Maleic anhydride

Respiratory sensitisation

Administrative data

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

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

review article or handbook

Title:

Maleic Anhydride and Maleic Acid, SIDS Initial Assessment Report For SIAM 18

Author:

OECD SIDS

Year:

2004

Bibliographic source:

OECD SIDS Initial Assessment Report For SIAM 18, Paris, France, 20-23 April 2004

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Maleic anhydride

EC Number:

203-571-6

EC Name:

Maleic anhydride

Cas Number:

108-31-6

Molecular formula:

C4H2O3

IUPAC Name:

2,5-dihydrofuran-2,5-dione

Details on test material:

- Name of test material (as cited in study report): Maleic anhydride
- Physical state: white briquettes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Test system

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 and discussion

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.

Any other information on results incl. tables

The analytical time-weighted averaged concentration of maleic anhydride was 500 and 317 µg/m³, for the induction and challenge phases, respectively.

Applicant's summary and conclusion

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.