Bis(2-ethylhexyl) maleate

Repeated dose toxicity: inhalation

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

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:

furan-2,5-dione

Test animals

Species:

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

Results and discussion

Effect levels

1

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

2

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).