Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine

EC Number:

948-066-8

Molecular formula:

C16H36NO6P C24H52NO8P C24H53NO11P2 C32H68NO10P C8H17N H3O4P

IUPAC Name:

Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine

Test material form:

liquid: viscous

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:WI Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7,
D-97633 Sulzfeld
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Number of animals: 9 animals, 3 animals / group
Sex: Female, nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats, 8-12 weeks old
Body weight at treatment: 194 – 257 g
Acclimation period: at least 5 days

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The test item was freshly formulated at concentrations of 200 and 30 mg/mL in the vehicle in the Pharmacy of Citoxlab Hungary Ltd. on the day of administration. Each formulation was stirred continuously with a magnetic stirrer until dose administration procedure was complete.

Name: Distilled water
Batch/Lot number: 180615
Manufacturer: MAGILAB Kft.
Expiry Date: 21 December 2018
Storage condition: Room temperature

Dose selection:
The initial dose level was selected by the Study Director to be that which is most likely to produce mortality in some of the dosed animals. A limit dose of 2000 mg/kg bw was selected as a starting dose.

Doses:

Initially three females (Group 1) were treated at a dose level of 2000 mg/kg bw. All three animals died, thus the second group (Group 2) were treated at the dose level of 300 mg/kg bw. Only one animal died in this group, thus a confirmatory group (Group 3) was treated at the same dose level. No mortality was observed in the confirmatory group, therefore no further testing was required according to the test guidelines (OECD 423, Commission Regulation (EC) No 440/2008 of 30 May 2008, B.1.Tris).

No. of animals per sex per dose:

group 1: 3 females treated at a dose level of 2000mg/kg bw
group 2: 3 females treated at a dose level of 300mg/kg bw
group 3: 3 females treated at a dose level of 300mg/kg bw

Control animals:

no

Details on study design:

PROCEDURE
A single oral gavage administration was followed by a fourteen-day observation or until death was noted. On the night before treatment, the animals were fasted. The food, but not water, was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.

OBSERVATIONS

1/ Clinical Observations

Clinical observations were performed on all animals at least at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter or until death was noted. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

2/ Body Weight Measurement

The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter or until the day of death.

NECROPSY

Macroscopic examination was performed on all animals. The surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal 40%;
Lot No.: 1609291-03, Expiry Date: 31 October 2019, Produced by: AlfasanNederland BV, Kuipersweg 9, Woerden, The Netherlands). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At a dose level of 2000 mg/kg bw, 3 out of 3 animals died rapidly 8, 30 minutes or 1 hour after treatment. At a dose level of 300 mg/kg bw 1 out of 6 animals died on the day of treatment.

Clinical signs:

other: At a dose level of 2000 mg/kg bw, decreased activity (score 1), tremors (continuous), clonic convulsion, respiratory rate increase (score 1 or 2) and/or hunched back were observed on the day of treatment before death. In the surviving animals at a dose l

Gross pathology:

No macroscopic findings were observed in three females received 2000 mg /kg bw.

In one female dosed at 300 mg/kg bw, yellow liquid material was seen in the digestive content of the stomach . This material appeared to be probably administered test item (high-viscous, colourless to yellowish liquid). The non-collapsed lungs were also noted in this female at necropsy.

No macroscopic findings were observed in the two survived females received 300 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Executive summary:

Under the conditions of this study, the acute oral LD₅₀value of the test item
Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine was found to be between 300 and 2000 mg/kg bw in female Crl:WI rats.

 

According to the GHS criteria, Ethanol, 2-(2-butoxyethoxy)-, reaction products with phosphorus oxide (P2O5), compds. with N,N-dimethylcyclohexanamine can be ranked as "Category 4" for acute oral exposure.