1,3-dibutyl-2-thiourea

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted.
Mice were exposed to DETU during seven weeks.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3-diethyl-2-thiourea

EC Number:

203-308-5

EC Name:

1,3-diethyl-2-thiourea

Cas Number:

105-55-5

Molecular formula:

C5H12N2S

IUPAC Name:

1,3-diethylthiourea

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River breeding Laboratories, Inc., Wilmington, Massachussets
- Age at study initiation: around 6 weeks-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: in polycarbonate cages suspended from aluminium racks.
- Diet (e.g. ad libitum): Wayne Lab-Blox (Allied Mills, Inc. Chicago, Ill.), ad libitum
- Water (e.g. ad libitum): aciduled water (pH 2.5) was suplied to animals in water bottles filled in an automated metering device, ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26°C
- Humidity (%):45-55%
- Air changes (per hr):12-15
- Photoperiod (hrs dark / hrs light): fluorescent lighlting 8h/day (9.00 am to 5.00 pm)

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

no

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

7 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

680 ppm

Doses / concentrations 2

Dose / conc.:

1 000 ppm

Doses / concentrations 3

Dose / conc.:

1 470 ppm

Doses / concentrations 4

Dose / conc.:

2 160 ppm

Doses / concentrations 5

Dose / conc.:

3 150 ppm

No. of animals per sex per dose:

5 males + 5 females per dose

Control animals:

yes, concurrent no treatment

Details on study design:

Post-exposure period: 1 week

Positive control:

no

Examinations

Observations and examinations performed and frequency:

Individual body weights and food consumption data were recorded twice weekly throughout the study.

Sacrifice and pathology:

Upon termination of the study, all survivors were sacrified and necropsied.

Other examinations:

no

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Details on results:

At 680 ppm, the mean body weight gain was decreased among males (-10%) and females (-8%) compared to control group.
=> The high concentration selected for administration to dosed mice in the main study was 500 ppm.

Effect levels

1

Dose descriptor:

other: maximum tolerated dose

Effect level:

500 ppm

Basis for effect level:

other: 500 ppm x 0.05 (assumed rodent food consymption per bw) = 25 mg/kg bw/d

2

Dose descriptor:

NOAEL

Effect level:

500 ppm

Basis for effect level:

other: No effects were observed at 500 ppm. 500 ppm x 0.05 = 25 mg/kg bw/d

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

According to this study, the maximum tolerated concentration was 500 ppm of DETU in diet for the mice.

Executive summary:

It's a range finding test for carcinogenicity test. In order to establish the maximum tolerated concentrations of DETU for administration to dosed animals in the chronic studies, subchronic toxicity tests were conducted.

Mice were exposed to DETU during seven weeks to 680, 1000, 1470, 2160 and 3150 ppm in diet.

At 680 ppm, the mean body weight gain was decreased among males (-10%) and females (-8%) compared to control group.

=> The high concentration selected for administration to dosed mice in the main study was 500 ppm.