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EC number: 203-571-6 | CAS number: 108-31-6
- 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
Endpoint summary
Administrative data
Description of key information
The potential of maleic anhydride to induce skin and respiratory sensitisation was tested in suitable in vivo test methods. Based on the results, the target substance can be considered a skin and respiratory sensitiser.
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Deviations:
- yes
- Remarks:
- (no positve controls, mice strain BALB/c used)
- GLP compliance:
- not specified
- Type of study:
- mouse local lymph node assay (LLNA)
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Harlan Seralab, Bicester, Oxfordshire, UK
- Age at study initiation: 6-12 weeks old
- Housing: 10 per cage (acclimation period), 4-5 per cage (during treatment)
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12
- Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 0, 0.1,0.25, 0.5, 1, 2.5% (w/v)
- No. of animals per dose:
- 4
- Details on study design:
- MAIN STUDY
Groups of mice (n= 4) were exposed topically on the dorsum of both ears to 25 µL of various concentrations of acid anhydrides or to vehicle (acetone:olive oil, AOO) alone, daily for three consecutive days. Five days after the initiation of exposure all mice were injected intravenously via the tail vein with 20 µCi of [3H] methyl thymidine in 250 µL of phosphate-buffered saline (PBS). Five hours later, mice were killed, and the draining auricular lymph nodes were excised and pooled for each experimental group. A single cell suspension of LNC was prepared by gentle mechanical disaggregation through 200-mesh stainless-steel gauze. Cells were washed twice with PBS and precipitated in 5% trichloroacetic acid (TCA) at 4 °C overnight. Pellets were then resuspended in 1 mL of 5% TCA and transferred to 10 mL of scintillation fluid. Incorporation of 3HTdR was measured by ß-scintillation counting as disintegrations per min (dpm) per node for each experimental group. In each case a stimulation index (SI) relative to the concurrent vehicle-treated control was derived. The estimated concentration of chemical required to induce SI= 3 relative to concurrent vehicle-treated controls i.e. the EC3 value was derived by linear interpolation. - Key result
- Parameter:
- EC3
- Value:
- 0.16
- Parameter:
- SI
- Value:
- 1.91
- Test group / Remarks:
- 0.1% w/v
- Parameter:
- SI
- Value:
- 4.86
- Test group / Remarks:
- 0.25 % w/v
- Parameter:
- SI
- Value:
- 6.32
- Test group / Remarks:
- 0.5% w/v
- Parameter:
- SI
- Value:
- 14
- Test group / Remarks:
- 1% w/v
- Parameter:
- SI
- Value:
- 15.98
- Test group / Remarks:
- 2.5% w/v
- Cellular proliferation data / Observations:
- For detailed results please refer to Table 1 in box "Any other information on results incl. tables".
- Interpretation of results:
- Category 1A (indication of significant skin sensitising potential) based on GHS criteria
- Conclusions:
- In this study under the given conditions the EC3 was calculated to be 0.16% w/v = 0.016 M. Therefore, the test item in this test can be considered to be a skin sensitizer category 1A according to the CLP Regulation (EC) 1272/2008.
- Executive summary:
In a dermal sensitization study conducted equivalent to OECD Guideline 429 young adult Balb/c mice (4 females per dose) were treated with 0.1, 0.25, 0.5, 1 and 2.5% maleic anhydride in acetone/olive oil (4:1, v/v). Five days after the initiation of exposure all mice were injected intravenously via the tail vein with 20 µCi of [3H] methyl thymidine in 250 µL of phosphate-buffered saline (PBS). Five hours later, mice were killed, and the draining auricular lymph nodes were excised and pooled for each experimental group. Incorporation of 3HTdR was measured by ß-scintillation counting as disintegrations per min (dpm) per node. Furthermore, in each case a stimulation index (SI) was derived.
