Ethyl diphenylphosphinite

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

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 non guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

5 rats per sex and dose are injected i.p. with different doses of the test substance. Clinical signs and lethality are evaluated during a 14 day observation period and the LD50 is determined. Surviving animals are necropsied and gross changes recorded.

GLP compliance:

no

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): Diphenylethoxyphospin
- Physical state: liquid
- Analytical purity: no data
- Expiration date of the lot/batch: October 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 on average: males: 170-210g, females 180-190g
- Fasting period before study: 16h, but water ad lib.
- Housing: 5 animal per steel mesh cage, type DK-III
- Diet (e.g. ad libitum): SSNIFF
- Water (e.g. ad libitum): VE water ad lib. (tab water ad lib. on weekends)
- Acclimation period: at least 1 week

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

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

other: 0.5% CMC in water (application form: emulsion)

Doses:

1210, 825, 562, 383mg/kg b.w.

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, 5h after application, daily on weekdays thereafter (on weekends: check for lethality)
- Frequendy of weighing: prior to and 2, 3, 7, 13 days after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 002 mg/kg bw

Based on:

test mat.

95% CL:

> 709 - < 1 661

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 508 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 713 mg/L

Based on:

test mat.

95% CL:

> 578 - < 889

Mortality:

Males:
4 of 5 males in the highest dose died after 1-2 days, and one male receiving 825mg/kg b.w.
Females:
All animals of the 2 highest doses died within 2 days (1 after 7 days), 4 females receiving 562mg/kg b.w. died within one week.

Clinical signs:

Dyspnoe, apathy, aggressivness, abnormal position, staggering gait, atony, cramps, piloerection, exsiccosis, exophthalmus, salivation, bad general state, no corneal reflex, no pain reflex, and anaesthesia-like state were observed in males and females in at least one group. The lowest dose only showed piloerection in both sexes.

For details see tables under additional information.

Body weight:

expected increase

Gross pathology:

no findings in necropsied survivors, dead animals: intraabdominal deposits of test material, frequently slight ascites

Any other information on results incl. tables

Males
	1210mg/kg	825mg/kg	562mg/kg	383mg/kg
Dyspnoe	15m-6d	15m-6d	15m-2d
Apathy	15m-6d	15m-6d	15m-2d
Aggressiveness		2d
abnormal position	5h - 1d	5h - 1d
staggering gait	15m-2d	15min-5h	15min-1d
Atony	5h-1d	5h-1d
no pain reflex	1d
no corneal reflex	1d
anaesthesia-like state	1d
spastic gait		2d	5h-2d
tonic cramps	1h-1d	1h-5h
clonic cramps	1d
piloerection	15min-7d	15min-7d	15min-2d	1h-1d
exsiccosis	4h-2d	4h-2d	1d
exophthalamus	5h-1d	1d-2d
salivation	1d	1d
impaired general state	15m-6d	15m-6d	15m-2d
Females
	1210mg/kg	825mg/kg	562mg/kg	383mg/kg
Dyspnoe	15m-5h	15m-2d	15m-8d
Apathy	15m-5h	15m-2d	15m-8d
abnormal position	5h	5h-1d	1d-2d
staggering gait	15m-5h	15m-2d	15m-2d
Atony	5h	5h-1d
no pain reflex		1d
no corneal reflex		1d
anaesthesia-like state		1d
spastic gait		2d	4h-7d
tonic cramps	1h-5h	1h-5h
piloerection	15m-5h	30m-2d	15m-9d	30m-1d/7d
exsiccosis	4h-5h	5h-2d	1d-2d
exophthalamus	5h	5h-1d	1d-2d
salivation		1d	1d-2d
impaired general state	15m-5h	15m-2d	15m-8d

m: minute, h:hour, d: day,

Applicant's summary and conclusion

Conclusions:

The medium lethal dose after i.p. injection in rats was calculated to be 1002mg/kg b.w. in males and 508mg/kg b.w. in females.