Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

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:
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals 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 / concentrationsopen allclose all
Dose / conc.:
147 ppm
Dose / conc.:
215 ppm
Dose / conc.:
316 ppm
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

open allclose all
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
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.