Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
A 6-month multispecies inhalation study with maleic anhydride
Author:
Short et al
Year:
1988
Bibliographic source:
Fundam. Appl. Toxicol. 10: 517-524.

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
CD rats, Engle hamsters, and Rhesus monkeys were exposed by inhalation (whole
body) to 0, 1.1, 3.3 and 9.8 mg/m³ (0, 0.3, 0.8, and 2.4 ppm) maleic anhydride for six hours/day,
five days/week for six months.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Maleic anhydride
EC Number:
203-571-6
EC Name:
Maleic anhydride
Cas Number:
108-31-6
Molecular formula:
C4H2O3
IUPAC Name:
furan-2,5-dione

Test animals

Species:
other: Multi species: CD rats, Engle hamsters, and Rhesus monkeys

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
rats
Effect level:
ca. 0.8 ppm
Based on:
test mat.
Sex:
not specified
Basis for effect level:
body weight and weight gain
other: nasal irritation
Dose descriptor:
NOAEL
Remarks:
hamster and monkey
Effect level:
ca. 2.4 ppm
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: nasal irritation

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Executive summary:

In the key study, CD rats, Engle hamsters, and Rhesus monkeys were exposed by inhalation (whole body) to 0, 1.1, 3.3 and 9.8 mg/m³ (0, 0.3, 0.8, and 2.4 ppm) maleic anhydride for six hours/day, five days/week for six months. Body weights were decreased in rats in the mid- and high-exposure groups at intervals during the study (<10%). However, at study termination, body weights were decreased only in the high-exposure group (6 – 8%). All other effects were limited to the respiratory tract and eye. In the high-exposure groups, nasal discharge, ocular irritation, and slight dyspnea with coughing and sneezing were observed. The effects were less severe in the animals from the mid- and low-exposure groups. In the rats and hamsters (but not monkeys), hyperplastic changes in the nasal tissues were present in the mid- and high-exposure groups only. Also in the rats and hamsters, metaplastic changes in the nasal tissues were present in all exposure groups. In all species, there was some mucosal and/or submucosal infiltration of neutrophils into the nasal tissues at all exposure groups. All of these effects were considered indicative of irritation and judged to be reversible. The NOAEL for rats is based on systemic effects (decreased body weights) and localized eye/nasal irritation effects and is considered to be 3.3 mg/m³ (0.8 ppm). The NOAEL for hamsters and monkeys is based on localized nasal irritation effects only and is considered to be 9.8 mg/m³ (2.4 ppm).