Phosphonic acid, P-2-propen-1-yl-, diethyl ester

Endpoint summary

Description of key information

In an acute oral study according to the fixed dose method, a single female rat dosed with the substance at 2000 mg/kg bw by gavage was terminated for humane reasons within 30 minutes after dosing. 5 females dosed with the substance at 300 mg/kg bw did not exhibit mortality, significant clinical signs, effect on body weight or gross pathology. Therefore the LD50 of the substance is between 300 and 2000 mg/kg bw

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:

16 Dec 2014 to 22 Jan 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 147-163 g
- Fasting period before study: yes, overnight and upto 3-4 hours post-dosing
- Housing: 4/solid floor polypropylene cage
- Diet: 2014CTeklad Global Rodent diet ad libitum
- Water: tap water ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: 2000 mg/kg bw as such, 300 mg/kg bw in distilled water

Details on oral exposure:

VEHICLE: distilled water (only at 300 mg/kg bw)

MAXIMUM DOSE VOLUME APPLIED: 10 mL at 300 mg/kg bw, 1.95 mL at 2000 mg/kg bw

Doses:

sighting study: 300 and 2000 mg/kg bw
main study: 300 mg/kg bw

No. of animals per sex per dose:

sighting study: 1 female/dose
main study: 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Body weight: at study start and weekly thereafter
- Clinical signs: ½, 1, 2, and 4 hours after dosing and then daily for 14 days
- Mortality/morbidity: twice daily
- Necropsy : macroscopic examination

Statistics:

NA

Preliminary study:

In the sighting study 1 female was treated at 300 mg/kg bw. No mortality or clear toxicity was observed. Therefore 1 female was dosed at 2000 mg/kg bw. This female was terminated for humane reasons within 30 minutes after dosing. The main test was therefore performed with 4 females dosed at 300 mg/kg bw.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

In the sighting study the female at 2000 mg/kg bw was terminated within 30 min after dosing
No mortality at 300 mg/kg bw

Clinical signs:

other: 2000 mg/kg bw: labored and noisy respiration, prostration, hypothemia and vocalisation 300 mg/kg bw: ataxia and hunched posture in all females 2-4 hours after dosing

Gross pathology:

2000 mg/kg bw: haemorraghic gastric mucosa, gaseous content and haemorraghic non-glandular epithelium of the stomach
300 mg/kg bw: no abnormalities

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the substance is between 300 and 2000 mg/kg bw

Executive summary:

In an acute oral study according to the fixed dose method, a single female rat dosed with the substance at 2000 mg/kg bw by gavage was terminated for humane reasons within 30 minutes after dosing. 5 females dosed with the substance at 300 mg/kg bw did not exhibit mortality, significant clinical signs, effect on body weight or gross pathology. Therefore the LD50 of the substance is between 300 and 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Quality of whole database:

The LD50 is between 300 and 2000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
Guideline study under GLP

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meet the criteria for classification according to Regulation (EC) 1272/2008 as harmful if swallowed (category 4, H302)