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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1995-01-31 to 1995-03-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
December 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted May 1981
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,2,2-trifluoroethyl methacrylate
EC Number:
206-525-3
EC Name:
2,2,2-trifluoroethyl methacrylate
Cas Number:
352-87-4
Molecular formula:
C6H7F3O2
IUPAC Name:
2,2,2-trifluoroethyl 2-methylprop-2-enoate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Trifluoroethyl Methacrylate (Matrife)

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males: app. 7 weeks, females: app. 10 weeks
- Weight at study initiation: males: 205 to 234 g, females: 206 to 239 g
- Fasting period before study: no
- Housing: in groups of 5 by sex in stainless steel cages
- Diet (e.g. ad libitum): complete pelleted rodent diet ad libitum (except exposure period of 4 h)
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 40-70%
- Air changes (per hr): at least 12/h
- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

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: 30 cm diameter aluminium alloy cylinder
- Exposure chamber volume: 60 L
- Method of holding animals in test chamber: each rat was placed in an individual polycarbonate restraining tube; the tube was attached to the chamber so that only the snout protruded into the chamber
- Source and rate of air: dry, oil-free compressed air 12 L/min; additional air was drawn passively from the room environment at a flow rate of 2.8 L/min
- System of generating particulates/aerosols: glass concentric jet atomiser
- Method of particle size determination: not performed
- Treatment of exhaust air: drawn from the base of the chamber (rate: 14.8 L/min) and vented to atmosphere after first passing through a filtration system
- Temperature, humidity in air chamber: mean temperature 20.8-22.6°C; mean humidity 34-46%

TEST ATMOSPHERE
The concentration of test material in the chamber was determined analytically for five samples taken during each main study exposure: samples were taken at flow rate of approximately 2.0 L/min, sample volume was measured using a wet type gas meter; analysis by gas chromatography
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
nominal (achieved) concentrations
males: 21.9 (21.1), 4.94 (4.54), 2.45 (2.42), 3.48 (3.20), 3.18 (2.95) mg/L
females: 21.9 (21.1), 4.94 (4.54), 9.77 (9.97), 7.06 (6.65), 8.08 (7.90) mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: immediately before exposure, 15, 30 min following the start of the exposure, 30 min intervals during exposure; 30 min intervals during the first two hours after exposure; subsequently twice daily for 14 d
- Frequency of weighing: daily
- Necropsy of survivors performed: yes
- Other examinations performed: organ weights (lungs with bronchi and trachea, liver, kidneys); samples from larynx, lungs with bronchi and trachea, liver, kidneys and tissues with macroscopic abnormalities taken for histopathology
Statistics:
log probit method

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
2.7 mg/L air (nominal)
Based on:
act. ingr.
95% CL:
>= 1.99 - <= 3.4
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
7.19 mg/L air (nominal)
Based on:
act. ingr.
95% CL:
>= 6.24 - <= 8.14
Exp. duration:
4 h
Mortality:
- 21.1 mg/L: 5/5 males and 5/5 females died between day 1 and 4
- 9.97 mg/L: 5/5 females died between day 1 and 3
- 7.90 mg/L: 3/5 females died between day 2 and 5
- 6.65 mg/L: 2/5 females died between day 2 and 5
- 4.54 mg/L: 4/5 males died between day 1 and 2
- 3.20 mg/L: 5/5 males were found dead on the morning following exposure
- 2.95 mg/L: 3/5 males were found dead on the morning following exposure
- 2.42 mg/L: 1/5 males was found dead on the morning following exposure
Clinical signs:
other: During exposure: - reduced respiratory rate in all animals - incidential findings: struggling in the restraint tube, exaggerated respiratory movements, increased respiratory rate During observation period: - 21.1 mg/L (males and females), 7.90 mg/L (fem
Body weight:
- 2.42 and 2.95 mg/L (males): loss in bodyweight on the day after treatment, reduced body weight gain for several days
- 4.54 mg/L (male): loss in bodyweight up to day 3 after treatment, reduced body weight gain during observation period
- 4.54 mg/L (females): loss in body weight on the day following exposure, normal body weight gain after day 2
- 7.90 and 9.97 mg/L (females): loss in body weight for two days following exposure, recovery to the pretreatment bodyweight took between six and ten days
Gross pathology:
- a number of observations recorded for animals that died prematurely but, in the absence of any concentration-relationship, all of them were attributed to post mortem change or were among common findings for control animals
- no treatment-related findings for animals that were killed after 14 days of post exposure observation
Other findings:
- relative lung, liver and kidney weights in animals that died prematurely were slightly higher then expected
- in surviving animals no clear evidence of any residual effect upon lung weight was noted; liver and kidney weights were unaffected

