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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:
17 Feb - 29 Jul 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1988
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
1984
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: MAFF Acute Oral Toxicity Study
Version / remarks:
1985
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium 2-biphenylate
EC Number:
205-055-6
EC Name:
Sodium 2-biphenylate
Cas Number:
132-27-4
Molecular formula:
C12H9NaO
IUPAC Name:
sodium 2-biphenylate
Details on test material:
Batch No.: MM940104

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratoris Inc., USA
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 167.2 - 226.1 g (males) and 120.7 - 143.2 g (females)
- Fasting period before study: Yes, animals were fasted overnight.
- Housing: 2 or 3 animals per cage were housed in animal care facilities.
- Diet: Purina Certified Rodent Chow #5002 (supplied by Purina Mills Inc., USA), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 17 Feb 1994 To: 29 Jul 1994

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 and 50%, respectively

DOSAGE PREPARATION: The test substance was administered as a 10 or 50% suspension in 0.5% methocel.
Doses:
100, 500, 1000 and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for clinical signs 30 min, 1, 4, 5 and 6 h post-dosing and thereafter at least once each working day throughout the 14-days observation period. The body weight was recorded 1 day before treatment, and thereafter on day 1, 2, 8 and 15.
- Necropsy of survivors performed: Yes, all rats submitted alive to necropsy were anesthetized by inhalation of methoxyflurane vapors and euthanized by decapitation and clamping of trachea.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
591 mg/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
846 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg bw: 5/5 males and 5/5 females died on day 1.
1000 mg/kg bw: 1/5 males and 1/5 females died on day 2. 2/5 males and 3/5 females died on day 5.
500 mg/kg bw: 1/3 males died on day 3 and 2/5 females died on day 5.
Clinical signs:
In-life observations noted were lacrimation, salivation, chromorhinorrhea, labored respiration, decreased activity, lateral recumbency, incoordination, decreased muscle tone, mouth breathing and urine and fecal soiling in the perineal area. Clinical signs began within a half hour of dosing. Most clinical signs resolved during the two-week observation period, although a few signs persisted in one male survivor from the 1000 mg/kg bw dose group and one female survivor from the 500 mg/kg bw dose group, through the 2-week observation period.
For details please refer to Table 1 under "any other information on results incl. tables".
Body weight:
Most surviving rats gained weight during the two-week observation period, with the exception of one female from the 500 mg/kg bw dose group that lost weight, and had a persistence of numerous clinical signs throughout the observation period.
Gross pathology:
The rats that died during the 2-week post-exposure observation period had treatment-related gross pathologic observations consisting of one or more of the following: hemolyzed blood in the digestive tract, perineal soiling, general visceral congestion, decreased amount of fat, pale liver, congested lungs, bloody urine and congestion, erosions and/ or ulcers, hemorrhage, or hyperemia of the stomach. The gross observations of the stomach and digestive tract were consistent with stress-induced alterations. The remaining observations in the animas that died were non-specific signs of toxicity.
There were no treatment-related gross pathologic observations in any of the surviving rats.

