Anthranilamide

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic 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:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A 2-year feeding study is being conducted in Crl:CD(SD) rats (SO/sex/concentration) with the test substance at dietary concentrations of 0, 20, 200, 2000, or 20000 ppm. This notification covers effects through the one-year interim sacrifice. The rats have been observed for mortality, clinical signs, body weight effects, and food consumption, and rats received an ophthalmologic examination after ~ 1 year of dosing. Ten rats/sex/concentration were designated for evaluation of chronic toxicity. These rats were evaluated for clinical pathology at ~6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Anthranilamide

EC Number:

201-851-2

EC Name:

Anthranilamide

Cas Number:

88-68-6

Molecular formula:

C7H8N2O

IUPAC Name:

2-aminobenzamide

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Duration of treatment / exposure:

12 months

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

20 ppm

Doses / concentrations 2

Dose / conc.:

200 ppm

Doses / concentrations 3

Dose / conc.:

2 000 ppm

Doses / concentrations 4

Dose / conc.:

20 000 ppm

No. of animals per sex per dose:

10

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

The rats have been observed for mortality, clinical signs, body weight effects, and food consumption, and rats received an ophthalmologic examination after ~ 1 year of dosing.

Sacrifice and pathology:

These rats were evaluated for clinical pathology at 6 and 12 months and for anatomic pathology (organ weights, gross and microscopic pathology) at the end of 12 months.

Results and discussion

Results of examinations

Details on results:

Mild reductions in mean body weight, body weight gain, food consumption, and food efficiency were observed in females in the 2000 ppm and 20000 ppm groups compared to control. Mild reductions in food efficiency were observed in the male 2000 ppm and 20000 ppm groups. Clinical observations included subdued behavior, ataxic gait, dragging hindlimbs, and tilted head.These were only observed in isolated cases involving 1 animal in any dose group throughthe one year time point, and did not exhibit a dose-response. The following clinical chemistry changes were observed in males (not all statistically significant or clear dose response and many differences of small magnitude) at 6 and/or 12 months: at 20000 ppm - HGB, MCRC, AST, bilirubin, ALKP, i Ca; at 2000 ppm - ! bilirubin, i hemoglobin distribution width, Ca, cholesterol, triglycerides, Na; At 200 ppm - ! RBC ghosts, i HGB, Na; and at 20 ppm - ! BUN.
The following clinical chemistry changes were observed in females (not all statistically significant) at 6 and/or 12 months: at 20000 ppm - ! prothrombin time (PT), triglycerides, AST,ALT, bilirubin, Cl, i red cell distribution width, cholesterol, Ca: at 2000 ppm - ! HGB, MCHC, RBC ghosts, prothrombin time (PT), AST, bilirubin, ired cell distribution width, activated partial thromboplastin time (APTT), cholesterol, Ca, total protein, globulin, CI; at 200 ppm - ! RBC ghosts, AST; and at 20 ppm i total protein, globulin. None of these differences was considered to be adverse or test substance related except the increased cholesterol in females at 2000 or 20000 ppm. No gross observations at necropsy were attributed to test substance exposure. Test substance-related increases in absolute and/or relative liver weights were observed in males and females at 2000 and 20000 ppm. Non-statistically significant elevations in liver weights were also observed in 20 and 200 ppm female groups. Correlative centrilobular hepatocellular hypertrophy (minimal or mild) was observed in 20000 ppm males and females and in 200 and 2000 ppm females. Minimal or mild vacuolar degeneration of the liver was also observed in 2000 and 20000 ppm males; however, no correlative clinical pathology effects were observed. Other statistically significant organ weight changes were increased relative kidney weight (2000 and 20000 ppm females), increased absoluteheart weight (2000 ppm males), and increased relative heart weigh (2000 ppm females). No microscopic pathology correlates were observed. Other microscopic pathology lesions attributed to test substance exposure were increased adrenal cortical microvesiculation (minimal) in 20000 ppm females and increased thyroid gland follicular cell hypertrophy (minimal) in 2000 and 20000 ppm females. Uterine squamous metaplasia (minimal) was observed in all dose groups, but not in controls. However, the incidence was highest in the 20 ppm group and did not display a doseresponse; therefore, the detennination of whether or not this lesion is test substance related will be made based on overall incidence at the end of the study.