Carbamic acid, N-butyl-, 2-propyn-1-yl ester

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: well documented GLP based study in accordance with EPA Guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: TSCA 40 CFR 798.1150

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-propynyl-butylcarbamate

EC Number:

616-291-8

Cas Number:

76114-73-3

Molecular formula:

C8H13NO2

IUPAC Name:

2-propynyl-butylcarbamate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): only common name based on sponsor informaion is given, equivalent to:
Chemical name: Carbarmic acid, N-butyl-,2-propyn-1-yl ester
CAS: 76114-73-3
- Physical state:Yellow liquid
- Analytical purity: no data available
- Impurities (identity and concentrations): no data available
- Lot/batch No.:no data available
- Storage condition of test material: The test article was stored at room temperature and humidity.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 2-8 weeks
- Weight at study initiation: 224-273 g (males), 212-253 g (females)
- Fasting period before study: no
- Housing: one animal per cage, suspended cages, bedding was place beneath the cages and changed at least three times/week
- Diet: Fresh Purina Rat Chow (Diet 5012) freely available except during four hour exposure period
- Water: freely available except during four hour exposure period
- Acclimation period: 1 week (quarantine period)

ENVIRONMENTAL CONDITIONS
in cages:
- Temperature: room temperature
- Photoperiod: 12 hour light/dark cycle

in inhalation chamber:
- Temperature (°C): 19 to 21°C
- Humidity (%): 32 to 60%
- Air changes (per hr): 10 to 15 (Airflow 25L/min)
- Photoperiod: 12 hour light/dark cycle
- Negative Pressure: 20 inches H2O

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: (= inhalation chamber): dynamic glass chamber
- Exposure chamber volume: 57 liter
- Method of holding animals in test chamber: chamber partitionated internally with wire screening into ten non-restraining cubicles with one animal per cubicle; after exposure animals were returned to individual housing
- air: 10 to 15 air changes per hr (Airflow 25L/min)
- System of generating particulates/aerosols: calibrated Havard Infusion Pump (Spraying Systems Model 1/8 JBC)
- Method of particle size determination: 8 stage Andersen cascade impactor
- Treatment of exhaust air: passed through filters before entering into rotameter and vaccuum pump
- Temperature (°C): 19 to 21°C
- Humidity (%): 32 to 60%
- Photoperiod: 12 hour light/dark cycle
- Negative Pressure: 20 inches H2O

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrical estimation (during exposure, chamber air was drawn over preweighed filters which were reweighted after exposure)
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass mean aerodynamic diameter):
0.52 mg/L test item: MMAD in-between 1.17 and 1.47 µm
0.71 mg/L test item: MMAD in-between 1.16 and 1.31 µm
2.2 mg/l test item: MMAD in-between 1.01 and 1.16 µm
-Fraction below 2.1µm (average from two measurements):
0.52 mg/L: 72.85%
0.71 mg/L: 80.6%
2.2 mg/L: 81.6%

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1. 0.52 mg/l Propargyl-N-butylcarbamat
2. 0.71 mg/l Propargyl-N-butylcarbamat
3. 0.52 mg/l Propargyl-N-butylcarbamat

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: Animals were observed at hourly intervals during exposure, at one hour post exposure and once daily thereafter for 14 days for toxicological and pharmacological effects. For mortality, animals were observed twice daily.
- Frequency of weighing: pretest, weekly, at death and at test termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The LC50 and 95% confidence limits were calculated by the method of Litchfield J.T.J & Wilcoxon F. (JPET 96:99).

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

> 0.71 - < 2.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 2

Sex:

female

Dose descriptor:

LC50

Effect level:

> 0.71 - < 2.2 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 3

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.8 mg/L air

Based on:

test mat.

95% CL:

0.94 - 3.5

Exp. duration:

4 h

Mortality:

The deaths occurred by day 2 after exposure and were preceded by physical signs.

Clinical signs:

other: lethargy, prostration, flaccid muscle tone, coma, ataxia, dyspnea, diarrhea, soiling and wetness of the anogenital area, fur coated with test article, wetness and red staining of nose/mouth area

Body weight:

Body weight loss was noted in some animals.

Gross pathology:

Abnormalities of the lungs,liver, kidneys, urinary bladder, eyes and gastrointestinal tract were found.

Other findings:

A brown staining of the nose/mouth area and wetness as well as soiling of the anogenital area were observed at dead individuals. Necrospsy results of surviving animals were generally normal. Darker than normal lungs were noted in some surviving animals exposed to 0.71 mg/L Carbamic acid.

Any other information on results incl. tables

Concentration [mg/l]	No. Exposed Animals (M/F)	No. Dead Animals (M/F)
0.52	5/5	0/0
0.71	5/5	1/0
2.2	5/5	2/4

Applicant's summary and conclusion

Interpretation of results:

other: see below.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Propargyl-N-butylcarbamat is classified as Acute toxicity Category 4, H332 according to EU CLP-criteria.

Executive summary:

The acute inhalation toxicity of Propargyl-N-butylcarbamat

was determined in rats according to the EPA guideline EPA OPP 81-3 (Acute inhalation toxicity). Three doses were tested. The test resulted in a LC50 value of 1.8 mg/L with 95% confidence limits of 0.94 to 3.5 mg/L.