Phenyl diamidophosphate

Endpoint summary

Description of key information

Under the conditions of the acute oral toxicity study the median lethal dose of Phenyl diamidophosphate after oral administration was found to be greater than 300 mg/kg and less than 500 mg/kg body weight in rats.

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

Study period:

2006-06-26 - 2007-02-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an internationally accepted guideline. All study parameters are based on the specific guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: Young adult animals (female animals approx. 8 – 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before
administration, but water was available ad libitum.
- Housing: The animals were housed in fully air-conditioned rooms.
Type of cage: Stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG)
Number of animals per cage: Single housing
- Diet (e.g. ad libitum): Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Acclimatization for at least 5 days before administration.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24°C
- Humidity (%):30 – 70%
- Air changes (per hr): fully air-conditioned
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Route of administration:

oral: gavage

Vehicle:

olive oil

Doses:

2000 mg/kg in 3 females, 500 mg/kg in 3 females, 300 mg/kg in 6 females

No. of animals per sex per dose:

see above

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study.
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual
animals; these records are maintained with the raw data.
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 500 mg/kg bw

Based on:

test mat.

Mortality:

All animals of the 2000 mg/kg administration group and two animals of the 500 mg/kg adminstration group were found dead from hour 1 through to hour 2 after application. No mortality occurred in the 300 mg/kg administration groups.

Clinical signs:

Clinical observation in the administration groups revealed impaired and poor general state, dyspnoea, apathy, excitation, abdominal position, staggering, tremor, twitching, fibrillar contractions, clonic convulsions, piloerection, smeared fur, diarrhea, exsiccosis, salivation, lacrimation, chromodacryorrhea and reduced feces. Findings were observed from hour 1 through to study day 5 after administration.

Body weight:

The mean body weights of the 300 mg/kg administration groups and the body weight of the surviving animal of the 500 mg/kg group increased throughout the study period.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals that died (2000 mg/kg: 3 females; 500 mg/kg: 2 females) and in the animals examined at termination of the study (500 mg/kg: 1 female; 300 mg/kg: 6 females).

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the median lethal dose of Phenyl diamidophosphate after oral administration was found to be greater than 300 mg/kg and less than 500 mg/kg body weight in rats.

Executive summary:

The study was performed according to OECD Guideline 423 to assess the acute toxicity following oral administration of Phenyl diamidophosphate in Wistar rats. Single doses of 2000, 500 and 300 mg/kg body weight of test material preparations in olive oil Ph.Eur./DAB were given to 4 administration groups of three fasted female animals each, (2000 mg/kg in 3 females, 500 mg/kg in 3 females, 300 mg/kg in 6 females) by gavage in a sequential manner. All animals of the 2000 mg/kg administration group and two animals of the 500 mg/kg adminstration group were found dead from hour 1 through to hour 2 after application. No mortality occurred in the 300 mg/kg administration groups. Clinical observation in the administration groups revealed impaired and poor general state, dyspnoea, apathy, excitation, abdominal position, staggering, tremor, twitching, fibrillar contractions, clonic convulsions, piloerection, smeared fur, diarrhea, exsiccosis, salivation, lacrimation, chromodacryorrhea and reduced feces. Findings were observed from hour 1 through to study day 5 after administration. The mean body weights of the 300 mg/kg administration groups and the body weight of the surviving animal of the 500 mg/kg group increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals that died and in the animals examined at the end of the observation period. Under the conditions of this study the median lethal dose of Phenyl diamidophosphate after oral administration was found to be greater than 300 mg/kg and less than 500 mg/kg body weight in rats.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The study is reliable without restriction and is adequate for C& L purposes.

Additional information

Justification for selection of acute toxicity – oral endpoint
Only one GLP-study available

Justification for classification or non-classification

The respective criteria are met.

The estimated LD50 of > 300 < 500 mg/kg bw. is below the treshold for hazard category 4 (<300 <2000 mg/kg bw).

PPDA is therefore classified in category 4 for acute oral toxicity.