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Toxicological information

Repeated dose toxicity: oral

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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:
OECD Guideline 409 (Repeated Dose 90-Day Oral Toxicity 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

Reference
Name:
Unnamed
Type:
Constituent
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.