2-Propenenitrile, polymer with 1,2-ethanediamine

Acute Toxicity: oral

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

Test material information

Constituent 1

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.