2-Propenenitrile, polymer with 1,2-ethanediamine

Endpoint summary

Description of key information

The substance is partly polymeric and the monomers and 'fragments' (groups) found by analysis using Mass Spectrometry have instead been assessed. Many of these low molecular weight amines are corrosive and are unsuitable for read-across, but data found for less irritating materials suggest low systemic toxicity. Low-molecular weight poltyamides are not considered hazardous at levels leading to GHS classification and are found in many uncooked and cooked foods.

There is no apparent target organ effect; effects observed appear to be related to local effects leading to poor weight gain and reduced vigour.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

28 days dosing with 2-week recovery groups

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:

Peer reviewed research performed on polyamines as dietary study.
Food intake and animal weights provided to allow determination of dosing in terms of mg/kg bodyweight.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Version / remarks:

Feeding study with recovery groups

GLP compliance:

not specified

Limit test:

no

Specific details on test material used for the study:

Common name spermidine

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: feed

Details on route of administration:

Administered in food

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Diet and drinking water given ad-lib

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Daily fee, 28 day exposure

Dose / conc.:

0 ppm

Dose / conc.:

200 ppm

Dose / conc.:

2 000 ppm

Dose / conc.:

10 000 ppm

Remarks:

Estimated 700 - 800 mg/kg/day as bodyweight

No. of animals per sex per dose:

five

Control animals:

yes, plain diet

Positive control:

No

Observations and examinations performed and frequency:

The rats were weighed once weekly, and observed daily for condition and behaviour.
Food intake was measured weekly, on a cage basis by weighing the feeders

Other examinations:

Blood samples were collected from the tip of the tail of all rats early in wk 5 and examined for haemoglobin concentration, packed cell volume and erythrocyte, leucocyte and thrombocyte counts

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Reduced food intake and body weights in the high dose group

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Reduced food intake at top dose

Food efficiency:

no effects observed

Ophthalmological findings:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Haematological findings:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Urinalysis findings:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Behaviour (functional findings):

no effects observed

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Gross pathological findings:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

Noted in paper that 'only significant observations are reported'; Methods imply full examinations took place and therefore, the absence of report effects means no significant effects were seen.

Dose descriptor:

LOAEL

Effect level:

> 700 - < 800 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Critical effects observed:

no

Conclusions:

Note that the report includes work on other polyamines; the more corrosive spermine showed adverse effects at high concentrations that were consistent with local damage. Spermine also showed blood parameter changes, but these may have been due to other adverse effects, including renal damage.
The report also suggests a metabolic pathway for some polyamines to explain the relatively low toxicity seen in most of the amines examined.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LOAEL

700 mg/kg bw/day

Study duration:

subchronic

Species:

mouse