Propane, 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethyl)-

Endpoint summary

Description of key information

An oral toxicity study performed according to OECD 423 guideline,

a dermal toxicity study performed according to OECD 402 guideline and an inhalation toxicity study performed according to OECD 403 guideline are reported.
According to Regulation EC No. 1272/2008, the substance is classified as following:
Acute oral toxicity Category 3
Acute Inhalation Toxicity Category 2.
The substance does not meet the classification criteria for Acute Dermal Toxicity

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:

18 January 2005 to 16 March 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline-conform study under GLP without deviations.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

300

Doses:

2000 mg/kg, 300 mg/kg, 50 mg/kg

No. of animals per sex per dose:

3 at dose of 2000 mg/kg
3 at dose of 300 mg/kg
6 at dose of 50 mg/kg

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

act. ingr.

Mortality

All three 2000mg/kg treated animals died within five and half hours after treatment. All three 300 mg/kg treated animals were founded dead on test day 2.

Clinical signs

Sightly ruffled fur was observed in all 2000 mg/kg treated animals from the 30 -minute reading to the 1- or 2 -hour reading and sligh to moderate ruffled fur persistent in one animal up to the 5 -hour reading. Hunched posture was noted in all three animlas of this group at the 30 -minute reading and persistent up to the 1 or 3 -hour observation in two animals. Slight to marked sedation was observed in all animals from the 30 -minute reading to the 1 -, 2 - or 5 -hour reading, respectively. Deep respiration was observed in one animal at the 3 -hour reading and was still noted at the 5 -hour examination. Ventral recumbency was seen in two animals one hour before death occurred.

In all animals treated with 300 mg/kg slightly ruffled fur and hunched posture was noted from the 1 -hour to the 5 -hour examination. Feces containing mucus was noted in two animals of the second-treated group at the 2 -hour or 3 -hour reading and persistent up to the 5 -hour observation in one animal. Hypothermia by hand-touch at the 5 -hour examination was noted in the same animals. All three animals in this group appeared slightly sedated at the 5 -hour observation.

The animals treated with 50mg/kg bw did not show any clinical signs.

Macroscopic findings

In all three 2000 mg/kg bw treated animals, liquid contents were found in the stomach, duodenum, jejunum and ileum and additionally in the caecum of two animals at the unscheduled necropsy after spontaneous death. Stomach containing liquid and distended with gas was observed at the unscheduled necropsy of all three 300mg/kg bw treated animals.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The median lethal dose of Octafluoroisobutyl methyl ether after single oral administration to female rats, observed over a period of 14 days is:
50 mg / kg bw < LD50 (female rats) < 300 mg /kg bw.

Executive summary:

The study has been conducted in accordance with OECD 423 guideline Acute Oral toxicity - Acute Toxic Class Method.

Four groups, each of three female HanBri: WIST (SPF) rats, were treated with Octafluoroisobutyl Methyl Ether by oral gavage administration at a dosage of 2000 mg/kg, 300 mg/kg, 50 mg/kg body weight.

The following animals were treated and percentage of mortality was observed:

3 females treated at 2000 mg/kg	100 %
3 females treated at 300 mg/kg	100 %
6 females treated at 50 mg/kg	0 %

 

All three 2000 mg/kg treated animals died within five and a half hours after treatment. All three 300 mg/kg treated animals were found dead on test day 2.

Sightly ruffled fur was observed in all 2000 mg/kg treated animals from the 30 -minute reading to the 1- or 2 -hour reading and sligh to moderate ruffled fur persistent in one animal up to the 5 -hour reading. Hunched posture was noted in all three animlas of this group at the 30 -minute reading and persistent up to the 1 or 3 -hour observation in two animals. Slight to marked sedation was observed in all animals from the 30 -minute reading to the 1 -, 2 - or 5 -hour reading, respectively. Deep respiration was observed in one animal at the 3 -hour reading and was still noted at the 5 -hour examination. Ventral recumbency was seen in two animals one hour before death occurred.

