Hexadecanedioic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Principles of method if other than guideline:

see Test Conditions

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dodecanedioic acid

EC Number:

211-746-3

EC Name:

Dodecanedioic acid

Cas Number:

693-23-2

Molecular formula:

C12H22O4

IUPAC Name:

dodecanedioic acid

Test animals

Species:

rabbit

Strain:

other: albino rabbits

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ORGANISMS:
- Strain: unspecified albino
- Weight at study initiation: 2.9-3.2 kg, mean 2.959 kg
- Controls: no

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

ADMINISTRATION:
- Area covered: trunk area (back) clipped free of hair; plastic collars
- Preparation of test substance: moistened with physiological saline
- Occlusion: Three 3" x 3" 12 ply gauze pads; under wrap plus gauze bandage; fixed with adhesive bandage
- Removal of test substance: 24 hours after administration washing with water and drying

Duration of exposure:

24 hours

Doses:

6000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

not specified

Details on study design:

EXAMINATIONS: 14-day recovery period
OTHER: The dose was based on a range finding study with 1 rabbit each dosed 5000 or 7500 mg/kg bw. There was difficulty adhering 7500 mg/kg bw to the rabbit's back. Both rabbits survived.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

> 6 000 mg/kg bw

Mortality:

No animal died during the study

Clinical signs:

Slight skin irritation, diarrhea and nasal discharge. Two rabbits had weight loss on the day after dosing and there was sporadic weight loss 3-13 days after dosing.

Body weight:

The mean body weight increased from 2.959 to 3.353 kg.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on a read across (category approach), no classification regarding acute dermal toxicity is required for hexadecanedioic acid.