Bis(2-ethylhexyl) maleate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-03-11 to 1994-04-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Remarks:

Statement included

Type of study:

Buehler test

Justification for non-LLNA method:

Th LLNA was not available at the time where the study was conducted.

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
- Chemical name: (Z)-2-Butendisäure-bis-(2ethyl)ester
- Substance type: active substance
- Physical state: colorless - yellow 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: in closed vessels in the flue

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Versuchstierzucht, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: less than 500g
- Housing: conventional housing in Makrolon type IV cages with a maximum of 5 animals per cage
- Diet: Ssniff G 4-Alleindiät for guinea pigs ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 - 70%
- Air changes: 15fold air changes per hour
- Photoperiod: 12-hours dark/12 hours light

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

2.5, 25, 50 and 100% (w/w)

Challenge

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Concentration / amount:

2.5, 25, 50 and 100% (w/w)

No. of animals per dose:

Five animals per test concentration, ten animal in the control group

Details on study design:

RANGE FINDING TESTS:
Three animal were shaved and the test item was applied at four different test concentrations with a gauze bandage on the shaved skim. The bandage were fixated by means of an occlusive patch for an exposure period of 6 hours. At the end of the exposure period, the patches were removed and the animals were monitored for skin reactions for a duration of 30 and 54 hours. No skin irritation could be observed.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 hours
- Test groups: 1 (3 animals)
- Control group: none
- Site: left flank
- Frequency of applications: day 0, day 7, and day 14
- Concentrations: 2.5, 25, 50 and 100% (w/w). Pure corn oil was applied in the control.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 28
- Exposure period: 6 hours
- Test groups: 1 (20 animals)
- Control group: 1 (10 animals)
- Site: right flank
- Concentration: 25% (w/w)
- Evaluation (hr after challenge): 30 and 54 hour after application

Challenge controls:

A 25% test solution was also applied in the control group.

Positive control substance(s):

yes

Remarks:

2-Mercaptobenzothiazol (2-MCBT)

Results and discussion

Positive control results:

The application of 2-Mercaptobenzothiazol resulted in strong sensiting effects at all test animals

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

30

Group:

test chemical

Dose level:

100% test item

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

54

Group:

test chemical

Dose level:

100% test item

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Results 3

Reading:

1st reading

Hours after challenge:

30

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Results 4

Reading:

2nd reading

Hours after challenge:

54

Group:

negative control

Dose level:

0

No. with + reactions:

0

Total no. in group:

0

Clinical observations:

none

Results 5

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

50% 2-MCBT

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

none

Results 6

Reading:

2nd reading

Hours after challenge:

72

Group:

positive control

Dose level:

50% 2-MCBT

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

none

Any other information on results incl. tables

No sensitizing effects were observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

As no effects could be observed, it can be concluded that dioctyl maleate is not a sensitizer in the Bühler-test.

Executive summary:

In a dermal sensitization study with dioctyl maleate dissolved in corn oil, 20 young adult female Dunkin-Hartley guinea pigs were tested using the method of Bühler. No sensitizing or irritating effects of the skin were observed during the test period. In this study, dioctyl maleate is not a dermal sensitizer.