Diethyl phenylphosphonite

Endpoint summary

Description of key information

Oral:LD50 > 2000mg/kg 
Inhalation: 2/6 animals died after either 4 or 7h exposure to the saturated vapour concentration

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1992-12-29

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomas GmbH, Biberach, FRG
- Age at study initiation: young adult animals
- Weight at study initiation: 150 g - 300 g (+/- 20% of the mean weight)
- Fasting period before study: 16 h
- Housing: single housing
- Diet: Kliba-Labordiät 343, Klingentalmuehle AG Kaiseraugst.,Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20-24
- Humidity (%):30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 and 40 g /100mL

CLASS METHOD
- Rationale for the selection of the starting dose: based on the physical and chemical characteristics of the substance and the composition a starting dose of 500 mg/kg body weight has been chosen with 3 male and 3 female animals. As no mortality ocured, 2000 mg/kg body weight were tested with 3 male and 3 female rats.

Doses:

500 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing shortly before application (day 0), weekly thereafter and at the end of the study, recording of signs and symptoms severals times on the day of administration, at least once each workday for the individual animals
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: One female animal of the high dose group: impaired general state, dyspnea, apathy, abdominal position, staggering, ataxia. The animal appeared normal one day after administration

Gross pathology:

Nothing abnormal detected

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Comparable to current guideline requirements and scientifically valid.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable study report, only 6 animals tested instead of 10 as requested in the guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981-05-12

Deviations:

yes

Remarks:

6 animals tested instead of 10

Principles of method if other than guideline:

The study procedure was based on the OECD Guidelines, Method 403, 1981 and the "range-finding toxicity test" published by H.F. Smyth et al., 1962.

GLP compliance:

yes

Remarks:

but no QAU audit of the report performed

Test type:

standard acute method

Limit test:

yes

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, FRG)
- Age at study initiation: 8-9 weeks
- Weight at study initiation: females: 190,6g +/- 7,4 g, males: 267,6g +/- 12,9 g
- Housing: single housing, DK III Becker cages, without bedding
- Diet: KLIBA laboratory diet 10 mm pellets, Klingentalmühle AG, Kaiseraugst, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C):20-24
- Humidity (%):30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose/head only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass generator containing product placed in a waterbath (20 °C), a stream of 200 L/h compressed air was bubbled through the the substance column, the inhalation atmosphere was passed through a downstream mixing chamber and a glass distributor to 6 glass tubes containing the animals
- Method of conditioning air: replacing generator after 30 minutes
- Temperature, humidity, pressure in air chamber: 19-25 °C

TEST ATMOSPHERE
- Brief description of analytical method used: The amount of test substance consumed was determined by reweighing the generators. The nominal concentration was calculated from the amount of test substance consumed and the total air volume used.

Analytical verification of test atmosphere concentrations:

no

Remarks on duration:

4 and 7 hours

Concentrations:

0.5 mg/L nominal (saturated vapour concentration = 0.32mg/L)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights of surviving animals were determined prior to exposure, after 7 days and at the end of the observation period. A check for overt clinical signs of toxicity or mortality as well as a check for feed and drinking water was made twice a day.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: gross-pathological examination of all animals

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.32 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: saturated vapour concentration

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.32 mg/L air

Based on:

test mat.

Exp. duration:

7 h

Remarks on result:

other: saturated vapour concentration

Mortality:

7-hour exposure and 4-hour exposure: 2/6 animals in each experiment

Clinical signs:

other: The animals which were exposed for 4 h showed attempts to escape, irregular and accelerated respiration, respiratory sounds, squatting posture and piloerection. In the animals exposed for 7 h apathy was observed additionally. No clinical symptoms were obs

Body weight:

Body weight development was decreased in the first post exposure week, but recovered in the second in both exposure groups.

Gross pathology:

During necropsy, agonal congestive hyperemia and focal dark red discoloration of the lungs was observed in the animals that died.
The animals examined at termination of the study showed no abnormalities.

Interpretation of results:

toxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

0.32 mg/m³ air

Quality of whole database:

scientifically valid but deviant from guideline concerning the amount of test animals

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral:

The study on the acute oral toxicity in rats was performed to asses the acute toxicity following oral administration of the test substance, applied as a solution in olive oil DAB 10, in Wistar rats. The study was based on the EU guideline B1 and modified according to the acute toxic class method. To two groups each of six fasted animals (three males and three females) a single oral dose of the test material preparation in olive oil DAB 10 at dose levels of 2000 mg/kg and 500 mg/kg body weight was given.

Signs of toxicity noted in 1 female animal of the 2000 mg/kg dose group were impaired general state, dyspnoea, apathy, abdominal position, staggering and ataxia. The animal appeared normal 1 day after application.

The expected body weight gain was generally observed in the course of the study.

No mortality occured.

No abnormalities were noted at necropsy of animals sacrificed at the end of the study.

Under the condtions of the study the median lethal dose of the test substance after oral application was found to be greater than 2000 mg/kg body weight for the male and female animals.

Inhalation:

In an inhalation hazard test groups of 3 male and 3 female Wistar rats were exposed to a nominal concentration of about 0.5 mg/L as determined by weight difference of the test substance container prior and after the exposure period (saturated vapor concentration calculated from extrapolated vapor pressure at 20°C is 0.32 mg/L). After 4 and 7 hours 2/6 and 2/6 animals died, respectively. The animals which were exposed for 4h showed attempts to escape, irregular and accelerated respiration, respiratory sounds, squatting posture and piloerection. In the animals exposed for 7 h apathy was observed additionally. No clinical symptoms were observed from post exposure day 7 onwards in either test group. Body weight development was decreased in the first post exposure week but recovered in the second in both exposure groups.

During necropsy, agonal congestive hyperemia and focal dark red discoloration of the lungs was observed in the animals that died. The animals examined at termination of the study showed no abnormalities.

From this study it can be concluded that the 4 - and 7- hour-LC50 of the test substance is above the saturated vapour concentration at room temperature (about 0.32 mg/L). Because less than 50% of the animals died, and the nominal concentration based on weight difference was 0.5mg/L (i.e. somewhat higher exposure might have occured), classification in category 2 according to GHS is proposed.

Justification for selection of acute toxicity – oral endpoint
only one reliable GLP and guideline study available

Justification for selection of acute toxicity – inhalation endpoint
only one study available

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and the acute inhalation study, Diethoxyphenlyphosphin needs to be regarded as toxic after inhalation (R23 according to Directive 67/548/EEC (DSD) and Cat. 2 according to Regulation (EC) No 1272/2008 (CLP).