Hexadecanedioic acid

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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:

guideline study with acceptable restrictions

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:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

: no positive control (not required by 1981 version of Test Guideline)

GLP compliance:

no

Type of study:

guinea pig maximisation test

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

Details on test material:

Dodecanedioic acid of Hüls AG.
Purity ca. 99 %;
main impurities: Homologous dicarboxylic acids

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Fa Winkelmann, 4799 Borchem, Germany
- Weight at study initiation: 324 g (mean test); 322 g (mean control)
- Housing: 1-5 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1°C
- Humidity (%): 60 +/- 5%
- Air changes (per hr):15 per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 14.2.1989 To: 10.03.1989

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

petrolatum

Induction 2

Concentration / amount:

1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 25 % occlusive epicutaneous

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Challenge 2

Concentration / amount:

1st application: Induction 0.5 % intracutaneous
2nd application: Induction 50 % occlusive epicutaneous
3rd application: Challenge 25 % occlusive epicutaneous

No. of animals per dose:

20

Details on study design:

ADMINISTRATION/EXPOSURE
- Induction schedule:
day 0 injection,
day 6 induction of slight inflammation (10 % sodium lauryl sulfate in petrolatum)
days 7-9 patch treatment (48 hours)
- Injection details: 0.1 ml each at 6 positions on shoulders:
2 x Freund's Complete Adjuvant / deionized water (50:50)
2 x test substance 0.5 % in corn oil
2 x test substance 0.5 % in Freund's Complete Adjuvant / corn oil (50:50)
simultaneous and symmetrical application of each solution
controls: corn oil instead of test substance
- Challenge schedule: 2 weeks after end of induction, patch treatment for 24 hours
- Concentrations used for challenge:
25 % in vehicle with filter paper on left side; petrolatum on opposite side readings 24 and 48 hours after removal of patch
- Rechallenge: no
- Positive control: no

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous. No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 1st application: Induction 0.5 % intracutaneous; 2nd application: Induction 50 % occlusive epicutaneous; 3rd application: Challenge 25 % occlusive epicutaneous . No with. + reactions: 0.0. Total no. in groups: 20.0.

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

RESULTS OF PILOT STUDY: no skin irritation at 50 %
RESULTS OF TEST
- Sensitization reaction: 
0/20 animals positive at 24 and 48 hours = no sensitization
no animals positive in control group
- Clinical signs: 
1st induction, FCA application sites: severe erythema and edema,  necroses
1st induction, test substance + vehicle application sites: slight  erythema and edema
1st induction, vehicle application sites: slight erythema
2nd induction, test and control group: severe erythema of the whole  shoulder region; inflammation of the FCA injection sites, in part with pus discharge and/or bleeding from scratching; eschar formation within 24 hours
- Other: Mean body weight gain 121 g in test group, 122 g in control  group = expected range

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study dodecanedioic acid is not a skin sensitizer. Based on a read across (category approach), no classification regarding the skin sensitisation is required for hexadecanedioic acid.