Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP-Study, no informations on Guideline followed in report.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Details on test animals or test system and environmental conditions:
Male Crl:CD®(SD)IGS BR rats were received from Charles River Laboratories, Inc., Raleigh,
North Carolina. Rats were housed singly in stainless steel, wire-mesh cages suspended above
cage boards. Each rat was assigned a unique identification number which was recorded on a card
affixed to the cage. The rats were tail-marked, using a water-insoluble marker, with the last 3
digits of the animal number. PMI Nutrition International, Inc. Certified Rodent LabDiet® 5002
and water were available ad libitum.
As specified in the Haskell Laboratory animal health and environmental monitoring program, the
following procedures are performed periodically to ensure that contaminant levels are below
those that would be expected to impact the scientific integrity of the study:
• Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead,
and other contaminants.
• Feed samples are analyzed for total bacterial, spore, and fungal counts.
• Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation
by the cagewashers.
Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional
requirements and not to exceed stated maximum concentrations of key contaminants, including
specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The
presence of these contaminants below the maximum concentration stated by the manufacturer
would not be expected to impact the integrity of the study.
The animal health and environmental monitoring program is administered by the attending
laboratory animal veterinarian. Evaluation of these data did not indicate any conditions that
affected the validity of the study.
Rats were quarantined, weighed, and observed for general health for 6 days. Animal rooms were
maintained on a timer-controlled, 12-hour light/12-hour dark cycle. Environmental conditions of
the rooms were targeted for a temperature of 23 ± 1°C and relative humidity of 50 ± 10%.
Excursions outside these ranges were of small magnitude and/or brief duration and did not
adversely affect the validity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test substance was suspended in corn oil and administered to 1 rat per dose rate by
intragastric intubation. The volumes administered were calculated based on the suspension
concentration and body weights collected on the day of dosing. Doses administered ranged from
2300 to 11,000 mg/kg of body weight in increments of approximately 50%. Additionally, 1 rat
was dosed at 670 mg/kg. The dosing day was test day 1; postexposure day 14 was test day 15.
Following administration of the test substance, rats were observed for clinical signs of toxicity.
Doses:
670, 2300, 3400, 5000, 7500, and 11,000 mg/kg
No. of animals per sex per dose:
1
Control animals:
no
Details on study design:
The rats were weighed and observed daily until signs of toxicity subsided, and then at least 3
times a week throughout the 14-day observation period. Observations for mortality and signs of
illness, injury, or abnormal behavior were made daily throughout the study. Pathology
examinations of test animals were not performed.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
The rat dosed at 7500 mg/kg exhibited wet chin on the day of dosing and yellow stained perineum on test day 2. The rat dosed at 11,000 mg/kg exhibited lung noise on the day of dosing. No other clinical signs were observed.
Body weight:
No biologically important body weight losses occurred during the study.
Gross pathology:
Pathology examinations of test animals were not performed.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Under the conditions of this study, the oral ALD for H-25286 was greater than 11,000 mg/kg of body weight. This substance is considered to be very low in toxicity (ALD greater than 5000 mg/kg) when administered as a single oral dose to male rats.