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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

Additional information

Justification for classification or non-classification