Ethyl diphenylphosphinite

Acute Toxicity: oral

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

Test material information

Constituent 1

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 levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 316 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 681 mg/kg bw

Based on:

test mat.

Effect levels 3

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