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Carcinogenicity

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Description of key information

A published chronic feeding studies with the disodium salt of the C10 analog dicarboxylic acid sebacic acid in both rats and rabbits at dose levels of up to 1000 mg/kg bw/day (4.06 mmol/kg bw/d corresponding to 935 mg dodecanedioic acid/kg bw/d) gave no signs of carcinogenic activity.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
carcinogenicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
peer reviewed, test procedure in accordance with generally accepted scientific standards with acceptable deficiencies in documentation; Disodium sebacate is the disodium salt of the C10 structural analog of dodecandioic acid (C12). Under physiological conditions there is an equilibrium between free acid and its dissociated ions.
Principles of method if other than guideline:
no reference to guideline
GLP compliance:
not specified
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
body weight at study initiation
males 175 g
females 142 g
Route of administration:
oral: feed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
180 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0; 500; 1000 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
10
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
Body weight was recorded at 15-day intervals
Blood chemistry and haematology (plasma glucose, BUN, serum creatine, SGOT,SGPT, Hb) were examined at the end of the study
Sacrifice and pathology:
Histological examination of the organs was performed
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):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
No adverse effects were noted.
Relevance of carcinogenic effects / potential:
No indication of carcinogenicity.
Dose descriptor:
NOAEL
Effect level:
935 mg/kg bw/day
Based on:
other: calculated for dodecanedioic acid
Sex:
male/female
Basis for effect level:
other: NOAEL for sebacic acid is 1000 mg/kg bw/day (4.06 mmol/kg bw/d corresponding to 935 mg dodecanedioic acid/kg bw/d)
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Conclusions:
No adverse effects were observed.
Executive summary:

In a chronic feeding study groups of 10 Wistar rats per sex received doses of 0, 500 or 1000 mg/kg bw/d for a period of 180 days.

Body weights were recorded, basic haematology and clinical chemistry were examined at termination and histopathology was performed. No adverse effects were noted.

Endpoint:
carcinogenicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
peer reviewed, test procedure in accordance with generally accepted scientific standards with poor documentation but acceptable restrictions; Disodium sebacate is the disodium salt of the C10 structural analog of dodecandioic acid (C12). Under physiological conditions there is an equilibrium between free acid and its dissociated ions.
Principles of method if other than guideline:
no reference to guideline
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
body weight at study initiation
males 1.34 kg
females 1.19 kg
Route of administration:
oral: feed
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
180 days
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0; 750; 1000 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
10
Control animals:
yes, plain diet
Observations and examinations performed and frequency:
Body weight was recorded at 15-day intervals
Blood chemistry and haematology (plasma glucose, BUN, serum creatine, SGOT,SGPT, Hb) were examined at the end of the study
Sacrifice and pathology:
Histological examination of the organs was performed
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):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Relevance of carcinogenic effects / potential:
No indication of carcinogenicity.
Dose descriptor:
NOAEL
Effect level:
935 mg/kg bw/day
Based on:
other: calculated for dodecanedioic acid
Sex:
male/female
Basis for effect level:
other: NOAEL for sebacic acid is 1000 mg/kg bw/day (4.06 mmol/kg bw/d corresponding to 935 mg dodecanedioic acid/kg bw/d)
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Conclusions:
No adverse effects were observed.
Executive summary:

In a chronic feeding study groups of 10 New Zealand rabbits per sex received doses of 0, 750 or 1000 mg/kg bw/d for a period of 180 days.

Body weights were recorded, basic haematology and clinical chemistry were examined at termination and histopathology was performed. No adverse effects were noted.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
935 mg/kg bw/day

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No signs of carcinogenic activity was noted in chronic feeding studies with the disodium salt of sebacic acid, the C10 analog of dodecanedioic acid at dose levels of up to 1000 mg/kg bw/day (4.06 mmol/kg bw/d corresponding to 935 mg dodecanedioic acid/kg bw/d) albeit the duration of exposure was only 180 days.

Based on read across to sebacic acid,and considering the lack of alert structural features for carcinogenicity and the lack of genotoxic activity as demonstrated in an array of short term tests and the fact that dodecanedioic acid is a natural intermediate in long-chain fatty acid catabolism in the organism, there is no indication for a carcinogenic activity of dodecanedioic acid

Justification for classification or non-classification

No carcinogenicity was observed in chronic feeding studies with sebacic acid, both in rats and rabbits. Sebacic acid is the the C-10 analog dicarboxylic acid. Based on read across, dodecanedioic acid is considered to be non carcinogenic and a classification is not required.