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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted may 12th, 1981
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethyl diphenylphosphinite
EC Number:
211-951-8
EC Name:
Ethyl diphenylphosphinite
Cas Number:
719-80-2
Molecular formula:
C14H15OP
IUPAC Name:
ethyl diphenylphosphinite
Details on test material:
- Name of test material (as cited in study report): Diphenylethoxyphopsphin
- Physical state: liquid
- Expiration date of the lot/batch: 10/1982

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach
- Age at study initiation: app. 12 weeks
- Weight at study initiation: 180g on average
- Fasting period before study: 16h (water ad lib.)
- Housing: in groups of 5 in V-II-A-meshed steel cages, type DK-III
- Diet (e.g. ad libitum): SSNIFF
- Water (e.g. ad libitum): VE water or tap water (only on holidays) ad lib.
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26°C
- Humidity (%): 45 - 75%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% CMC in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.81; 4.64; 3.16; 2.15% (w/v)
- Amount of vehicle (if gavage): 10ml/kg b.w.
- Justification for choice of vehicle: aqueous solution comparable to physiological media

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg b.w.
Doses:
681mg/kg
464mg/kg
316mg/kg
215mg/kg
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: >15min, 15min, 30min, 1h, 2h, 4h, and 5h after application, twice daily on workdays and daily on holidays thereafter
- Frequency of weighing: day 0, 2, 7, 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology of findings during gross pathology
Statistics:
LD50 (m+f) calculated according to Finney, D.J., probit analysis, cambridge university press, 1971

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 316 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 681 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 456 mg/kg bw
Based on:
test mat.
95% CL:
> 357 - < 650
Mortality:
Males
681mg/kg: 3 animals died within 24h, no mortality occured in any other test group
Females
681mg/kg, 464mg/kg: all except one animal of the highest dose died within 24h, the last animal died within 2days
316mg/kg: 2 animals died within 24h
215mg/kg: 1 animal died within 24h
Clinical signs:
Dyspnoe, apathy, staggering gait, impaired general state in all groups
abnormal position, atony, tonic cramps, piloerection, exsiccosis , exophthalmus in some groups
no corneal reflex, no pain reflex, anaesthesia-like state in females in the two mid dosages
for details see tables 1 and 2 under additional information
Body weight:
normal weight gain in all male survivers
stagnation in females up to day 2, normal weight gain thereafter
Gross pathology:
Discoloration (whitish grey to clay colored) of liver and kidney in animals found dead.
Marks on the peripheral lobuli of the liver in 2 surviving male animals receving 464mg/kg, diagnosed as lipophanerosis during histopathological examination.
No further abnormalities were noted.

Any other information on results incl. tables

Table 1

Males
  681mg/kg 464mg/kg 316mg/kg 215mg/kg
Dyspnoe 15m-2d 15m-2d 15m-2d 15m-2d
Apathy 15m-2d 15m-2d 15m-2d 15m-2d
abnormal position 1h-5h 2h-1d    
staggering gait 30m-2d 30m-2d 30m-2d 30m-5h
Atony 1h-5h 2h-1d    
tonic cramps 2h-5h 2h-5h    
piloerection 30m-6d   2h-6d 2d-7d
exsiccosis 1h-5h 2h-2d 1d-2d  
exophthalamus 2h-5h 2h    
impaired general state 15m-2d 15m-2d 15m-2d 15m-2d
Table 2
Females
  681mg/kg 464mg/kg 316mg/kg 215mg/kg
Dyspnoe 15m-1d 15m-5h 15m-2d 15m-2d
Apathy 15m-1d 15m-5h 15m-2d 15m-2d
abnormal position 1h-5h 1h-5h 2h-1d  
staggering gait 30m-1d 30m-5h 30m-2d 30m-2d
Atony 15m-1d 1h-5h 2h-1d  
no pain reflex   2h 2h  
no corneal reflex   2h 2h  
anaesthesia-like state   2h 2h  
tonic cramps 2h-5h   2h-5h  
piloerection 30m-5h 2h-5h 2h-6d 2h-6d
exsiccosis 2h-5h 1h-5h 2h-2d 2d
exophthalamus 2h-5h 2h-5h 2h-1d  
impaired general state 15m-1d 15m-5h 15m-2d 15m-2d

m: minute, h: hour, d: day

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information