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Administrative data

Description of key information

GPMT, not sensitising (OECD 406, GLP, K, Rel. 1)

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:
17/09/1997-24/10/1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
According to the OECD Guideline and in compliance with GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of study completion (1997), the LLNA OECD test method was not adopted.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Weight at study initiation: 277-351 g
- Housing: animals were kept in pair in MAKROLON-cages at room temperature. Granulated textured wood was used as bedding material in the cages.
- Diet (e.g. ad libitum): Altromin 3022, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 60±20
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
other: sesame oil (DAB)
Concentration / amount:
1% suspension of the substance in sesame oil
Day(s)/duration:
Day 0
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil (DAB)
Concentration / amount:
8% suspension of the substance in sesame oil
Day(s)/duration:
Day 7 / 48 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: sesame oil (DAB)
Concentration / amount:
0.1% suspension of the substance in sesame oil
Day(s)/duration:
Day 22 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
vehicle control: 5 animals
substance: 10 animals
positive control: 20 animals
Details on study design:
PRELIMINARY STUDY
Six concentrations of test material were tested (0.1, 1, 5, 10, 20 and 50%) by intracutaneous injection.
Six concentrations of test material were tested (2, 5, 10, 20, 50 and 100%) by topical application without depilation
Six concentrations of test material were tested (0.01, 0.1, 1, 5, 20 and 50%) by topical application with depilation

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: first by intracutaneous application and 7 days later by topical administration (48 h) on shoulder area
- Concentrations:
Intracutaneous
0.1 mL of the prepared test compound (suspension at 1%) was administered intracutaneously (sholder region).
Topical
2 mL of the test preparation (suspension at 8%) were applied to a gauze patch

8 animals were used for the preliminary test: 6 animals for the topical administration and 2 animals for the intracutaneous administration.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Exposure period: 24 h on flanks area
- Concentrations: 0.1% suspension in sesame oil
Positive control substance(s):
yes
Remarks:
potassium dichromate
Positive control results:
Potassium dichromate induced skin sensitisation indicating the validity of the study.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
animal n°10 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
animal N°10 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
animal n°10 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
animal n° 5 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
animal n° 5 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
animal n° 5 died prematurely
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
potassium dichromate
No. with + reactions:
14
Total no. in group:
19
Clinical observations:
animal n°18 died prematurely
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
potassium dichromate
No. with + reactions:
17
Total no. in group:
19
Clinical observations:
animal n°18 died prematurely
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
positive control
Dose level:
potassium dichromate
No. with + reactions:
17
Total no. in group:
19
Clinical observations:
animal n°18 died prematurely
Remarks on result:
positive indication of skin sensitisation

PRELIMINARY STUDY

Six concentrations of test material were tested (0.1, 1, 5, 10, 20 and 50%) by intracutaneous injection. From 1% to 50% concentration, it caused a slight to moderate irritation in a concentration-related way at the injection sites.

Six concentrations of test material were tested (2, 5, 10, 20, 50 and 100%) by topical application without depilation. From 5% to 100% suspension in sesame oil, it caused a slight to moderate irritation.

Six concentrations of test material were tested (0.01, 0.1, 1, 5, 20 and 50%) by topical application with depilation. At the 20% and 50% concentration, the animal died during the 24h-exposure. At the 1% and 5% concentration, a slight to well defined irritation on the depilated skin of the animals was observed.

Hence, for the main study, it was decided to use a 1% concentration in sesame oil for the 1st induction stage, a 8% concentration for the 2nd induction stage and a 0.1% concentration for the challenge.

MAIN STUDY

Examination of the substance in the skin sensitisation test in guinea-pigs according to MAGNUSSON and KLIGMAN - skin reactions -

