Ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

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:

Acute toxicity upon intraperioneal injection within a 14-observation period.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate

EC Number:

282-810-6

EC Name:

Ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate

Cas Number:

84434-11-7

Molecular formula:

C18H21O3P

IUPAC Name:

ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate

Details on test material:

- Name of test material (as cited in study report): Initiator 654
- Physical state: liquid
- Expiration date of the lot/batch: Feb. 1983

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Acclimatization period: Acclimatization in the animal care unit for at least one week.
Age of animals at beginning of study: About 12 weeks
Type of cage: Type DK-III stainless steel wire mesh cages (supplied by Becker & Co., Castrop-Rauxel, FRG)
Number of animals per cage: 5
Animal identification: Identification groups using cage cards
Room temperature: 20 - 26°C
Relative humidity: 45 - 75%
Change of air: 15 - 20 times/hour
Day/night rhythm: 12 h/12 h (6.00 - 18 00 hours/18.00 - 6.00 hours)
Drinking water: Fully demineralized water each workday, ad libitum; tap water on public holidays, ad libitum
Diet: SSNIFF R; Ssniff Versuchstierdiäten, Soest, FRG
Fasting period: 16 hours before administration, water available ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% in water

Details on exposure:

Preparation with 0.5% aqueous carboxymethyl cellulose
Reason for the vehicle: Aqueous formulation corresponds to the physiological medium
Form of administration: Emulsion
Application volume: 10 ml/kg

Doses:

215, 681, 1000, 1470, 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Observation period: 14 days
Cageside observation: Recording of signs and symptoms < 15', 15', 30', 1 h, 2 h, 4 h, and 5 h after administration of test substance and then once each workday. Check for moribund and dead animals twice each workday and once daily at weekends and on public holidays.
Pathology: Withdrawal of feed 16 hours before sacrifice with CO2, followed by necropsy and gross-pathological examination. All animals that died were necropsied as early as possible.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 470 mg/kg bw

Mortality:

215, 681 and 1000 mg/kg: no deaths after 14 days; 1470 mg/kg: 4/10 died within 2 days; 2000 mg/kg: 10/10 died within 1 day

Clinical signs:

Male animals:
All groups showed dyspnea, apathy, staggering, and poor general state.
Animals of the 3 highest doses also showed atonia, paresis, clonic convulsions, fasciculation, and abnormal position (also oberseved in animals treated with 681mg/kg)
Furthermore, high dose animals exhibited stertor, spasmodic respiration, absent pain reflex, narcotic like state, exsiccosis, and salivation (also in the 1470mg/kg group)
Additionally, trembling, twitching, tonus with stretching or bending, straub reaction, piloerection, erythema, and disequilibrium were oberserved in some of the dose groups.

Female animals:
All groups showed dyspnea, apathy, staggering, and poor general state.
All except low dose animals exhibited atonia, paresis, abnormal position.
Fasciculation and salivation were observed in the 3 highest doses.
In high dose females spasmodic respiration, absent pain reflex, narcotic like state, trembling (also animals receiving 1470mg/kg), exsiccosis, disequilibrium, clonic convulsions (also animals receiving 1470mg/kg) were also noted.
Additionally, twitching, tonus with stretching or bending, straub reaction, piloerection, erythema, exopthalamus, and cachexia were oberserved in some of the dose groups.

Clinical signs were observed for a maximum of 2 h in the two lowest dose groups, up to about 1 day in the mid dose animals, and for several days or until death in the two highest dose groups.

Body weight:

Mean body weight male animals: 194 g at study start, 280 g after 13 days
Mean body weight female animals: 188 g at study start, 230 g after 13 days

Gross pathology:

Animals that died (male & female): Intraabdominal precipitates of the test substance.
Sacrificed animals (male & female): Liver: Considerably rounded lobes and adhesions of the individual lobes to each other; liver/spleen/kidneys: milky coatings, adhesions of liver, stomach, and spleen occasionally.