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Toxicological information

Acute Toxicity: inhalation

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Administrative data

acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 403 (Acute Inhalation Toxicity)
according to guideline
EPA OPP 81-3 (Acute inhalation toxicity)
according to guideline
other: MAFF Testing Guideline for Acute Inhalation Toxicity Study (59 NohSan No. 4200)
GLP compliance:
Test type:
acute toxic class method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
(E)-[1-(methylsulfanyl)ethylidene]amino N-methylcarbamate
Test material form:
solid: crystalline
Specific details on test material used for the study:
- Substance name: Ethanimidothioic acid,N-[[(methylamino)carbonyl]oxy]-, methyl ester
- Substance ID: DPX-X1179
- Lot#: X1179-427
- Purity: 97.7%

Test animals

other: Crl:CD BR
Details on test animals or test system and environmental conditions:
- Source: Charles River Breeding Laboratories, Kingston, New York
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: Males: 223 to 272 grams; Females: 183 to 219 grams
- Fasting period before study: Not specified
- Housing: Rats were housed either singly or in pairs (sexes separate) in 8" x 14" x 8" suspended, stainless steel, wire-mesh cages.
- Diet: Purina Certified Rodent Chow # 5002 ad libitum
- Water: Tap water ad libitum
- Acclimation period: 6 days

- Temperature: 23 ± 2°C
- Humidity: 50 ± 10%
- Photoperiod: 12 hrs dark / hrs light

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
other: Distilled water
Mass median aerodynamic diameter (MMAD):
>= 1.3 - <= 3.8 µm
Geometric standard deviation (GSD):
>= 2.3 - <= 2.9
Details on inhalation exposure:
- Exposure apparatus: An atmosphere of test substance was generated by suspending the solid in distilled water at a concentration of 3% and generating an aerosol using an Airlife Solo-Sphere nebulizer.
- Exposure chamber volume: 29-L
- Method of holding animals in test chamber: During exposure, rats were restrained in perforated, polycarbonate cylinders with conical nose pieces. The restrainers were inserted into the face plate of a 29-L, cylindrical, glass exposure chamber so that only the nose of each rat protruded into the chamber.
- Source and rate of air: Pressurized air introduced at the Solo-Sphere (7.8-12 L/min) atomized the test material and swept the resulting aerosol into the 29-L, cylindrical, glass exposure chamber. Filtered dilution air was introduced into the chamber at rates of 4.5-13 L/min.
- System of generating aerosols: Using Airlife Solo-sphere nebulizer
- Method of particle size determination: Gravimetric analysis
- Treatment of exhaust air: The chamber atmosphere was exhausted through a glass bubbler filled with water and an MSA particulate filter prior to being discharged in to the fume hood.
- Temperature, humidity, pressure in air chamber: Airflow during the exposures ranged from 14.4-22.4 L/min. Chamber temperatures ranged from 21 to 25°C, relative humidity ranged from 70% to 100%, and the oxygen concentration was 21%.

- Brief description of analytical method used: Chromatographic analyses of the gravimetric filters from exposures are used for measuring mean total analyrtical concentration.
- Samples taken from breathing zone: yes. The atmospheric concentration of test substance was determined at approximately 30-minute intervals during each exposure using gravimetric
analysis. Four to 10 litre samples of chamber atmosperes were drawn from breathing zone of the rats through a 25 mm filter cassette that contained a preweighed Gelman glass fiber (Type A/E) filter. Cahn Model C-31 Microbalance and then placed in a dessicator. Concentration of test subatnce was calculated from the difference in the preand post-sampling dry filter weights.

- Particle size distribution: Chamber test atmospheres consisted of 6.2 to 40% of the particles less than 1 µm, 38 to 84% less than 3 µm, and 85 to 99% less than 10 µm.
- MMAD (Mass median aerodynamic diameter) and Geometric standard deviation: 1.3 to 3.8µm and GSD ranged from 2.3 to 2.9
Analytical verification of test atmosphere concentrations:
The mean analytical concentrations of test substance were 0.126, 0.160, 0.179, 0.215, and 0.304 mg/L for 0.137, 0,181, 0.182, 0.232, and 0.326, respectively.
Duration of exposure:
4 h
0.137, 0.181, 0.182, 0.232, and 0.326 mg/L
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were weighed and observed for clinical signs of toxicity daily, excluding test Days 5, 11, and 12 for the 0.137 mg/L group, test Days 4, 10, and 11 for the 0.181 mg/L group, test Days 6, 7, 13, and 14 for the 0.182 mg/L group, test Days 4 , 5, 11, and 12 for the 0.232 group, and test Days 6, 7, 13, and 14 for the 0.326 mg/L group.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
0.258 mg/L air
Based on:
test mat.
Exp. duration:
4 h
No rats died that were exposed to concentrations of 0.137 or 0.181 mg/L. In other exposures, 1 of 10 rats died at 0.182 mg/L, 6 of 10 rats died at 0.232 mg/L, and 7 of 10 rats died at 0.326 mg/L. All rats that died did so during the exposures. There was no difference between the response of the male and female rats based on mortality.
Clinical signs:
other: Clinical signs of toxicity assessed during the exposure included nasal discharge and salivation. Nasal movement was assessed to determine mortality of the rats. Upon removal of the rats from the restrainers immediately following exposure, the clinical sig
Body weight:
By the first day post exposure, most of the rats exhibited weight loss. Rats began gaining weight by the second day of recovery and despite some transient weight losses experienced an overall gain by the end of recovery.
Gross pathology:
All exposed rats were sacrificed and subjected to a gross pathological examination 14 days after exposure. Gross abnormalities found in rats which were found dead included expanded lungs and edema of the pleural cavity. These abnormalities are considered to be associated with stress resulting from systemic toxicity. Gross observations included small bilateral testes and seminal vesicles in 1 male rat and a unilateral dilatation of the renal pelvis in another male rat. These findings were considered to be incidental. No target organ was identified in these rats.

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
LC50 Rat (Male/Female): 0.258 mg/L
Executive summary:

The study was conducted according to test guideline OECD 403 and US EPA 81-3 to determine the acute inhalation toxicity of test substance in rats. Five groups of 5 male and 5 female CRL:CD BR rats each were exposed to an atmosphere of test substance for a single, 4-hour exposure period. The test atmosphere was generated by suspending the test material in distilled water and aerosolizing the mixture. During the exposure, the concentration of the test aerosol was determined by gravimetric analysis A subsequent liquid chromatographic analysis of the eluent from the desorption of select gravimetric filters was carried out to determine the amount of test substance collected. In the pursuant 14-day recovery period, rats were weighed and observed for clinical signs of toxicity. All rats underwent gross pathological examination at the end of the recovery period.

Rats were exposed to dry weight concentrations of 0.137, 0.181, 0.182, 0.232, and 0.326 mg/L of test substance. Total particulate was determined to be homogeneously distributed in the exposure chamber. The test aerosol during the exposure was characterized by measurement of a mass median aerodynamic diameter (MMAD). The MMAD of the aerosols generated ranged from 1.3 to 3.8 µm with 6.2 to 40% of the particles being less than 1 µm and 38 to 84% of the particles being less than 3 µm.

1 of 10 rats exposed to test substance died following exposure at 0.182 mg/L. 6 of 10 rats exposed at 0.232 mg/L died and 7 of 10 rats died following exposure at 0.326 mg/L. All rats exposed to test substance at 0.137 or 0.181 mg/L survived exposure and pursuant recovery period.

Clinical signs of toxicity observed immediately following exposures included diarrhea, lethargy, and ocular or nasal discharge. Rats surviving exposures at levels which produced mortality also showed signs of abnormal gait or mobility, low posture, tremors, hyperactivity, hyperreactivity, and muscle fasciculations. These clinical signs were transient and were absent on the day following their initial observation. These clinical signs are consistent clinical signs commonly observed in materials from the family of methyl carbamate insecticides. Wet fur, a common sign associated with the restrainers used for nose-only exposure, was noted in most of the rats immediately following the exposure. Other clinical signs observed during the recovery period included stained and/or ruffled fur, diarrhea, hunched posture, ocular and/or nasal discharge, irregular respiration, and lethargy. Corneal opacity was noted in one animal exposed to 0.232 mg/L of test substance. Rats that survived exposures experienced some weight loss immediately following exposure and some transient weight loss later in the recovery, but all rats showed an overall weight gain by the end of the 14-day recovery period. Gross pathological examination revealed no evidence of organ-specific toxicity in any rats.

Under the conditions of this test, the LC50, for test substance was 0.258 mg/L. On an acute inhalation basis, test substance was considered to have moderate toxicity (LC50, between 0.2 mg/L and 0.8 mg/L).