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Administrative data

Description of key information

The substance is a gas, therefore acute toxicity studies by dermal and oral route are not feasible.
The LC50 (4h, rat) value for acute toxicity by inhalation was found to be between 10000 and 15000 ppm.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is not GLP, it is equivalent to OECD guideline 403, however a definitive LC50 value has been derived and the concentrations tested are much higher than that tested in the supporting study (1988) which may be the reason for toxic effects observed.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: ChR-CD
Sex:
male
Route of administration:
inhalation: gas
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
A measured flow of the test gas and air were allowed to mix in a copper coil and flow into an 8-liter bell jar containing four ChR-CD male rats of initial body weight 250-304 grams.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
nominal concentration: 20000, 15000, 10000, 5000, 2500ppm
No. of animals per sex per dose:
4 male ChR-CD male rats were used.
Control animals:
no
Statistics:
no data
Sex:
male
Dose descriptor:
other: (approximate lethal concentration)ALC
Effect level:
10 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
10 000 - 15 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
At 20000 and 15000 ppm, mortality ratio is 4/4; at 10000 ppm, the ratio is 1/4; at 5000 and 2500ppm, the ratio is 0/4.
Clinical signs:
other: Lethal concentrations (20000, 15000, 10000 ppm) > mild polypnea followed by dyspnea with pumping respiration, inactivity, bloody discharge around nose and mouth, ruffled fur, unresponsiveness and lacrimation. Following exposure to lethal concentrations >
Body weight:
At lethal concentrations, animals showed large initial weight losses. Rats surviving lethal concentrations showed weight losses 2-6 days after exposure, but appeared normal thereafter. Animals exposed to sublethal concentrations showed larges initial weight losses 1-4 days after exposure at 5000 ppm. No weight loss was observed at the lowest concentration.
Gross pathology:
All rats that died had massive pulmonary edema and congestion. This was the probable cause of death. No other histological effects due to the exposures were observed in any of the survivors or in any of the other tissues examined. No liver weights were available.
Other findings:
no data

See results attached to the field "Attached background material".

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The perfluoromethyl ether used for studies is a pulmonary irritant with an approximate lethal concentration (ALC) of 10000 ppm(67893 mg/m3).
Executive summary:

Four male rats were used to investigate the acute inhalation toxicity of the test substance. The animals were exposed at five concentrations (20000, 15000, 10000, 5000, 2500 ppm) for 4 hour. During exposure, adverse clinical signs were observed. After exposure, the rats showed no clinical signs of toxicity. All rats that died showed massive pulmonary edema and congestion. Weight losses were observed at test concentrations except the lowest concentration. The approximate lethal concentration(ALC) of the test gas is 10000 ppm, which can be considered as a LOAEC. According to the test result, the LC50 can be deduced to be greater than 10000 ppm but lower than 15000 ppm. Test item can be classified as acute toxicity category 4 (via inhalation) according to CLP (Regulation EC No.1272/2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
67 901.84 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

As the test substance is a gas at room temperature, the test is not technically feasible through oral and dermal routes.

Detailed data through the inhalation route is available. A GLP test (Elphinstone Research Centre of IRI, 1988) following OECD guideline 403 showed that no evidence of toxicity was observed following a 4h exposure to air containing > 20mg/L (ca. 2954 ppmV) of the test substance but the definitive LC50 value was not derived as the only concentration tested is not enough high to show toxic effects.

Another study indicated that the test substance is a pulmonary irritant with an approximate lethal concentration of 10000 ppm. In this study mortalities were observed at doses of 10000, 15000 and 20000 ppm. The LC50 is observed to be between 10000 and 15000 ppm. Breathing difficulties were observed at lethal and sub-lethal concentrations exposure. At pathology examination, all rats that died following exposure to lethal concentrations had massive and pulmonary edema and congestion and this was stated as the probable cause of the death since no other histological effects due to the exposure to PMVE were observed in any of other tissues.


Justification for selection of acute toxicity – oral endpoint
In accordance with section 1 of REACH (Regulation (EC) No 1907/2006) Annex XI the acute oral toxicity study (required in section 8.5.1 Annex VII) does not need to be conducted as the test substance is a gas at the room temperature. In addition according to column 2 of Annex VIII (section 8.5) if there is only one route of exposure, information for only that route need be provided. The only route of exposure is inhalation.

Justification for selection of acute toxicity – inhalation endpoint
The study is not GLP but it is equivalent to an OECD guideline 403 study and the tested concentrations allow the identification of a LC50 value.
(10000 ppm > LC50 >15000 ppm) corresponding to (67901.84 mg/m3 > LC50 > 101852.76 mg/m3).

Justification for selection of acute toxicity – dermal endpoint
In accordance with section 1 of REACH (Regulation (EC) No 1907/2006) Annex XI the acute dermal toxicity study (required in section 8.5.3 Annex VIII) does not need to be conducted as the test substance is a gas at the room temperature. In addition according to column 2 of Annex VIII (section 8.5) if there is only one route of exposure, information for only that route need be provided. The only route of exposure is inhalation.

Justification for classification or non-classification

PMVE is classified as Acute Toxicity by Inhalation Category 4 based on the (LC50 > 10000 ppm, <15000 ppm) (Report HLR-28-65).

Since the local effects on the respiratory system have been defined as the probable cause of lethality and considering that effects of respiratory irritation have been observed only at concentrations close or equal to the lethal levels, the hazard category STOT SE 3 for Respiratory Tract Irritation is not applicable.

In fact, STOT SE 3 covers “transient effects” occurring after single exposure. According to CLP classification criteria, the hazard category STOT SE 3 for Respiratory Tract Irritation would occur only when more severe organ effects in the respiratory system are not observed (CLP Regulation, Annex I, Point (e) Paragraph 3.8.2.2.1.).