Maleic acid

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. Reliability adopted from OECD SIDS Draft.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

1983

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1983

Reference 3

Reference Type:

secondary source

Title:

A 6-month multispecies inhalation study with maleic anhydride

Author:

Short, R.D., Johannsen, F.R., Ulrich, C.

Year:

1988

Bibliographic source:

Appl. Toxicol. 10: 517-524; cited in OECD SIDS Draft for CAS. Nos. 108-31-8/ 110-16-7, 2005

Reference 4

Reference Type:

secondary source

Title:

Chronic Dietary Administration of Maleic Anhydride

Author:

Preach, M.

Year:

1983

Bibliographic source:

cited in: EPA: Health and environmental effects profile for maleic anhydride, 06/1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 451 (Carcinogenicity Studies)

Deviations:

not applicable

Remarks:

due to missing details in the OECD SIDS

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Details on test material:

- Name of test material (as cited in study report): Maleic anhydride

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The analysis of the diet for maleic anhydride was conducted 2 to 4 years after completion of the in-life phase of the study. A sample of each diet was removed, refrigerated or frozen for future chemical determination of the concentration of maleic anhydride. The GC-MS measurements were (on average of random samples) 69-75% of the expected for male and female diets, respectively.

Duration of treatment / exposure:

2 years

Frequency of treatment:

7 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 10, 32, 100 mg/kg/day
Basis:
nominal conc.

No. of animals per sex per dose:

126

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: Yes


BODY WEIGHT: Yes


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption : Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data


OPHTHALMOSCOPIC EXAMINATION: Yes


HAEMATOLOGY: Yes
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 5 animals of each sex from the control and each test group at 6 and 12 months and on approximately 20 animals from each group at 18 and 24 months.


CLINICAL CHEMISTRY: Yes
- Animals fasted: No data
- How many animals: 5 animals of each sex from the control and each test group at 6 and 12 months and on approximately 20 animals from each group at 18 and 24 months.


URINALYSIS: Yes
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data


NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY: no data


BODY WEIGHT AND WEIGHT GAIN: small (<6%), but dose-related, decrease in body weights of male rats fed 32 and 100 mg/kg/day compared to the controls. The female rats fed 32 and 100 mg/kg/day also had reduced body weights, but the reductions were smaller and of shorter duration than those observed in males.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): slightly reduced during limited periods during the study for animals in the mid- and high-dose groups.


FOOD EFFICIENCY: no data


OPHTHALMOSCOPIC EXAMINATION: no data


HAEMATOLOGY: no data


CLINICAL CHEMISTRY: no data


URINALYSIS: no data


ORGAN WEIGHTS: no data


GROSS PATHOLOGY: no data


HISTOPATHOLOGY: NON-NEOPLASTIC: no data


HISTOPATHOLOGY: NEOPLASTIC: No increases in tumor incidence that were considered related to maleic anhydride exposure. There was an unusally high incidence of uterine adenocarcinomas in this study. The tumors were present in similar numbers in both the control and treated animals (23/86 and 20/82, respectively). The report stated that “Uterine adenocarcinomas is not a common spontaneous lesion in this strain of rat,” although no historical control data was provided. The authors speculated that this may have been related to altered hormonal status caused by the continuous light exposure.

Effect levels

1

Dose descriptor:

NOEL

Effect level:

>= 100 other: mg/kg/day

Sex:

male/female

Basis for effect level:

other: overall effects

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

2

Dose descriptor:

NOEL

Effect level:

10 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: reduced body weight (& food consumption)

Remarks on result:

other: Effect type: toxicity (migrated information)