Diethyl (hydroxymethyl)phosphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and appropriate guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

n/a

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diethyl (hydroxymethyl)phosphonate

EC Number:

221-391-6

EC Name:

Diethyl (hydroxymethyl)phosphonate

Cas Number:

3084-40-0

Molecular formula:

C5H13O4P

IUPAC Name:

diethyl (hydroxymethyl)phosphonate

Constituent 2

Reference substance name:

Diethoxyphosphoryl methanol

IUPAC Name:

Diethoxyphosphoryl methanol

Test material form:

other: "medium viscosity" liquid

Details on test material:

E06-16 (Lot No. 1041-37-6, T# 184), a colotless liquid. Stored in dark at room temp. (Approximately 25oC).
The test material was stable for the duration of the study.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Laboratories, Inc.
Age: Approximately 4 weeks old. Bodyweight: 77.2 to 104.6 gr. Daily average animal room temperature and relative humidity: 72 ± 3oF and 28 ± 5%, respectively. 12 hours light/dark cycle.
Conditions in animal room were in general agreement with the Guideline for the Care and Use of Laboratory Animals (1996).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

Oral gavage, using a syringe equipped with a stainless steel ball-tipped intubation needle. Neat at a dose of 5 g/kg of body weight.
Fasting Food was withheld overnight prior to dosing until approx. 4 hours after administration of the test substance.
Frequency: Single dose on day 1. 14 days observation.

Doses:

5 gr/kg (5000 mg/kg) of fasted body weight using a dosing volume of 4.34 ml/kg body weight (equivalent to 5 g/kg considering the density was determined to be 1.15 g/ml)..

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

All animals were dosed 5000mg/kg bodyweight, once only, by gavage. The animals were observed for mortality/moribundity or over sight of toxicity for 14 days. At the end of the study, the animals were killed and subjected to gross pathological examination.

Frequesncy of observation:
Mortality/Viability- Twice daily
Body weights- Prior to fasting, Days 1 (pre administration), 8 and 15.
Clinical signs- At periodic intervals on day of dosing (day 1) and once daily thereafter.until day 15.
Necropsy- At the end of the observation period, all animals were sacrificed by asphyxiation using oxygen/carbon dioxide procedure and subjected
to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Statistical analysis was limited to calculation of means and standard deviations of body weight and body weight change.

Results and discussion

Preliminary study:

n/a

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None of the rats died during the study

Clinical signs:

other: The clinical signs of toxicity observed consisted of hypoactivity in one mail rat, wet inguinal fur in three males and alopecia of the forelimbs in two femails.

Gross pathology:

No necroscopy findings were observed.

Other findings:

no further information

Any other information on results incl. tables

no further information

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 5000 mg/kg bw

Executive summary:

The Acute oral toxicity test of E06 -16 was conducted in male and female rats. There were no deaths during the study. The clinical signs of toxicity observed consisted of hypoactivity in one mail rat, wet inguinal fur in three males and alopecia of the forelimbs in two femails. No macroscopic abnormalities were detected. The acute oral median lethal dose (LD50) of the test material in the Sparague- Dawley CD strain rat was found to be greater than 5000 mg/kg body weight.