Naphthenic acids, bismuth salts

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Although no indication that it is a GLP study, the available robust study summary published in the "robust study information on reclaimed substances: Naphthenic acid" by the API sufficient detail is provided to make a conclusion about its validity.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

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:

comparable to guideline study with acceptable restrictions

Remarks:

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:

designed as combined OECD 402 and 404 study

Principles of method if other than guideline:

This study is a combined study where Acute 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 24 h, 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

Remarks:

of 4 animals

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

Remarks:

of 4 animals

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 atter 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:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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, after 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.

Data source

Reference

Reference 1

Reference Type:

other: robust study summary

Title:

Unnamed

Year:

2003

Report date:

2003

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

designed as combined OECD 402 and 404 study

Principles of method if other than guideline:

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

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Raw naphthenic acid derived from kerosene

IUPAC Name:

Raw naphthenic acid derived from kerosene

Test material form:

other: liquid

Details on test material:

MRD-79-10 (Raw naphthenic acid derived from kerosene)

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

3.16 g/kg naphthenic acid was applied dermally to the clipped abraded abdomens of each animal. The area was covered with gauze and secured by a thick plastic binder, which was removed after 24 hours, and the skin washed with water or corn oil.

Duration of exposure:

24 hours

Doses:

3.16 g/kg naphthenic acid was applied dermally to the clipped abraded abdomens of each animal

No. of animals per sex per dose:

2 per sex

Control animals:

not specified

Details on study design:

According to experimental protocol, if no deaths occurred at the initial level, no addition animals were dosed. If one animal died, the experiment was to be repeated using 3 more groups of animals dosed at varying levels.
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.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 3 160 mg/kg bw

Based on:

test mat.

Mortality:

no

Clinical signs:

other: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces

Gross pathology:

No

Other findings:

No deaths occurred at the 3.16 g/kg dose level. Most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed. 3 out of 4 animals (1 male, 2 female) showed signs of toxicity until day 12 or 13. During the first 5 days, all animals displayed one or more of the following symptoms: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.
The LD50 was determined to be greater than 3.16 g/kg bw
Redness and irritation scores were recorded at 24 hr, 3, 7, 10 and 14 days post-washing. 4 Hour occluded sites (DOT, OECD methods)
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.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 to rabbits was found being > 3160 mg/kg bw.

Executive summary:

New Zealand white rabbits were dermally treated with 3.16 g/kg Naphthenic acids under occlusive dressing for 24 hours, after 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. Most of the animals (3/4) appeared normal during the first 2 to 4 hours of dosing, after which symptoms of toxicity were observed. 3 out of 4 animals (1 male, 2 female) showed signs of toxicity until day 12 or 13. During the first 5 days, all animals displayed one or more of the following symptoms: lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces.