Dimethyl maleate

Endpoint summary

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:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no GLP, analytical purity not reported, only few information on animal environmental conditions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

no GLP, analytical purity not reported, only few information on animal environmental conditions.

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK.
- Housing: animals were housed in standard conventional single cages.
- Diet (e.g. ad libitum): Standard diet ( “Ssniff K4” Versuchstierdiäten GmbH, Soest/Westfalen) ad libitum.
- Water (e.g. ad libitum): ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C.
- Humidity (%): 40-60%.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated skin area served as control.

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

The day before the application of the test substance the flank skin of each animal was shaved with an electric hair clipper on both sides on an area of about 6x6 cm.
For the treatment of each animal, 0.5 mL of the undiluted test substance was applied to a gauze patch (2.5 x 2.5 cm²).
The patch was then placed on the flanks of the animal and secured with an elastic, air permeable adhesive bandage.
After 4 hours the bandages were removed, and the exposed skin was washed with water.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

No sign of irritation or corrosion was found on the application site right after the exposure, and during and at the end of observation time.

Table 1. The individual skin reactions are collected in the following table.

Animal number	1 hours		24 hours		48 hours		72 hours		7 days		14 days
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
7	0	0	0	0	0	0	0	0	0	0	0	0
8	0	0	0	0	0	0	0	0	0	0	0	0
10	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Executive summary:

Suberg (1985)

In a primary dermal irritation study, the skin irritation/corrosion potential of dimethyl maleate was tested according to OECD guideline 404 with acceptable restrictions (no GLP, analytical purity not reported, only few information on animal environmental conditions). The shaved flank of 3 male New Zealand White rabbits was exposed to 0.5 mL dimethyl maleate for 4 hours under semiocclusive conditions. The rabbits were observed up to 14 days. Skin reactions were assessed using the Draize scheme approx. 1, 24, 48 and 72 hours after removal of the test substance. No sign of irritation or corrosion was found on the application site right after the exposure, and during and at the end of observation time. Based on the study results, the dimethyl maleate was assessed as not irritating according to EU classification criteria.

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:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

no GLP, analytical purity not reported, only few information on animal environmental conditions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

no GLP, analytical purity not reported, only few information on animal environmental conditions.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hacking& Churchill Ltd., Huntingdon, UK.
- Housing: single housing in standard conventional cages.
- Diet (e.g. ad libitum): Standard diet ( “Ssniff K4” Versuchstierdiäten GmbH, Soest/Westfalen) ad libitum.
- Water (e.g. ad libitum): ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C.
- Humidity (%): 40-60%.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 d

Number of animals or in vitro replicates:

3

Details on study design:

After application, the eye lids were held together for approximately 1 second.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with NaCl phisiological solution.
- Time after start of exposure: 24 hours after application.

SCORING SYSTEM: Draize.

TOOL USED TO ASSESS SCORE: fluorescein.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, and 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, and 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

All animals showed slight corneal opacity after application, slight iritis, partially scaled pupil, as well as slight redness and swelling of the conjunctiva with lacrimation. 7 days after application none of the mentioned symptoms were observed anymore and no change from the normal physiological findings was recorded in the eyes.

Table 1: Results of eye irritation test

				Conjunctiva
Rabbit No./ sex	Scoring [h]	Cornea	Iris	Redness	Chemosis
42/male	1	2	1	2	3
	24	2	1	3	2
	48	2	0	2	1
	72	1	0	1	0
	168	0	0	0	0
Mean (24, 48, 72 h)		1.7	0.3	2	1
43/male	1	1	1	2	2
	24	1	1	3	1
	48	1	0	1	1
	72	1	0	1	0
	168	0	0	0	0
Mean (24, 48, 72 h)		1	0.3	1.7	0.7
44/male	1	1	1	2	2
	24	1	0	2	1
	48	1	0	1	1
	72	1	0	1	0
	168	0	0	0	0
Mean (24, 48, 72 h)		1	0	1.3	0.7

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Conclusions:

Based on the study results, dimethyl maleate is  is classified as Category 2B (mildly irritating to eyes) according to UN-GHS regulation and classificed as Category 2 according to EU-CLP.

Executive summary:

Suberg (1985)

 

In an eye irritation study, 0.1 mL of undiluted dimethyl maleate was instilled into the conjunctival sac of one eye of three male New Zealand White rabbits. Animals were observed for 7 days. Irritation was scored according to the method of Draize. All animals showed slight corneal opacity after application, slight iritis, partially scaled pupil, as well as slight redness and swelling of the conjunctiva with lacrimation. 7 days after application none of the mentioned symptoms were observed anymore and no change from the normal physiological findings was recorded in the eyes. Based on the study results, dimethyl maleate is  is classified as Category 2B (mildly irritating to eyes) according to UN-GHS regulation and classificed as Category 2 according to EU-CLP.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

Skin irritation:

According to the OECD TG404 (1985) study resulst, dimethyl maleate is not classified according to EU-CLP.

 

Eye irritation:

According to the OECD TG 405 study results, dimethyl maleate is classified as Category 2B (mildly irritating to eyes) according to UN-GHS regulation and classificed as Category 2 according to EU-CLP.