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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-06-28 to 1999-7-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
May 1981
Deviations:
yes
Remarks:
: no detail on animals and environmental conditions. A 7 day observation period after the completion of exposure instead of 14 days.
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,2,2 trifluoroethanol (TFEA)
- Physical state: no data
- Lot/batch No.: 905033
- Expiration date of the lot/batch: no data
- Stability under test conditions: assumed to be stable during the test (sponsor responsibility)
- Storage condition of test material: no data
- Other:

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapor generator ; model GEL-1A, Shibata Scientific Technology LTD). The test substance was introduced from the top part of the inhalation chamber through a pre-filter and HEPA filter after mixing and dilution with the air inside the breathing chamber and then ejected normally from the lower part (one pass method). The concentration of the test substance was adjusted by changing the mix ratio of the test substance gas and the dilution air.
- Exposure chamber volume: 384L
- Method of holding animals in test chamber: no data
- Source and rate of air: Airflow, 100L/min
- Method of conditioning air: The ejected test substance was processed through an activated charcoal filter, diluted through a dilution tank and then released into the atmosphere.
- System of generating particulates/aerosols: no data
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: see details in table 7.2.2/1.

TEST ATMOSPHERE
- Brief description of analytical method used: Sampling of the animal-breathing chamber was taken and the concentration was measured by equipment analysis (see details in Table 7.2.2/2). Sampling was conducted using a sampling rate if approximately 1.0 L/min at 60 and 80 minutes from the start of exposure.
- Samples taken from breathing zone: yes

VEHICLE
No data

TEST ATMOSPHERE (if not tabulated)
Not applicable
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see Table 7.2.2/3
Duration of exposure:
4 h
Concentrations:
Low, Middle and high dose: 150; 450 and 1350 ppm (0.62; 1.87 and 5.6 mg/L)
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: the animals were observed for clinical signs and to see if death occured at 1, 2, 3, and 4 hours after exposure completion and then each day up to day 7. The animals are weighed at day 1, 3, 5 and 7.
- Necropsy of survivors performed: yes
Statistics:
no data

Results and discussion

Preliminary study:
not applicable
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
784 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: corresponding to 3.25 mg/L (1 ppm= 4.16 µg/mL)
Mortality:
yes - See details in Table 7.2.2/4.
Clinical signs:
other: At the low dose, no abnormalitie were detected in male and female rats. At the middle (males only) and the high doses (males and females) decreased spontaneous locomotion, decreased respiratory rate, ptosis, and staining around anus were observed.
Body weight:
At the middle dose, the animals survived at day 7 but they presented clinical signs of suffering.
The body weight gain at day 7 was less than for the animals exposed to the low dose.
See details in Table 7.2.2/5.
Gross pathology:
At the high dose, staining around nose and mouth (only for one female rat), pale kidney, dark reddish change of the lung, reddish region of mucosa of the glandular stomach and cecum were observed.
Other findings:
no other findings

Any other information on results incl. tables

Table 7.2.2/4: Mortality after an inhalation exposure for 4h

Sex

Exposure group

Mortality (Number of dead animals/Number of animals)

Time of death

LD50 (ppm)

Male

Low dose

0/5

-

784

Middle dose

0/5

-

High dose

5/5

Day 1 (4 rats), Day 2 (1 rat)

Female

Low dose

0/5

-

784

Middle dose

0/5

-

High dose

5/5

Day 1 (2 rats), Day 2 (3 rats)

 

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
With a 4h LC50 between 2 and 10 mg/L (vapour), under the test conditions, 2,2,2 Trifluoroethanol is classified in category 3 (Toxic if inhaled, H331) according to the criteria of Annex VI of the Regulation (EC) No 1272/2008.
Executive summary:

In an acute inhalation toxicity study, performed according to the OECD guideline No. 403 with acceptable restrictions, groups of Crj: CD (SD) male and female rats (5 animals/sex/dose) were exposed by inhalation route by whole body exposure to 2,2,2 Trifluoroethanol for 4 hours at concentrations of 0.62; 1.87; 5.6 mg/L (150, 450 and 1350 ppm).  Animals then were observed for 7 days. Clinical signs (at 1, 2, 3, 4 hours and each day after exposure completion), body weight (at day 0, 1, 3, 5, and 7) and gross pathology (at the sacrifice or death of animal) were observed.

 

LC50Males = 3.25 mg/L

      Females = 3.25 mg/L

At the middle (only for male rats) and high doses (for male and female rats), a decreased spontaneous locomotion, a decreased respiratory rate, ptosis, a staining around anus were observed. At the middle dose, the surviving animals presented clinical signs of suffering at day 7 and showed a body weight gains lower than those of the animals exposed to the low dose. At the high dose, a staining around nose and mouth (only for one female rat), a pale kidney, a dark reddish change of the lung, a reddish region of mucosa of the glandular stomach and cecum were observed.

Under the test conditions, 2,2,2 Trifluoroethanol is classified in category 3 (Toxic if inhaled, H331) according to the criteria of Annex VI of the Regulation (EC) No 1272/2008.

This study is considered as acceptable as the main criteria of the guideline are respected.