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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:
From Aug. 04, 1981 to Dec. 31, 1981
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 11583B15
- Physical state: Clear, colorless liquid
- Analytical purity: 91.58 %
- Density at 25 °C: 1.06749 g/cm3 (equivalent to 1067.49 mg/mL)
- Stability under test conditions: Stable at room temperature or below and slowly reacts with water
- Storage condition of test material: Refrigerator

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Inc.
- Weight at study initiation:
Range finding study: Males: 272-303 g ; Females: 206-247 g
Main study: Male: 203- 268 g ; Females: 175-210 g
- Fasting period before study: Overnight
- Housing: Stainless steel cage with wire-mesh floors
- Diet: Purina Certified Rodent Chow, ad libitum
- Water: Filtered tap water, ad libitum
- Acclimation period: 7 d

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 20/hr
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light


IN-LIFE DATES: From: Aug. 04, 1981 To: Sep. 23, 1981

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1 mL/kg


CLASS METHOD
- Rationale for the selection of the starting dose: Based on the range finding study
Doses:
Range finding study: 1.3, 1.6, 2.0, 2.5, 3.2, 4.0, 5.0, 6.3, 8.0 and 10.0 mL/kg
Main study: 0, 2.8, 3.6, 4.5, 5.6 and 7.1 mL/kg
No. of animals per sex per dose:
Range finding study: 2 animals/sex/dose
Main study: 5 animals/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Observed twice daily for clinical signs and mortality; Body weights were recorded on Days -1, 1, 2, 3, 4, 7, 11 and 15 or at time of death if prior to scheduled sacrifice on Day 15
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, mortality and gross necropsy
Statistics:
Litchfield and Wilcoxon method (1949) was used to calculate LD50, 95 % confidence limits and dose-response curve

Results and discussion

Preliminary study:
Clinical signs: Diarrhea, dried feces around anus, red sore in anal opening, soft stool, salivation, nasal discharge, lacrimation, wheezing, urine-soaked fur, crusty nose, crusty material around face, crusty eyes, crusty material on front paws, swollen feet, area of face around nose and mouth swollen, crusty material around urethra, yellow discharge from vagina and urethra, vocalization when touched, lethargic, moribund and cold body temperature.

Gross pathology: Range finding study: Organs/tissues affected included stomach (distended with air. bluish in color, blood vessels prominent, filled with dark brown material, pinkish fluid, yellow fluid and distended with fluid), small intestines, cecum and colon (distended with gas, distended with yellow fluid, filled with yellow-green gelatinous substance, yellow material, red material and distended with fluid), the lungs (dark red with raised white spots) and the carcass (urine-soaked fur, autolysis and crusty nose and dried feces around anus)
Effect levelsopen allclose all
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
5 mL/kg bw
95% CL:
>= 4.4 - <= 5.7
Remarks on result:
other: equivalent to 5337 (4697-6085) mg/kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
4.6 mL/kg bw
95% CL:
>= 2.5 - <= 8.4
Remarks on result:
other: equivalent to 4910 (2669-8967) mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 mL/kg bw
95% CL:
>= 4 - <= 6.2
Remarks on result:
other: equivalent to 5337 (4270-6618) mg/kg bw
Mortality:
Please see 'Table 1' for mortality data
Clinical signs:
- Clinical signs were present at various intervals throughout the main study period and did not appear to increase in frequency and variety with increased dose level
- Clinical signs included diarrhea, crusty material around the anus, soft stool, crusty material around face, paws, eyes, nose, and scrotum, cream-colored material around mouth, alopecia, swollen feet, edema around anus, nasal discharge, red-colored nasal discharge, tachypnea, lacrimation, lethargic, urine-soaked fur, piloerection, ataxia, moribund, cold body temperature and tremors
- Untreated control animals appeared normal throughout the study
Body weight:
Reduced weight gain and weight loss from Days 1-3
Gross pathology:
- Perineal skin (crusty, hair loss, eschar formation, peeling of scabs and of skin, peeling around anus, appeared light brown on tail and anus and scrotum exhibited a constricted scar), stomach (brownish-black, yellow, clear and creamy fluids), intestines (yellow, clear, creamy and yellowish-red fluids and distended with gas), lung (dark red and glistening), inguinal lymph nodes (bilateral and red) and carcass (urine-soaked fur, nasal discharge, crusty eyes, rigor mortis, red material around nose, red at base of tail, swollen and red around anus and crusty material around anus)
- The above abnormal findings were not dose- or sex-related
Other findings:
None

Any other information on results incl. tables

Table1. Summary of mortality data

Dose Level

mL/kg

MALES

Number Dead/

Number Tested

FEMALES

Number Dead/

Number Tested

COMBINED

Number Dead/

Number Tested

0.0

0/5

0/5

0/10

2.8

0/5

2/5

2/10

3.6

0/5

1/5

1/10

4.5

2/5

3/5

5/10

5.6

3/5

2/5

5/10

7.1

5/5

5/5

10/10

Calculations:

LD50 (mg/kg bw) = LD50 (mL/kg bw) X Density (mg/mL)

where, density of the test material = 1.06749 g/cm3 = 1067.49 mg/mL

Applicant's summary and conclusion

Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the test conditions, the LD50 of the test material was determined to be 5.0 (4.4 - 5.7) and 4.6 (2.5 -8.4) mL/kg for males and females, respectively. The combined LD50 of the test material was calculated to be 5.0 (4.0-6.2) mL/kg [equivalent to 5337 (4270-6618) mg/kg bw].
Executive summary:

A study was conducted to determine the acute oral toxicity of the test substance in Sprague-Dawley rats. The study was performed according to a method similar or equivalent to OECD Guideline 401 in compliance with GLP. Test substance was administered orally (gavage) to 5 animals/sex/dose at 0, 2.8, 3.6, 4.5, 5.6 and 7.1 mL/kg. Body weights were obtained on Days-1, 1 (Day of dosing), 2, 3, 4, 7, 11 and 15 or at time of death if prior to Day 15. Animals were frequently observed for clinical signs and mortality on the day of dosing and twice daily thereafter for 14 days. Animals found dead and all those surviving for the duration of the study were subjected to gross necropsy. Treated animals gained less weight than untreated animals and lost weight for 1 to 3 days after test substance administration. Clinical signs noted were lethargy, diarrhoea, urine-soaked fur and lacrimation. These signs may have negatively affected the intake of food, resulting in reduced body weight. Clinical signs and gross necropsy findings were seen throughout all dose levels and did not indicate any sex or dose related trends. Under the test conditions, the LD50 of the test substance were determined to be 5.0 (4.4 - 5.7) and 4.6 (2.5 -8.4) mL/kg for males and females, respectively. The combined LD50 of the test substance was calculated to be 5.0 (4.0-6.2) mL/kg [equivalent to 5337 (4270-6618) mg/kg bw] (Calkins, 1981).