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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 Nov 1989 - 13 Dec 1989
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Internal guideline

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
equivalent or similar to guideline
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
Test performed before the guieline was set, but the test was performed in a similar "fixed dose" way.
Principles of method if other than guideline:
Internal guideline
GLP compliance:
Test type:
fixed dose procedure
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
Specific details on test material used for the study:
Clear liquid

Test animals

Details on test animals or test system and environmental conditions:
This study was performed on male and female Crl:CD BR Sprague-Dawley rats whose weights were within a 50 gram range for each sex (females 208.1 g to 257.4 g, males 296.5 to 342.9 g) and were approximately eight weeks old. Upon arrival, the test animals were transferred to a quarantine room where they were kept in individual stainless steel, hanging cages with mesh floors throughout the quarantine and study period. All animals were given a permanent ear tag bearing a unique animal number upon their receipt into the facility. All animals were examined and found to be healthy. All rats were quarantined for seven days. Prior to dosing, the animals were moved to the test room where they received Purina Certified Rodent Chow and tap water ad libitum. All animals were reexamined to assure normal health prior to dosing. The animal room temperature was 67°F-74°F.The relative humidity ranged from 25% to 47%. The light cycle was 12 hours light and 12 hours dark per day.

Administration / exposure

Route of administration:
oral: gavage
not specified
Details on oral exposure:
Animals were dosed orally with a stainless steel 16GA X 3" biomedical animal feeding needle.
1 dose; 51.87 mL/kg (100g/kg)
No. of animals per sex per dose:
Control animals:
Details on study design:
The present study was an oral toxicity study to determine the acute toxicity of the substance. The test article was administered orally to rats which were necropsied at varying time intervals (30 minutes, 1 hour, 6 hours, 24 hours, 1 week and 2 weeks). The liver, spleen and complete gastrointestinal tract were analyzed for microscopic pathology. This study was designed as a limit dose test to deliver a very high dose of the test article to the animal. Previous studies have shown that the test article is orally non-toxic at high doses in multiple species.All rats were fasted for approximately 16 hours prior to dosing. Animals in Groups B, C, D, E, F, and G were dosed once orally with a stainless steel 16GA X 3" biomedical animal feeding needle with 51.87 mL/kg of test article. The dose administered represents approximately a 4X safety factor over the intended human clinical dose. The Group A animals were the control animals and were not dosed. The animals were then euthanized at varying time intervals.

Results and discussion

Effect levels
Key result
Remarks on result:
not determinable due to absence of adverse toxic effects
Clinical signs:
No toxic symptoms were noted. The general health of all the animals was good throughout the study and all animals survived until their scheduled necropsy.
Body weight:
All animals gained weight during the study period.
Gross pathology:
One male rat had a small amount of blood in the cecum, all other rats had no abnormal gross pathological observations.
Other findings:
Histopathological examination noted four instances of inflammation in the esophagus (this was noted in one Group E male,one Group G male and two Group E females) which is considered by the pathologist to be sporadic and does not indicate a test article effect. In rats of both sexes, a variety of other microscopic changes were observed in controls and treated rats. These changes are consistent with anticipated background effects typically found in untreated rats of this age and strain and do not indicate any relationship to the treatment.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
The substance is considered to be nontoxic to rats at an oral dosage level of 51.87 mL/kg (100g/kg).
Executive summary:

Seventy Crl:CD BR Sprague-Dawley rats (35 males and 35 females) were used to test the acute oral toxicity. The rats were divided into seven groups of 5 males and 5 females each. One group (A) of ten animals was the control group and was untreated, the other animals were orally dosed with 51.87 mL/kg of the substance. This dose level was chosen as a limit dose and is approximately four times the clinical dose level. The animals were observed daily for fourteen days for any toxic symptoms and twice daily for morbidity/ mortality. The animals were euthanized and necropsied at varying time intervals (30 minutes, 1 hour, 6 hours, 24 hours, 1 week and 2 weeks). At the time of necropsy the spleen, liver and complete gastrointestinal tract (esophagus, stomach, ileum, jejunum, duodenum, transverse colon, cecum, rectum) were removed, placed in 10% buffered Formalin and analyzed for microscopic pathology. Sections of the bone with marrow, lung, adipose tissue, spleen, liver and blood collected in EDTA tubes were collected, placed in air-tight containers, immediately frozen in liquid nitrogen and sent to the sponsor on dry ice. Other evaluation parameters included body weight, twice daily observations, gross pathology observations and histopathologic evaluation of tissues. No test material-related systemic toxic effects were seen in any of the evaluation parameters listed. No toxic symptoms were noted in any of the animals and only one minor gross observation was noted during necropsy. According to the pathology report all the microscopic changes observed in the rats were consistent with the anticipated background effects typically found in untreated rats of this age and strain and are regarded as random and unrelated to the test article. This study supports the safety of the substance at the dose of 51.87 mL/kg (100g/kg) when administered orally.

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