Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24.10.2007.- 23.04.2008.
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
GLP compliance:
yes (incl. QA statement)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: Albino laboratory rat
Strain:
other: Wistar Han
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: water for injection
Duration of treatment / exposure:
28 days
Frequency of treatment:
All the time
No. of animals per sex per dose:
Number of animals (male) Dose (mg/kg) or concentration (mg/l)
5 0
5 50
5 150
5 300
5 0
5 300

Number of animals (female) Dose (mg/kg) or concentration (mg/l)
5 0
5 50
5 150
5 300
5 0
5 300

Examinations

Observations and examinations performed and frequency:
MORTALITY
No mortality occured during the study.

CLINICAL SIGNS
The negative effect of the test substance on clinical status
of animals was recorded at all dose levels. Soft stool or diarrhoea, chromodacryorrhea (it means excessive outpouring of the red secretion of the Harderian gland which may be provoked by non-specific stimuli such as stress) and flabby body were observed and frequency of incidence of these symptoms was dependent on dose level (occurence at the middle and the lowest dose level was sporadical). After ending of application of the test substance the symptoms faded away - effect had reversible character.

FUNCTIONAL OBSERVATIONAL BATTEARY
No important differences were recorded during functional observation of treated and control animals.

FOOD CONSUMPTION
No significant effects on food consumption were noted.

BODY WEIGHT
Growth of animals (body weight, weigh increments, food conversion) was not changed seriously.

WATER CONSUMPTION
The water consumption of males at the dose level 300 mg/kg/day was markedly increased compared to control - this effect was reversible. The water consumption of males of the lowest and the middle dose level was similar to control males.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
effects observed, treatment-related
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
effects observed, treatment-related
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: see 'Remark'

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Administration of the test substance 3-(2,2,2-Trimethylhydrazine)methylpropionate bromide had negative effect especially on clinical status of animals, metabolism of water and ions and probably it affected the function of liver. These effects demonstrated in results of clinical observations (soft stool or diarrhea, chromodacryorrhea, flabby body, slightly decreased activity), biochemical examination of blood (hyperchloraemia, hyponatraemia, decreased values of liver enzymes) and urinalysis (decreased volume of urine, increased value of specific gravity, increased value of pH, proteinuria, haematuria, leucocyturia) of treated males and females and high incidence of significant or statistically significant differences was recorded at the middle and especially at the highest dose level. Changes at the lowest dose level had only mild intensity and were not considered as adverse. Effect of the test substance on growth of animals and biometry of organs was not serious. In haematological (red blood component and blood coagulation) and histopathological examination (stomach, kidney) changes were diagnosed but they were not biologically significant. No sex differences in the reaction of animals to the treatment by the test substance have been detected.