Naphthalene-2,6-dicarboxylic acid

Endpoint summary

Description of key information

Under conditions of a Buehler study, the test item exhibited little or no potential to produce dermal sensitization in guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 16, 1981 (animal receipt) to June 30, 1981 (final report issued)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPP 81-6 (Skin Sensitisation)

Deviations:

no

Principles of method if other than guideline:

This study was peformed at Bio/dynamics, Inc. Mettlers Road, Est Millstone, New Jersey 08873. The procedures used were based on the methods described by E.V. Buehler in "Delayed contact Hypersensitivity in the guinea Pig" Arch. Dermatol 91: 171-175 (1965) and H.L. Ritz and E.V Buehler in "Planning, conduct and Interpretation of Guinea Pig Sensitization Patch Tests" in Current Concepts in Cutaneous toxicity (Victor A. Drill and Paul Lazar, eds.) pp. 25-40 Academic press, 1980.

GLP compliance:

no

Type of study:

Buehler test

Justification for non-LLNA method:

This study was conducted before the LLNA guidelines were even being discussed

Specific details on test material used for the study:

2,6-naphthalene was held confidential in the report and suppled as C-217. It was supplied by Celanese as very fine white powder, for storage at room temperature. The suggested vehicle was paraffin oil.

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

40 (21 males and 19 females) Hartley Albino Guinea Pigs were obtained from Dutchland Laboratories, Inc. Denver, PA. They were housed individually in suspended stainless steel cages, with an equilibrium/acclimatization period of 23 days. They were fed Charles River Vitamin C-fortified guinea Pig Diet, ad libitum. Water was supplied ad libitum from the municipal water supply (Elizabethtown Water company. 12 hour light/12 hr dark schedule.

Males weighed between 323 and 432 grams, and females weighed between 316 and 401 grams when received on March 16, 1981. They were evaluated for health status before being randomly assigned to the dose groups. Each animals was identified with a monel ear tag bearing its unique animal number.

Route:

epicutaneous, semiocclusive

Vehicle:

paraffin oil

Concentration / amount:

0.2 grams of test material moistened with 0.2 ml of paraffin oil

Day(s)/duration:

9 inductions at 6 hours each, 3 inducitons/week.

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, semiocclusive

Vehicle:

paraffin oil

Concentration / amount:

Positive control DNCB was added to 80% ethanol (0.1% mixture)

Day(s)/duration:

9 inductions over 3 weeks with challenge 14 days after last induction

Adequacy of induction:

highest technically applicable concentration used

No.:

#20

Route:

epicutaneous, semiocclusive

Vehicle:

paraffin oil

Concentration / amount:

0.2 grams in 0.2 ml of vehicle

Day(s)/duration:

single challenge, 14 days after last induction

Adequacy of challenge:

other: limit concentration

No. of animals per dose:

20 for test material, 12 for positive control, and 8 for irritation controls. For positive control substance iritation controls, the animals were shared with another study.

Details on study design:

On the day prior to the first application, the hair on the dorsal and lateral surfaces was clipped short with an electric clipper. 0.2 g of the test material was administered to each animal and moistened with 0.2 ml of paraffin oil, and control material mixtures were administered in a volume of 0.2 ml beneath a surgical guaze square, 1 inch by one inch, eight single layers thick, placed directly on the test site. The test site was the right side of the midline, as close to the midline as possible. The patch was covered by overlapping, inpermeable plastic. This was firmly secured by an elastic adhesive bandage which was wound around the torso of the animal. The patch was left in place for 6 hours after which it was removed and the skin was piped free of any excess material. This was repeated three times for a week for three weeks, for a total of nine insults.

Fourteen days after the last sensitization expousre, the challenge treatment was administered. Animals were clipped as before. the substances were administered in the same manner as the induction phase at a second site on the left side of the midline. After six hours of exposure, the patches were removed and the skin wiped free of any excess material.

Viability was checked twice daily. In life observations were preformed prior to treatment, and at 7, 14, 21, 28, and 35 days. Evaluation of the dermal responses were checked twice after challenge: at 24 hours and 48 hours after dosing.

Challenge controls:

In order to differentiate dermal reactions produced by irritation from those produced by sensitization, eight animals (previously untreated) wer subjected to the same challenge procedures as the animals which received the nine sensitizing exposures.

Positive control substance(s):

yes

Remarks:

DNCB

Positive control results:

The postivie control substance, DNCB, elicited a positve response in the study. Thus, sensitivity of the test method was concurrently demonstrated.

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.2 g of 2,6-naphthalene dicarboxylic acid

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.2 g of 2,4-naphthalene dicarboxylic acid in paraffin oil

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Under conditions of this study (9-induction Buehler), 2,6-naphthalene dicarboxylic acid exhibited little or no potential to produce dermal sensitization in guinea pigs.

Executive summary:

In a nine induction Buehler assay, only two animals in the test substance treated group of 20 animals exhibited irritation scores of 1 after challenge. Scores of 2 or greater for erythema were considered to represent sensitization; scores of 1 (barely perceptible) were not considered to be definitive.

Animals treated with DNCB exhibited evidence of sensitization, thus confirming the susceptibility of this group of animals to sensitization.

Under conditions of this study, 2,6 -naphthalene dicarboxylic acid exhibited little or no potential to produce dermal sensitization in the guinea pigs.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Justification for classification or non-classification

Based on the available data, the test item does not have to be classified as sensitising according to Regulation (EC) No 1272/2008.