Maleic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from handbook or collection of data, read-across from maleic anhydride

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents)

Deviations:

not specified

Principles of method if other than guideline:

Maleic anhydride was administered to dogs in the feed for 90 days. Several observations were made, including hematology, urinalysis, various clinical chemistry and others.

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

Details on test material:

Maleic anhydride (>99.5%). However, maleic anhydride hydrolyses under test conditions. As a result, it is believed that maleic acid and its salts were the test materials investigated in this study. See also SIDS Initial Assessment.

Test animals

Species:

dog

Strain:

Beagle

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

7 days/week, ad libitum

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 20, 40, 60 mg/kg body weight / day
Basis:
nominal in diet

No. of animals per sex per dose:

4

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

Body weights and food consumption were recorded, and the dogs were observed for signs of toxicity. Clinical parameters were evaluated by determination made prior to the beginning of the study and at intervals throughout the test period. These included hematological studies, urinalysis and various clinical chemistry studies.

Sacrifice and pathology:

Gross examination was conducted at necropsy after the exposure period, organ weights were examined, and tissues were obtained for histopathological evaluation.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

food intake decreased for the first few weeks in both sexes at 60 mg/kg

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

equivocal decreases in packed cell volume and hemoglobin concentration of male dogs at 60 mg/kg bw after 83 days

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

Food intake was decreased for the first few weeks in both sexes of dogs receiving 60 mg/kg/day. Hematological studies conducted after 83 days of exposure indicated equivocal decreases in packed cell volume and hemoglobin concentration of male dogs receiving 60 mg/kg/day. No other changes were observed that were considered relatable to the ingestion of diets containing maleic anhydride.

Effect levels

Dose descriptor:

NOEL

Effect level:

60 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: clinical signs; mortality; body weight; haematology; clinical chemistry;

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOEL of a 90-days dietary feeding study with Beagle dogs was 60 mg/kg/day, which was the highest concentration tested.

Executive summary:

Maleic anhydride was mixed with the food and administered on 7 day/week ad lib., for 90 consecutive days to four Beagle dogs/sex/dose. Doses were 0, 20, 40 or 60 mg/kg body weight.

Body weights and food consumption were recorded, and the dogs were observed for signs of toxicity. Clinical parameters were evaluated by determination made prior to the beginning of the study and at intervals throughout the test period. These included hematological studies, urinalysis and various clinical chemistry studies. Gross examination was conducted at necropsy after the exposure period, organ weights were examined, and tissues were obtained for histopathological evaluation.

Food intake was decreased for the first few weeks in both sexes of dogs receiving 60 mg/kg/day. Hematological studies conducted after 83 days of exposure indicated equivocal decreases in packed cell volume and hemoglobin concentration of male dogs receiving 60 mg/kg/day. No other changes were observed that were considered relatable to the ingestion of diets containing maleic anhydride.

The NOEL was defined to be 60 mg/kg/day for both sexes of Beagle dogs.