatment.

PBS 856 DS was graded as a mild sensitiser according to the Magnusson and Kligman maximisation scale.

Owing to a sensitization rate below 30%, classification of PBS 856 DS according to Council Directive 67/548/EEC, Commission Directive 93/21/EEC for Classification, Labelling and Packaging of Dangerous Substances, is not required.