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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance as a suspension in corn oil was administered by intragastric intubation to 6 male Crl:CD®(SD)BR rats. Rats were dosed at 2200 mg/kg/day for 10 days (weekends excluded) over a 2 week period. Six control rats were simultaneously dosed with corn oil. At the end of the dosing period, 3 rats per group were killed for pathologic examination. The remaining rats were observed for 14 days after dosing, and were given similar pathologic examinations.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity: 96.4%

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)BR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York
- Age at study initiation: Young adult (No more details are available)
- Weight at study initiation: Mean of 6 rats was 239.7 g
- Fasting period before study: No data
- Housing: housed singly in suspended, stainless steel, wire-mesh cages
- Diet (e.g. ad libitum): Purina Certified Rodent Chow® #5002
- Water (e.g. ad libitum): Tap water
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hour/1-Z-hour light/dark cycle

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
The test substance as a suspension in corn oil was administered by intragastric intubation to 6 male Crl:CD®(SD)BR rats.
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
5 days a week
Doses / concentrations
Dose / conc.:
2 200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control:
No

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily, weekends excluded

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily, weekends excluded

BODY WEIGHT: Yes
- Time schedule for examinations: Daily, weekends excluded

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes: Rats were killed by chloroform anesthesia and exsanguination. Organs and tissues examined were the liver, kidneys, urinary bladder, lungs, heart, spleen, thymus, pancreas, adrenal glands, thyroid gland, trachea, esophagus, brain, stomach, duodenum, jejunum, ileum, cecum, colon, rectum, mesenteric lymph node, testes, epididymides, sternum, bone marrow, eyes and gross lesions.

HISTOPATHOLOGY: No
Statistics:
Data were statistically analyzed by a one-way analysis of variance. Test rats were compared with controls by least significant difference and Dunnett's tests. Significance was judged at the 0.05 probability level.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Apparent compound related lesions occurred in the proximal tubules of the kidneys in 2 of 3 test animals killed on the last day of exposure and in 1 of 3 test animals killed after a recovery period of 14 days. Large numbers of epithelial cells contained intracytoplasmic protein droplets. This lesion was moderately severe in one animal killed on the last day of exposure and in one 14-day-recovery animal and mildly severe in one animal killed on the last day of exposure. Occasional scattered necrotic epithelial cells were noted in kidneys of all affected animals. Other lesions seen in these animals were considered incidental and not compound related.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
LOEL
Effect level:
2 200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
gross pathology
Remarks on result:
other: Kidney effects

Applicant's summary and conclusion

Conclusions:
Gross pathological changes were evident in the kidneys of 2 of 3 test animals killed on the last day of exposure and in 1 of 3 test animals killed after a 14-day recovery period.
Executive summary:

The test substance as a suspension in corn oil was administered by intragastric intubation to 6 male Crl:CD®(SD)BR rats. Rats were dosed at 2200 mg/kg/day for 10 days (weekends excluded) over a 2 week period. Six control rats were simultaneously dosed with corn oil. At the end of the dosing period, 3 rats per group were killed for pathologic examination. The remaining rats were observed for 14 days after dosing, and were given similar pathologic examinations.

 

Mean body weights for test and control rats were similar throughout the dosing and recovery periods. There were no clinical signs of toxicity observed in the test animals. There were no significant differences in organ weights or organ to body weight ratios when test animals were compared to controls. The test substance was mildly toxic to the epithelial cells of the proximal·tubules of the kidney. Recovery was not complete in animals killed after a 14-day recovery period.