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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb 1992-July 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Justification for type of information:
Guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OTS 798.1175 (Acute Oral Toxicity)
Principles of method if other than guideline:
US 40 CFR 798, subpart A, standard Acute Oral Toxicity Method, similar to OECD 420.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Purity 100%, Brownish White Flaky Solid, Lot # 11202AB
Specific details on test material used for the study:
Lot 11202AB, brownish white flaked solid, 116 g/100 ml solubility in water

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Healthy, young adult, outbred Sprague-Dawley albino rats were used in the study.
Animals were purchased from a registered commerical breeding laboratory (Charles River Laboratories, Wilmington, MA) and quarantined for 6 days.

Animals were group housed in polycarbonate cages
Hardwood chips were used as contact bedding.
Animal rooms were maintained at 68±3 °F, with a relative humidity at 30-70% with a minimum of 10 to 13 complete air exchanges per hour
12 hour light/dark cycles with full spectrum flourescent lights were used.

Animals were supplied with a commercial rodent ration (Agway Prolab, Waverly, NY) and municipal tap water ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
After overnight fasting, animals were administered a single dose of the test substance by intragastric intubation, a ball tip gavaging needle and a syringe.
All animals were dosed within a 24 hour period.
Doses:
Dose levels of 4.0, 2.0, 1.0, 0.6, and 0.3 g/kg were selected for the range finding trial; 2 animals at each dose
Dose levels of 0.8, 0.5, and 0.2 g/kg were selected for the LD50 trial based on the results of the Range Finding Trial
No. of animals per sex per dose:
10 animals were used with each unique dose.in the main study
Control animals:
no
Details on study design:
Clinical observations were conducted daily for 14 days.
Any animal found dead was necropsied as soon as possible, but in no case later than 12 hours.
A gross necropsy was performed on all animals whether found dead or sacrificed at the end of the study at day 14.

Results and discussion

Preliminary study:
8 of 10 animals died during the initial 4 hour observation period. The 2 animals in lowest dose (0.3 g/kg bw) survived. Gross necropsy of deceased animals showed hemorrhaging in the stomach and small intestine. No leasions were seen in the surviving animals.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
440 mg/kg bw
Based on:
test mat.
Mortality:
All animals at 0.50 g/kg bw and above died before the end of the study.
Clinical signs:
At 0.8 g/kg, alll animals showed signs of cyanosis during the initial 4 hour observation period before succumbing to death. Surviving animals at the 0.5 g/kg dose showed catalepsy and temors during the first 4 hours; 9 of 10 animals died. At the 0.2 g/kg dose, no toxicity was seen during the observation period.
Body weight:
Surviving animals gained body weight during the course of the study.
Gross pathology:
Gross pathologies of animals that died showed hemorrhaging in the stomach and small intestine.
Discoloration of the kidneys were also found in the animals which died during the observation period.

Any other information on results incl. tables

The LD50 of the test material in rats was found to be around 0.44 g/kg bw.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline acute oral toxicity study in CD rats, the LD50 of the test material was found to be 0.44 g/kg bw.