Phthalic anhydride

Endpoint summary

Description of key information

In 2 valid skin irritation studies, phthalic anhydride was found slightly/moderately irritating (Thyssen, Muermann). In 2 reliable published studies the test substance was characterised as not irritating or slightly irritating.
In a valid eye irritation study with phthalic anhydride conjunctivae effects were not reversible within 7 days (observation period) (Thyssen). Published studies found phthalic anhydride irritating/extremely irritating.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited documentation, no data on compound purity, animals were dosed at the ear for 24 hours

Principles of method if other than guideline:

1 male + 1 female New Zealand White rabbit, ear, 500 mg/rabbit moisted with water, fixed with a tape, exposure time: 24 h, then cleaning with water, soap and oil, post exposure observation time: 14 days

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

White New Zealand rabbits, weight 3 - 4 kg

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

other: moisted with water

Controls:

not required

Amount / concentration applied:

Amount: 500 mg

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

2

Details on study design:

No further data

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 0, 2 d, 7 d

Score:

0

Max. score:

4

Reversibility:

other: score was 0 at any time point

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

no data

Other effects:

no data

Both rabbits: no reaction was observed (score: 0).

Interpretation of results:

GHS criteria not met

Executive summary:

Method: application of 500 mg/animal of the test substance at the inside of rabbit ears of 2 animals

Result: substance is not irritating, no edema and no erythema was seen at any time point

Reference: Thyssen/Bayer AG (1979)

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Observation time 7 days, short documentation, low dose 50 mg

Principles of method if other than guideline:

1 male and 1 female New Zealand white rabbit, 50 mg/rabbit was applied into the conjunctival sac of one eye of each rabbit, observation time: 7 days, evaluation according Draize

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

White New Zealand rabbits, weight 3-4 kg

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount: 50 mg

Duration of treatment / exposure:

7 days

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

2

Details on study design:

No further data

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48 h

Score:

ca. 1

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48 h

Score:

1.5

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

>= 1

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

0.5

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Score:

>= 0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: not measured/tested

Remarks:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

>= 0

Max. score:

2

Reversibility:

not specified

Remarks on result:

other:

Remarks:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Score:

>= 0

Max. score:

2

Reversibility:

not specified

Remarks on result:

other:

Remarks:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Score:

>= 0

Max. score:

2

Reversibility:

not specified

Remarks on result:

other:

Remarks:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

1.5

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

>= 0

Max. score:

3

Reversibility:

not specified

Remarks on result:

other:

Remarks:

not measured/tested

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Other effects:

no data

Scores:
rabbit1 - rabbit2
cornea (maximal score 4):
1h: 1 - 1
24h: 1 - 1
day 2: 1 - 0
day 7: 0 - 0
transitional slight cloudiness of the cornea
Iris (maximal score: 2):
1h: 1 - 1
24 h and later: 0 - 0
conjunctiva, redness (maximal score 3):
1h: 2 - 2
24h: 1 - 2
day 2: 1 - 1
day 7: 1 - 1
conjunctiva, swelling (maximal score 4):
1h: 2 - 1
24 h and later: 0 - 0
lacrimation:
1h: 1 - 1
24 h and later day 14: 0 - 0
The cornea was temporary cloudy. The observed effects were not fully reversible during the 7 days observation period.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Executive summary:

Method: 2 animals received a dose of 50 mg/animal in the conjunctival sac, postexposure period 7 days.

Result: Not fully reversible within 7 days, cornea temorarily in parts opaque.

Reference: Thyssen/Bayer AG (1979)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion and eye irritation is covered by several studies. The most reliable studies for skin irritation stated the test substance as slightly/moderately irritating. Also for eye irritation the most valid study stated phthalic anhydride as irritating.

Effects on skin irritation/corrosion: irritating
Effects on eye irritation: irritating

Justification for classification or non-classification

According to the harmonized classification - Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation) phthalic anhydride is classified as Skin Irrit. 2 (H315) and Eye Dam. 1 (H318).

This classification will be adopted.