L-methionine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Study was originally judged Klimisch 1. However, according to the "Practical guide 6: How to report read-across and categories" the maximum score for read-across is 2.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Justification for non-LLNA method:

Study performed before REACH become into force

Test material

Test material information

Constituent 1

Reference substance name:

DL-methionine

EC Number:

200-432-1

EC Name:

DL-methionine

Cas Number:

59-51-8

Molecular formula:

C5H11NO2S

IUPAC Name:

methionine

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9 days
- Weight at study initiation: 246-313 g (excluding positive control group), positive control group: 230- 335 g
- Fasting period before study: overnight
- Housing:in pairs/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 50% +/- 15%
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: 0.9% NaCl solution

Induction 2

Concentration / amount:

lnduction (test day 1 ): Two (2) mL of the D,L-Methionin suspension (50%) were applied to the left flank . The exposure time was 6 hours. This
procedure was repeated on test days 7 and 14 using 2 mL of the same test substance concentration per animal.
Challenge (test day 29): Two weeks after the last epicutaneous application the right flanks of the same animals were shaved and depilated for a
further epicutaneous application. Again 2 mL of the above mentioned D,L-Methionin concentration were applied but to the right flank. The
exposure time was 6 hours.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: 0.9% NaCl solution

Challenge 2

Concentration / amount:

lnduction (test day 1 ): Two (2) mL of the D,L-Methionin suspension (50%) were applied to the left flank . The exposure time was 6 hours. This
procedure was repeated on test days 7 and 14 using 2 mL of the same test substance concentration per animal.
Challenge (test day 29): Two weeks after the last epicutaneous application the right flanks of the same animals were shaved and depilated for a
further epicutaneous application. Again 2 mL of the above mentioned D,L-Methionin concentration were applied but to the right flank. The
exposure time was 6 hours.

No. of animals per dose:

10 animals: Negative control (vehicle)
20 animals: D,L-Methionin (50% in 0.9% NaCI solution tor all 4 stages)
20 animals: Positive control: 2% aqueous p-phenylene diamine dihydrochloride solution

Positive control substance(s):

yes

Remarks:

2% aqueous p-phenylene diamine dihydrochloride solution

Results and discussion

Positive control results:

The positive control 2% aqueous p-phenylene diamine dihydrochloride solution revealed pronounced sensitising properties. An erythema of grade 1 was noted in 13 of 20 animals during the challenge phase 54 hours after start of treatment.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

30

Group:

test chemical

Dose level:

2 ml 50% suspension in 0.9% NaCl solution

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 30.0. Group: test group. Dose level: 2 ml 50% suspension in 0.9% NaCl solution. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

54

Group:

test chemical

Dose level:

2 ml 50% suspension in 0.9% NaCl solution

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 54.0. Group: test group. Dose level: 2 ml 50% suspension in 0.9% NaCl solution. No with. + reactions: 0.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the present test conditions D,L-Methionin revealed no sensitising properties in guinea-pigs in a skin sensitisation test according to
E. V. BUEHLER. The positive control 2% aqueous p-phenylene diamine dihydrochloride solution revealed pronounced sensitising properties.