2[2'-Hydroxy-5'-(phenyl)ureylenphenyl]benzothiazole

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 jan 2018 to 08 feb 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (nulliparous and non-pregnant): yes
- Age at study initiation: Young adult animals (approximately 8 weeks old)
- Weight at study initiation: 145 to 164 g.
- Fasting period before study: Yes ( maxi o 20 hours prior to dosing and until 3-4 hours after administration of the test item.
- Housing: polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8- 15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) ad libitum
- Water : Municipal tap-water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24°C
- Humidity (%): 40-70%
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air
- Photoperiod (hrs dark / hrs light): A 12-hour light/12-hour dark cycle
- Ventilation: At least 10 air changes per hour

IN-LIFE DATES: From: To: 18 Jan 2018 / 1 Feb 2018

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Supplier: Merck, Darmstadt, Germany / Specific gravity: 1.036

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

two consecutive groups of three female Wistar rats at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Hunched posture, uncoordinated movements, piloerection and/or rales were noted for all animals between Days 1 and 4.
The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.No abnormalities were found at macroscopic post mortem examination of the animals.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred

Clinical signs:

other: Hunched posture, uncoordinated movements, piloerection and/or rales were noted for all animals between Days 1 and 4.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, test item) does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this study was to determine the potential toxicity of the test item, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

The study was carried out in compliance with the guidelines described in:

* OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

* EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method"

* EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

* JMAFF Guidelines (2000), including the most recent revisions.

test item was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture, uncoordinated movements, piloerection and/or rales were noted for all animals between Days 1 and 4.

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50 value of test item in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, test item does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globallyn Harmonized System of Classification and Labelling of Chemicals (GHS) of the United

Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).