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Description of key information

A guinea pig maximisation test is available, performed according to OECD guideline 406.

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:
March 6, 1992 - February 9, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: US EPA Pesticide Assessment Guidelines, Subdivision F, Part 81-6 (Magnusson-Kligman)
Qualifier:
equivalent or similar 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:
The study was performed before the LLNA was validated.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Age at study initiation: no data
- Weight at study initiation:
test group (22): 377 +/- 31.84 g
vehicle group (22): 368.2 +/- 18.25 g
- Housing: guinea pigs per cage: 1-4
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 degrees Celsius
- Humidity (%): 45-65%
- Air changes (per hr): 12-15 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: August 4, 1992 To: September 25, 1992
Route:
intradermal and epicutaneous
Vehicle:
other: vaseline (challenge) and paraffin oil (induction)
Concentration / amount:
Concentration used at induction: a) 0,2 % in paraffin oil (injection) b) 1.0 % in vaseline (patch) Concentration used for each challenge: 0,01 % in vaseline (patch)
Route:
epicutaneous, occlusive
Vehicle:
other: vaseline (challenge) and paraffin oil (induction)
Concentration / amount:
Concentration used at induction: a) 0,2 % in paraffin oil (injection) b) 1.0 % in vaseline (patch) Concentration used for each challenge: 0,01 % in vaseline (patch)
No. of animals per dose:
Number of animals in test group: 22
Number of animals in control: 22
Details on study design:
RANGE FINDING TESTS:
1) To determine the concentration which causes only slight irritation for the use in the intradermal exposure of the main study:
Intradermal injection with 0.2, 1, 5 and 10% dissolved in paraffin oil
2) To determine the concentration which causes no irritation and the highest
concentration which causes only mild irritation
for the use in the 2 dermal applications of the main study:
Two times 10 animals received topical applications at concentrations of:
0.005, 0.01, 0.05, 0.2, 1, 4, 10 and 25% in vaseline

MAIN STUDY
Test animals: 22
Control animals: 22

A. INDUCTION EXPOSURE
- No. of exposures: 2

1)Intradermal injections on day 0:
- Concentration: 0.2% in paraffin oil
- Site: r + l shoulder
Three pairs of intradermal injections:
1) 0.1 mL: FCA
2) 0.1 mL: 0.2% of the substance
3) 0.1 mL: 0.2% of the substance + FCA

2)Topical application on day 7:
-Concentration: 1% in vaseline
-Exposure period: 48 hours (occlusive)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: day 21 (14 days after last induction)
- Exposure period: 24 hours (occlusive)
- Site: left flank
- Concentrations: 0.01% in vaseline
- Evaluation (hr after challenge):
24 hours after patch removal (day 23) and on day 24
Positive control substance(s):
yes
Remarks:
DNCB
Positive control results:
Positive in all animals
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.01%
No. with + reactions:
7
Total no. in group:
21
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.01%. No with. + reactions: 7.0. Total no. in groups: 21.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.01%
No. with + reactions:
16
Total no. in group:
21
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.01%. No with. + reactions: 16.0. Total no. in groups: 21.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
N/A
No. with + reactions:
0
Total no. in group:
22
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: N/A. No with. + reactions: 0.0. Total no. in groups: 22.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
N/A
No. with + reactions:
1
Total no. in group:
22
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: N/A. No with. + reactions: 1.0. Total no. in groups: 22.0.

In the preliminary test it was determined that the dose used for the challenge, does not show any irritation. This dose will therefore be used for deriving the DNEL acute - dermal, local effects.

Interpretation of results:
other: Category 1A in accordance with CLP Regulation EC No 1272/2008
Conclusions:
Based on the results of a guinea pig maximisation test performed according to OECD guideline 406, the substance was considered to have skin sensitising properties.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

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

Harmonized classification and labelling (see Annex VI Table 3.1 of EC Regulation No 1272/2008; Catalogus number: 615 -029 -00 -X)

Justification for classification or non-classification

Skin sensitisation


According to the harmonized classification and labelling the substance needs to be classified as skin sensitiser category 1 (harmonized classification and labelling (see Annex VI Table 3.1 of EC Regulation No 1272/2008; Catalogus number: 615 -029 -00 -X)). However, the harmonized classification has been determined before sub-categorisation was applicable and the entry has not been adjusted ever since. As in the Guinea pig maximisation test in at least 30% of the animals positive skin reactions were observed after treatment with the maximum non-irritant concentration of the substance (0.01%), the substance is classified as category 1A in accordance with the CLP regulation (Regulation No 1272/2008). 


Respiratory sensitisation


Based on observations in the acute inhalation study and human experience, the substance needs to be classified as respitatory sensitiser in accordance with the CLP Regulation (harmonized classification and labelling (see Annex VI Table 3.1 of EC Regulation No 1272/2008; Catalogus number: 615 -029 -00 -X).