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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Repeated dose
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Study performed on polyamine in mice
Part of a repeat-dose study, but dose levels of 50 g/kg/day demonstrates low acute and sub-acute toxicity
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
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.
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
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
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
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
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
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.
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no

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.

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

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD 407
Version / remarks:
Repeat dose study, but performed at up to 50 g/kg/day and therefore demonstrates low toxicity.
GLP compliance:
not specified
Test type:
other: Dietart testing at up to 50 g/kg/day
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

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Doses:
0, 0.5, 5 and 50 g/kg/day
No. of animals per sex per dose:
Five in main treatment groups.
Additional five in recovery groups
Control animals:
yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
>= 50 000 mg/kg bw
Based on:
test mat.
Mortality:
No
Clinical signs:
other: No
Gross pathology:
No
Other findings:
Increase in kidney weight at 50 g/kg/day in females

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
This supporting study demonstrates the low toxicity of the substance.