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
The 4 h LC50 of TFMEA in rats was 2.7 mg/L (95% C.I. 1.99 - 3.4 mg/L) in males and 7.19 mg/L (95% C.I. 6.24 - 8.14 mg/L) in females
Executive summary:

In an acute inhalation toxicity study according to OECD Guideline 403, adopted May 1981 and EU method B.2, December 1992, 5 male and 5 female young adult CD rats were exposed by inhalation route to vapourised TFMEA (94.94% a.i.) for 4 hours to nose only at nominal (analytical) chamber concentrations of 21.9 (21.1), 4.94 (4.54), 2.45 (2.42), 3.48 (3.20), 3.18 (2.95) mg/L (males) and 21.9 (21.1), 4.94 (4.54), 9.77 (9.97), 7.06 (6.65), 8.08 (7.90) mg/L (females). Animals then were observed for 14 days.

At 2.42, 2.95, 3.20, 4.54 and 21.1 mg/L 1/5, 3/5, 5/5, 4/5 and 5/5 males died, respectively.

At 6.65, 7.9, 9.97 and 21.1 mg/L 2/5, 3/5, 5/5 and 5/5 females died respectively.

 

During the exposure period all animals showed a reduced respiratory rate; incidential findings were: struggling in the restraint tube, exaggerated respiratory movements, increased respiratory rate.

During the observation period staggering, gait, piloerection, flaccid musculature, poor coordination, hunched posture, hypoactivity, eyes closed, ocular discharge, hypothermia, blanching were observed in males and females of the 21.1 mg/L group and in females of the 9.97 and 7.9 mg/L groups.

The other treatment groups showed poorly groomed appearance and hypoactivity.

 

Additional clinical signs in animals that died during the observation period were: fascicular or whole body tremors, unconsciousness, lethargy, prone posture, rales, irregular respiratory movements, exaggerated respiratory movements, cyanosis, gasping, pigmented staining on the snout, salivation, eyes closed, hypothermia, diarrhoea, thin appearance.

 

Occasional incidences of hunched posture, tremors, staggering gait, lethargy, prone posture, rales, irregular respiratory movements, exaggerated respiratory movements, pigmented staining on the snout, salivation, closed eyes were also observed in the surviving animals. However, survivors had recovered within 3 to 6 days.

 

Reduced on body weight gain was observed in all treatment groups. The females of the 4.54 mg/L group showed normal body weigh gain after day 2.

 

At necropsy a number of observations were recorded for the animals that died prematurely, but, in the absence of any concentration-relationship, all of them were attributed to post mortem change or were among common findings for laboratory animals. No treatment-related findings were recorded for animals that were killed after 14 days of post exposure observation.

 

In animals that died prematurely relative lung, liver and kidney weights were slightly higher then expected. In the surviving animals no clear evidence of any residual effect upon lung weight was noted; liver and kidney weights were unaffected.

4 h LC50 (males) = 2.7 mg/L (95% C.I. 1.99 - 3.4 mg/L)

4 h LC50 (females) = 7.19 mg/L (95% C.I. 6.24 - 8.14 mg/L)