O-isopropyl ethylthiocarbamate

Endpoint summary

Description of key information

Acute tox oral: OECD 425; Crl: CD(SD)rats; LD50 568 mg/kg bw

Acute toxicity inhalation: rats; 4h; LC50 20 mg/L air

 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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]

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

568 mg/kg bw

Based on:

act. ingr.

95% CL:

> 256 - < 568

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

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.   

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

568 mg/kg bw

Quality of whole database:

Robust guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Based on a Safety Data Sheet

Species:

rat

Route of administration:

inhalation

Duration of exposure:

4 h

Sex:

not specified

Dose descriptor:

LC50

Effect level:

20 mg/L air

Based on:

not specified

Interpretation of results:

study cannot be used for classification

Conclusions:

4-hour inhalation (Rat) LC50: 20 mg/L

Executive summary:

A LC50 (rat- 4-hour inhalation) value of 20 mg/L  was indicated in a test substance safety data sheet. Due to lack of study data (reliability), the value is not considered for substance classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

20 000 mg/m³ air

Quality of whole database:

Unknown, data from published sds

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Material Safety Data Sheet

Species:

rabbit

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mL/kg bw

Interpretation of results:

not classified

Conclusions:

Acute dermal toxicity (Rabbit) LD50: >2000 mg/kg

Executive summary:

A LD50 (rabbit) value of > 2000 mg/kg bw was indicated in a test substance safety data sheet. Due to lack of any study data (reliability), the value is not considered for substance classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Unknown, data from published sds

Additional information

Acute toxicity – oral endpoint
One GLP OECD study available for oral toxicity (key, LD50= 568 mg/kg bw). Three other LD50/ LC50 values for oral. inhalation and dermal toxicity found in publicly available material (published safety data sheets), had no further information on test methods etc. Performance of acute inhalation and dermal toxicity studies were waived.

Acute toxicity – inhalation endpoint
Only data value available, reliability is unknown. Performance of an acute inhalation study was waived.  

Acute toxicity – dermal endpoint
Only data value available, reliability is unknown. Performance of an acute dermal study was waived.  

Justification for classification or non-classification

An GLP OECD oral toxicity study performed with the registered substance showed an LD50 of 568 mg/kg bw, which falls within the classification criteria for classification as Acute Oral Toxicity Category 4, according to Regulation (EC) No 1278/2008 (CLP).