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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Annex V to Council Directive 67/548/EEC, published in the 17th adaptation, Commission Directive 92/69/EEC, OJ L383A 29.12.92 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
methyl (2E)-3-methoxy-2-[2-({[6-(trifluoromethyl)pyridin-2-yl]oxy}methyl)phenyl]acrylate
EC Number:
601-478-9
Cas Number:
117428-22-5
Molecular formula:
C18H16F3NO4
IUPAC Name:
methyl (2E)-3-methoxy-2-[2-({[6-(trifluoromethyl)pyridin-2-yl]oxy}methyl)phenyl]acrylate
Test material form:
solid
Details on test material:
- Purity: 98.8% w/w

Test animals

Species:
rat
Strain:
other: Alpk:APfSD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Rodent Breeding Unit, Alderley Park
- Age at study initiation: Young adult (8-12 weeks)
- Weight at study initiation: Males: 264-347 g; Females: 207-285 g
- Housing: The rats were housed 5 per cage, sexes separately, in multiple rat racks suitable for animals of this strain and weight range expected during the course of the study. The rats were transferred to clean cages and racks, as necessary, during the study.
- Diet: ad libitum (except during exposure)
- Water: ad libitum (except during exposure)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 30-70%
- Air changes: At least 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
clean air
Mass median aerodynamic diameter (MMAD):
>= 5.89 - <= 6.81 µm
Geometric standard deviation (GSD):
>= 1.73 - <= 3.65
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: PERSPEX expousre chamber
- Exposure chamber volume: 27.6 L
- Method of holding animals in test chamber: Nose-only exposure in restraining tubes
- Source and rate of air: Clean, dry air (dried and filtered using equipment supplied by Atlas-COPCO, Sweden) was passed at a nominal flow rate of 25 L/minute
- System of generating particulates/aerosols: PALAS rotating brush generator (RBG)
- Method of particle size determination: Marple cascade impactor
- Temperature, relative humidity in air chamber: 18.6-19.7°C, 2.0-11.0%, respectively

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.26 mg/L (5.96 µm/2.65 and 6.31 µm/2.81); 2.22 mg/L (6.81 µm/2.57 and 6.27 µm/3.65); 4.64 mg/L (6.21 µm/3.20 and 5.89 µm/1.73)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentrations: 1.0, 2.0, 5.0 mg/L (1.26 ± 0.18, 2.22 ± 0.49, 4.64 ± 0.80 mg/L)
Analyzed concentrations: 1.23, 2.12, 4.59 mg/L
Particulate concentrations: 1.26, 2.22, 4.64 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 and weighing: During exposure, rats were observed for clinical signs frequently and at the end of the 4-hour exposure period. Each rat was given a detailed clinical examination. The body weight of each rat was recorded on day -1 (to ensure animals of one sex were within a similar weight range), 1, 8, and prior to termination on day 15.
- Necropsy: All rats were killed by exsanguination under terminal anaesthesia. All animals were subjected to an examination post mortem. This involved an external observation and a careful examination of all thoracic and abdominal viscera, brain and cranial cavity.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LC50
Effect level:
3.19 mg/L air
Based on:
test mat.
Remarks:
particle size 5.9-6.8 μm MMAD
Exp. duration:
4 h
Key result
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2.12 - < 4.59 mg/L air
Based on:
test mat.
Remarks:
particle size 5.9-6.8 μm MMAD
Exp. duration:
4 h
Mortality:
There were no deaths in animals in the 1.23 mg/L group during the exposure or observation periods. One female rat in the 2.12 mg/L group, three male and four female rats in the 4.59 mg/L group died during the exposure period. The remaining animals survived until scheduled termination.
Clinical signs:
other: During exposure: Abnormalities generally associated with restraint (wetness, staining around the snout ) were seen in all groups. Test substance around the snout was also seen in all groups and is a common occurrence in studies involving nose only exposur
Body weight:
All surviving animals, with the exception of one 1.23 mg/L female and the one remaining 4.59 mg/L female, had gained weight by day 8. All had gained weight by day 15, with the exception of the remaining 4.59 mg/L female.
Gross pathology:
In the intercurrent animals exposed to the highest concentration (4.59 mg/L), 3 out of 4 female animals, and all male animals had dark liver, which is indicative of typical post mortem changes. In addition, 2 male animals had mottled lungs though it is unclear whether this effect is related to treatment.

There were no gross findings at terminal necropsy related to treatment.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The median lethal concentration was 3.19 mg/L for female rats and >2.12 but <4.59 mg/L for male rats.
Executive summary:

Groups of five male and five female rats were exposed nose-only for a single four-hour period to aerosolized test substance at target concentrations of 1, 2 or 5 mg/L. Test atmospheres were analyzed for particulate concentration and test substance. The particle size distribution of each test atmosphere was analyzed at least twice during the exposure period. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and bodyweights were recorded and at the end of the scheduled period, the animals were killed and subjected to an examination post mortem.

A number of deaths occurred during exposure (1 female rat at 2.12 mg/L; 3 male rats and 4 female rats at 4.59 mg/L). Clinical signs indicative of toxicity were seen in the remaining animals at these concentrations, from which the surviving animals had made a complete recovery by the end of the study.

The median lethal concentration was 3.19 mg/L for female rats and in excess of 2.12 mg/L for male rats.

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