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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and appropriate guidelines
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Annex V. B7
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Principles of method if other than guideline:
not relevant
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Identity: PB-370
Reference: #E8200-58
Description: Fine white powder
Storage: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
30 male and 30 female Sprague-Dawley rats were received from Charles River Labs, Portage, Michigan.
Age: 5 weeks upon receipt.
Housed individually in stainless steel cages.
Fluorescent light/dark cycle of 12 hr/12 hr
Temperature: 68-73 Deg F
RH: 26-95%
Diet: Purina Certified Rodent Chow 5002 offered ad libitum
Domestic water supply, untreated with additional HCL or chlorine was provided via an automatic watering system.

Administration / exposure

Route of administration:
oral: feed
Vehicle:
corn oil
Details on oral exposure:
See attached document on diet preparation and administration
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
See attached document on analytical verification of concentrations
Duration of treatment / exposure:
Test duration: 28 days
Frequency of treatment:
Dosing regime: once daily, 7 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 4000, 8000, 20000 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
Four groups of rats (5 per sex per group)
Control animals:
yes
Details on study design:
See attached document on materials and methods
Positive control:
Yes, See attached document on materials and methods

Examinations

Observations and examinations performed and frequency:
See attached document on materials and methods
Sacrifice and pathology:
See attached document on materials and methods
Other examinations:
See attached document on materials and methods
Statistics:
See attached document on materials and methods + illustration 1

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
not attributed to the administration of the test material (see document on results)
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
not attributed to the administration of the test material (see document on results)
Urinalysis findings:
not specified
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
See attached document on results

Effect levels

Dose descriptor:
NOEL
Effect level:
20 000 ppm
Sex:
male/female
Basis for effect level:
other: corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study the No Observable Effect Level (NOEL) was 20000 ppm, corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))
Executive summary:

Four groups of Charles River Sprague-Dawley CD rats (5 per sex per group) were administrated graded doses of PB-370 in the diet for 28 consecutive days. The dosage levels were 0, 4000, 8000 or 20000 ppm. Clinical signs were recorded daily. Body weights and food consumption were recorded weekly. Blood was collected prior to terminal sacrifice for hematology and clinical chemistry determinations. A complete necropsy was performed on study day 28 and selected tissues were saved, weighed and evaluated for histopathologic lesions.

There were no deaths during the study. there were no treatment related clinical signs noted in any animal. Body weights, overall body weight gains and food consumption were not statistically different among treated groups when compared to controls.

There were no haematology or clinical chemistry parameter differences that were attributed to the administration of the test material. There were no statistically significant differences in organ weights or organ:brain weight ratios when comparing treated animals to control animals. There were no compound related macroscopic or microscopic observations noted during histopathological evaluation. All changes observed were related to spontaneous disease or were an artifact. Their incidence and sevirity were typical of rats of this age and strain.

Under the conditions of the study the No Observable Effect Level (NOEL) was 20000 ppm, corresponding with an actual consumption of 1361-1959 mg/kg/day (males) and 1691-2081 mg/kg/day (females))