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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (mostly due to reduced reporting in times before GLP)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report date:
1974

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Triphenylphosphine oxide
EC Number:
212-338-8
EC Name:
Triphenylphosphine oxide
Cas Number:
791-28-6
Molecular formula:
C18H15OP
IUPAC Name:
triphenylphosphine oxide
Details on test material:
- Name of test material (as cited in study report): Triphenylphosphinoxid
- Purity: pure

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Weight at study initiation: males: 222 (170 - 252) g; females: 176 (153 - 188) g

ENVIRONMENTAL CONDITIONS
not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 - 30% aqueous suspension with carboxymethyl cellulose and 2 - 3 drops of Cremophor EL.

MAXIMUM DOSE VOLUME APPLIED: 21.4 mL/kg bw
Doses:
6400; 3200; 1600; 800; 400; 320; 200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Body weight was measured on the application day, on day 3 and 4, respectively, and on day 7. Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes
Statistics:
Calculation of LD50 by method of Litchfield and Wilcoxon.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
685 mg/kg bw
Based on:
test mat.
95% CL:
486 - 966
Remarks on result:
other: mortality was observed in doses of 320 mg7kg bw and higher
Mortality:
see table "any other information"
Clinical signs:
Convulsions, dyspnea, apathy, tremors, salivation, eye discharge, partial exophthalmus, ventral or lateral body position, staggering, exsiccosis, paresis of hind limbs.

6400 and 3200 mg/kg bw:
15 minutes after application convulsions, dyspnea, cower position.
Hours later apathy, tremors, cower position, at 6400 mg/kg bw additionally gasping for breath, partial exophtalmus.
During observation period lateral position, dyspnea, apathy, partially secretion out of eyes and mouth, cower position.

1600 mg/kg bw:
Hours after application dyspnea, cower position, apathy, lateral body position, staggering, clonic convulsions.
Symptoms stable for the following days, additionally tremors and secretion out of mouth and eyes.

800 - 320 mg/kg bw:
Hours after application staggering, partially cower position and creeping, at 800 and 400 mg/kg bw additionally convulsions, latero-abdominal position, dyspnea, aggressiveness, partially weakness of hind limbs, biting convulsions, partially tremors, salivation.
Amelioration of symptoms during the following days, 800 mg/kg additionally exsiccosis.
Animals free of symptoms around day 4.

200 mg/kg bw:
Hours after application cower position, slight apathy.
Animals free of symptoms on day 2.
Body weight:
Body weight gain stagnated during observation period in survivors of all dose groups.
Gross pathology:
Hyperemia, dilatation of heart and gastroesophageal vestibule, fine ulcerations, diarrhoeic intestinal content, discoloration of kidneys and liver in animals that died. Nothing abnormal found in sacrificed animals.

Any other information on results incl. tables

Mortality

mg/kg
   %  #   1h   24h   48h   7d
------------------------------------------
6400
   30  5M  0/5  5/5   5/5   5/5
            5F  0/5  5/5   5/5   5/5
3200
   30  5M  0/5  4/5   5/5   5/5
            5F  0/5  3/5   4/5   5/5
1600
   16  5M  0/5  2/5   2/5   5/5
            5F  0/5  5/5   5/5   5/5
800
     8  5M  0/5  1/5   1/5   2/5
            5F  0/5  2/5   4/5   4/5
400
     4  5M  0/5  0/5   0/5   0/5
            5F  0/5  0/5   1/5   2/5
320
     4  5M  0/5  0/5   0/5   0/5
            5F  0/5  0/5   1/5   1/5
200
     2  5M  0/5  0/5   0/5   0/5
            5F  0/5  0/5   0/5   0/5
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Applicant's summary and conclusion