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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 12 Oct 2004 to 3 Nov 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the females were approximately 8-week old
- Mean body weight at study initiation: 280 ± 15 g for the males and 199 ± 2 g for the females.
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methylcellulose aqueous solution
Details on oral exposure:
Three animals of one sex were used for each step. Males were used in the initial step.
As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose of 200 mg/kg was chosen.
After the first assay, as 0/3 animals died, another assay was carried out on three males at the next After the second assay, as 1/3 animals died, the results were confirmed in three females at 2000 mg/kg.

The dosage form preparations were administered to the animals under a volume of 10 mL/kg.
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 5 mL glass syringe (0.05 mL graduations).
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.
Doses:
200 and 2000 mg/kg.
No. of animals per sex per dose:
200 mg/kg: 3 males
2000 mg/kg : 3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: All study animals were subjected to a macroscopic examination as soon as possible after death.
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.
Statistics:
no

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 1/6 died at 2000 mg/kg/d
Mortality:
At 200 mg/kg: No mortality occurred.
At 2000 mg/kg : In males, 1/3 animals were found dead on day 2; hypoactivity or sedation, piloerection and dyspnea were recorded prior to death. In females, no mortality occurred.
Clinical signs:
At 200 mg/kg: Only hypoactivity, piloerection and dyspnea were observed in all animals on day 1.
At 2000 mg/kg : In all male surviving animals, hypoactivity, piloerection and dyspnea were noted from day 1 up to day 4. Hypoactivity and piloerection were observed in all females on day 1; then hypoactivity, piloerection and dyspnea were recorded in 1/3 females on day 2. No clinical signs were noted thereafter in females and males.
Body weight:
The overall body weight gain of the animals treated at 200 mg/kg was not affected by treatment with the test item.
At the 2000 mg/kg dose-level, a slightly reduced body weight gain was seen in all surviving animals during the first week of the study, when compared to historical control animals.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under these experimental conditions, the oral LD50 of the test item Dibutyl thiourea is higher than 2000 mg/kg in rats.
Executive summary:

The acute oral toxicity of the test item Dibutyl thiourea was evaluated in rats according to OECD (No. 423, 22 March 1996) and EC (96/54/EC, B.1 tris, 30 July 1996) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was prepared as a suspension in 0.5% methylcellulose and was administered by oral route (gavage), under a volume of 10 mL/kg, to groups of three fasted Sprague-Dawley rats. At first, three males were treated with 200 mg/kg bw; then after, three males and three females were treated with 2000 mg/kg bw. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

At 200 mg/kg bw: No mortality occurred. Only hypoactivity, piloerection and dyspnea were observed in all animals on day 1.

At 2000 mg/kg bw : In males, 1/3 animals were found dead on day 2; hypoactivity or sedation, piloerection and dyspnea were recorded prior to death. In all surviving animals, hypoactivity, piloerection and dyspnea were noted from day 1 up to day 4.

In females, no mortality occurred. Hypoactivity and piloerection were observed in all animals on day 1; then hypoactivity, piloerection and dyspnea were recorded in 1/3 females on day 2. No clinical signs were noted thereafter.

The overall body weight gain of the animals treated at 200 mg/kg was not affected by treatment with the test item. At the 2000 mg/kg dose-level, a slightly reduced body weight gain was seen in all surviving animals during the first week of the study, when compared to historical control animals. At necropsy, no apparent abnormalities were observed.

Under these experimental conditions, the oral LD50 of the test item Dibutyl thiourea is higher than 2000 mg/kg in rats.