O-isopropyl ethylthiocarbamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

O-isopropyl ethylthiocarbamate

EC Number:

205-517-7

EC Name:

O-isopropyl ethylthiocarbamate

Cas Number:

141-98-0

Molecular formula:

C6H13NOS

IUPAC Name:

N-ethyl(propan-2-yloxy)carbothioamide

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): IPETC
- Physical state: liquid
- Stability under test conditions: stable
- Storage condition of test material: ambient

Test animals

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories,Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 163 - 209 g
- Fasting period before study: 16 hours
- Housing: kept individually in MAKROLON cages (type III plus)
- Diet (e.g. ad libitum): Commercial ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany; served as food ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 18-207 mg/ml
- Amount of vehicle (if gavage): 1,7-2,1 ml
- Lot/batch no. (if required): Batch no. 5135601; Henry Lamotte Oils GmbH, 28197 Bremen, Germany

MAXIMUM DOSE VOLUME APPLIED: 2,1 ml:

Doses:

181 mg/kg b.w.
568 mg/kg b.w.
1809 mg/kg b.w.
2067 mg/kg b.w.

No. of animals per sex per dose:

181 mg/kg b.w. : 5
568 mg/kg b.w. : 5
1809 mg/kg b.w. : 1
2067 mg/kg b.w. : 1

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration, thereafter daily. Weighing: recorded before administration of the test item and thereafter in weekly intervals up to the end of the study and at death . Changes in weight were calculated if survival exceeds one day.
- Necropsy of survivors performed: yes
- Other examinations performed: cDuring the follow-up period (two weeks), changes of skin and fur, eyes and mucous membranes, respiratory and circulatory function, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

The LD50 value and the confidence interval were calculated using the software “AOT425statpgm (Version: 1.0) . Acute Oral Toxicity (OECD Test Guideline 425) Statistical Programme (AOT 425 StatPgm). Version: 1.0, 2001. [http://www.oecd.org/chemicalsafety/testingofchemicals/¬section4software.htm]

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

568 mg/kg bw

Based on:

act. ingr.

95% CL:

> 256 - < 568

Effect levels 2

Key result

Sex:

female

Dose descriptor:

other: NOEL(No observed effect level)

Effect level:

< 181 mg/kg bw

Based on:

act. ingr.

Mortality:

181 mg/kg b.w. : None of 5 animals died during the 14 days obserservation period after administration
568 mg/kg b.w. 4 of 5 animals died within 24 hours after administration, 1 animal survived during the 14 days obserservation period after administration
1809 mg/kg b.w. 1 of 1 animal died within 24 hours after administration.
2067 mg/kg b.w. 1 of 1 animal died within 24 hours after administration.

Clinical signs:

other: Clinical signs, see "Remark"

Body weight:

other body weight observations

Remarks:

163-209 g

Gross pathology:

No signs or abnormalities were observed at necropsy. All surviving animals gained the expected body weight.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

based on EU GHS

Conclusions:

LD50 of test item : 568 mg/kg b.w., by oral administration

Executive summary:

An acute oral study in rats was performed according to OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure). Different number of rats in four dose groups were administered with the test substance in sesame oil as follows:  181 mg/kg bw. : 5 rats,   568 mg/kg bw. : 5 rats, 1809 mg/kg bw. : 1 rat, 2067 mg/kg bw. : 1 rat. Mortality was observed in the 568 (4/5), 1809 (1/1), 2067 (1/1) mg/kg bw dose groups. In the 181 mg/kg bw dose group ataxia, reduced muscle tone and dyspnoea in all 5 of 5 animals were observed. In gross pathology, no signs or abnormalities were observed. All surviving animals gained the expected body weight. Based on the study results a LD50 of 568 mg/kg bw of 568 mg/kg bw was determined. Consequently, the test substance is classified for acute oral toxicity Cat. 4, H302 according to Regulation (EC) No 1272/2008.