In all animals treated with 300 mg/kg slightly ruffled fur and hunched posture was noted from the 1 -hour to the 5 -hour examination. Feces containing mucus was noted in two animals of the second-treated group at the 2 -hour or 3 -hour reading and persistent up to the 5 -hour observation in one animal. Hypothermia by hand-touch at the 5 -hour examination was noted in the same animals. All three animals in this group appeared slightly sedated at the 5 -hour observation.

The animals treated with 50mg/kg bw did not show any clinical signs.

The body weight of the animals was within the range commonly recorded for this strain and age.

In all three 2000 mg/kg bw trated animals, liquid contents were found in the stomach, duodenum, jejunum and ileum and additionally in the caecum of two animals at the unscheduled necropsy after spontaneous death. Stomach containing liquid and distended with gas was observed at the unscheduled necropsy of all three 300mg/kg bw treated animals.

In conclusion the median lethal dose of Octafluoroisobutyl methyl ether after single oral administration to female rats, observed over a period of 14 days is:

50 mg / kg bw < LD50 (female rats) < 300 mg /kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

50 mg/kg bw

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:

19 March 2004 to 01 March 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline-conform study under GLP without deviations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Sampling of test atmosphere was performed 4 times during the inhalation exposure period of groups 1, 2, 3 and twice during the inhalation exposure period of group 4. Samples were analyzed by GC-MS.

Duration of exposure:

4 h

Concentrations:

ca. 20 mg/L air (19.63 mg/L air)
ca. 2 mg/L air (2.197 mg/L air)
ca. 0.5 mg/L air (0.827 mg/L air)
ca. 0.2 mg/L air (0.178 mg/L air)

No. of animals per sex per dose:

10 (5 males + 5 females)

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.06 mg/L air

Based on:

act. ingr.

95% CL:

> 0.64 - < 2.42

Exp. duration:

4 h

For calculation of the LC50 estimates, mean chemically determined concentrations of the test item in the test atmosphere samples of Group 1 (0.178 mg/L air), Group 2 (0.827 mg/L air), Group 3 (2.197 mg/L air) were used. The no toxic effect level was set at 0.178 mg/L air, as there were no deaths, no clinical signs and no macroscopic pathology findings at this atmosphere concentration.

One of ten animals died in Group 2 (0.827 mg/L air) and all animals died in Group 3 (2.197 mg/L air) and 4 (19.63 mg/L air).

Clinical signs were only seen in decedent animals and comprised effects on breathing in Groups 2, 3 and 4, in addition to decreased spontaneous activity, ventral recumbency and ruffled fur in Group 3, and somnolence in Group 4.

Mortality and clinical signs were attributed to treatment with the test item. Whether or not transient retardation in body weight gain or transient body weight losses in several male and female survivoers of Groups 1 and 2 were attributable to the treatment remained unclear.

Necropsy revealed dark red or reddish discoloration of the lungs in the one decedent animal of Group 2 and all animals of Groups 3 and 4, in addition to an isolated grey white focus of 2 mm diameter in the lungs of the one affected animal of Group 2.A relationship of the finding of lung discoloration to treatment remained unclear. The single incidence of an isolated grey white focus was not attributed to the treatment.

There was no indication of relevant sex-related differences in toxicity of the test item.

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

The LC50 of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane for acute inhalation toxicity (4h) in male and female rats observed for a period of 15 days was estimated to be:
LC50 = 1.06 mg/L air (0.64 - 2.42 mg/L air)

Executive summary:

The study has been conducted in accordance with OECD 403 guideline Acute Inhalation toxicity.

Four groups, each of five male and five female Wistar rats, were treated with nebulized Octafluoroisobutyl Methyl Ether at concentration of ca. 20 mg/L air, ca. 2 mg/L air, ca. 0.5 mg/L air mg/kg, ca. 0.2 mg/L air.

Calculation of the saturation point of the test item, revealed that virtually all of the test atmosphere was a vapour at any of the atmosphere concentrations tested in the present study.

