Acetic acid, 2,2-difluoro-2-[[2,2,4,5-tetrafluoro-5-(trifluoromethoxy)-1,3-dioxolan-4-yl]oxy]-, ammonium salt (1:1)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-03-09 to 2009-12-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

cC6O4 ammonium salt

IUPAC Name:

cC6O4 ammonium salt

Constituent 2

Reference substance name:

Acetic acid, 2,2-difluoro-2-[[2,2,4,5- tetrafluoro-5-(trifluoromethoxy)-1,3- dioxolan-4-yl]oxy]-, ammonium salt (1:1)

IUPAC Name:

Acetic acid, 2,2-difluoro-2-[[2,2,4,5- tetrafluoro-5-(trifluoromethoxy)-1,3- dioxolan-4-yl]oxy]-, ammonium salt (1:1)

Constituent 3

Reference substance name:

ammonium 2,2-difluoro-2-{[2,2,4,5-tetrafluoro-5-(trifluoromethoxy)-1,3-dioxolan-4-yl]oxy}acetate

EC Number:

682-238-0

Cas Number:

1190931-27-1

Molecular formula:

C6H4F9NO6

IUPAC Name:

ammonium 2,2-difluoro-2-{[2,2,4,5-tetrafluoro-5-(trifluoromethoxy)-1,3-dioxolan-4-yl]oxy}acetate

Details on test material:

- Name of test material (as cited in study report): cC6O4 cyclic (SOLUTION 16%)
- Substance type: pure substance in water solution
- Physical state: Liquid yellowish/colourless to yellow, clear solution
- Analytical purity: not reported
- Impurities (identity and concentrations): NH4F=28 (mg/l), NH4Cl=601(mg/l), the organic impurities are dioxolan based and represent the 0.8% by mol on total mol of organic phase of sample.
- Purity test date: not reported
- Lot/batch No.: 150/28
- Expiration date of the lot/batch: 31 December 2020
- Stability under test conditions: not reported
- Storage condition of test material: Ambient condition

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 150 to 174 grams
- Fasting period before study: Overnight prior to dosing (Day –1)
- Housing: Polycarbonate cages measuring 59x38.5x20 cm, with stainless steel mesh lid and floor
- Diet (e.g. ad libitum): 4 RF 18 ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 25 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 2009-03-11 To: 2009-04-03

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- Concentration in vehicle: (160mg(dry salt)/ml) and 24 mg(dry salt)/ml
- Amount of vehicle (if gavage): Dose volume of 12.5 ml/kg of body weight for each animal.
- Justification for choice of vehicle: no justification given
- Lot/batch no. (if required): n.a.
- Purity: distilled water

MAXIMUM DOSE VOLUME APPLIED: Dose volume of 12.5 ml/kg of body weight for each animal.

DOSAGE PREPARATION (if unusual): n.a.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg(dry salt)/kg body weight, as limit dose for acute oral toxicity category IV (GHS/CLP)

Doses:

300 and 2000 mg (dry salt)/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Allocation (Day-1), Days 1, 2, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no statistics applied

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality occurred in the 3 female animals dosed at 2000 mg(dry salt)/kg body weight (step 1); animals were found dead approximately 3 hours after dosing. No mortality was observed in the female animals dosed at 300 mg (dry salt)/kg body weight.

Clinical signs:

other: 2000 mg (dry salt)/kg body weight: Lethargy, difficult breathing, piloerection, tremors and salivation were observed prior to death with a various incidence. At 300 mg (dry salt)/kg body weight clinical signs were limited to piloerection observed at 2 and

Gross pathology:

At necropsy examination, performed on the early decedent animals dosed at 2000 mg(dry salt)/kg (step 1), abnormal colour of the liver (dark), abnormal contents (brown gelatinous) or areas (dark) in the stomach and red staining on the muzzle were recorded in all animals. In addition, abnormal colour (red) of the thymus was recorded in two animals.
No abnormalities were observed at necropsy examination performed at the end of the observation period on the animals dosed at 300 mg(dry salt)/kg body weight (steps 2 and 3).

Other findings:

none reported

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

cC6O4 ammonium salt has a toxic effect on the rat following oral administration of a single dose at a level of 2000 mg(dry salt)/kg.
The mortality pattern of the test item, cC6O4 ammonium salt, demonstrates the LD50 to be greater than 300 mg(dry salt)/kg but less than 2000 mg(dry salt)/kg body weight.
These results meet the criteria for European CLP Regulation classification as : Acute oral toxicity - Category 4.

Executive summary:

The acute toxicity of cC6O4 ammonium salt was investigated after a single oral administration (12.5 ml/kg in water) to female Sprague Dawley rats followed by a 14-day observation period. The animals were sacrificed at the end of the observation period and subjected to necropsy examination.

A first sub-group of 3 female animals was initially dosed at 2000 mg(dry salt)/kg body weight (step 1).

Mortality occurred in all animals between 2 and 4 hours after dosing. Lethargy, difficult breathing, piloerection, tremors and salivation were observed prior to death with various incidence.

At necropsy examination, performed on the early decedent animals, dark colour of the liver, brown gelatinous contents or dark areas in the stomach and red staining on the muzzle were recorded in all animals. In addition, red colour of the thymus was recorded in two animals.

A second and third subgroup, each composed of 3 females, were then dosed at 300 mg(dry salt)/kg body weight (steps 2 and 3). No mortality was recorded in any animal. Clinical signs were limited to piloerection observed on the day of dosing.

A very slight body weight loss was detected in two animals on Day 15, without any toxicological significance. Body weight changes were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed at the end of the observation period in these animals.

These results indicate that the test item, cC6O4 ammonium salt, has a toxic effect on the rat following oral administration of a single dose at a level of 2000 mg(dry salt)/kg. The mortality pattern demonstrates the LD50 to be greater than 300 mg(dry salt)/kg but less than 2000 mg(dry salt)/kg body weight. Based on criteria in the European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions), the classification is the following:

Classification : Acute oral toxicity - Category 4

Signal word : Warning

Hazard statement (Oral) : H302: Harmful if swallowed