Registration Dossier

Administrative data

Description of key information

Skin irritation, rabbits: slightly irritating

Eye irritation, rabbits slightly irritating with irreversible effects observed

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 January to 2 February 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study carried out in compliance with an internationally recognised guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: reputable supplier of laboratory animals
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.72 to 2.90 kg
- Housing: suspended metal cage
- Diet (e.g. ad libitum): free access to commercially available rabbit feed
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 20
- Humidity (%): 50 to 65
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

IN-LIFE DATES: From: To: 28 January to 2 February 1998
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours after application
Observation period:
Approximately one hour, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: not reported
- % coverage: not reported
- Type of wrap if used: cotton gauze pad secured by surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 3 mis, 1 hr and 4hrs after application

SCORING SYSTEM: Draize classification scheme.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24,48,72 hrs
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Max. score:
0

4 -hour exposure period - very slight erythema was noted at all treated skin sites at the 24 and 48 -hour observations. All treated skin sites appeared normal at the 72-hour observation.

1 -hour exposure period - very slight erythema was noted at the treated skin site at the 24 -hour observation. The treated skin site appeared normal at the 48 -hour observation.

3 - minute exposure period - no evidence of skin irritation was noted during the study.

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
21 February and 12 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study carried out in compliance with an internationally recognised guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: A reputable supplier
- Age at study initiation: 46 weeks
- Weight at study initiation: 3.84 kg
- Housing: plastic cage with perforated floors
- Diet: 125 g of a standard laboratory rabbit diet per day. Dietary supplement of hay was offered during acclimatisation until two days prior to dose instillation, for the remainder of acclimatisation and throughout the study observation period wholemeal bread was offered
- Water: ad libitum.
- Acclimation period: 26 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): relative humidity within 40 to 70%.
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 light/12 hours dark

IN-LIFE DATES: From: To: 21 February to 12 March 2013
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
Observation period (in vivo):
1, 24, 48, 72 hours and after 8 days
Number of animals or in vitro replicates:
1
Details on study design:
SCORING SYSTEM: as prescribed in the test guideline


Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
2
Irritant / corrosive response data:
A crimson-red or beefy-red conjunctival appearance was evident throughout the first 72-hours after instillation. Very-slight or slight chemosis and slight or moderate discharge were apparent during this time. From 24-hours after instillation scattered or diffuse areas of opacity covering up to three quarters of the corneal surface were evident. Iritis was apparent 72-hours after instillation.
Other effects:
One week after instillation (Days 8 and 9) injection of the conjunctival blood vessels, scattered or diffuse area of opacity covering up to a quarter of the corneal surface and an area of pannus were evident. Pannus is regarded as an irreversible effect, consequently the study was terminated after the Day 9 assessment and no further animal was committed to the study.
Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Pannus is regarded as an irreversible effect and under the criteria of the Globally Harmonised System of classification (United Nations 2005 and more recent revisions) as adopted by the European Commission (European Communities Regulation 1272/2008) DMI was assigned to Category 1 (Irreversible effects on the eye).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

A dermal irritation test was performed to assess the irritation to skin caused by DMI. The study was conducted according to official test guidelines, and in compliance with GLP. 0.5 ml of test substance was applied to the skin of three albino rabbits and held in place with a semi occlusive dressing for four hours. At the end of the exposure period, the test substance was washed off with water. The treatment site was observed approximately one hour, 24, 48 and 72 hours after application. There was no evidence of skin irritation for three minutes expsoure. Very slight erythema was noted with one hour exposure (24 hour observation period). A very slight erythema was noted with all treated skin sites after 4 hours exposure at the 24 and 48 observation periods, but appeared normal at the 72 hour observation period.

Eye irritation

Eye irritation An eye irritation test was performed to determine the potential of DMI to cause irritation in the eye. The study was conducted in accordance with official test guidelines, and in compliance with GLP. One rabbit was administered a single ocular dose of a volume of 0.1 mL of the test substance and observed for nine days after instillation. A crimson-red or beefy-red conjunctival appearance was evident throughout the first 72-hours after instillation. Very-slight or slight chemosis and slight or moderate discharge were apparent during this time. From 24-hours after instillation scattered or diffuse areas of opacity covering up to three quarters of the corneal surface were evident. Iritis was apparent 72-hours after instillation. One week after instillation (Days 8 and 9) injection of the conjunctival blood vessels, scattered or diffuse area of opacity covering up to a quarter of the corneal surface and an area of pannus were evident. Pannus is regarded as an irreversible effect, consequently the study was terminated after the Day 9 assessment and no further animal was committed to the study.

Justification for selection of skin irritation / corrosion endpoint:

This study is conducted in accordance with a recognised, well established test method. Of the other available studies available for this endpoint, one is unassignable (Klimisch code 4) and the other, although well conducted under GLP, is carried out as an assessment of the test site in a dermal developmental/teratology study. It therefore does not follow strictly the test conditions as prescribed in the test methods used for classification of substance for dermal irritancy, however the data do serve to support the finding that DMI is not irritating to the skin.  

Justification for selection of eye irritation endpoint:

An in vitro study did not show conclusively that the substance is an eye irritant and therefore an in vivo study was undertaken. The in vivo study takes precedence over the in vitro study in the classification of DMI for eye irritancy effects.

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Although DMI is slightly irritating, effects are reversible and not sufficient for the substance to be classified as corrosive or irritant.

DMI is slightly irritating to the eye, but some effects (pannus) are not reversible. DMI therefore is classified as Category 1 (Irreversible effects on the eye).