Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

9 August 1990 and 16 August 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD404 used to draw a conclusion on the non corrosive/ non-irritating properties to skin of the tested substance, which differs slightly from registered substance. Compostion of tested substance available from another report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-butylphthalimide

EC Number:

216-157-5

EC Name:

N-butylphthalimide

Cas Number:

1515-72-6

Molecular formula:

C12H13NO2

IUPAC Name:

2-butyl-1H-isoindole-1,3(2H)-dione

Constituent 2

Reference substance name:

N-sec-butylphthalimide

EC Number:

233-295-1

EC Name:

N-sec-butylphthalimide

Cas Number:

10108-61-9

Molecular formula:

C12H13NO2

IUPAC Name:

2-sec-butyl-1H-isoindole-1,3(2H)-dione

Constituent 3

Reference substance name:

N-propylphthalimide

EC Number:

226-189-1

EC Name:

N-propylphthalimide

Cas Number:

5323-50-2

Molecular formula:

C11H11NO2

IUPAC Name:

2-propyl-1H-isoindole-1,3(2H)-dione

additive 1

Reference substance name:

Reference substance 006

Cas Number:

120792-34-9

additive 2

Reference substance name:

Reference substance 001

Cas Number:

67762-26-9

Test material form:

liquid

Details on test material:

Description: dark straw-coloured liquid
Container: plastic screw-top container
Date of arrival: 26 July 1990
Storage conditions: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd.,Moston, Sandbach, Cheshire, u.K
- Age at study initiation: Approx 12-16 weeks old
- Weight at study initiation: 2.20 - 2.35 kg
- Housing: individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum Rabbit Diet, Preston Farmers Limited, New Leake, Boston, Lincolnshire, U.K
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 -24°C
- Humidity (%): 60 - 69%
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12h dark/ 12 h light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

4 hours

Observation period:

Approximately one hour following the removal of the patches and 24, 48 and 72 hours later

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: gauze patch soaked with 0.5 ml test substance. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
one hour following the removal of the patches and 24, 48 and 72 hours later

SCORING SYSTEM:
- Method of calculation: Draize J.H.(1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs
and Cosmetics"

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks:

after 7 days stil desquamation visible

Remarks on result:

other: Reaction extends beyond treatment site, Desquamation

Remarks:

Hemorrhage of dermal capillaries was observed after 1 h, but dissapeared after 24 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible within: 7 Days

Remarks:

after 7 days stil desquamation visible

Remarks on result:

other: Reaction extemds beyond treatmetn site. Desquamation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Reaction extends beyond treatmetn site, Desquamation

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0.7

Max. score:

1

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

1

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

To evaluate the classification of the substances according to CLP Regulation, the raw data was reinterpreted.
The mean value from gradings at 24, 48 and 72 hours after patch removal calculated in at least 2 of 3 tested animals were the following:
- erythema/eschar: score 7/6=1.17 (2 out of 3 animals)
- oedema: 3/6=0.5 (2 out of 3 animals)

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The results of the available OECD 404 study shows that the test item Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide is not corrosive and not irritating to skin according to the regulation 1272/2008/EC after reinterpretation of the raw data.

Executive summary:

A study was performed to assess the irritancy potential of the test material Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide to the skin of the New Zealand white rabbit. The method used followed that described in the OECD Guidelines for Testing of chemicals(1981) No' 404 "Acute Dermal Irritation/Corrosion" referenced as Method 84 in commission Directive 84/449/EEC. The results may be used as a basis for classification and labelling according to the Regulation 1272/2008/EC after reinterpretation of the raw data.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight oedema.

The mean value from gradings at 24, 48 and 72 hours after patch removal calculated were the following:

- erythema/eschar: score 7/6=1.17 (2 out of 3 animals)

- oedema: 3/6=0.5 (2 out of 3 animals)

Incidents of desquamation and haemorrhage of the dermal capillaries were also noted. On occasions the reactions extended beyond the treatment sites. No corrosive effects were noted.

The test material is not corrosive and not irritant to skin according to the regulation 1272/2008/EC.