The stimulation indices (SI) were 1.91 (0.1%), 4.86 (0.25%), 6.32 (0.5%), 14.00 (1%) and 15.98 (2.5%). Based on the results, the extrapolated EC3 value was determined to be 0.16%. Thus, maleic anhydride must be considered as a dermal sensitizer and classification as Skin Sens 1A, H317 according to the criteria of the CLP Regulation (EC) 1272/2008 is warranted.
Reference
Table 1: Local lymph node assay responses to maleic anhydride
Concentrations (% w/v) | DPM per node | SI |
0 | 245 | 1 |
0.1 | 467 | 1.91 |
0.25 | 1181 | 4.86 |
0.5 | 1548 | 6.32 |
1 | 3431 | 14 |
2.5 | 3915 | 15.98 |
5 | ND | |
10 | ND |
ND = not determined
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
In a dermal sensitization study conducted equivalent to OECD Guideline 429 young adult Balb/c mice (4 females per dose) were treated with 0.1, 0.25, 0.5, 1 and 2.5% maleic anhydride in acetone/olive oil (4:1, v/v). Five days after the initiation of exposure all mice were injected intravenously via the tail vein with 20 µCi of [3H] methyl thymidine in 250 µL of phosphate-buffered saline (PBS). Five hours later, mice were killed, and the draining auricular lymph nodes were excised and pooled for each experimental group. Incorporation of 3HTdR was measured by ß-scintillation counting as disintegrations per min (dpm) per node. Furthermore, in each case a stimulation index (SI) was derived. The stimulation indices (SI) were 1.91 (0.1%), 4.86 (0.25%), 6.32 (0.5%), 14.00 (1%) and 15.98 (2.5%). Based on the results, the extrapolated EC3 value was determined to be 0.16%.Thus, maleic anhydride is a dermal sensitizer and classification as Skin Sens 1A, H317 according to the criteria of the CLP Regulation (EC) 1272/2008 is warranted. Supporting evidence for the potential of maleic anhydride to induce skin sensitisation was derived from data published in the OECD SIDS for maleic anhydride. In this study, a dermal sensitization study (according to OECD guideline 406 and EPA OPPTS 870.2600) with maleic anhydride in mineral oil 20Crl: (HA)BR guinea pigs were tested using the method of Buehler. The guinea pigs were exposed with 5% (w/v) maleic anhydride in mineral oil during the three-application induction phase. The maleic anhydride produced very faint to moderate erythema reactions in all 20 test animals (eight animals with scores of 0.5, and 12 animals with scores of 1.0 to 2.0). Pinpoint areas of subcutaneous haemorrhaging were also observed in two of these animals. None of the vehicle control animals reacted to the initial challenge application of the test material. None of the test or vehicle control animals reacted to the vehicle control material. All reactions to maleic anhydride in the test group (scores of 0.5 to 2.0) exceeded the highest reaction in the vehicle control group (score of 0.0). In this study maleic anhydride is a dermal sensitizer. Furthermore, maleic anhydride is generally considered as skin sensitizer in humans and was positively tested in patch and prick tests.
Respiratory sensitisation
Link to relevant study records
- Endpoint:
- respiratory sensitisation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- To determine the sensitising potential of Maleic anhydride, rats were exposed to a maleic anhydride aerosol 6 hours/day for five days. Following a 3-week rest period, the animals were challenged for 6 hours. One group was not challenged (i.e., nonexposed/nonchallenged control).
- GLP compliance:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Route of induction exposure:
- inhalation
- Route of challenge exposure:
- inhalation
- Vehicle:
- not specified
- Concentration:
- 500 µg/m³ (induction and challenge period)
- No. of animals per dose:
- 10/sex
- Details on study design:
- A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 6 hrs
- Frequency of applications: every day
- Duration: 5 days
- Concentrations: 500 µg/m³
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 26
- Exposure period: 6 hrs
- Concentrations: 500 µg/m³ - Positive control substance(s):
- none
- Negative control substance(s):
- other: unexposed group
- Results:
- The maleic anhydride-exposed/maleic anhydride-challenged animals had small, but statistically significant (p< 0.05), increases in maleic anhydride-specific serum IgG antibody compared to the controls (challenged and nonchallenged; females higher than males). Two rats of the MA-exposed/nonchallenged group had more than 10 lung foci (i.e., positive response); however, mean values for lung foci, weight, and volume were not significantly different from control values. Microscopic lung lesions were minimal and provided no evidence of pulmonary sensitization. The serum IgG antibody levels of the maleic anhydride-exposed group were significantly increased over those of the MA-exposed and challenged males and the challenged and nonchallenged control males.
