Registration Dossier

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

Referenceopen allclose all

Reference Type:
secondary source
Title:
Unnamed
Year:
1983
Reference Type:
publication
Title:
Unnamed
Year:
1983
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 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:
OECD Guideline 451 (Carcinogenicity Studies)
Deviations:
not applicable
Remarks:
due to missing details in the OECD SIDS
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
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

open allclose all
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)
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)

Applicant's summary and conclusion