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Toxicological information

Acute Toxicity: dermal

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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:
other: Although no indication that it is a GLP study, the availeble 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

Data source

Referenceopen allclose all

Reference Type:
other: robust study summary
Title:
Unnamed
Year:
2003
Report date:
2003
Reference Type:
publication
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:
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
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Naphthenic acids
EC Number:
215-662-8
EC Name:
Naphthenic acids
Cas Number:
1338-24-5
Molecular formula:
For the acidic (naphthenic) fraction: CnH2n+zO2, where n = carbon number and z = homologous group series number: z = 0 when no ring structures are present, z = -2 when 1 ring is present, z = -4 when 2 rings are present etc. For the non-acidic fraction: not applicable
IUPAC Name:
Naphthenic acids
Test material form:
liquid
Details on test material:
Physical state: Viscous liquid
Appearance: Pale yellow to dark amber

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 atfter 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 thereatter. 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. Ananimals 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:
lethargy, diarrhea, ptosis, adipsia, anorexia, and few feces
Body weight:
No data
Gross pathology:
No
Other findings:
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.
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:
GHS criteria not met
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. 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.