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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Information from public copy of a correspondance letter to US EPA, reliability not known but contributing to a weight of evidence assessment.

Data source

Reference
Reference Type:
other: Public copy of a correspondance letter to US EPA
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Anthranilamide

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:
- Concentration in vehicle: dietary concentrations of 0, 300, 1500, or 5000 ppm
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
300, 1500, and 5000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
5 - 7
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
Body weights, food consumption, and clinical signs were evaluated weekly.
Sacrifice and pathology:
Clinical pathology endpoints were evaluated during week 4. After 4 weeks of treatment all surviving rats were euthanized and given a gross and microscopic pathological examination.

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
- Test substance-related mortality was observed in 3/7 high dose female rats on the first day of dosing. Following the first day of dosing no adverse clinical signs were observed in any dose group.

BODY WEIGHT AND WEIGHT GAIN
-Body weight gain was approximately 10 and 20% lower in male and female rats fed 5000 ppm, respectively, compared to the controls.

FOOD CONSUMPTION AND COMPOUND INTAKE
- Food consumption was 13 % lower in female rats fed 5000 ppm compared to the control rats.

FOOD EFFICIENCY
- Male and female food efficiency was 6 % lower in rats fed 5000 ppm compared to the control rats.

ORGAN WEIGHTS
- Absolute and relative liver weights were statistically higher in male and female rats fed 1500 and 5000 ppm compared to the control rats.

HAEMATOLOGY
- Prolongation of prothrombin time and activated partial thromboplastin time were observed in male rats fed 5000 ppm (30 and 33% prolongation compared to control group means, respectively). Increased clotting times were not observed in female rats at any dietary concentration.

HISTOPATHOLOGY: NON-NEOPLASTIC
- Hepatocellular hypertrophy was observed in male and female rats fed all dietary concentrations of test substance.
- Thyroid hypertrophy was observed in male and female rats fed 5000 ppm and also in male rats fed 1500 ppm. Colloid depletion was observed in male rats fed 5000 ppm.

Effect levels

Dose descriptor:
NOAEL
Effect level:
300 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Only effect observed at this dose level was hepatocellular hypertrophy, but this effect is considered to be an adaptive physiologic response to exposure to a xenobiotic and not biologically adverse.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion