Naphthenic acids

Endpoint summary

Description of key information

This substance is moderately to severely irritating to skin based on a key and supporting study providing enough detail given to make correct conclusion about the irritating properties of this substance.

Indications for eye irritation were obtained from a secondary source, therefore classification was proposed and further eye irritation testing was waived based on the available data and Column 2 adaptations of REACH Annex VIII.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: although no indication that it is a GLP study, sufficient detail is provided to make a conclusion about its validity.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

This study is a combined study where Accute Dermal Toxicity is considered together with skin irritation.

Principles of method if other than guideline:

This study is a combined study where Accute Dermal Toxicity is considered together with skin irritation.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Duration of treatment / exposure:

24 hours

Observation period:

14 days
Dermal irritation was recorded at 24h, 3, 7, 10 and 14 days.

Number of animals:

2 per sex

Details on study design:

3.16 g/kg naphthenic acid was applied dermally to the clipped abraded abdomens of 2 female and 2 male New Zealand White Rabbits. The area was covered with gauze and secured by a thick plastic binder, which was removed atfter 24 hours, and the skin washed with water or corn oil.
Following the skin wash, animals were observed for mortality and toxic effects at 2 hr and 4 hr, and once daily thereafter. Body weights were recorded pretest and at termination. Dermal irritation was recorded at 24 hr, 3, 7, 10 and 14 days.
The rabbits were observed 1, 2, 4 and 6 hours after dosing and once daily for 14 days. Mortality, toxicity and pharmacological effects were recorded. Body weights were recorded pretest and in the survivors at 14 days. At 14 days the survivors were sacrificed. Animals were examined for gross pathology.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.69

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Other effects:

The initial response of the skin to the test material was slight. with Iittle difference in response between intact or abraded sites.

Table 1. Erythema scores

Animal	1 day	3 day	7 day	10 day	14 day
Number
1M	2	2	4	4	1
2M	1	2	4	4	1
3F	2	4	4	4	0
4F	2	3	4	4	0
Note: All animals showed signs of scar formation after 14 days.

Table 2. Edema scores

Animal	1 day	3 dav	7day	10 day	14 day
Number
1M	3	2	2	2	1
2M	2	3	2	2	0
3F	3	3	2	2	0
4F	3	3	2	2	0

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The material was judged to be moderately to severely irritating to the occluded skin.

Executive summary:

New Zealand white rabbits were dermally treated with 3.16 g/kg Naphthenic acids under occlusive dressing for 24 hours, afeter which the skin was washed with water or corn oil. The rabbits were observed 1, 2, 4 and 6 hours after dosing and once daily for 14 days. No deaths occurred at the 3.16 mg/kg dose level. Redness and irritation scores were recorded at 24 hr, 3, 7, 10 and 14 days post-washing. Mean values (24, 48 & 72 hours) for erythema and edema at the intact sites were 1.69 and 1.3 respectively. The initial response of the skin to the test material was slight, with little difference in response between intact or abraded sites. Erythema and edema were partly reversible after 14 days; all animals showed signs of scar formation after 14 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Dermal irritation was confirmed in 2 combined acute dermal toxicity/irritation in New Zealand white rabbits:

- In a Key study, 3.16 g/kg was applied in 4 rabbits (2/sex) under occlusive dressing for 24 hours, after which the skin was washed with water or corn oil (HPVIS, 2003; Exxon, 1979). The initial response of the skin to the test material was slight, with little difference in response between intact or abraded sites. Mean values (24, 48 & 72 hours) for erythema and edema at the intact sites were 1.69 and 1.3 respectively. Erythema and edema were partly reversible after 14 days; all animals showed signs of scar formation after 14 days.

- In a supporting study according to 16 CFR 1500.40, the test material was administered to six animals (3/sex) at a single dose level of 20.0 g/kg (Auletta, 1979). The test material was held in contact for 24 hours under occlusive dressing. No evaluation of erythema of the application site could be made at the twenty-four hour dermal observation because the test material masked the true color of the skin. Half of the animals exhibited very slight edema and half exhibited slight edema at the application site. The value of this study is limited to derive a proper classification, and is only supportive

Indications of eye irritation were described in a supporting study in New Zealand white rabbits (HPVIS, 2003; Exxon, 1979). One animal had a positive corneal score that was noted on days 1 and 2. One animal had a positive iris score which was noted during hours 1 and 4. All animals exhibited positive conjunctival scores at some point during the first three days of observation, however by day 4, no animals showed positive scores.As the substance was shown to be a skin irritant, a worst case classification as eye irrit 2 was proposed and further testing deemed unnecessary in view of animal welfare. This complies with Column 2 of REACH Annex VIII: 8.2.1 (the study does not need to be conducted if: the substance is classified as irritating).

Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Further eye irritation testing was waived based on the available data and based on Column 2 of REACH Annex VIII

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

According to available data and the criteria of the CLP regulation (No. 1272/2008 of 16 December 2008), Naphthenic acids is classified as Category 2 skin irritant, with signal word 'warning' and hazard statement: H315 - Causes skin irritation. 

For the eye irritation endpoint, Naphthenic acids is classified as Category 2, with signal word 'warning' and hazard statement: H319 -Causes serious eye irritation.