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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Toxicity of disodium sebacate
Author:
Greco A.V., Mingrone G., Mastrimattei A. E., Finotti E., Castagneto M.
Year:
1990
Bibliographic source:
DRUGS EXPTL. CLIN. RES. XVI (10) 531-536

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Deviations:
yes
Remarks:
6 month exposure period, two dosages
Principles of method if other than guideline:
Two groups of twenty Wistar rats (ten ♂ and ten ♀) were fed for 6 months a pellet diet containing Disodium sebacate at two different dosages.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium sebacate
EC Number:
241-300-3
EC Name:
Disodium sebacate
Cas Number:
17265-14-4
Molecular formula:
C10H18O4.2Na
IUPAC Name:
disodium sebacate
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Average weight at study initiation:
♂ 174.6 ±6.3 g; 176.8 ±13.2 g
♀ 142.2 ±7.13 g; 141.7 ±7.54 g

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: pellet diet containing the test substance
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 months
Frequency of treatment:
continuously
Doses / concentrationsopen allclose all
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
10
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: every 15 days

ORGAN: yes
- Time schedule for examination: at death or after sacrifice.
- Organs examined: no data

CLINICAL CHEMISTRY and HAEMATOLOGY: Yes
- Parameters checked: plasma, glucose, BUN, serum creatinin, SGOT, SGPT, Hb.
Sacrifice and pathology:
Surviving animals were sacrificed 181 days after the start of the treatment. Macro- and microscopic examinations of the organs were performed.
Statistics:
The disodium sebacate concentration used and percentage of mortality were respectively plotted on abscissa and ordinate of a logarithmic paper according to Miller and Tainter The best fitting straight line of the plotted points allows calculation of the LD50 which is the dosage value at 50 % of mortality. The standard error (s .e.) was estimated by this formula : (doses 84 % - 16 %) x square root of 2N, where N is the number of animals contributing to the values plotted.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
The general conditions of the animals determined by physical examination and general observation did not show qualitative toxic signs.
Mortality:
no mortality observed
Description (incidence):
No death occurred during the chronic toxicity study.
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food and water consumption were normal, as confirmed by the analysis of body weight gains which were not different from those values obtained from the controls.
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
Biological parameters (plasma glucose, BUN, serum creatinine, SGOT,SGPT and Hb) were similar to those of the controls .
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Description (incidence and severity):
No histological alterations were observed in any of the tissues and organs examined.

Effect levels

Dose descriptor:
NOEL
Effect level:
>= 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no adverse effects reported

Target system / organ toxicity

Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
When compared to the control animals, no significant differences in biological parameters (clinical, chemical and haematological values, growth curves and histological findings for the different organs) were observed in the test groups during the treatment period.