Any other information on results incl. tables

Table 1: Clinical signs in males

Time post- dosing   100 mg/kg bw 500 mg/kg bw 1000 mg/kg bw 5000 mg/kg bw
30 min survivors 5 5 5 5
 salivation - 5 4 4
urine soiling - 2 - -
fecal soiling - 1 1 -
decreased activity - - 4 1
incoordinated - - 3 1
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
mouth breathing - - - 2
1 h survivors 5 5 5 4
 salivation - 5 4 3
urine soiling - 1 - -
fecal soiling - 1 - -
decreased activity - 1 4 1
incoordinated - 1 2 1
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
lacrimation - - 1 3
4 h survivors 5 5 5 4
 salivation - 5 4 2
urine soiling - 2 1 1
fecal soiling - 1   -
decreased activity - 1 4 -
incoordinated - 1 3 -
decreased muscletone - - - 3
 laterally recumbent - - - 4
mouth breathing - - 1  
irregular respiration - - - 1
lacrimation - 1 - 4
5 h survivors 5 5 5 1
 salivation - 5 4 -
urine soiling - 3 - -
fecal soiling - 2 - -
decreased activity - 1 4 -
incoordinated - 1 3 -
decreased muscletone - - - 1
 laterally recumbent - - - 1
irregular respiration - - - 1
lacrimation - - - 1
6 h survivors 5 5 5 0
 salivation - 5 4 -
urine soiling - 3 3 -
fecal soiling 1 2 - -
decreased activity - 1 4 -
incoordinated - 1 3 -
mouth breathing - - 1 -
chromorhinorrhea - - 1 -
lacrimation - 1 - -
Day 2 survivors 5 5 4 0
 salivation - 5 3 -
urine soiling - 3 3 -
fecal soiling - 2 - -
decreased activity - 1 3 -
incoordinated - 1 2 -
mouth breathing - - 1 -
chromorhinorrhea - - 1 -
lacrimation - 1 1 -
Day 5 survivors 5 4 2 0
 salivation - - 1 -
urine soiling - 1 1 -
fecal soiling - 1 - -
decreased activity - - 1 -
Day 6 survivors 5 4 2 0
 salivation - - 1 -
urine soiling - - 1 -
fecal soiling - 1 - -
decreased activity - - 1 -
Day 7 survivors 5 4 2 0
urine soiling - - 1 -
fecal soiling - 1 1 -
Day 8 + 9 + 12 survivors 5 4 2 0
urine soiling - - 1 -
Day 13 + 14 + 15 survivors 5 4 2 0
fecal soiling - - 1 -

Table 2: Clinical signs in females

Time post- dosing   100 mg/kg bw 500 mg/kg bw 1000 mg/kg bw 5000 mg/kg bw
30 min survivors 5 5 5 5
 salivation - 5 5 5
urine soiling - - 2 -
fecal soiling - - 2 1
decreased activity - 1 4 2
incoordinated - - 4 2
decreased muscletone - - 1 3
 laterally recumbent - - 1 3
lacrimation - - 2 3
1 h survivors 5 5 5 2
 salivation - 5 5 2
urine soiling - - 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - - 4 -
decreased muscletone - - 1 2
 laterally recumbent - - 1 1
lacrimation - 1 1 1
4 h survivors 5 5 5 1
 salivation - 5 5 1
urine soiling - 3 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - 1 4 -
decreased muscletone - - 1 1
 laterally recumbent - - 1 1
lacrimation - 2 3 1
5 h survivors 5 5 5 1
 salivation - 5 5 1
urine soiling - 3 2 -
fecal soiling - - 2 -
decreased activity - 1 4 -
incoordinated - 1 4 -
decreased muscletone - - 1 1
 laterally recumbent - - 1 1
chromorhinorrhea - 1 - -
lacrimation - 2 2 1
6 h survivors 5 5 5 1
 salivation - 4 5 1
urine soiling - 4 2 -
fecal soiling - - 2 -
decreased activity - 3 4 -
incoordinated - 3 4 -
decreased muscletone - - 1 1
chromorhinorrhea - 1 - -
lacrimation - 1 2 1
Day 2 survivors 5 5 4 0
 salivation - 4 4 -
urine soiling - 4 4 -
decreased activity - 3 4 -
incoordinated - 2 2 -
chromorhinorrhea - 2 1 -
lacrimation - 2 1 -
Day 5 + 6 survivors 5 3 1 0
 salivation - 2 1 -
urine soiling - 2 1 -
incoordinated - - - -
decreased activity - 1    
Day 7 + 8 survivors 5 3 1 0
decreased activity - 1 - -
salivation - 2 - -
urine soiling - 2 1 -
fecal soiling - 1   -
Day 9 survivors 5 3 1 0
salivation - 2 - -
fecal soiling - 1 - -
decreased activity - 1 - -
urine soiling - 1 1  
Day 12 survivors 5 3 1 0
salivation - 2 - -
fecal soiling - 1 - -
decreased activity - 1 - -
chromorhinorrhea - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 13 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
chromorhinorrhea - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 14 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
labored respiration - 1 - -
urine soiling - 1 - -
Day 15 survivors 5 3 1 0
salivation - 1 - -
fecal soiling - 1 - -
decreased activity - 1 - -
labored respiration - 1 - -
thin - 1 - -
urine soiling - 1 - -

Applicant's summary and conclusion

Interpretation of results:
other: Acute oral 4, H302 according to Regulation (EC) No. 1272/2008
Conclusions:
CLP: Acute oral 4, H302

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