The following groups were treated and percentage of mortality was observed:

	Analytical Concentration	Mortality    (Both genders)	Mortality (Males Only)	Mortality (Females Only)
GROUP 1	0.178 mg/L air	0 %	0 %	0 %
GROUP 2	0.827 mg/L air	10 %	20 %	0 %
GROUP 3	2.197 mg/L air	100 %	100 %	100 %
GROUP 4	19.63 mg/L air	100 %	100 %	100 %

 

The no toxic effect level was set at 0.178 mg/L air, as there were no deaths, no clinical signs and no macroscopic pathology findings at this atmosphere concentration. One of ten animals died in Group 2 (0.827 mg/L air) and all animals died in Group 3 (2.197 mg/L air) and 4 (19.63 mg/L air). Clinical signs were only seen in decedent animals and comprised effects on breathing in Groups 2, 3 and 4, in addition to decreased spontaneous activity, ventral recumbency and ruffled fur in Group 3, and somnolence in Group 4. Mortality and clinical signs were attributed to treatment with the test item. Whether or not transient retardation in body weight gain or transient body weight losses in several male and female survivoers of Groups 1 and 2 were attributable to the treatment remained unclear. Necropsy revealed dark red or reddish discoloration of the lungs in the one decedent animal of Group 2 and all animals of Groups 3 and 4, in addition to an isolated grey white focus of 2 mm diameter in the lungs of the one affected animal of Group 2.A relationship of the finding of lung discoloration to treatment remained unclear. The single incidence of an isolated grey white focus was not attributed to the treatment. The was no indication of relevant sex-related differences in toxicity of the test item.

The LC50 of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane for acute inhalation toxicity (4h) in male and female rats observed for a period of 15 days was estimated to be:

LC50 = 1.06 mg/L air (0.64 - 2.42 mg/L air)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

1 060 mg/m³ air

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:

19 January 2005 to 1 March 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline-conform study under GLP without deviations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 (5 males and 5 females)

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality

No deaths occurred during the study.

Clinical / Local signs

Exophtlamus was noted in one male animal from test day 13 to the end of the observation period. No clinical signs were observed during the course of the study.

Body weights

The body weight of the animals was within the range commonly recorded for this strain and age.

Macroscopic findings

No macroscopic findings were observed at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of Octafluoroisobutyl methyl ether after single dermal administration to rats of both sexsx, observed over a period of 14 days is: LD50 (rat) > 2000 mg/kg bw.

Executive summary:

The study has been conducted in accordance with OECD 402 guideline - Acute Dermal toxicity.

Five males and females HanBri: WIST (SPF) rats were treated with Octafluoroisobutyl methyl ether at 2000 mg/kg bw by dermal application.

No deaths occurred during the study.

Exophtlamus was noted in one male animal from test day 13 to the end of the observation period. No clinical signs were observed during the course of the study in all other animals.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.

In conclusion the median lethal dose of Octafluoroisobutyl methyl ether after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat) greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

An oral toxicity study performed according to OECD guideline 423, a dermal toxicity study performed according to OECD guideline 402 and an inhalation toxicity study performed according to OECD 403 guideline are reported.

The median lethal dose of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane after single oral administration to female rats, observed over a period of 14 days is:

50 mg / kg bw < LD50 (female rats) < 300 mg /kg bw.

The LC50 of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane for acute inhalation toxicity (4h) in male and female rats observed for a period of 15 days was estimated to be:

LC50 = 1.06 mg/L air (0.64 - 2.42 mg/L air)

The median lethal dose of 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane ether after single dermal administration to rats of both sexes, observed over a period of 14 days is:

LD50 (rat) > 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Available study, conducted under GLP and according to recognized international standard guideline.

Justification for selection of acute toxicity – inhalation endpoint
Available study, conducted under GLP and according to recognized international standard guideline.

Justification for selection of acute toxicity – dermal endpoint
Available study, conducted under GLP and according to recognized international standard guideline.

Justification for classification or non-classification

 2-[difluoro(methoxy)methyl]-1,1,1,3,3,3-hexafluoropropane meets the GHS classification criteria both for acute oral and inhalation toxicity, therefore the substance, according to Regulation EC No. 1272/2008, is classified as following:

Acute oral toxicity Category 3

Acute Inhalation Toxicity Category 2.

The substance does not meet the classification criteria for Acute Dermal Toxicity.