O-isobutyl ethylthiocarbamate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

other: published data

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1994

Reference 2

Reference Type:

publication

Title:

Final Report of acute neurotoxicity study of isobutanol in sprague-dawley rats

Author:

EPA

Year:

1995

Bibliographic source:

TSCATS/OTS0556315

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 40 CFR 799 Multi-Substance Rule for the Testing of Neurotoxicity; 40 CFR Part 798.1150 Inhalation Test Guidelines; Test Guidelines 798.6050 & 798.6200 updated by Neurotoxicity Guideline 81-8, Subdivision F

Principles of method if other than guideline:

Male and female rats (10/sex) were exposed by inhalation for 6 hours to a vapor of isobutanol at 0, 1500, 3000 and 6000 ppm. The animals were observed for 14 days.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-methylpropan-1-ol

EC Number:

201-148-0

EC Name:

2-methylpropan-1-ol

Cas Number:

78-83-1

Molecular formula:

C4H10O

IUPAC Name:

2-methylpropan-1-ol

Test material form:

aerosol dispenser: not specified

Details on test material:

- Name of test material (as cited in study report): Isobutanol
- Physical state: liquid- Analytical purity: > 99.9 %

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Raleigh, NC, USA
- Age at study initiation: 8 weeks
- Weight at study initiation: males: 288-388 g; females: 187-290 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24 °C
- Humidity (%): 40-60 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Exposure Chambers: Four 2000-liter stainless steel and glass Hazelton H-2000 chambers
- Animal Housing during Exposure: Individual stainless steel wire mesh cages, positioned in one tier in the chamber
Exposure Duration: 6 hours
- Test Atmosphere Generation System: Test material was fed into a Laskin-type nebulizer mounted in a filtered supply air inlet at top of the inhalation chamber. Exposure concentrations were controlled by using an adjustable-flow valveless pump to regulate the
rate at which isobutanol was delivered to the nebulizer.
- Test Atmosphere Sampling Method: Six test atmosphere samples were drawn through a Miran 1A infrared detector calibrated for isobutanol.
Sampling Location: In the animal breathing area from a port halfway down on the chamber door
- Chamber Atmosphere Distributions: Chamber atmospheres were sampled in 2 different locations for all 3 exposure concentrations.
- Gas Chromatography Analysis: Samples of the chamber atmospheres were collected in two impingers, in series, containing methanol. The solutions were analyzed for isobutanol content using gas chromatography with a flame ionization detector.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

0, 1500, 3000, 6000 ppm (0, 4.54, 9.09, 18.18 mg/m3)

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Checks for mortality and moribundity and noteworthy signs of toxicity were made daily from the day of randomization until the day of sacrifice; weighing: day 0, day 7 and day 14
.- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

A two-way ANCOVA and Duncan’s multiple comparison test was used to determine statistical significance. The FOB evaluation was similar to methods published by Mosher (1991).

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 18 180 mg/m³ air

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: Decreases in motor activity were noted post-exposure in the 6000 ppm (18,18 0 mg/m3 )

Mortality:

1/10 male animals died at 6000 ppm. This death was attributed to an ophthalmic examination where atropine drops were applied to its eyes.All other animals survived.

Clinical signs:

other: during exposure: There was clear evidence of generalized depression of the central nervous system (animals were non-responsive to tapping on side of inhalation chambers) and labored respiration in rats during the 6 hours of exposure to 6000 and 3000 ppm o

Body weight:

Body weights of male rats in the 3000 and 6000 ppm groups were significantly lower than the male controls throughout the study. These statistically significant results are due to pretest differences and not because of exposure to the chemical.

Gross pathology:

There were no treatment-related lesions or other gross changes in the tissues and organs examined during necropsy. Enlarged, dilated, distended uteri were observed at necropsy in the low, mid, and high groups at incidences of 3/10, 1/10, and 1/10, respectively. This finding was not observed in the control group. The severity was minimal in all instances. This is a common observation and usually reflects physiologic changes related to the estrus cycle. This is further substantiated by the inverse dose response. Therefore, although histologic examination was not conducted, it appears that these observations are unassociated with treatment and reflect the normal variation expected with different stages of the estrus cycle.

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Inhalation LC50 values for vapor exposures were >6,000 ppm (18180 mg/m3) in male and female rats.Decreases in motor activity were noted post-exposure in the 6000 ppm (1818 0 mg/m3 ) groups but not the 3000 or 1500 ppm (9090 or 4550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14-day time points. No exposure-related effects were noted in the FOB assessment.
Isobutyl alcohol is reagents used in the manufacture of O-isobutyl ethylthiocarbamate (IBETC). Therefore, the health effects of Isobutyl alcohol need to be considered in the assessment of O-isobutyl ethylthiocarbamate (IBETC) .

Executive summary:

Male and female rats exposed to atmospheric vapor levels of 0, 1500, 3000, or 6000 ppm (0, 4550, 9090, 18180 mg/m3) for six hours were evaluated in a neurobehavioral battery (motor activity determination and a functional observational battery) within two hours post-exposure. Hypoactivity and diminished response to a startle reflex (during the inhalation exposure) was observed during exposure for the 3000 and 6000 ppm (9090 and 18180 mg/m3) exposures. Decreases in motor activity were noted post-exposure in the 6000 ppm (1818 0 mg/m3 ) groups but not the 3000 or 1500 ppm (9090 or 4550 mg/m3 )groups. No effect on motor activity was detected at the 7 and 14-day time points. No exposure-related effects were noted in the FOB assessment. Inhalation LC50 values for vapor exposures were >6,000 ppm (18180 mg/m3) in male and female rats.