- Positive control results:
- not available
- Negative control results:
- Accumulation of alveolar macrophages was seen histologically in one control rat and no maleic anhydride-exposed rats.
- Interpretation of results:
- Category 1 (respiratory sensitising) based on GHS criteria
- Conclusions:
- Based on the results of this study, maleic anhydride is considered to be a respiratory sensitiser. In accordance with ATP13 to CLP regulation 1272/2008 classification as Resp. Sens. 1, H334 is warranted.
- Executive summary:
In a respiratory sensitisation study, Sprague- Dawley rats (n=10/sex) were exposed to a particulate aerosol target concentration of 0 or 500 µg/m³ maleic anhydride, 6 hours/day for five days. Following a 3-week rest period, the animals were challenged with 500 µg/m³ for 6 hours. The analytical time weighted averaged concentration of maleic anhydride was 500 and 317 µg/m³, for the induction and challenge phases, respectively. The maleic anhydride-exposed/maleic anhydride-challenged animals had small, but statistically significant (p< 0.05), increases in maleic anhydride-specific serum IgG antibody compared to the controls (challenged and nonchallenged; females higher than males). However, other prominent features of respiratory sensitization reactions in this rat model (such as increased numbers of external hemorrhagic lung foci, increased lung weight and volume, and extensive lung pathology) were not evident.
Based on the results of this study, maleic anhydride is considered to be a respiratory sensitiser. In accordance with ATP13 to CLP regulation 1272/2008 classification as Resp. Sens. 1, H334 is warranted.
Reference
The analytical time-weighted averaged concentration of maleic anhydride was 500 and 317 µg/m³, for the induction and challenge phases, respectively.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (sensitising)
- Additional information:
In a respiratory sensitisation study, Sprague- Dawley rats (n=10/sex) were exposed to a particulate aerosol target concentration of 0 or 500 µg/m³ maleic anhydride, 6 hours/day for five days. Following a 3-week rest period, the animals were challenged with 500 µg/m³ for 6 hours. The analytical time weighted averaged concentration of maleic anhydride was 500 and 317 µg/m³, for the induction and challenge phases, respectively. The maleic anhydride-exposed/maleic anhydride-challenged animals had small, but statistically significant (p< 0.05), increases in maleic anhydride-specific serum IgG antibody compared to the controls (challenged and nonchallenged; females higher than males). However, other prominent features of respiratory sensitization reactions in this rat model (such as increased numbers of external hemorrhagic lung foci, increased lung weight and volume, and extensive lung pathology) were not evident. Based on the results of this study, maleic anhydride is considered to be a respiratory sensitiser. Furthermore, several publications described occupational asthma due to maleic anhydride (Lee et al. 1991; Gannon et al. 1992; Graneek et al. 1986, Val. 4). When all subjects were included and all three acid anhydrides were taken into account there was no consistent evidence for an exposure-response relation, but with the analysis restricted to a factory where only trimellitic anhydride (TMA) was in use, there was an increased prevalence of sensitisation to acid anhydrides and work related respiratory symptoms with increasing full shift exposure. This relation was apparent within the current occupational exposure standard of 40 μg/m³ and was not modified significantly by smoking or atopy.
Justification for classification or non-classification
Based on the available data and in accordance with ATP13 to CLP regulation 1272/2008 classification as Skin Sens 1A, H317 and Resp. Sens. 1, H334 is warranted.
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