Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 205-451-9 | CAS number: 141-05-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 12 March to 12 May 1999
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 999
- Report date:
- 1999
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.6 (Skin Sensitisation)
- Deviations:
- no
- GLP compliance:
- yes
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- The testing using the guinea pig maximisation test protocol was completed on 12 May 1999. The LLNA OECD Guideline 429 was not formally adopted by the OECD until 22 July 2010.
Test material
- Reference substance name:
- Diethyl maleate
- EC Number:
- 205-451-9
- EC Name:
- Diethyl maleate
- Cas Number:
- 141-05-9
- Molecular formula:
- C8H12O4
- IUPAC Name:
- diethyl (Z)-but-2-enedioate
- Details on test material:
- - Name of test material (as cited in study report): Diethylmaleinate
- CAS No.: 141-05-9
- Trade name: DEM
- Physical state: Colourless liquid
- Purity: 99 %
- Lot/batch No.: EMAM 201
- Expiration date of the lot/batch: June 1999
- Storage condition of test material: In the refrigerator, in the dark
Constituent 1
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, Gartenstrasse 27, D-33178 Borchen.
- Age at study initiation: Approx. 6 weeks at the first application
- Weight at first application: 281 g - 369 g
- Housing: Single caging in Makrolon cages type III (23 cm x 39 cm x 18 cm) with wire mesh lids
- Diet (ad libitum): Altromin Standard Diet No. 3022. Analysis of the feed for ingredients and contaminants are performed randomly by Altromin GmbH, D-32791 Lage.
- Water (ad libitum): Tap water, acidified with HCl to pH = 3, offered in Makrolon bottles with stainless steel canules ad libitum.
- Acclimation period: Approx. 2 weeks.
ENVIRONMENTAL CONDITIONS
- Temperature: Approx. 22 °C
- Humidity: Approx. 60 %.
- Air changes (per hr): 12
- Photoperiod: 12 hrs dark, 12 hrs light
IN-LIFE DATES: From: 24 March 1999 To: 22 April 1999
Study design: in vivo (non-LLNA)
Inductionopen allclose all
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: corn oil for intradermal and acetone for challenge exposure
- Concentration / amount:
- 5 % (v/v) in corn oil for the intradermal induction
100 % (undiluted) for the epicutaneous induction and
25 % (v/v) in acetone for the challenge exposure
Challengeopen allclose all
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: corn oil for intradermal and acetone for challenge exposure
- Concentration / amount:
- 5 % (v/v) in corn oil for the intradermal induction
100 % (undiluted) for the epicutaneous induction and
25 % (v/v) in acetone for the challenge exposure
- No. of animals per dose:
- 20 animals were used for as test substance group and 10 animals as negative control group. Spare animals: One additional animal per group was kept and administered under the same conditions as the other animals of the respective group. Findings on the spare animals were only to be incorporated into this report if other animals of the test substance group or of the control group would have died spontaneously. Otherwise, the skin reactions of these animals were not used for the interpretation of the results.
- Details on study design:
- RANGE FINDING TESTS:
To obtain the appropriate concentrations of the test substance for the definitive study, a preliminary test was carried out with 3 female guinea pigs. 4 different concentrations of the test substance and FCA were administered intradermally and 7 days later 4 concentrations of the test substance were administered epicutaneously.
The modes of application were the same as in the definitive study. The duration of the epicutaneous exposure was 24 hours.
The test substance was dissolved in corn oil for the intradermal injections and in acetone for the epicutaneous administration.
For results see "Any other information on results incl. tables".
MAIN STUDY
A. INDUCTION EXPOSURE
- Day of exposures: Intradermally on Day 1; epicutaneously on Day 7.
- Method, intradermally: Hair was clipped. The application site for all injections was an area of about 2 cm x 4 cm in the interscapular region. In each of the injection rows listed in "Any other information on methods and materials incl. tables" two intradermal injections were made side by side.
A volume of 0.1 ml was applied for each injection site.
- Method, epicutaneously: Test patches (Pur Zellin-Tupfer, obtained by Fa. Hartmann , A-2355 Wiener Neudorf), about 2 cm x 4 cm, soaked with the test substance (test substance group) and with deionised water (control group), respectively, were applied to the area of the intradermal injections. They were fixed with a strip of non-irritating tape ("Blenderm*" surgical tape, hypoallergenic, 3M, made in USA, Medical Products Division, St. Paul, MN 551444). The area of administration was then covered occlusively with aluminium foil and finally fixed with "Fixomull* stretch" (self adhesive non woven fabric, hypoallergenic, made by Beiersdorf AG, D-20245 Hamburg). The exposure time was 48 hours.
- Concentrations: 5 % (v/v) in corn oil for the intradermal induction, 100 % (undiluted) for the epicutaneous induction.
