Dialkyl C18 and C18-unsaturated phosphonates

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 July to 19 July 2017.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was a GLP-compliant OECD guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

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)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dialkyl C18 and C18-unsaturated phosphonates

EC Number:

701-298-1

Cas Number:

64051-29-2

Molecular formula:

Not applicable for a UVCB Substance

IUPAC Name:

Dialkyl C18 and C18-unsaturated phosphonates

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Alkenyl phosphonate
- Expiration date of the lot/batch: 09 September 2017
- Purity test date: 08/06/2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25 ºC, below 70 RH%)
- Stability under test conditions: yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH.
- Age at study initiation: 10 weeks old
- Weight at study initiation: 225 – 238 g
- Fasting period before study: yes
- Housing: 3 animals / cage (Type II. polypropylene/polycarbonate).
- Food consumption (e.g. ad libitum): ad libitum
- Water consumption (e.g. ad libitum): ad libitum
- Acclimation period: 21-22 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 – 24.3 °C
- Humidity (%): 31 – 70 %
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12hr/12hr

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): BCBS1795V
- Purity: no data

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

DETAILS ON STUDY DESIGN
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter.
- Frequency of weighing: The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: yes on day 15
- Other examinations performed: macroscopic examination at necropsy (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities)

Statistics:

no data

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Alkenyl phosphonate did not cause mortality at a dose level of 2000 mg/kg bw.

Clinical signs:

other: There were no systemic clinical signs noted in any animal throughout the study.

Gross pathology:

There was no evidence of the macroscopic observations at necropsy at a dose level of 2000 mg/kg bw.

Any other information on results incl. tables

None.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item Alkenyl phosphonate was found to be above 2000 mg/kg bw in female Crl:WI rats. Therefore, no classification is required according to EU criteria.

Executive summary:

In an acute oral toxicity study (OECD 423, Kr.1, GLP),Two groups of three female Crl:WI rats were treated with Alkenyl phosphonate at a dose level of 2000 mg/kg (Group 1 and Group 2). The test item was administered formulated in PEG 400 at a concentration of 200 mg/mL at a dose volume of 10 mL/kg bw. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore, no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.tris. Animals were observed for 14 days.

Alkenyl phosphonate did not cause mortality at a dose level of 2000 mg/kg bw. There were no systemic clinical signs noted in any animal throughout the study. There were no treatment related body weight changes. Body weight gains of Alkenyl phosphonate treated animals during the study showed no indication of a test item-related effect. There was no evidence of the macroscopic observations at necropsy at a dose level of 2000 mg/kg bw.

Under the conditions of this study, the acute oral LD₅₀value of the test item Alkenyl phosphonate was found to be above 2000 mg/kg bw in female Crl:WI rats. Therefore, no classification is required according to EU criteria.