But-3-yn-2-ol

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: Acceptable publication which meets basic scientific principles

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

skin sensitisation, other

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
According to Article 13 and Annex XI Section 1.5 of the REACH regulation [(EC) 1907/2006], a read-across or category approach can be used to fulfil REACH information requirements avoiding unnecessary testing. The read-across from a supporting substance (structural analogue or surrogate) was considered to be approprate for the endpoint skin sensitisation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance is 2-methylbut-3-yn-2-ol, CAS no. 115-19-5, which has a similar chemical structure compared to the target substance 3-butyn-2-ol, CAS no. 2028-63-9. The source substance only differs in an additional methyl-group. This read-across was also proposed by the QSAR Toolbox 3.4.0.17 [BASF, April 2017].
The concentration range for 3-butyn-2-ol is 96.5 - 100 % containing non-specificed impurities up to 3.5 %. The concentration for 2-methylbut-3-yn-2-ol is > 99.5 % containing non-specificed impurities up to 3.5 %. However, there are no details available about purity and impurities of 2-methylbut-3-yn-2-ol used for the skin sensitisation test.

3. ANALOGUE APPROACH JUSTIFICATION
As summarized in the data matrix, the physicochenica data of the source and the target chemical are very similar, as both sustances are liquids with an boiling point of about 100°C and a moderate vapour pressure of 20 or 11 hPa, respectively, being miscible with water at any ratio. According to the acute toxicity, the target chemical is more toxic, as it is toxic after oral, inhalation and dermal exposure, whereas the source chemical is only toxic after dermal exposure. Only the target chemical is irritating to the skin, but both substances can induce irreversible damage to the eyes.
To cover the information requirements for the skin sensitisation potential of 3-butyn-2-ol, a Modified Split Adjuvant Test with 2-methylbut-3-yn-2-ol was taken into account [Rao, 1981]. Ten male Hartley Guinea pigs received four applications of 2-methyl-3-butyn-2-ol as induction to the clipped and depilated back of the animals. At the time of the third application, 0.2 ml of Freund's Adjuvant was injected intradermal at one point adjacent to the insult site. After a two week rest period, the animals received an application of pure 2-methylbut-3-yn-2-ol and reactions were evaluated 24 and 48 hours thereafter. As result, no sensitizing reactions could be observed.
Therefore, also 3-butyn-2-ol is considered not to be sensitizing to the skin.

4. DATA MATRIX
see "Attached justification".

The data for 2-methylbut-3-yn-2-ol are derived from the respective REACH registration dossier, CAS no. 115-19-5 (see https://echa.europa.eu/information-on-chemicals/registered-substances).
The data for but-3-yn-2-ol can be found in this IUCLID data set (section 1, 4 and 7).

Reason / purpose for cross-reference:

read-across source

Data source

Reference

Reference 1

Reference Type:

publication

Title:

A collection of guinea pig sensitization test results - grouped by chemical class

Author:

Rao KS et al.

Year:

1981

Bibliographic source:

Drug. Chem. Toxicol. 4, 331-351

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2000

Reference 3

Reference Type:

secondary source

Title:

SIDS Initial Assessment Report - 2-Methylbut-3-yn-ol

Author:

Rao KS et al.

Year:

2002

Bibliographic source:

OECD SIDS

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method: in compliance with Maguire H. C.: J. Soc. Cosmet. Chem. 24, 151, 1973

GLP compliance:

not specified

Type of study:

other: modified Split adjuvant test

Justification for non-LLNA method:

There is a reliable non-LLNA study available, published in 1981.

Test material

Test material information

Constituent 1

Reference substance name:

2-methylbut-3-yn-2-ol

EC Number:

204-070-5

EC Name:

2-methylbut-3-yn-2-ol

Cas Number:

115-19-5

Molecular formula:

C5H8O

IUPAC Name:

2-methylbut-3-yn-2-ol

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Weight at study initiation: ca. 300 g
- Diet (e.g. ad libitum): ad libitum, urina guinea pig chow supplemented with green vegetables
- Water (e.g. ad libitum): ad libitum

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, open

Vehicle:

no data

Induction 2

Concentration / amount:

no data given

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

no data

Challenge 2

Concentration / amount:

no data given

No. of animals per dose:

10

Details on study design:

RANGE FINDING TESTS: yes
- test substance was applied to clipped flank; if irritation was observed dilutions were prepared
- The highest concentration which did not cause primary irritation was used for the guinea pig sensitization test


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4
- Test groups: 10 animals
- Site: clipped and depilated back of animals
- Frequency of applications: 4 times in 10 days
- Concentrations: no data
- Additions: at the time of the third application, 0 .2 ml of Freund's Adjuvant was injected intradermally at one point adjacent to the insult site


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) after induction: 2 weeks
- Control: solvent control on other flank of the same animal; 10 animal for positive control
- Site: clipped flank
- Concentration: 100%
- Evaluation (hr after challenge): 24, 48 h


Evaluation:
- A moderate erythema and/or edema in two or more guinea pigs was considered sufficient to classify the test material as a potential human skin sensitizer .

Challenge controls:

- solvent

Positive control substance(s):

yes

Remarks:

Epoxy Resin

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information