Reaction mass of Dimethyl [3-[(hydroxymethyl) amino]-3-oxopropyl] phosphonate and Dimethyl (3-amino-3-oxopropyl)phosphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30.10.2003 - 03.04.2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Nederland GLP

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

EC Number:

243-528-9

EC Name:

Dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

Cas Number:

20120-33-6

Molecular formula:

C6H14NO5P

IUPAC Name:

dimethyl [3-[(hydroxymethyl)amino]-3-oxopropyl]phosphonate

Constituent 2

Reference substance name:

Dimethyl (3-amino-3-oxopropyl)phosphonate

EC Number:

219-765-9

EC Name:

Dimethyl (3-amino-3-oxopropyl)phosphonate

Cas Number:

2526-69-4

Molecular formula:

C5H12NO4P

IUPAC Name:

dimethyl (3-amino-3-oxopropyl)phosphonate

Test material form:

liquid: viscous

Details on test material:

Technical product

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 137244-407
- Expiration date of the lot/batch: July 2004

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding facility, Jai research foundation, India
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks old at the time of dosing
- Weight at study initiation: 173-190 g
- Fasting period before study: Overnight
- Housing: 3 animals/cage; Polypropylene rat cages covered with stainless steel grid top
- Diet: Rat pellet diet (Amrut brand) manufactured by Pranav Agro Industries Limited, Pune, Maharashtra, India, ad libitum
- Water: ad libitum
- Acclimation period: 5 days (step 1) and 8 days (step 2) prior to commencement of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24
- Humidity (%): 63 - 66
- Air changes (per hr): 17
- Photoperiod: 12 h artificial light and 12th darkness, light hours being 06:00 - 18:00 h

IN-LIFE DATES: From: 17 Feb 2004 To: 5 March 2004

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual):
Required quantities of Aflammit KWB were weighed on a calibrated weighing balance in glass beakers. The test substance was then dissolved in a small volume of distilled water and transferred in to calibrated 10 mL measuring cylinder. The beaker was rinsed twice with small volume of distilled water and transferred into the measuring cylinder. Finally, the total volume of the dose solution was made up to 10 mL with distilled water and mixed thoroughly.
CLASS METHOD
- Rationale for the selection of the starting dose: Not provided

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females in two groups of three

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for overt signs of toxicity and mortality at 30 minutes, 1, 2, 3, 4, hours and once per hour thereafter, after dosing (on day 0). Subsequently, the animals were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. The clinical signs were recorded once a day. Individual body weights were recorded prior to dermal application (day 0) and on days 7 and 14 following dermal application. In addition, observations such as mortality and gross pathology was carried out.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were observed in the animals treated with Aflammit KWB at the dose level of 2000 mg/kg body weight.

Gross pathology:

External examination of animals sacrificed at the termination did not reveal any pathological lesion/abnormality

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of DMPPA_701-402-5 in Wistar rats is considered to be greater than 5000 mg/kg body weight.

Executive summary:

An acute oral toxicity study was carried out to assess the acute oral toxicity of Aflammit KWB (supplied by THOR GmbH, Landwehrstrasse I , 67346 Speyer, Germany) in Wistar rats. The rnethod followed was as per the guidelines of: OECD 423 "Acute Oral Åcute Toxic Class Method".

A selected group of rats comprising of 3 females were given a single dose of 2000 mg Aflammit KWB/kg body weight (step I). Since no mortality was another set of 3 female rats were given a single dose of 2000 mg Aflammit KWB/kg body weight after two days (step 2). Both sets of animals were observed daily for a period of 14 days after dosing. No mortality was observed at the dose level of 2000 mg Aflammit KWB/kg body weight in either set. Animals were starved overnight prior to dosing and upto three hours post dosing.

All animals were subjected to gross pathological examination at the end of the observation period.

The acute oral median lethal dose (LD₅₀, cut off value) of Aflammit KWB in Wistar rats is 5000 mg/kg body weight by this test method. According to GHS Aflammit KWB/DMPAA can be classified into Category 5 or Unclassified.