Propanamide, N-(aminothioxomethyl)-2-methyl-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March - May 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2-methylpropanoyl)thiourea

EC Number:

807-595-3

Cas Number:

6965-58-8

Molecular formula:

C5H10N2OS

IUPAC Name:

(2-methylpropanoyl)thiourea

Test material form:

solid: bulk

Details on test material:

- Name of test material (as cited in study report): N-Isobutyrylthiourea
- Substance type: organic
- Physical state: solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 9-12 weeks old
- Weight at study initiation: 156 - 210 g
- Fasting period before study:Prior to the administration food was withheld from the test animals for 18-19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
- Housing: The animals were kept individually groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102141114)
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1239)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least five days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Details on oral exposure:

In order to get the test item in a solution or suspension, which is applicable to the animals, cottonseed oil (Sigma-Aldrich, lot MKBQ5465V, expiry date: 31 May 2015) was evaluated as vehicle and was found to be adequate.
Homogeneity of the test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before every dose administration.
For animals no. 1, 3 and 5, 1.75 mg of the test item were dissolved in the vehicle to gain a final volume of 10 mL and to achieve a dose of 1.75 mg/kg body weight at a dose volume of 10 mL/kg body weight.
For animals no. 2, 4 and 6, 5.50 mg of the test item were dissolved in the vehicle to gain a final volume of 10 mL and to achieve a dose of 5.50 mg/kg body weight at a dose volume of 10 mL/kg body weight.
The dose formulations were made shortly before each dosing occasion.

Doses:

1.75 and 5.50 mg/kg body weight

No. of animals per sex per dose:

3 females (nulliparous and non-pregnant) per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: see any other information on materials and methods incl. tables
- Necropsy of survivors performed: yes
- Other examinations performed: see any other information on materials and methods incl. tables

Results and discussion

Preliminary study:

not applicable

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3.102 mg/kg bw

Based on:

test mat.

95% CL:

1.75 - 5.5

Mortality:

All three out of three animals treated with the test item at a dose of 5.50 mg/kg body weight had to be sacrified for ethical reasons on the day of the treatment.

Clinical signs:

other: The most relevant clinical findings in the animals treated with the test item at a dose of 5.50 mg/kg bw were reduced spontaneous activity, piloerection, eyes half closed, bradykinesia, kyphosis, prone position, tachypnoea, abnormal breathing and ataxia.

Gross pathology:

Macroscopic findings of surviving animals: At necropsy, no macroscopic findings were observed in any animal.
Macroscopic findings of animals not having survived until the end of the observation period: Necropsy revealed liquid residues of the test item in abdominal cavity.

Other findings:

no data

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

Under the conditions of the present study the estimated LD50 of the test item N-Isobutyryl-thiourea in rats is 3.102 mg/kg body weight.

Executive summary:

In an acute oral toxicity study according to OECD 425 with N-Isobutyryl-thiourea all three animals treated with a dose of 5.50 mg/kg body weight had to be sacrified for ethical reasons on the day of treatment. The most relevant clinical findings in the animals treated with the test item at a dose of 5.50 mg/kg bw were reduced spontaneous activity, piloerection, eyes half closed, bradykinesia, kyphosis, prone position, tachypnoea, abnormal breathing and ataxia.

All three out of three animals treated with the test item at a dose of 1.75 mg/kg bw survived until the end of the study showing signs of toxicity. The most relevant clinical findings in the animals treated with the test item at a dose of 1.75 mg/kg bw were reduced spontaneous activity, piloerection and eyes half closed.

Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.

Macroscopic findings of surviving animals:

At necropsy, no macroscopic findings were observed in any animal.

Macroscopic findings of animals not having survived until the end of the observation period:

Necropsy revealed liquid residues of the test item in abdominal cavity.

Therefore under the conditions of the present study the estimated LD50 of the test item N-Isobutyryl-thiourea in rats is 3.102 mg/kg body weight.