Allyltributylphosphonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiation dated : 03 September 2018 and experimental completion date 12 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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

Test material

Test material information

Constituent 1

Reference substance name:

Allyltributylphosphonium chloride

EC Number:

216-231-7

EC Name:

Allyltributylphosphonium chloride

Cas Number:

1530-48-9

Molecular formula:

C15H32P.Cl

IUPAC Name:

tributyl(prop-2-en-1-yl)phosphanium chloride

impurity 1

Reference substance name:

Tetrahydrothiophene 1,1-dioxide

EC Number:

204-783-1

EC Name:

Tetrahydrothiophene 1,1-dioxide

Cas Number:

126-33-0

Molecular formula:

C4H8O2S

IUPAC Name:

tetrahydrothiophene 1,1-dioxide

impurity 2

Reference substance name:

Tributyl-1-propen-1-yl-phosphonium chloride

Molecular formula:

C15H32P.Cl

IUPAC Name:

Tributyl-1-propen-1-yl-phosphonium chloride

Test material form:

other: solid : wax like

Details on test material:

Homogeneity : homogeneous if totally melted
Note: For every use the test item was completely melted and the melted test item
was used for the test.

Specific details on test material used for the study:

Test Item Allyltributylphosphonium chloride
Lot Number INT 18 192
CAS No 1530-48-9
EINECS-No 216-231-7
Purity 95.0 % (NMR 1H and 31P)
Molecular formula C15H32P.Cl
Molecular weight 278.8413 g/mol
Appearance Beige crystallised mass
Composition
Allyltributylphosphonium chloride ≥ 94.5 %;
Allyltributylphosphonium chloride Isomere ≤ 2 %;
Sulfolane ≤ 3.5 %
Homogeneity homogeneous if totally melted
Production Date not stated
Expiry Date 2019-10-17
Storage Room Temperature (20 ± 5°C);
Test Item Handling and
Storage
According to S0PA-00147-BIO, Test and Reference Items

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Age at First Dose :8-9 weeks; female animals were non-pregnant and nulliparous
Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.
Acclimation :The animals were acclimated under the conditions identical to the conditions during the experiment 5 days prior to the start of treatment.
The acclimation was according to the standard operation procedure.
Housing Condition : The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central airconditioning. The average room temperature was maintained within the range of 22.23 ± 0.17 °C, relative humidity within 53.44 ± 5.00 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures.
Diet : The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available at libitum. The certificate of analysis is included in the raw data.
Water : The animals received tap water for human consumption. Supply of drinking was unlimited. The quality of drinking water is periodically analysed and recorded; certificate of analysis is included in the raw data.
Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
Animals Identification: The animals in the cage were marked by a line (I-III) on the tail with a waterproof marker. Each cage was marked with the study code, ID of animals and date of administration of the test item.
Justification for the Choice of Species: Normally females are used for testing according to OECD TG 423 because females are typically the more sensitive gender.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Aqua pro injectione

Details on oral exposure:

Vehicle Aqua pro injectione
Lot Number 18E2302
Expiry Date 04/2021
Manufacturer Bieffe Meditel S.p.A., Italy
Storage 20 ± 5 °C
Justification for the Choice of
Vehicle
Aqua pro injectione is a common vehicle in toxicity studies like
OECD TG 423

Doses:

Dose Preparation : The required amount of the test item (according to the body weight and dose) was dissolved in vehicle (aqua pro injectione) shortly before administration. The dose of 2000 mg/kg and 300 mg/kg was administered in a volume of 5 mL/kg body weight.
Dose Administration: The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.

No. of animals per sex per dose:

The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test item-related mortality was observed 10 minutes after administration of the test item in two animals. In a second step 3 females were treated at the dose of 300 mg/kg body weight. All females survived 24 hours and therefore another 3 females (third step) were treated at the same dose of 300 mg/kg body weight.

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 000 mg/kg bw

Mortality:

All animals were necropsied. During necropsy, no macroscopic findings were observed.

Clinical signs:

other: Test item-related mortality in females treated with the test item at the dose of 2000 mg/kg body weight was observed within ten minutes after administration of the test item in animals No 1 and No 2. Immediately after administration of the test item, pilo

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

It can be concluded that the test item “Allyltributylphosphonium chloride” is according to GHS criteria classified in Category 4 with a LD50 cut off value 1000 mg/kg body weight

Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Allyltributylphosphonium chloride” when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used.

A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 3 females at a limit dose of 2000 mg/kg body weight caused death of 2/3 animals. Piloerection, tremor and lethargy were observed during the observation period. The body weight of one survived animal increased during the study. During necropsy, no macroscopic findings were observed.

No signs of toxicity were observed during the first 4 hours in females and the 14-day observation period thereafter in females treated with the dose of 300 mg/kg body weight. The body weights of all animals increased during the study. A slight decrease of body weight in one animal treated with the dose of 300 mg/kg was noted one week after administration of the test item. No body weight losses were observed between the first and second week after administration. During necropsy, no macroscopic findings were observed. The LD50 of the test item “Allyltributylphosphonium chloride” is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.

Based on Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight of OECD Guideline 423 it can be concluded that the test item “Allyltributylphosphonium chloride” is according to GHS criteria classified in Category 4 with a LD50 cut off value 1000 mg/kg body weight, after

single oral administration to Wistar rats.

.