6-hydroxy-2-naphthoic acid

Endpoint summary

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP status not stated; Well-documented, method employed consistent with OECD 406.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

GLP compliance:

not specified

Type of study:

Buehler test

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

A total of 45 animals (23 male; 22 female) were obtained for study.

TEST ANIMALS
- Source: Dutchland Breeding Farms; Denver, PA
- Age at study initiation: not stated
- Weight at study initiation: not stated
- Housing: Individually housed, type of housing not described.
- Diet (e.g. ad libitum): Base diet not described, fresh greens were used to supplement the diet.
- Water (e.g. ad libitum): not stated
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- not stated

Route:

epicutaneous, occlusive

Vehicle:

peanut oil

Concentration / amount:

Test article was prepared as a suspension of 25% (w:v) 6-hydroxy-2-naphthoic acid in peanut oil. The preparation was blended to produce an homogenous suspension.

Route:

epicutaneous, occlusive

Vehicle:

peanut oil

Concentration / amount:

Test article was prepared as a suspension of 25% (w:v) 6-hydroxy-2-naphthoic acid in peanut oil. The preparation was blended to produce an homogenous suspension.

No. of animals per dose:

Group 1 - Peanut Oil (Vehicle Control): 15 total (8M & 7F)
Group 2 - DCNB (Positive Control): 15 total (8M & 7F)
Group 3 - Test Article: 15 total (8M & 7F)

Details on study design:

Dosing Procedure:
- Sensitization Period: Test article application site was prepared (clipped free of hair) 24 hours prior to the initial dosing of each animal. All animals in all groups received 0.2 mL dosing solution applied to the back, on the right side of the spinal column below an "Elastopatch(R), with 3/4" x 1" Webril pad. The trunk of each animal was wrapped in an Elastoplast(R) bandage to occlude and secure the patches. After treatment, the animals were returned to their cages. Six hours after application, the bandages and patches were removed. Sensitization was performed three times a week for three weeks, for a total of 9 sensitizing exposures.

- Challenge Procedure: On the thirteenth day following the last Sensitization treatment, the treatment area of each animal was once again clipped free of hair and depilated with Neet(R). On the following day, all animals received the first challenge dose. However, in the challenge phase, two sites (one on either side of the spinal column) were treated. After 6 hours, both sites were evaluated for erythema and edema. Challenges were repeated at 24 and 48 hours.

Challenge controls:

As an additional control, a group of 5 unsensitized animals were treated with the test material.

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (DCNB)

Positive control results:

DCNB (positive control) was a strong sensitizer in this study, confirming the susceptibility of this group of animals to dermal sensitization.

Reading:

1st reading

Hours after challenge:

6

Group:

negative control

Dose level:

Vehicle Control

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

No edema observed in any animals; Very mild erythema observed in 2/10 animals. In one, erythema not bi-lateral, but persisted from 24 to 48 hours post-challenge. In other animal, erythema was bi-lateral, but only present at 24 hours post-challenge.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 6.0. Group: negative control. Dose level: Vehicle Control. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: No edema observed in any animals; Very mild erythema observed in 2/10 animals. In one, erythema not bi-lateral, but persisted from 24 to 48 hours post-challenge. In other animal, erythema was bi-lateral, but only present at 24 hours post-challenge..

Reading:

1st reading

Hours after challenge:

6

Group:

positive control

Dose level:

1% DCNB in peanut oil

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Erythema observed in all animals; Mild edema observed in 1/10 animals

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 6.0. Group: positive control. Dose level: 1% DCNB in peanut oil. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema observed in all animals; Mild edema observed in 1/10 animals.

Reading:

1st reading

Hours after challenge:

6

Group:

test chemical

Dose level:

25% 6-hydrox-2-naphthoic acid in peanut oil

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No observations of erythema or edema in any animals

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 6.0. Group: test group. Dose level: 25% 6-hydrox-2-naphthoic acid in peanut oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No observations of erythema or edema in any animals.

Reading:

rechallenge

Hours after challenge:

48

Group:

negative control

Dose level:

Vehicle Control

No. with + reactions:

4

Total no. in group:

10

Clinical observations:

No edema observed in any animal; 3 animals had single mild erythema obs, one-sided; One animal had bi-lateral erythema at 48 hours post Challenge 2.

Remarks on result:

other: see Remark

Remarks:

Reading: rechallenge. . Hours after challenge: 48.0. Group: negative control. Dose level: Vehicle Control. No with. + reactions: 4.0. Total no. in groups: 10.0. Clinical observations: No edema observed in any animal; 3 animals had single mild erythema obs, one-sided; One animal had bi-lateral erythema at 48 hours post Challenge 2..

Reading:

rechallenge

Hours after challenge:

48

Group:

positive control

Dose level:

1% DCNB in peanut oil

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

Erythema (slight to well-defined) observed in all animals; Very slight to slight edema observed in 3/10 animals.

Remarks on result:

other: see Remark

Remarks:

Reading: rechallenge. . Hours after challenge: 48.0. Group: positive control. Dose level: 1% DCNB in peanut oil. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: Erythema (slight to well-defined) observed in all animals; Very slight to slight edema observed in 3/10 animals. .

Reading:

rechallenge

Hours after challenge:

48

Group:

test chemical

Dose level:

25% 6-hydroxy-2-naphthoic acid in peanut oil

No. with + reactions:

2

Total no. in group:

10

Clinical observations:

One animal with a single, one-sided observation of very slight edema @ 24 hours post-challenge 2; one animal with single, one-sided observation of slight erythema at 24 hours post-challenge 2.

Remarks on result:

other: see Remark

Remarks:

Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25% 6-hydroxy-2-naphthoic acid in peanut oil. No with. + reactions: 2.0. Total no. in groups: 10.0. Clinical observations: One animal with a single, one-sided observation of very slight edema @ 24 hours post-challenge 2; one animal with single, one-sided observation of slight erythema at 24 hours post-challenge 2..

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Under the conditions of this study, no potential to produce dermal sensitization in the guinea pig was demonstrated by 6-HNA.

Executive summary:

No signs of systemic toxicity were noted in any animals during this study. Sporadic incidences of urinary and fecal staining of the abdomen, soft stool, piloerection, and animal thinness were noted during this study. There was no severe dermal response noted in any of the animals treated with 6 -HNA. The reactions following each challenge were similar for both control animals and those treated with 6 -HNA. DCNB (positive control) was a strong sensitizer in this study, confirming the susceptibility of this group of animals to dermal sensitization.

Under the conditions of this study, no potential to produce dermal sensitization in the guinea pig was demonstrated by 6 -HNA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Based on the results of a GLP compliant study, which was similar/equivalent to OECD Guideline 406 (Skin Sensitisation), 6 -HNA was determined to not have the potential to cause skin sensitization.

Migrated from Short description of key information:
In a GLP compliant study, the substance of record, 6-hydroxy-2-naphthoic acid (6-HNA) was determined to have no potential to cause dermal sensitization. The study was performed using appropriate controls, and the test system responded to the positive controls as expected.

Justification for selection of skin sensitisation endpoint:
Lack of dermal sensitization potential was established in a study similar/equivalent to OECD Guideline, and was performed under GLPs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of a GLP compliant OECD Guideline study, 6 -HNA was determined to not have sensitization potential via the dermal route of exposure. No data are available regarding respiratory sensitization. However, based on the fact that 6 -HNA is exclusively imported as a reacted monomer in a polymer backbone, the risk of respiratory exposure is low, and the risk of respiratory sensitization is considered to be negligible.