Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-08-01 to 2017-09-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

IUPAC Name:

Reaction mass of Reaction product of 1-chloro-3-{[1-chloro-3-(dodecyloxy)propan-2-yl]oxy}propan-2-ol with methyl diethanolamine and [3-(dodecyloxy)-2-hydroxypropyl]bis(2-hydroxyethyl)methylammonium chloride

Test material form:

other: solid, very viscous yellow paste

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

HUSBANDRY
The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central airconditioning.
The average room temperature was maintained within the range of 23.1 ± 0.5° C, relative humidity within 55.4 ± 3.3 %.
The light regimen was set to a 12-hour light/12-hour dark cycle.
The sanitation was performed according to the standard operation procedures.

DIET
A laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered in recommended doses each day approximately at the same time.

WATER
The animals received tap water for human consumption. Supply of drinking was unlimited.

BEDDING
Lignocel S3/4, Lufa - ITL GmbH, Germany

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted prior to dosing (food but not water were withheld over-night). Following the period of fasting, the animals were weighted and the test item was administered. After the test item had been administered, food was withheld for further 3-4 hours.

Doses:

- limit dose of 2000 mg/kg bw (step 1 and 2)
- 300 mg/kg bw (step 3 and 4)

No. of animals per sex per dose:

- step 1, 2, 3 and 4: 3 females per step (total 12 females)

Control animals:

no

Details on study design:

OBSERVATIONS

Clinical observations
The animals were observed individually immediately after the administration of the test item and then 0.5, 1, 2, and 4 hours later. Then each animal was inspected daily for the next 14 days. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weights
Individual weights of animals were determined shortly before the test item was administered and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy and result were recorded for each animal.

Statistics:

n.a.

Results and discussion

Preliminary study:

n.a.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

5/6 animals at dose of 2000 mg/kg bw
0/6 animals at the dose of 300 mg/kg

Clinical signs:

other: - 2000 mg/kg bw: test item-related mortality in females treated with the test item in dose of 2000 mg/kg body weight was observed during the 24 hours. Lethargy was observed in all animals between 1-4 hours post-treatment. On post-treatment Day 1 animals N

Gross pathology:

Animals No 2 and 3 (dose 2000 mg/kg) could not be necropsied because cadavers were autolysed.
Alopecic place behind the ears was registered in animal surviving the 14-day observation period.
All animals treated with dose of 300 mg/kg body weight were necropsied.
During necropsy, no macroscopic findings were noticed.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of the test item is higher than 300 mg/kg bw and lower than 2000 mg/kg bw after single oral administration to female Wistar rats.

Executive summary:

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

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 not observed within 24 hours and therefore in a next step 3 females were treated with the same dose. Test item-related mortality was observed on Day 5 after administration in the animals of the first step and on Day 1 and Day 2 in the animals of the second step. In the third step another 3 females were treated at the dose of 300 mg/kg body weight. All females survived 24 hours and thereafter 3 females (fourth step) were treated with the dose of 300 mg/kg body weight.

The test item was administered to 6 females at dose of 2000 mg/kg body weight caused death of 5/6 animals. Lethargy was observed during the observation period. Alopecic place behind the ears was registered in the animal surviving the 14-day observation period. Six of six females survived the dose of 300 mg/kg. Piloerection was observed during the first 4 hours and no signs of toxicity within the 14-day observation period thereafter in females treated with dose of 300 mg/kg body weight. Body weight stagnation was observed between week 1 and week 2. During necropsy, no macroscopic findings were observed.

The LD50 of the test item is higher than 300 mg/kg body weight and lower than 2000 mg/kg body weight after single oral administration to Wistar rats.