Hexadecanedioic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

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:

1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
Dicarboxylic acids are organic compounds that contain two carboxylic acid functional groups. They have the general type formula HOOC-(CH2)n-COOH. The present defined category comprises dicarboxylic acids with straight carbon chain having a “n” value from 6 to 16.
The physical and chemical properties as well as the toxicology and environmental fate and effects show that substances in this category have a similar order of toxicological and environmental fate properties, which supports the grouping of these substances as a category. (see attached justification)

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL)
There are number of unifying considerations justifying the similarity between these substances in some important aspects. These include:
(1) Similarity of Use: these dicarboxylic acids have several industrial uses in the production of adhesives, plasticizers, lubricants, copolymers (such as polyamides and polyesters), etc.
(2) Similarity of Functional groups: all these substances contain two common functional groups (2 carboxyl groups). The only difference between the substances of this group lies in the length of the carbon chain.
(3) Similarity of Physical / Chemical properties: the similarity of physical / chemical properties for these substances (see attached justification)
(4) Similarity of Metabolism: Dicarboxylic acids were shown to be rapidly absorbed from the gastrointestinal tract, introduced into the fatty acid catabolism and therefore extensively metabolized by the organism and excreted (Passi, S. et al, 1983).
(5) Similarity of Mammalian Toxicity: The constituents of this class have similar toxicological properties. They are not acutely toxic, irritating to skin or sensitizing. However, they all present, except for dodecanedioic acid, irritating effects on the eyes (from moderate to high effects). They do not produce systemic effects in repeated dose studies. They are neither mutagenic nor carcinogenic and do not produce developmental/reproductive toxicity. (see attached justification)
(6) Similarity of Environmental Toxicity and Fate Properties: The substances in this category have similar environmental effects properties. The environmental effects data are similar for most category members in that most members do not exhibit acute toxicity. (see attached justification)

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

Principles of method if other than guideline:

After gavage of the test animals with a single dose of the test substance, the animals were examined for signs of toxicity and substance-dependent mortality. Gross pathological findings and body weights of the animals too were also monitored and recorded during the experiment. Necropsy was performed on animals that died before the end of the experiment. All surviving animals were sacrificed at the end of the examination period and necropsied.

GLP compliance:

not specified

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Disodium sebacate (DSS)

IUPAC Name:

Disodium sebacate (DSS)

Constituent 2

Reference substance name:

Disodium sebacate

EC Number:

241-300-3

EC Name:

Disodium sebacate

Cas Number:

17265-14-4

IUPAC Name:

disodium sebacate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Doses higher than 5000 mg/kg bw were not used, since the DSS-containing volumes would have been too large for the stomach capacity of the animals tested
- Control groups of rats (4 male/4 female) were given NaCl solutions, whose sodium content corresponded to that of the test substance administered. Glucose was added to reach the same osmolarity of the test dose

Doses:

500; 1,000; 1,500; 2,000; 3,000; 4,000; 5,000 mg/kg bw

No. of animals per sex per dose:

4

Control animals:

yes

Statistics:

The DSS 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 the 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

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Effect levels 2

Sex:

male/female

Dose descriptor:

other: NOAEL

Effect level:

>= 5 000 mg/kg bw

Mortality:

No substance related mortality was seen

Clinical signs:

No substance related clinical effects were seen

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

After oral administration of disodium sebacate to rats, no oral toxicity was found. Based on a read across (category approach), no classification regarding the acute oral toxicity is required for hexadecanedioic acid.

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