Carbamic acid, N-[(butylthio)thioxomethyl]-, butyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 July 2013 - 18 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Also in accordance to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

butyl N-[(butylsulfanyl)methanethioyl]carbamate

EC Number:

691-061-8

Cas Number:

1001320-38-2

Molecular formula:

C10H19NO2S2

IUPAC Name:

butyl N-[(butylsulfanyl)methanethioyl]carbamate

Test material form:

solid

Remarks:

yellow grease-like solid

Specific details on test material used for the study:

Molecular formula: C10H19NO2S2
Name: n-butoxycarbonyl n-butyl dithiocarbamate (active ingredient)
CAS Number: 1001320-38-2

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 150 - 169 g
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Fasting period before study: overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. The test substance was melted for a maximum of approximately 3 hours at a maximum temperature of 26ºC. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and the test substance. No correction was made for purity of the test substance.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Piloerection and lethargy were seen for most animals on Day 1. Piloerection, hunched posture and chromodacryorrhoea (snout) were seen at a lower frequency on Days 2-4. The animals recovered from the symptoms between Days 2 and 4.

Gross pathology:

No abnormalities were found at the macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD 423 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined for the test material.

Executive summary:

The test material was tested in an acute oral toxicity study with female rats, performed according to OECD 423 guideline and GLP principles. The substance was administered via gavage at 2000 mg/kg bw.

No mortality occurred. Piloerection and lethargy were seen for most animals on Day 1. Piloerection, hunched posture and chromodacryorrhoea (snout) were seen at a lower frequency on Days 2-4. The animals recovered from the symptoms between Days 2 and 4. Body weight gain was considered to be normal. No abnormalities were found at the macroscopic post mortem examination.

The LD50 was established to be >2000 mg/kg bodyweight.