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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
hypothesis As a hypothesis, methanol is the critical constituent of the substance (S-Ethanol, composition 2) based on its amount and with regards to its hazardous properties. It is the major constituent affecting the classification and labeling of the target substance (S-Ethanol). Therefore, data from methanol is used in the read-across approach in order to update the hazard assessment of this substance. Other impurities are taken into account for self-classification but there were no need to consider evaluating their properties in hazard assessment because of low concentrations. Analogue approach justification This substance (S-Ethanol, composition 2) has degree of ethanol purity between 76.4-81.9 %. Methanol is the main impurity of the target substance (conc. 13-14 %), and considered the major driver for adverse effects based on its properties and relative quantity in the substance. For chemical safety assessment certain physico-chemical properties are relevant for both human health and environmental health assessment. Also they are important for self-classification and for updating of the exposure assessment of the target substance. For toxicological endpoints, methanol is considered the major drivers for classification and overall safety assessment of the target substance. Therefore, methanol properties were included for chemical safety assessment and the endpoint robust summaries were provided also for methanol.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Induction phase comprised 1st and 2nd induction, each subdivided into intradermal and epidermal treatment with 1-week-intervals between each treatment.
Principles of method if other than guideline:
Study was performed as modification of the Magnusson-Kligman test before the actual guideline was adopted.
GLP compliance:
no
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): methanol, substance no. 78/333
- Analytical purity: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Firma Hagemann, Lippische Versuchstierzucht, 4923 Extertal
- Weight at study initiation: 449 - 824 g
- Diet (e.g. ad libitum): Ssniff K, ad libitum
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
50 %
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
50 %
No. of animals per dose:
1st study: 10 test, 5 control
2nd study: 12 test, 5 control
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4
- Exposure period: d 0 (1st intradermal), 7 (1st epicutaneous), 14 (2nd intradermal), 21 ( 2nd epicutaneous)
- Test groups: 1st intradermal: 6 parallel injections with Freund's adjuvant, 50% methanol and Freund's adjuvant + 50% methanol, respectively; 2nd intradermal: 4 parallel injections with 50% methanol and Freund's adjuvant + 50% methanol, respectively; both epidermal: conc. methanol
- Control group: no induction treatment
- Site: shoulder region
- Frequency of applications: weekly
- Duration: epicutaneous: 48 h occlusive
- Concentrations: 50% intradermal, 100% epicutaneous


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 34 days after 1st intradermal induction
- Exposure period: 24 h occlusive
- Test groups: 1st study: right 50% methanol, left 25% formaldehyde epicutaneous; 2nd study: concentrated methanol epicutaneous
- Control group: 1st study: right 50% methanol, left 25% formaldehyde epicutaneous; 2nd study: concentrated methanol epicutaneous
- Site: flank
- Concentrations: 50% methanol and 25% formaldehyde, respectively (study 1), 100% methanol (study 2)
- Evaluation (hr after challenge): 24, 48 and 72 hours
Challenge controls:
Control groups (no induction treatment)
Positive control substance(s):
no

Results and discussion

Positive control results:
Positive controls not performed.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
other: 1st study test group
Dose level:
50 %
No. with + reactions:
3
Total no. in group:
10
Clinical observations:
slight erythema (score 1)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 1st study test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
other: 1st study test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading:
Reading:
1st reading
Hours after challenge:
24
Group:
other: 2nd study test group
Dose level:
50 %
No. with + reactions:
1
Total no. in group:
12
Clinical observations:
slight erythema (score 1)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group:
Reading:
2nd reading
Hours after challenge:
48
Group:
other: 2nd study test group
Dose level:
50 %
No. with + reactions:
1
Total no. in group:
12
Clinical observations:
slight erythemy (score 1)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group:
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
other: 2nd study test group
Dose level:
50 %
No. with + reactions:
0
Total no. in group:
12
Clinical observations:
none
Remarks on result:
other: Reading:

Any other information on results incl. tables

In the first study, 3/10 females exhibited a slight skin response (erythema score 1) 24 h after challenge, in the parallel test with formaldehyde 1/10 females exhibited a slight skin response (erythema score 1) 24 h after challenge, which can be interpreted as weak sensitizing potential.

In the second study using 12 female animals at a concentration of 50 % methanol, 1/12 exhibited a slight skin response (erythema score 1) 24 and 48 h after challenge which can be interpreted as a weak sensitising potential.

The intracutane inductions produced necroses and some open ulcerations in both studies.

In summary, the low number of 4/22 animals with slight erythema (score 1) gives no evidence of a notable sensitisation potential of methanol.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information