Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

The reaction mass of methyl acetate and methanol is assessed on the basis of the individual constituents methyl acetate and methanol using a read-across approach from the supporting substances (structural analogue or surrogate).


 


Skin sensitisation


Methyl acetate


In two supporting studies (Klimisch score 4), no skin sensitising properties were observed for methyl acetate in humans.


Methanol


In an in vivo skin sensitisation study similar to OECD guideline 406 (Klimisch score 2), methanol induced slight erythema in guinea pigs but gives no evidence of a notable sensitisation potential.


 


Conclusion


Based on the results of skin sensitisation studies with the two source substances methyl acetate and methanol, skin sensitising properties of the reaction mass of methyl acetate and methanol is assessed. Both substances were found to be non-sensitisers. Therefore, the reaction mass of methyl acetate and methanol is not considered to have skin sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
review of literature and assessment of available human, animal and alternative data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
review of literature and assessment of available human, animal and alternative data
GLP compliance:
not specified
Type of study:
other: review of literature and assessment of available human, animal and alternative data
Justification for non-LLNA method:
Study performed in 2003; when LLNA has not been an accepted OECD test method.
Species:
other: human volunteers
Key result
Reading:
other: Not applicable as summary of several individual studies
Hours after challenge:
0
Group:
test chemical
Dose level:
Not applicable as summary of several individual studies
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No senstisation observed in studies. No sensitizing properties from experience
Remarks on result:
other: Summary of several individual studies
Key result
Reading:
other: long experience with human exposure to the substance
Hours after challenge:
0
Group:
negative control
Dose level:
No negative control tested
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
Not measured/tested
Remarks on result:
not measured/tested
Remarks:
No negative control exists due to a maximisation test with 25 volunteers long experience with human exposure to the substance
Key result
Reading:
other: long experience with human exposure to the substance
Hours after challenge:
0
Group:
positive control
Dose level:
No positive control tested
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
Not measured/tested
Remarks on result:
not measured/tested
Remarks:
No positive control exists due to a maximisation test with 25 volunteers and a long experience with human exposure to the substance.

"Total no. in group" refers to study by Kligman, only. This study is citied in EU-RAR, 2003.

Interpretation of results:
GHS criteria not met
Conclusions:
Taking into account the long experience with human exposure to the substance, and the absence of any reports on contact allergy in exposed persons, methyl acetate is not expected to exhibit skin sensitizing properties, especially since the substance is hydrolysed in contact with water by non-specific tissue esterases to methanol and acetic acid. For these substances a skin sensitisation potential is either absent (methanol, Fisher, 1986) or restricted to a few cases (acetic acid, Weil and Rogers, 1951).
Executive summary:

The result meets the long experience from human exposure to humans.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
in human
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Principles of method if other than guideline:
10% methylacetat induction and challenge
GLP compliance:
not specified
Type of study:
other: maximization test in humans
Justification for non-LLNA method:
Study performed in 1979, LLNA method was not available.
Species:
other: human
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
In a human maximization study, 25 healthy, male (11) and (14) female subjects aged 18-31 years old were used. Test material was applied under occlusion to the same site on the volar forearm ot back of all subjects for five alternate-day 48 hour periods. The patch site was pre-treated for 24 hours with 2.5% aqueous sodium lauryl sulfate (SLS) under occlusion. Prior to challenge, 5 to 10% SLS was applied to test site for one hour before application of test material. Challenge site was read on patch removal and 24 hours thereafter.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
no sensitisation observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
No negative control tested
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
Not measured/tested
Remarks on result:
not measured/tested
Remarks:
There is no negative control group as it is a maximisation test with 25 volunteers.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
No negative control tested
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
Not measured/tested
Remarks on result:
not measured/tested
Remarks:
There is no positive control group as it is a maximisation test with 25 volunteers.

The study result meets the long experience from human exposure to humans. The test method of a maximization test is justified in this case.

Interpretation of results:
not sensitising
Conclusions:
The study result meets the long experience from human exposure to humans. The test method of a maximization test is justified in this case.
In this human maximization study no skin sensitisation was observed.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitisation, methyl acetate


Skin sensitisation, human, RL4


In a maximisation test with 25 volunteers no sensitisation was observed after exposure to 10% methyl acetate in petrolatum (Kligman, 1976). Taking into account the long experience with human exposure to the substance, and the absence of any reports on contact allergy in exposed persons, methyl acetate is not expected to exhibit skin sensitizing properties, especially since the substance is hydrolysed in contact with water by non-specific tissue esterases to methanol and acetic acid. For these substances a skin sensitisation potential is either absent (methanol, Fisher, 1986) or restricted to a few cases (acetic acid, Weil and Rogers, 1951).


 


Skin sensitisation, human, RL4


In the EU Risk Assessment Report on Methyl acetate (European Union Chemicals Bureau, 2003), methyl acetate was not considered to be a skin sensitiser.


 


Skin sensitisation, methanol


Skin sensitisation, guinea pig, RL2


In a guinea pig maximization assay, 3/10 females exhibited a slight skin response (erythema score 1) 24 h after induction and challenge with a 50% aqueous methanol solution (0.1 mL), which can be interpreted as weak sensitizing potential. In another 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 also be interpreted as a weak sensitising potential. The intracutaneous 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.


 


Conclusion:


From the overall data base and the long term experience with methyl acetate and methanol it is concluded that both source substances have no sensitisation potential. Based on a read across and following a weight of evidence approach the target substance (reaction mass of methyl acetate and methanol) is considered to be not sensitising.


 


 


Literature


Kligman AM (1976). Report to RIFM (18.05.1976). Cited in: Opdyke (1979), Food Cosmet. Toxicol. 17, 859-861.


Fisher AA (1986). Contact Dermatitis. 3rd edition. Lea & Febiger, Philadelphia 1986, p. 853 and 886.


Weil AJ, Rogers HE (1951). Allergenic reactivity to simple aliphatic acids in man. J. Invest. Dermatol. 17, 227-231.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

 

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The reaction mass of methyl acetate and methanol is assessed in a read-across approach, using the individual constituents methanol and methyl acetate. The available experimental test data for the individual substances are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on the available data, the source substances are not considered to be skin sensitising. Using a read-across approach with the source substances methyl acetate and methyl acetate, the target substance (reaction mass of methyl acetate and methanol) is not classified as skin sensitising according to Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217.