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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 days, plus supplementary group for 14 days post dosing
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Justification for type of information:
Study following OECD guidelines and well documented.
Surrogate polyamine substance used for assessment; considered representative of the registered substance.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
yes
Remarks:
Performed as part of a medical research project; assumed to conform to GLP
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-azaoctamethylenediamine
EC Number:
204-689-0
EC Name:
4-azaoctamethylenediamine
Cas Number:
124-20-9
Molecular formula:
C7H19N3
IUPAC Name:
4-azaoctamethylenediamine

Test animals

Species:
mouse
Strain:
Balb/c
Sex:
male/female
Details on test animals or test system and environmental conditions:
Groups of 5 individuals.
Autoclaved nest material and paper houses served as cage enrichment, with access to food and water was provided ad libitum

Administration / exposure

Route of administration:
oral: feed
Details on oral exposure:
Food supplemented with a polyamine-rich extract to provide a dose level of 0.5 g/kg, 5 g/kg or 50 g/kg animal bodyweight daily
Duration of treatment / exposure:
Treatment period 28 days
14 days post treatment animals were included in recovery groups
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
5 000 mg/kg bw/day (nominal)
Dose / conc.:
50 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Five
Control animals:
yes, plain diet

Examinations

Observations and examinations performed and frequency:
Weekly for their external appearance
Bodyweight of all animals was recorded weekly
Sacrifice and pathology:
Whole blood was collected immediately after euthanasia
Animals were thoroughly examined for neo-plasias and visible abnormalities.
Various organs were weighed and samples retained frozen

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Relative kidney weight to bodyweight ratio was significantly increased in female mice treated with 50 g/kg bodyweight.
Relative kidney weight was increased by 12% in this group compared to control animals.
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
The polyamines used in the study were found in the blood and are clearly absorbed following ingestion.

Effect levels

Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:
no

Any other information on results incl. tables

Bodyweight of animals of all treatment groups did not differentiate from the control group

Relative kidney weight to bodyweight ratio was significantly increased in female mice treated with 50 g/kg bodyweight. Relative kidney weight was increased by 12% in this group compared to control animals and is considered to likely be an adaptive change.

Applicant's summary and conclusion

Conclusions:
No adverse effects following treatment with polyamine at up to 50 g/kg/day, other than an adaptive change in relative kidney weight.