Bis(2-ethylhexyl) maleate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-02-18 to 1994-04-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) maleate

EC Number:

205-524-5

EC Name:

Bis(2-ethylhexyl) maleate

Cas Number:

142-16-5

Molecular formula:

C20H36O4

IUPAC Name:

bis(2-ethylhexyl) but-2-enedioate

Constituent 2

Reference substance name:

Dioctyl maleate

EC Number:

220-835-6

EC Name:

Dioctyl maleate

Cas Number:

2915-53-9

Molecular formula:

C20H36O4

IUPAC Name:

dioctyl but-2-enedioate

Details on test material:

- Name of test material (as cited in study report): Dioctylmaleinat; (Z)-2-Butendisäure-bis-(2ethylhexyl)ester
- Substance type: active substance
- Physical state: colourless-yellowish liquid
- Analytical purity: 96.1%
- Lot/batch No.: Ch 35559, Beh. 828
- Expiration date of the lot/batch: August 1994
- Storage condition of test material: Under exclusion of oxygen in a tightly closed container under a laboratory flu

Test animals

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Biberach an der Riss, Germany
- Age at study initiation: adult
- Weight at study initiation: 2.3 - 2.6 kg
- Sex: male
- Housing: individual housing
- Diet: Ssniff K 4 - Alleindiät for rabbits ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 cm³ of the undiluted test item

Duration of treatment / exposure:

Animals were exposed over a period of 4 hours.

Observation period:

30 - 60 min, 24, 48 and 72 hours after patch removal and on Day 6, 8, 10 and 13 after patch removal

Number of animals:

Three. Each animal was individually labelled with an earmark.

Details on study design:

TEST SITE
- Area of exposure: skin area of about 6 cm²
- % coverage: 100% of the exposed area
- Type of wrap if used: gauze bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After patch removal, the skin was washed with warm water
- Time after start of exposure: 4


SCORING SYSTEM: according to the guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 6 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 6 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 6 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 6 days

Irritant / corrosive response data:

A table describing the effects observed for each animal is given in the sector "Remarks on results"

Other effects:

At day 6 after the end of the exposure period, dandering skin has been observed at all animals. On day 13 of exposure, no skin effects were observed anymore.

Any other information on results incl. tables

Table 1:Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 2
30 - 60 min	2/2/1	2/1/0
24 h	2/2/2	2/2/2
48 h	2/2/2	1/1/1
72 h	2/2/2	1/1/1
Average 24h, 48h, 72h	2/2/2	1.33/1.33/1.33
Reversibility*)	c/c/c	c/c/c

*) Reversibility: c. = completely reversible;= not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the observations, dioctyl maleate is a mild or slightly skin irritating but does not require classification.

Executive summary:

In a primary dermal irritation study, three adult male Himalayan rabbits were dermally exposed to 0.5 cm³ of dioctyl maleate (purity 96.1%) for 4 hours to about 6 cm² of the body surface area.  Animals then were observed for 13 days.  Irritation was scored by the method of OECD 404.

At 24 hours after end of exposure, all animals showed clearly defined erythema and slight edema. After 48 to 72 hours after the end of the exposure period, all animals still showed clearly defined erythema, but only minimal edema and fully reversible within 8 days.