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

Endpoint summary

Description of key information

Skin irritation:

In an in vivo skin irritation study in New Zealand White rabbits according to OECD Guideline 404 (Safepharm, 1990), test material “Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide”, was observed to be not corrosive and not irritating to skin.

Eye irritation:

In an in vivo acute eye irritation study in New Zealand White rabbits according to OECD Guideline 405 (Safepharm, 1990), test material “Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide”, was observed to be not to be not an eye irritant. Mean scores of 0 at 24, 48 and 72 hours after installation of the test material for corneal opacity, iritis, conjunctivae, and chemosis (3 of 3 tested animals) were observed.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

not specified

GLP compliance:

yes

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

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"

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

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

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

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

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

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)

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.

Reference 2

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 September 1990 - 10 September 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study according to OECD405 used to draw a conclusion on the non corrosive/ non-irritating properties to the eyes of the tested substance, which differs slightly from registered substance. Compostion of tested substance available from another report.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: approx. 10 - 16 weeks
- Weight at study initiation: 2.42 - 2.85 kg
- Housing: individually housed 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): 19 - 21 °C
- Humidity (%): 58 - 65%
- Air changes (per hr): Approx. 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml instilled into the conjunctival sac of the right eye

Duration of treatment / exposure:

The upper and lower eyelids were held together for about one second immediately after instillation, to prevent loss of the test material, and then released.

Observation period (in vivo):

Assessment of ocular damage/imitation was made approximately 1 hour and 24,48 and 72 hours following treatment

Number of animals or in vitro replicates:

3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: 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"

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

All treated eyes appeared normal at the 24-hour observation.
Mean scores of 0 following gradings at 24, 48 and 72 hours after installation of the test material for corneal opacity, iritis and conjunctivae (3 of 3 tested animals) were observed.

Other effects:

Minimal conjunctival irritation was noted in all treated eyes one hour after treatment.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material Reaction mass of N-butylphthalimide and N-sec-butylphthalimide and N-propylphthalimide did not produce any positive response in an OECD 405 study. Mean scores of 0 at 24, 48 and 72 hours after installation of the test material for corneal opacity, iritis, conjunctivae, and chemosis (3 of 3 tested animals) were observed. The results allows clear decision that the test item is not corrosive and not irritating to the eyes according to the regulation 1272/2008/EC.

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 eye of the New Zealand white rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method 85 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 data.

A single instillation of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal 24 hours after treatment.

The test material did not produce a positive response in any of the rabbits. Mean scores of 0 following gradings at 24, 48 and 72 hours after installation of the test material for corneal opacity, iritis,

conjunctivae and chemosis (3 of 3 tested animals) were observed. The results allows clear decision that the substance is not corrosive and not irritating to the eyes according to the regulation 1272/2008/EC.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available