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Diss Factsheets

Administrative data

Description of key information

Based on a reliable study according to OECD 406 the test substance is considered to be a strong skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
GPMT
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986/04 to 1986/05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1981 [GPMT]
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EC Guideline (Acute Toxicity - Sensitisation of Skin, Amtsblatt der Europaeischen Gemeinschaften No. L 251/113-116 of 19.9.1984).
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The in vivo test was done before LLNA as first-choice method for in-vivo testing was set into force.
Species:
guinea pig
Strain:
other: SPF, DHPW
Sex:
male
Details on test animals and environmental conditions:
Body weight of the test animals: 312 - 379 g
Age: 5-7 weeks
Acclimatisation period: 8 days
Housing: The animals were kept, five to a Makrolon cage type IV, on lowdust wood granules.

Temperature: approx. 21° - 24° C
Humidity: approx. 30 % - 55 %
light/dark rhythm: twelve hours.
A forced ventilation system was installed
Route:
intradermal
Vehicle:
physiological saline
Concentration / amount:
0.1% / 0.1 mL
Day(s)/duration:
day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25% / 0.5 mL
Day(s)/duration:
1 week after intradermal induction for 48 hours
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
25% / 0.5 mL
Day(s)/duration:
3 weeks after intradermal induction / 24 hours
No.:
#2
Route:
epicutaneous, occlusive
Vehicle:
physiological saline
Concentration / amount:
2.5% / 0.5 mL
Day(s)/duration:
5 weeks after intradermal induction / 24 hours
Adequacy of challenge:
other: This concentration was chosen to establish whether the findings obtained after the first challenge were present at a much lower concentration.
No. of animals per dose:
Three groups (one test compound, propineb, and two control groups), test compound, propineb consisting of 20 males. Two control groups with 10 males/group
Details on study design:
Intradermal induction: An 0.1 % substance formulation was used, since this came closest to the degree of healing of the control in the pilot test. Starting at the back of the neck, three intra-dermal injections were given parallel on each side. The intervals between the injection sites were approx. 1 to 2 cm. The volume injected per site was 0.1 mL. The skin was shorn 24 hours before administration.

in the test group, the first injection site pair (cranial): Freund's complete adjuvant (Difco Lab.) diluted 1:1 with sterile physiological saline solution. The second injection site pair (medial): 0.1 % test substance, formulated in sterile physiological saline solution. The third injection site pair (caudal): 0.1 % test substance , formulated in sterile physiological saline solution and with Freund's complete adjuvant in equal parts.

In the control group, animals were treated in the same way as the test compound group, but the formulations for injection site pairs 2 and 3 did not contain any test compound. Topical induction occurred one week after intradermal induction. A 25 % formulation was used, since higher homogeneous concentrations could not be produced. Hypoallergenic dressings (2x4 cm) were placed between or on the injection sites, covered with aluminium foil, and fastened to the skin for 48 hours with Fermoflex adhesive tape.

The application sites were shorn and irritated with 10 % sodium lauryl sulphate, formulated in paraffin oil, 24 hours before application. The hypoallergenic dressings were treated or soaked with a volume of 0.5 mL as follows. The test compound group had 25 % test substance, formulated in sterile physiological saline solution. The control groups used a vehicle (sterile physiological saline solution).


- No. of exposures: 2
- Day(s) of challenge: 1
- Exposure period: 24 hours
- Test groups: test compound in physiological saline
- Control group: physiological saline
- Site: left flank
- Concentrations: First challenge: 25%, second challenge: 2.5%
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
A similar control dressing was applied to the right flank. This was soaked only with the vehicle (sterile physiological saline solution). The volume applied was 0.5 mL.
Positive control substance(s):
yes
Remarks:
2% formaldehyde
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0% intradermal induction, 25% 1. challenge
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0% intradermal induction, 25% 1. challenge
No. with + reactions:
4
Total no. in group:
10
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1% intradermal induction, 25% challenge
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
scores 1 to 3
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1% intradermal induction, 25% challenge
No. with + reactions:
19
Total no. in group:
19
Clinical observations:
score 1 to 2 and scaly areas
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0% intradermal induction, 2.5%
No. with + reactions:
4
Total no. in group:
10
Clinical observations:
score 1
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0% intradermal induction, 2.5% challenge
No. with + reactions:
0
Total no. in group:
10
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1% intradermal induction, 2.5% challenge
No. with + reactions:
19
Total no. in group:
19
Clinical observations:
mainly score 3 and encrustation in the treatment area
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1% intradermal induction, 2.5%
No. with + reactions:
19
Total no. in group:
19
Clinical observations:
scores 1 to 3 and encrustrations in treatment area
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
2%
No. with + reactions:
7
Total no. in group:
20

