Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
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, 20-23 April 2004

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
No guideline available found in the published report.
GLP compliance:
not specified

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:
2,5-dihydrofuran-2,5-dione

Test animals

Species:
other: rats, hamsters, and monkeys

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
not specified
Duration of treatment / exposure:
six month
Doses / concentrationsopen allclose all
Dose / conc.:
9.8 mg/m³ air
Dose / conc.:
3.3 mg/m³ air
Dose / conc.:
1.1 mg/m³ air
Dose / conc.:
0 mg/m³ air
Details on study design:
In a six-month inhalation study in which rats, hamsters, and monkeys were exposed to 0, 1.1, 3.3, or 9.8 mg/m3 (0, 0.3, 0.8, or 2.4 ppm)

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
hamsters and monkeys
Effect level:
9.8 mg/m³ air
Based on:
not specified
Sex:
not specified
Basis for effect level:
clinical biochemistry
clinical signs
Dose descriptor:
NOAEL
Remarks:
rat
Effect level:
3.3 mg/m³ air
Based on:
not specified
Sex:
not specified
Basis for effect level:
clinical biochemistry
clinical signs

Target system / organ toxicity

open allclose all
Critical effects observed:
yes
Lowest effective dose / conc.:
9.8 mg/m³ air
System:
other: respiratory tract and eye;hamsters and monkeys
Organ:
other: not specific
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified
Critical effects observed:
yes
Lowest effective dose / conc.:
3.3 mg/m³ air
System:
other: respiratory tract and eye; rat
Organ:
other: not specific
Treatment related:
yes
Dose response relationship:
yes
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
In a six-month inhalation study in which rats, hamsters, and
monkeys were exposed to 0, 1.1, 3.3, or 9.8 mg/m3 (0, 0.3, 0.8, or 2.4 ppm), respiratory tract and eye irritation were
observed in rats and hamsters exposed to 3.3 or 9.8 mg/m3 (0.8 or 2.4 ppm) and monkeys to 9.8 mg/m3 (2.4 ppm), with body weight reductions only in male rats from the high-exposure group at study termination. Hyperplastic
changes in the nasal tissues, which ranged in severity from trace to mild, were present in rats at all exposure levels and
in hamsters in the mid- and high-exposure levels. Metaplastic changes in the nasal tissues occurred in both rats and
hamsters at all exposure levels. Both the hyperplastic and metaplastic changes in the nasal passages are considered
indicative of irritation and judged to be reversible. The NOAEL for rats is 3.3 mg/m3 (0.8 ppm) and the NOAEL for
hamsters and monkeys is 9.8 mg/m3 (2.4 ppm).