Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2004 may 25th to 2004 june 16th
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to the OECD Guideline 420.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes
Test type:
fixed dose procedure

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
SRID No. : DEV75332
Physical State and Appearance : Solid, Tan powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Test System
Female Sprague-Dawley rats (Crl:CD(SD)IGS BR) were obtained from Charles River
Laboratories, Stone Ridge (Kingston), NY. All female rats used for this study were from the
same shipment. These animals were 8 to 10 weeks of age and weighed 18 1.35 to 23 1.63 grams
on the day of dosing (Day 0). All animals were randomly assigned to dose groups, Rats were
chosen for this study because they are a common representative species for toxicity studies. The
rat is the preferred rodent species recommended for use in the Organisation for Economic
Cooperation and Development (OECD) and European Community (EC) Test Guidelines. The
protocol for this study was approved by the Institutional Animal Care and Use Committee.
Husbandry
Housing
Animals were housed in an Association for Assessment and Accreditation of Laboratory
Animal Care International-accredited vivarium in accordance with the Guide for the Care
and Use of Laboratory Animals (National Research Council, 1996). The rats were singly
housed in suspended, stainless-steel, wire mesh cages. Cages and racks were washed
once a week. Absorbent paper, used to collect excreta, was changed at least three times a
week.
Environmental Conditions
The study room was maintained at 19.8 to 23.1 °C and 42.7 to 68.3% relative humidity.
A photoperiod of 12 hours light was maintained.
Acclimation Period
The animals were isolated upon arrival and allowed to acclimate for a period of 5 days.
Animals were judged to be healthy prior to testing.
Feed
Certified Rodent Diet (PMI #5002, pelleted) was available ad libitum. Feed containers
were cleaned and refilled at least once a week. No known contaminants which would
interfere with the outcome of this study were present in the feed. Analyses of feed are
maintained on file within the testing laboratory.
Water
Water was available ad libitum through an automatic watering system. The source of the
water was the local public water system. There have been no contaminants identified in
periodic water analyses that would be expected to interfere with the conduct of the study.
Semiannual analyses of water are maintained on file within the testing laboratory.
Identification
Upon arrival, all rats were identified by uniquely-numbered metal ear tags. During
randomization, study-specific animal numbers were assigned to each animal. Cage cards
contained the study-specific animal number and the ear tag number.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Doses:
Determination of Dose Levels
In a preliminary sighting study, an initial dose of 300 mg/kg of the test substance was
administered to a single female rat. Since no abnormal clinical signs were noted for this
animal on the day of or the day following dosing, a higher dose of 2000 mg/kg was
administered to a second female rat. Based on the results of the sighting study,
2000 mg/kg was administered to an additional four female rats.
Test Substance Exposure
A single dose of the test substance was administered by gavage to animals that had been
fasted overnight.
PreDaration of Test Substance in the Vehicle
For the 2000 and 300 mg/kg dose levels, the test substance was administered as a 20 or
3% suspension in the vehicle, respectively. The vehicle was corn oil.
No. of animals per sex per dose:
Study Type Dose Level Number Of Animal Animal Numbers
Sighting 300 mg/kg 1 Female 481
Sighting & Main 2000 mg/kg 1 Female 482
Main 2000 mg/kg 4 Females 483 - 486
Control animals:
no
Details on study design:
Clinical Observations
Animals were observed three times on the day of dosing (Day 0), and once each day
thereafter for the duration of the experiment. Observations included, but were not limited
to, examination of the hair, skin, eyes, mucous membranes, motor activity, feces, urine,
respiratory system, circulatory system, autonomic nervous system, central nervous
system, and behavior patterns.
Necropsy
All animals were euthanatized and necropsied at the completion of the 14-day
observation period.

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Remarks on result:
other: rat 481
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: rat 482
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: rat 483
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: rat 484
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: rat 485
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: rat 486
Mortality:
No mortality was observed during the 14-day observation period for rats administered a dose of
2000 mg/kg of the test substance.
LD50 for female rats: > 2000 mg/kg (95% C.I. = No Range Calculable)
Clinical signs:
Summary and individual clinical signs are presented in the Appendix on pages 2 - 4. In the
preliminary sighting study, no abnormal clinical signs were noted during the observation period
for single 300 mg/kg rat or the five 2000 mg/kg rats.
Body weight:
Mean and individual body weights and body weight gains are presented in the Appendix on
pages 5 - 6. All animals gained weight during both weeks of the study.
Other findings:
Necropsy Findings
Summary and individual gross pathology tables are presented in the Appendix on pages 7 - 9.
No treatment-related changes were observed at necropsy, and no tissues were collected for
microscopic examination.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the oral LD50 for female rats, the test substance was classified as, at most, slightly toxic
according to the criteria set forth by Hodge and Sterner (1949) and requires no toxicity
classification as defined in the 28th Adaptation of the EC Classification, Packaging and Labelling
of Dangerous Substances Directive.
Executive summary:

In a preliminary sighting study for the acute oral toxicity study, an initial dose of 300 mg/kg of the test substance was administered by gavage to a single female rat. The test substance was administered as a 3% suspension in a corn oil vehicle. Since no clinical signs or signs of toxicity were noted for this rat, a higher dose of 2000 mg/kg was administered to a second female rat. At the 2000 mg/kg dose level, the test substance was administered as a 20% suspension in the same corn oil vehicle. No abnormalities were noted for the 2000 mg/kg female used in the sighting study. Based on these results, 2000 mg/kg was selected as the main study beginning dose. For the main study, four additional female rats were administered a single dose of 2000 mg/kg of the test substance by gavage, thereby creating a group of five animals at this dose level. No abnormal clinical signs were noted for the additional four 2000 mg/kg females. No mortality was observed, and all animals gained weight. No treatment-related changes were observed at necropsy and no tissues were collected for histological examination. The acute oral LD50 for this test substance was greater than 2000 mg/kg for female rats.