Autopsy findings
Abdominal cavity filled with much blood; liver very pale and coated with coagulated blood; kidneys and spleen pale; wall of forestomach torn.


 


 


 


Table one


First challenge of Positively reacting animals:









test compound group (20 animals)1st control group (10 animals)
















compound
dressing		control
dressing		compound
dressing		control
dressing
20000

 


 


Table two


Second challenge with Positively reacting animals









test compound group (19 animals)2nd control group (10 animals)
















compound
dressing		control
dressing		compound
dressing		control
dressing
19151
Interpretation of results:
Category 1A (indication of significant skin sensitising potential) based on GHS criteria
Conclusions:
The registered substance was evaluated in a sensitization test (MAGNUSSON and KLIGMAN's maximisation test) for possible skin-sensitising potential for guinea pigs. The study conformed to the OECD Guideline for Testing of Chemicals "Skin Sensitisation" No. 406, adopted 12.5.1981, and the EC Guideline. The test compound was examined to see if it had any a skin-sensitising effect concentrations that were applied for the Intra-dermal induction: 0.1 %, for the topical induction: 25 %, for the first challenge: 25 % and for the second challenge: 2.5 % . The result of the second challenge confirmed that of the first, although the concentration used was lower by a factor of ten. A clear sensitising potential for guinea pigs was therefore noted for the test compound under the described test conditions.
Executive summary:

The fungicidal, propineb was evaluated in a sensitisation test (MAGNUSSON and KLIGMAN's maximisation test) for possible skin sensitising potential for guinea pigs. The following concentrations were applied during the study. Intra-dermal induction: 0.1 %, Topical induction: 25 %, First challenge: 25 %, Second challenge: 2.5 %. After the first challenge (test compound concentration 25 %), twenty animals in the test compound group, which consisted of twenty animals, reacted positively, as against no positive reactions in the first control group, which consisted of ten animals. After the second challenge (test compound concentration 2.5 %), eighteen animals in the test compound group, which consisted of nineteen animals, reacted positively, as against four positive reactions in the second control group, which consisted of ten animals. The study therefore detected clear indications of the test compound's skin-allergenic potential for guinea pigs.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A key skin sensitisation study according to OECD 406 and GLP is available (M-053641-01-1). The test substance was evaluated in a guinea pig maximisation test. The following concentrations were applied during the study. Intra-dermal induction: 0.1 %, Topical induction: 25 %, First challenge: 25 %, Second challenge: 2.5 %. After the first challenge (test compound concentration 25 %), twenty animals in the test compound group, which consisted of twenty animals, reacted positively, as against no positive reactions in the first control group, which consisted of ten animals. After the second challenge (test compound concentration 2.5 %), eighteen animals in the test compound group, which consisted of nineteen animals, reacted positively, as against four positive reactions in the second control group, which consisted of ten animals. A positive control study with 2% formaldehyde performed earlier showed clear positive effects, showing the validity of the test.


Based on the results of this study the test substance is considered to be a strong skin sensitiser.


In a supporting study (Bühler test) no skin sensitising potential was observed. However, no positive control was included which devalidates the study result. 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available data on skin sensitisation meet the criteria for classification according to Regulation (EC) 1272/2008, and the registered substance is therefore classified as Skin Sens. Category 1A (H317).