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 hours
- Site: left flanks: test substance, right flanks: vehicle
- Concentrations: 25 % in acetone
- Evaluation: 24 h after the end of the exposure period (Day 23) and a second skin examination further 24 h later (Day 24). - Challenge controls:
- A negative control group (10 animals) was tested in parallel.
- Positive control substance(s):
- yes
- Remarks:
- HEXYL CINNAMIC ALDEHYDE (HCA), controls tests performed periodically, data attached to the report
Results and discussion
- Positive control results:
- Positive control group:
Vehicle site: no positive skin reaction in any animal at any reading time.
Substance site: very slight to severe erythema and/or oedema in 7/10 animals 24 and/or 48 hours after the challenge exposure.
7/10 animals had a "positive skin reaction".
In vivo (non-LLNA)
Resultsopen allclose all
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- Test substance 25 % in acetone (v/v)
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: Test substance 25 % in acetone (v/v). No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: none.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- Test substance 25 % in acetone (v/v)
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Clinical observations:
- none
- Remarks on result:
- other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: Test substance 25 % in acetone (v/v). No with. + reactions: 19.0. Total no. in groups: 20.0. Clinical observations: none.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- Test substance 25 % in acetone (v/v)
- No. with + reactions:
- 1
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: Test substance 25 % in acetone (v/v). No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: none.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- Test substance 25 % in acetone (v/v)
- No. with + reactions:
- 19
- Total no. in group:
- 20
- Clinical observations:
- none
- Remarks on result:
- other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: Test substance 25 % in acetone (v/v). No with. + reactions: 19.0. Total no. in groups: 20.0. Clinical observations: none.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- Test substance 10% in acetone (v/v)
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- Test substance 10 %in acetone (v/v)
- No. with + reactions:
- 7
- Total no. in group:
- 10
- Clinical observations:
- none
- Remarks on result:
- positive indication of skin sensitisation
Any other information on results incl. tables
Results (scores) of the preliminary test:
Intradermal exposure:
test substance |
scores for animal Nos. * |
||
concentration (w/v) |
16 |
17 |
18 |
20.0 % |
3/3# |
3/3# |
3/3# |
5.0 % |
1/0 |
3/3# |
0/0 |
1.0 % |
0/0 |
0/0 |
0/0 |
0.1 % |
0/0 |
0/0 |
0/0 |
* first numbers / second numbers: scores 24/48 hours after intradermal injection
# eschars
Epicutaneous exposure:
test substance |
scores for animal Nos. * |
||
concentration (w/w) |
16 |
17 |
18 |
100 % |
2/0 |
3/1 |
2/2 |
50 % |
1/0 |
2/0 |
1/2 |
10 % |
0/0 |
0/0 |
0/0 |
1 % |
0/0 |
0/0 |
0/0 |
* first numbers / second numbers: scores 24/48 hours after the end of the epicutaneous exposure
Results of the main study:
All animals survived till the end of the study.
There were no significant differences in the mean body weights between teh test substance group and the control group on Day 0. A significantly lower mean body weight of the thest substance group animals on Day 24, compared to the controls, was possibly caused by a systemic effect of the test substance.
No abnormal behaviour or clinical signs were detected during the experiment in the animals.
The net rate of animals with positive skin reactions was 85 %.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Conclusions:
- One out of 10 control animals and 19 out of 20 test animals had a positive skin reaction after the challenge exposure. Diethylmaleinate is therefore considered to be a skin sensitiser.
- Executive summary:
Method
The "maximisation test" of B. Magnusson and A.M. Kligman was performed to reveal a possible sensitising potential of"DIETHYLMALEINATE".
Twenty female guinea pigs were used as a test substance group and another 10 females were used as a negative control group. There were two induction exposures (intradermally and epicutaneously) and one epicutaneous challenge exposure. Test substance concentrations were
5 % (v/v) in corn oil for the intradermal induction,
100 % (undiluted) for the epicutaneous induction and
25 % (v/v) in acetone for the challenge exposure.
Investigations performed were in conformance with the OECD-Guideline 406 and with the Directive 96/54/EC, B.6. Application of Freund's complete adjuvant was included in the intradermal exposure of both groups to enhance a possible sensitisation. Occlusive dressings were used for the epicutaneous exposures.
Results
All animals survived till the end of the study. Sensitisation excluded, no other adverse effects were noted.
Skin reactions after the challenge exposure:
The control sites of all animals of both groups were normal at each reading time.
In the test substance group, positive skin reactions (well defined to severe erythema and/or oedema) were noted in 19/20 animals (95 % of the animals) at the test substance treated areas 24 and/or 48 hours after the end of the challenge exposure. As 1/10 animals of the control group (10 % of the animals) had severe erythema and/or oedema at the test substance treated site, the net rate of animals in the test substance group regarded as sensitised is therefore 85 % (95 % - 10 %).Diethylmaleinate is therefore considered to be a skin sensitiser.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.