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Administrative data

Description of key information

Various results from two OECD 404 skin irritation studies tests were obtained (mid-intensity or negative) with no clear explaination on variability. Among these results, those of the study from 1988 are the less favorable and showed in particular "Desquamation persisted at two treated skin sites on day fourteen": this leads the substance to be classified as skin irritant Category 2 (according to criteria in CLP, Annex I, 3.2.1, 3.2.2 and Figure 3.1 from Guidance on the Application of the CLP Criteria, Version 5.0 – July 2017).

Besides, results in an OECD 404 eye irritation test were obtained showing the substance is non-irritant for eyes. Nevertheless, the following considerations are taken into account :

- no information on tested materials purity is available

-the impurity methyl acetoacetate has an Harmonised classification according to Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation) for Eye irritation (H319). It is present in the substance below the cut-off value of 10% then not considered "relevant" from a regulatory point of view but taken into account in eye hazard classification reasonning (see corresponding endpoint study summary).

- slight irritation effects are observed on eye and mid-effects on skin on test materials A1/1/0 and A6/4/6

- severe effects are observed with test material SA2/1/OA although only abstract is available and deviations to OECD 405 protocol were observed (1 animal only, killed after 10 minutes in particular)

Therefore the substance is classified Eye Damage Category 1, in a worst-case approach and in accordance with CLP guidance and Annex I, tables 3.3.1 and 3.3.2

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
first version of 1981
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours
Number of animals:
3
Details on study design:
Approximately twenty-four hours prior to the commencement of the test, each of a group of three rabbits was prepared by closely clipping the fur from the dorsal/flank areas using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm gauze patch and. placed in position on the shorn skin. The patch was secured in position over the test material with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP). The animals were then returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.667
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Irritant / corrosive response data:
No adverse dermal reactions were noted one hour after removal of the wrappings. Very slight erythema was noted at two treatment sites at the 24, 48 and 72-hour observations. The remaining treated skin site showed no evidence of erythema or oedema during this period.

Desquamation was noted at one treatment site at the 24-hour observation and at all treatment sites at subsequent 48 and 72-hour observations.
Other effects:
Adverse dermal reactions on day seven were confined to desquamation at two treatment sites.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material A1/1/0 was found to be non-irritant to 3 rabbit skin in an OECD 404 test.
Executive summary:

The pure test material A1/1/0 was found to be non-irritant to 3 rabbit skin in an OECD 404 test.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1990
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
first version of 1981
GLP compliance:
yes
Specific details on test material used for the study:
liquid
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
not specified
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours
Number of animals:
3
Details on study design:
single apllication
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 1.2
Max. score:
1.3
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.43
Max. score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
Well-defined erythema was noted in two of the three animals at the 24 hours observations. At all other observation periods erythema was either very slight or absent.
No more than very slight odema (barely perceptible) was seen in any of the three animals at any of the observation periods, After 7 days, no erythema or odema was observed,

Reaction

Hours

 animal 1

animal 2

animal 3

Erythema/eschar

 

0

0

 

 

24

2

1

2

 

48

1

1

 

 

72

1

1

 

Odema

 

0

0

1

 

24

1

0

1

 

48

1

0

0

 

72

1

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Substance SA2/1/0A is a mild irritant but is not irritating to skin, according to the criteria of Annex VI of Directive 57/548/EEC.
Executive summary:

Substance SA2/1/0A is a mild irritant but is not irritating to skin, according to the criteria of Annex VI of Directive 57/548/EEC.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
first version of 1981
GLP compliance:
yes
Specific details on test material used for the study:
The test material was supplied by Alcan Chemicals Ltd., as follows: Description : clear, pale straw-coloured liquid
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
24, 48 and 72 hours
Number of animals:
3
Details on study design:
Approximately twenty-four hours prior to the commencement of the test, each of a group of three rabbits was prepared by closely clipping the fur from the dorsal/flank areas using veterinary clippers.
Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position over the test material with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals from interfering with the patches the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP). The animals were then returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
Approximately one hour following removal of the patches. and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale of Draize J.H. (1959)
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 2
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.76
Max. score:
1
Reversibility:
fully reversible
Irritant / corrosive response data:
Well-defined erythema was noted at all treated skin sites one hour after removal of the patches and at subsequent 24, 48 and 72-hour observations. These reactions regressed to very slight erythema at the day seven observation, with addtitional signs of desquamation, possible hyperkeratinisation and haemorrhage of the dermal capillaries. Desquamation persisted at two treated skin sites on day fourteen.

Very slight to moderate oedema was noted at all treated skin sites one hour after removal of the patches. This regressed to very slight oedema at all treated skin sites at the 24-hour observation and at two treated skin sites at the 48 and 72-hour observations.
Other effects:
No other adverse reactions were noted during the study period.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test material produced reversible irritation in 3/3 rabbits according to the EEC labelling regulations and was classified as IRRITANT to rabbit skin.
Executive summary:

The test material produced reversible irritation in 3/3 rabbits according in an OECD 404 test.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987 - 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Version of 1981
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
0,1 mL
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
A volume of 0.1 ml of the test material was instilled into the right eye of each rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test material was dropped. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material from the eye, and then released. The left eye remained untreated and was used for control purposes.
Assessment of damage/irritation was made 1, 24, 48 and 72 hours following treatment, according to the numerical evaluation given {i.e. Oraize J.H., 1959 Association of Food and Drug Officials of the United States, Austin)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1/24/48/72h
Score:
ca. 0
Max. score:
0
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1/24/48/72h
Score:
ca. 0.1
Max. score:
0.3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1/24/48/72h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1/24/48/72h
Score:
ca. 0.23
Max. score:
0.7
Reversibility:
fully reversible
Irritant / corrosive response data:
A dulling of the normal lustre of the corneal surface was noted in one treated eye one hour after instillation and at the 24-hour observation. No other corneal effects were noted.
Iridial inflammation was noted in two treated eyes one hour after treatment but was confined to one treated eye at the 24-hour observation. No other adverse iridial effects were noted. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment. The conjunctival irritation regressed and minimal conjunctival irritation persisted in one treated eye at subsequent 24 and 48- hour observations. The other two treated eyes appeared normal during this period and all treated eyes appeared normal at the 72-hour observation.
The test material was found to be non-irritant to the rabbit eye
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was found to be non-irritant to the rabbit eye
Executive summary:

In an OECD 405 assay in 3 New-Zealand rabbits, the test material was found to be non-irritant to the rabbit eye

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification