1,1,1,3,3,3-hexafluoro-2-methoxypropane

Endpoint summary

Description of key information

In a GLP guideline study conducted according to US EPA OPPTS 870.1100 (2002) to assess the acute oral toxicity with 3 female Sprague-Dawley young adult rats, no mortalities were observed at the limit dose of 5000 mg/kg-bw. All animals were healthy and active throughout the study and 14 -day observation period and there were no gross abnormalities observed at necropsy. Therefore, the Oral LD50 is >5000 mg/kg-bw.

In a GLP guideline study conducted according to OECD Method 403 (2009) to assess the acute inhalation toxicity with 5 male and 5 female Sprague-Dawley young adult rats, no mortalities were observed at either 7322 ppm or 24685 ppm for 4 -hours. All animals exhibited irregular respiration immediately following exposrue but recovered by day 1 and were healthy and active throughout the remainder of the 14 -day observation period. There were no gross abnormalities observed at necropsy. Therefore, the 4 -hour LC50 is >24685 ppm (183.82 mg/L).

In a GLP guideline study conducted according to US EPA OPPTS 870.1200 (1998) to assess the acute dermal toxicity with 5 male and 5 female Sprague-Dawley young adult rats, no mortalities were observed at the limit dose of 5000 mg/kg-bw. All animals were healthy and active throughout the study and 14 -day observation period and there were no gross abnormalities observed at necropsy. Therefore, the Dermal LD50 is >5000 mg/kg-bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 August 2017 thru 6 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Specific details on test material used for the study:

CASNo.: 13171-18-1
Lot #: HFMOP17004
Storage: Room Temp.
Purity: >99.99%
Description: Clear Liquid
pH: Neutral molecule
Stability: Expected to be stable for the duration of testing.

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAGE Labs on August 16, 2017
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks (young adults)
- Weight at study initiation: 155-161
- Fasting period before study: Yes
- Housing: Stainless steel cages with enrichment (e.g. toy) and litter paper beneath the cage changed at least 3 times per week.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet #2016 ad libitum.
- Water (e.g. ad libitum): Filtered tap water ad libitum.
- Acclimation period: 6 - 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 45 - 62
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5000 mg/kg limit dose

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: 30 minutes post-dosing, during first several hours, and at least once daily thereafter. Weights taken prior to dosing and on days 7 and 14.
- Necropsy of survivors performed: yes. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Cage-side observations for mortality, signs of gross toxicity, behavior changes; including gross evaluation of skin and fur, eyes and mucous membranes, repiratory, circulatory, autonomic and central nervious systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None. All animals were active and healthy throughout the study.

Gross pathology:

No gross abnormalities

Other findings:

None

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is non-toxic in rats up at a limit dose of 5000 mg/kg. Therefore, the Oral LD50 is >5000 mg/kg-bw.

Executive summary:

In a GLP guideline study conducted according to US EPA OPPTS 870.1100 (2002) to assess the acute oral toxicity with 3 female Sprague-Dawley young adult rats, no mortalities were observed at the limit dose of 5000 mg/kg-bw. All animals were healthy and active throughout the study and 14 -day observation period and there were no gross abnormalities observed at necropsy. Therefore, the Oral LD50 is >5000 mg/kg-bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 February 2019 thru 17 April 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

CASNo.: 13171-18-1
Lot #: HFMOP17004
Storage: Room Temp.
Purity: >99.99%
Description: Clear Liquid
pH: Neutral molecule
Stability: Expected to be stable for the duration of testing.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAGE Labs on February 20 and March 27, 2019
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Young adult (8 - 9 weeks)
- Weight at study initiation: males; 252 - 313 grams Females; 160 - 201 grams
- Fasting period before study: Yes
- Housing: Stainless steel cages with enrichment (e.g. toys) and litter paper under the cage changed at least once per week.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Diet ad libitum except during exposure.
- Water (e.g. ad libitum): Filtered tap water ad libitum except during exposure.
- Acclimation period: 7 or 8 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 37 - 69
- Air changes (per hr): 13
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG Developments LTD 28 liter (Nose-Only Inhalation Chamber)
- Exposure chamber volume: 28 liter
- Method of holding animals in test chamber: polycarbonate holding tubes
- Source and rate of air: Filtered generator air delivered by an air compressor
- Method of conditioning air: Filtered
- System of generating particulates/aerosols: not applicable
- Method of particle size determination: not applicable
- Temperature and humidity in air chamber: 21 - 23 deg C; 27 - 49%

TEST ATMOSPHERE
- Brief description of analytical method used: Air samples collected on Anosorb CSC tubes (SKC Lot #2000), desorbed with toluene, and analyzed by GC-FID. See OSHA Method 106 "Desflurane".
- Samples taken from breathing zone: yes

VEHICLE
- Composition of vehicle (if applicable): air
- Concentration of test material in vehicle (if applicable): 243.12 mg/L nominal
- Justification of choice of vehicle: not applicable.
- Lot/batch no. (if required): not applicable.
- Purity: not applicable.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not applicable.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not applicable.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: A nominal starting concentration of 7500 ppm was chosen based on an LC50 for the substance for which the reliability could not be determined. Since there were no deaths at that concentration, the study was performed at the nominal limit dose of 20000 ppm.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

7322 ppm (measured) and 24685 ppm (measured)

No. of animals per sex per dose:

5 males, 5 females at each dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Upon removal from the chamber and at least once daily
- Necropsy of survivors performed: yes. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

Statistical analysis was limited to the calculation of the mean and standard deviation

Preliminary study:

No deaths reported at 7322 ppm.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 24 685 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: (analytical)

Remarks:

molecular weight=182.07

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 183.82 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Key result

Sex:

male/female

Dose descriptor:

LC0

Effect level:

24 685 ppm

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: Following exposure, all rats exhibited irregular respiration. However, all animals recovered by Day 1 and appeared active and healthy for the remainder of the 14-day observation period.

Body weight:

Normal

Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

None.

Interpretation of results:

GHS criteria not met

Remarks:

Substance is a highly volatile liquid. GHS-criteria for gases was applied.

Conclusions:

The substance (vapor only) was found to be non-toxic to rats at the limit concentration of 24685 ppm (183.82 mg/L) for four hours. Therefore, the 4-hour LC50 in rats is >24685 ppm.

Executive summary:

In a GLP guideline study conducted according to OECD Method 403 (2009) to assess the acute inhalation toxicity with 5 male and 5 female Sprague-Dawley young adult rats, no mortalities were observed at either 7322 ppm or 24685 ppm for 4 -hours. All animals exhibited irregular respiration immediately following exposrue but recovered by day 1 and were healthy and active throughout the remainder of the 14 -day observation period. There were no gross abnormalities observed at necropsy. Therefore, the 4 -hour LC50 is >24685 ppm (183.82 mg/L).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 August 2017 thru 6 September 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

CASNo.: 13171-18-1
Lot #: HFMOP17004
Storage: Room Temp.
Purity: >99.99%
Description: Clear Liquid
pH: Neutral molecule
Stability: Expected to be stable for the duration of testing.

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SAGE Labs on August 16, 2017
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks (young adults)
- Weight at study initiation: males 261 - 280 grams; females 173-205 grams
- Fasting period before study:Yes
- Housing: Stainless steel cages with enrichment (e.g. toy) and litter paper beneath the cage changed at least 3 times per week.
- Diet (e.g. ad libitum): Envigo Teklad Global 16% Protein Rodent Diet #2016 ad libitum.
- Water (e.g. ad libitum): Filtered tap water ad libitum.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 45 - 60
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal
- % coverage: 10%
- Type of wrap if used: gauze pad and Durapore tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with 3% soap solution followed by tap water rinse and wiped with clean paper towel.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg-bw
- Concentration (if solution): 100%
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable.

VEHICLE: None

Duration of exposure:

24 hours

Doses:

5000 mg/kg-bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: During the first several hours and at least once daily thereafter. Weights taken prior to dosing and on days 7 and 14.
- Necropsy of survivors performed: yes. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Cage-side observations for mortality, signs of gross toxicity, behavior changes; including gross evaluation of skin and fur, eyes and mucous membranes, repiratory, circulatory, autonomic and central nervious systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Statistics:

Limited to calculation of the mean density value for dosing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

None.

Clinical signs:

other: None. All animals were healthy and active throughout the study.

Gross pathology:

No gross abnormalities observed.

Other findings:

None.

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is non-toxic in rats up at a limit dose of 5000 mg/kg. Therefore, the Dermal LD50 is >5000 mg/kg-bw.

Executive summary:

In a GLP guideline study conducted according to US EPA OPPTS 870.1200 (1998) to assess the acute dermal toxicity with 5 male and 5 female Sprague-Dawley young adult rats, no mortalities were observed at the limit dose of 5000 mg/kg-bw. All animals were healthy and active throughout the study and 14 -day observation period and there were no gross abnormalities observed at necropsy. Therefore, the Dermal LD50 is >5000 mg/kg-bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Justification for classification or non-classification

The substance is not classified as acutely toxic by oral, inhalation, or dermal routes based on a reported Oral LD50 >5000 mg/kg-bw, a Dermal LD50 >5000 mg/kg-bw, and a 4 -hour inhalation LC50 >24685 ppm from reliable GLP guideline studies.