1,3-diethyl-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.
Rats 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-diethyl-2-thiourea

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Frederick Cancer Research Center, Frederick, Maryland.
- 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

Duration of treatment / exposure:

7 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

147 ppm

Doses / concentrations 2

Dose / conc.:

215 ppm

Doses / concentrations 3

Dose / conc.:

316 ppm

Doses / concentrations 4

Dose / conc.:

464 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:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

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 316 ppm concentration: Mean body weight gain increased by 3 % among male rats compared to control group while it decreased by 11% in female rats. 1 female rat died and another had an arched back and rough coat.
- At 215 ppm concentration: Mean body weight gain decreased by 10 % among male rats compared to control group while it decreased by 1% in female rats.
=> The maximum tolerated concentration was around 250 ppm.

Effect levels

1

Key result

Dose descriptor:

other: Maximum tolerated dose

Effect level:

250 ppm

Sex:

male/female

Basis for effect level:

other: 250 ppm x 0.05 (assumed rat food consumption per bw) = 12.5 mg/kg bw/d

2

Key result

Dose descriptor:

NOAEL

Effect level:

147 ppm

Sex:

male/female

Basis for effect level:

other: Changes of bw were observed at 215 and 316 ppm. 147 ppm x 0.05 = 7.35 mg/kg bw

Target system / organ toxicity

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

According to this study, the maximum tolerated concentration was 250 ppm of DETU in diet for the rats.

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. Rats were exposed to DETU in diet during seven weeks to 147, 215, 316 and 464 ppm.

- At 316 ppm concentration: Mean body weight gain increased by 3 % among male rats compared to control group while it decreased by 11% in female rats. 1 female rat died and another had an arched back and rough coat.

- At 215 ppm concentration: Mean body weight gain decreased by 10 % among male rats compared to control group while it decreased by 1% in female rats.

=> The maximum tolerated concentration was around 250 ppm.