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

Endpoint summary

Description of key information

Two studies are availbale on the acute oral toxicty of N-Isobutyryl-thiourea. They were performed according to OECD 423 and OECD 425. 
In conclusion, the LD50 of  N-Isobutyrylthiourea is 3.1 mg/kg bw.

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:

March - May 2015

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)

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

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

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

Preliminary study:

not applicable

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

3.1 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two study are available on the acute oral toxicty of N-Isobutyryl-thiourea. They were performed according to OECD 423 and OECD 425.

In the study according to OECD 423 ("Acute Oral Toxicity- Acutes Toxic Class Method") three female rats per group were dosed with 50 and 5 mg/kg body weight. All animals died spontaneously on the day of administration. Therefore the LD50 cut-off (rat) was below 5 mg/kg bw.

A second study was performed according to OECD 425 ("Acute Oral Toxicity- Up-and-down-Procedure"). In this test three femal rats per group were dosed with 1.75 and 5.50 mg/kg body weight. All animals treated with 5.50 mg/kg bw had to be sacrified for ethical reasons.

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. 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.

No data is available on dermal or inhalation toxicity.

Justification for classification or non-classification

According to REGULATION (EC) No 1272/2008 a classification as Acute Tox 1 for N-Isobutyryl-thiourea (H300: Fatal if swallowed) is warranted based on an LD50 of 3.102 mg/kg bw.