Mixed LOF

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report similar or equivalent to OECD TG 411 performed on an analogue substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Naphtha (petroleum), light catalytic cracked

EC Number:

265-056-2

EC Name:

Naphtha (petroleum), light catalytic cracked

Cas Number:

64741-55-5

IUPAC Name:

Naphtha (petroleum), light catalytic cracked

Constituent 2

Reference substance name:

Light catalytically cracked naphtha

IUPAC Name:

Light catalytically cracked naphtha

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on exposure:

Dermal exposures

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days per week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
30 mg/kg/day
Basis:
nominal per unit body weight

Doses / concentrations 2

Remarks:

Doses / Concentrations:
125 mg/kg/day
Basis:
nominal per unit body weight

Doses / concentrations 3

Remarks:

Doses / Concentrations:
300 mg/kg/day
Basis:
nominal per unit body weight

No. of animals per sex per dose:

15 male and 15 female rats per dose

Control animals:

yes, sham-exposed

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY: All rats survived to the end of the study and were euthanized after thirteen weeks of treatment. Moderate erythema, slight edema (in males only), and flaking of the skin were observed in the treated groups during the dosing phase of the study.

BODY WEIGHT AND WEIGHT GAIN: Final body weight data did not show any treatment-related effects.

CLINICAL CHEMISTRY: The results suggest that 13 weeks of dermal treatment with LCCN marginally affected normal serum chemistry of male Sprague-Dawley rats without affecting female rats.

ORGAN WEIGHTS: Final organ weight date did not show any treatment-related effects.

GROSS PATHOLOGY: Findings included various skin lesions - scabs, erosion, scratches, scaling, dry skin and red-brown spots - were observed in fifty percent or more of the treated rats and in none of the controls.

HISTOPATHOLOGY: NON-NEOPLASTIC: Microscopic examination of the skin indicated mild to moderate epidermal hyperplasia, mild inflammation of the superficial dermic, and ulceration. The degree of skin reaction was surprising since the material was not covered and appeared to evaporate from the skin within minutes.

Effect levels

1

Dose descriptor:

NOEL

Remarks:

dermal irritation

Effect level:

< 30 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

dermal irritation

2

Dose descriptor:

NOEL

Remarks:

systemic effects

Effect level:

> 300 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical biochemistry

gross pathology

histopathology: non-neoplastic

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Repeated dose dermal applications of light catalytically cracked naphtha at 30 mg/kg, 125 mg/kg, and 300 mg/kg resulted in slight to moderate dose-dependent dermal irritation effects. Based on these findings, the dermal irritation NOEL was determined to be less than 30 mg/kg/day. The systemic NOEL was determined to be greater than 300 mg/kg.

Executive summary:

Light catalytically cracked naphtha was administered dermally to rats (15 males and 15 females per group) at concentrations of 30, 125, and 300 mg/kg five days per week for 13 weeks to evaluate the subchronic toxicity of the test material. Slight to moderate dose-dependent dermal irritation in all dose groups was seen during the study. No animals died. There were no effects on body weight gain or organ weights. Statistically significant results were concluded from the gross pathological and histopathological examinations and the serum chemistry analyses. Based on these findings, the dermal irritation NOEL was determined to be less than 30 mg/kg/day. The systemic NOEL was determined to be 300 mg/kg.