1-Propanaminium, 2-hydroxy-N,N,N-trimethyl-3-[(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)thio]-, chloride (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 October, 2015 - 02 November, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

{2-hydroxy-3-[(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)sulfanyl]propyl}trimethylazanium chloride

EC Number:

811-523-6

Cas Number:

88992-45-4

Molecular formula:

C14 H19 F13 N O S . Cl

IUPAC Name:

{2-hydroxy-3-[(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)sulfanyl]propyl}trimethylazanium chloride

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): NS-4000
- Appearance: White powder
- Storage condition of test material: refrigerated (2ºC to 8ºC) in a desiccator

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: Young adult animals (approx. 8 - 9 weeks old)
- Weight at study initiation: 170 to 195 g, ± 20% of the mean
- Fasting period before study: Overnight prior to dosing and food was returned approximately 4 hours after dosing.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to basal diet (PMI Nutrition International, LLC, Certified Rodent LabDiet® 5002)
- Water: Free access to municipal water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.3 – 21.1
- Humidity (%): 34.7 - 51.6
- Air changes (per hr): minimum of 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: deionized water

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE:
The vehicle used in preparation of the test substance formulation was deionized water (prepared on-site).

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.

DOSAGE PREPARATION: On each day of dosing, a sufficient amount of test substance was weighed into a glass mortar and ground to fine powder. A small volume of vehicle was added to the mortar, and the contents were ground with a pestle until a uniform mixture was obtained. This mixture was quantitatively transferred into a glass container. The remaining vehicle was added. The contents were mixed using a sonicator to achieve a uniform formulation. The final pH of the first formulation at each concentration was measured using a pH meter (7.39 for 200 mg/mL and 7.29 for 30 mg/mL). The contents were stirred continuously throughout use with a magnetic stirrer.

Doses:

2000 and 300 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: The rats were observed at approximately 15 minutes (± 5 minutes) and 1, 2 and 4 hours post-dosing on study day 0 and twice daily, once in the morning and once in the afternoon, thereafter for 14 days.
Body weights: Body weights were obtained and recorded on study days 0 (initiation), 7, and 14 (termination).
Clinical observations: The rats were observed at approximately 15 minutes (± 5 minutes) and 1, 2, and 4 hours post-dosing on study day 0 and once daily thereafter for 14 days.
- Necropsy of survivors performed: On study day 14, the rats were euthanized by carbon dioxide inhalation. The major organ systems of the cranial, thoracic, and abdominal cavities and the eyes and skin were examined for all animals.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All 3 females in the 2000 mg/kg bw group were found dead or euthanized in extremis on study day 1. All animals in the 300 mg/kg bw group survived to the scheduled necropsy (study day 14).

Clinical signs:

other: Clinical observations noted for the 2000 mg/kg bw group females that were found dead or euthanized in extremis consisted of abnormal feces (diarrhea, mucoid feces, soft feces and decreased defecation), yellow material on various body surfaces (hind limbs,

Gross pathology:

For the unscheduled deaths, internal gross necropsy findings were limited to 2 of the 3 females. One female had a distended, gas-filled stomach and intestine, dark red discoloration of all lobes of the liver, foamy contents in the trachea, and dark red contents in the cranial cavity (surrounding brain and pituitary). One female had dark red discoloration of the right adrenal gland, lungs (all lobes) that were not fully collapsed, and dark red contents in the cranial cavity (submeningeal). There were no macroscopic findings at the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD 423 test guideline, the LD50 of NS-4000 as a single dose in female rats is greater than 300 mg/kg bw but less than 2000 mg/kg bw (Category 4).

Executive summary:

The acute oral toxicity of NS-4000 was determined in accordance with OECD 423 guideline and according to GLP principles.

NS-4000 was administered to female rats by a single dose of 2000 and 300 mg/kg bw. All 3 females in the 2000 mg/kg bw group were found dead or euthanized in extremis on study day 1. All animals in the 300 mg/kg bw group survived to the scheduled necropsy (study day 14). Clinical observations noted for the 2000 mg/kg bw group females that were found dead or euthanized in extremis consisted of abnormal feces (diarrhea, mucoid feces, soft feces and decreased defecation), yellow material on various body surfaces (hind limbs, urogenital and anogenital areas, and ventral trunk), dermal atonia, decreased respiration rate, blue extremities, and clear ocular discharge. For the 300 mg/kg bw group females that survived to study termination, clinical observations were limited to abnormal feces (mucoid feces, soft feces, and decreased defecation), yellow material on the anogenital area, and wet clear material around mouth. For the unscheduled deaths, internal gross necropsy findings were limited to 2 of the 3 females. One female had a distended, gas-filled stomach and intestine, dark red discoloration of all lobes of the liver, foamy contents in the trachea, and dark red contents in the cranial cavity (surrounding brain and pituitary). One female had dark red discoloration of the right adrenal gland, lungs (all lobes) that were not fully collapsed, and dark red contents in the cranial cavity (submeningeal). There were no macroscopic findings at the scheduled necropsy. The oral LD50 of NS-4000 as a single dose in female rats is greater than 300 mg/kg bw but less than 2000 mg/kg bw.

Based on the results of this study, NS-4000 shall be classified for acute oral toxicity Category 4 and shall be labelled with H302: Harmful if swallowed, according to Regulation (EC) No 1272/2008 on classification, labelling and packaging.