(8α,9R,8'''α,9'''R)-1,1'-[(2,3,5,6-tetrafluoro-1,4-phenylene)bis(methylene)]bis(6'-methoxycinchonan-1-ium-9-ol) dibromide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(8α,9R,8'''α,9'''R)-1,1'-[(2,3,5,6-tetrafluoro-1,4-phenylene)bis(methylene)]bis(6'-methoxycinchonan-1-ium-9-ol) dibromide

EC Number:

857-673-6

Cas Number:

1879067-61-4

Molecular formula:

C48H52F4N4O4.2Br

IUPAC Name:

(8α,9R,8'''α,9'''R)-1,1'-[(2,3,5,6-tetrafluoro-1,4-phenylene)bis(methylene)]bis(6'-methoxycinchonan-1-ium-9-ol) dibromide

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
Housing: Type II polypropylene/polycarbonate cages with deep wood sawdust (SAFE 3/4 S wooden chips, Arbocel crinklets natural nest building material)
Food: ssniff SM R/M autoclavable complete diet for rats and mice - breeding and maintenance, ad libitum
Water supply: tap water from municipal supply from 500 mL bottles ad libitum
Light: 12 hours daily, from 6 am to 6 pm
Temperature: 21.2 to 25.9 °C
Relative humidity: 30 - 70%
Ventilation: 15 - 20 air exchanges per hour
Number: 5 animals
Sex: female, nulliparous and non-pregnant
Age: young adult, 11-12 weeks old
Body weigth: 224 - 238 g
Acclimatisation before test: at least 25 days
Randomisation: selected by hand at time of delivery

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

The test substance was freshly formulated at concentrations of 17.5, 55 and 200 mg/mL in the vehicle, 0.5% carboxymethyl cellulose (batch BCBN1690V, Sigma-Aldrich) in distilled water (batch 8060219, Hungaro-Gal Kft). The dosed volume was between 2.2 and 2.4 mL (10 mL/kg bw).

Doses:

175, 550 and 2000 mg/kg bw

No. of animals per sex per dose:

175 mg/kg: one
550 mg/kg: one
2000 mg/kg: three

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: after 30 minutes, 1, 2, 3, 4 and 6 hours, then daily
- Frequency of weighing: on the day before treatment prior to removal of food, directly before dosing, on day 7 and on day 14 of the observation period
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Individual observations were performed on the skin, fur, eyes, mucous membranes, somatomotor activity and behaviour pattern as well as respiratory, circulatory, autonomic and central nervous systems

Statistics:

The LD50 was calculated using the AOT425StatPgm program. This program was prepared for the US Environmental Protection Agency by Westat, May 2001 and updated by the US EPA June 2003. This program was constructed using the most appropriate method to estimate the LD50.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Not effects observed

Clinical signs:

other: Animals were symptom-free

Gross pathology:

No effects observed

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance was not acutely toxic to female rats following a single oral dose by gavage of 2000 mg/kg bw. The acute oral LD50 values were >2000 mg/kg.

Executive summary:

The acute oral toxicity of the substance to young adult female Wistar rats was studied under GLP to OECD TG 425. Healthy, nulliparous and non-pregnant animals were used in the study after an acclimatisation period of at least 25 days. The body weight of animals was between 224 and 238 g immediately before dosing. Animals were housed individually in polypropylene/polycarbonate cages with deep wood sawdust bedding, at a temperature ranging from 21.2 to 25.9 °C, a relative humidity of 35 to 70% and with 12 hours of light per day. The animals received standard rodent feed and water ad libitum. All animals were fasted overnight prior to treatment, but water was still available ad libitum overnight. Food was provided again three hours after the treatment. Animals were administered a single oral dose by gavage of the test substance dissolved in 0.5% aqueous carboxylmethyl cellulose. The administered volume was 10 mL/kg bw. The first animal was treated with an initial dose of 175 mg/kg bw, which was selected due to the lack of information on toxicity of the substance. Since no adverse effects were observed, a second animal was treated with a dose of 550 mg/kg bw, which also did not show any adverse effects. Therefore, three further animals were treated with 2000 mg/kg bw. All animals were observed for a period of 14 days after dosing. No mortality occurred during the study. No adverse clinical signs and no effects on body weight were observed. There were no findings during the gross observations at necropsy.