Animal No 1st Stage 2nd stage   3rd stage
  Hours after start of treatment
  shoulder shoulder flanks
  25 48 49 73 24 48 72
            l r l r l r
Group 1: Vehicle control (sesame oil)
1 E2 E2 E0 E0 0 0 0 0 0 0
2 E2 E2 E0 E0 0 0 0 0 0 0
3 E2 E2 E0 E0 0 0 0 0 0 0
4 E2 E2 E0 E0 0 0 0 0 0 0
5 E2 E2 died prematurely
Group 2: test material
6 E2 E2 E2 E2 0 0 0 0 0 0
7 E2 E2 E2 E2 0 0 0 0 0 0
8 E2 E2 E2 E2 0 0 0 0 0 0
9 E2 E2 E2 E2 0 0 0 0 0 0
10 E2 E2 died prematurely
11 E2 E2 E2 E2 0 0 0 0 0 0
12 E2 E2 E2 E2 0 0 0 0 0 0
13 E2 E2 E2 E2 0 0 0 0 0 0
14 E2 E2 E2 E2 0 0 0 0 0 0
15 E2 E2 E2 E2 0 0 0 0 0 0
Group 3: Positive control (potassium dichromate)
16 E1 0 E1 0 E2 0 E2 0 E3 0
17 E1 0 E1 0 E3 0 E2 0 E2 0
18 E1 0 died prematurely
19 E1 0 E1 0 E1 0 E1 0 E1 0
20 E1 0 E1 0 0 0 E2 0 E2 0
21 E1 0 E1 0 0 0 E2 0 E1 0
22 E1 0 E1 0 E2 0 E2 0 E2 0
23 E1 0 E1 0 E1 0 E2 0 E2 0
24 E1 0 E1 0 E3 0 E1 0 E1 0
25 E1 0 E1 0 E3 0 E2 0 E2 0
26 E1 0 E1 0 0 0 0 0 0 0
27 E1 0 E1 0 E1 0 E1 0 E1 0
28 E1 0 E1 0 E3 0 E3 0 E3 0
29 E1 0 E1 0 E1 0 E1 0 E2 0
30 E1 0 E1 0 E2 0 E1 0 E1 0
31 E1 0 E1 0 E3 0 E2 0 E2 0
32 E1 0 E1 0 E1 0 E1 0 E1 0
33 E1 0 E1 0 0 0 E1 0 E1 0
34 E1 0 E1 0 0 0 0 0 0 0
35 E1 0 E1 0   E3 0 E3 0 E2 0

The animals no.5 and 10 died prematurely on the 1st day after the start of the 2nd stage

The animal no. 18 died prematurely on the 2nd day after the start of the 2nd stage.

The deaths were probably cause by the stress-associated with the shaving procedure and the patch test techinique: guinea-pigs are very prone to stress-associated death.

l=left

r=right

E=erythema

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, test substance is not classified as skin sensitiser according to the CLP Regulation (EC) No. 1272/2008 and to the GHS.
Executive summary:

The purpose of this study was to determine the potential of the substance to provoke skin sensitisation reactions in guinea-pigs in a test model according to MAGNUSSON and KLIGMAN (OECD TG 406). The substance concentration chosen for the 1st (intracutaneous) induction stage produced a well-defined irritation in all animals: a 1% suspension in sesame oil. The 2nd (topical) induction stage with a 8% suspension in sesame oil revealed also a well-defined irritation in all animals. The challenge with a 0.1% suspension in sesame oil-the maximum sub-irritating concentration to the depilated skin-showed no sensitising properties. The vehicle control animals treated with sesame oil in the same way during stages 1 and 2 and a 0.1% test suspension during the third stage revealed no skin reactions. In each group, one animal died prematurely due to the stress-associated with the shaving procedure and the patch test technique. In the remaining animals, behaviour remained unchanged, body weight gain was within the normal range. Animals treated with potassium dichromate exhibited a sensitising reaction.

The overall sensitisation rate was 0% in the test group.

Under the test conditions, test substance is not classified as skin sensitiser according to the CLP Regulation (EC) No. 1272/2008 and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin sensitisation endpoint.

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

A Key study was identified (LPT, 1997). in this dermal sensitisation study performed according to the OECD test Guideline No. 406 and in compliance with GLP, the test material was tested in Guinea Pigs using the Magnusson and Kligman method (10 treated + 5 controls). The preliminary study determined the concentrations to be used for the induction and challenge phases of the main study. The test material diluted in sesame oil at 1% was administered by injection for intradermal induction on Day 0. On Day 7, the animals received a topical induction with test material diluted in sesame oil at 8%. For the challenge, on Day 21, the test material was applied topically at 0.1%.

The positive control induced skin sensitisation. The test system was therefore considered to be valid.

In both groups, one animal died prematurely, due to the stress-associated with the shaving procedure and the patch test technique. No clinical signs were noted. The overall sensitisation rate was 0%.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Based on the available data no additional self-classification is proposed according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.