Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 January 2017 - 28 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008 (including most recent amendments)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
November 2000 (including most recent partial revisions)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Tributyl-2-thiourea
EC Number:
219-350-2
EC Name:
Tributyl-2-thiourea
Cas Number:
2422-88-0
Molecular formula:
C13H28N2S
IUPAC Name:
1,1,3-tributylthiourea
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Tri butyl thiourea
- Appearance: Clear pale to medium brown liquid
- Storage conditions: At room temperature

Test animals

Species:
rat
Strain:
other: Crl:WI (Han) (outbred, SPF-Quality)
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: approx. 8-9 weeks old
- Weight at study initiation: 139 - 166 g
- Fasting period before study: yes
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): set to maintain 18 to 24°C
- Humidity (%): set to maintain 40 to 70%
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: from: 30 January 2017 to: 28 February 2017

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.12 mL/kg bw

DOSAGE PREPARATION (if unusual): The test item was kept at room temperature for a maximum of 4 hours prior to dosing and dosed undiluted (as delivered).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to OECD test guideline 423.
Doses:
Dosing was performed in a stepwise manner, starting at a dose level of 2000 mg/kg body weight. The presence of mortality determined the lower dosing of 300 mg/kg body weight.
No. of animals per sex per dose:
3 female animales per dosing group; 1 groups of females was exposed to 2000 mg/kg bw, 2 groups of 3 females were exposed to 300 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (mortality/viability): twice daily
- Frequency of weighing: day 1 (pre-administration), 8 and 15 and at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals treated at 2000 mg/kg were found dead on Day 2. No further mortality occurred in the treatment group of 300 mg/kg body weight.
Clinical signs:
At 2000 mg/kg, hunched posture, uncoordinated movements, slow breathing, piloerection, diarrhoea, salivation watery discharge from the eyes and/or ptosis were noted for the animals on Days 1 and/or 2.
At 300 mg/kg, hunched posture and piloerection were noted for all animals on Day 1.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
At 2000 mg/kg, beginning autolysis was noted for the animals found dead at Day 2. This finding was considered not indicative of toxicity.
At 300 mg/kg, reddish discoloration of the thymus was noted for one animal. No further abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

The results were evaluated according to:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments).

- Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
/Category 4 (labeled as H302) based on Regulation (EC) No 1272/2008
Conclusions:
In an acute toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 was established to be within the range of 300-2000 mg/kg body weight. Based on the results obtained in this study, Tri butyl thiourea should be classified as Category 4 based on GHS and Regulation (EC) No. 1272/2008 (labeled as H302: harmful if swallowed).