Hydrotreated mixture of middle straight-run gas oil and soybean oil

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose 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: Standard method, GLP-compliant, adequate experimental details for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

yes

Remarks:

substance applied 3 times per instead of 5 or 7 times per week

Principles of method if other than guideline:

Subacute dermal toxicity test as described. Micropathology limited to control and high-dose animals

GLP compliance:

yes

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Type:

Constituent

Details on test material:

Clear liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on exposure:

Method of administration:
6hr topical application under occlusion, 3x weekly for 4 weeks

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Duration of exposure per day: 6 hours
3 times per week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 200 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Male: 5 animals at 2000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 200 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 2000 mg/kg bw/day

Control animals:

yes, sham-exposed

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

See details on results

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

See details on results

Mortality:

mortality observed, treatment-related

Description (incidence):

See details on results

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

See details on results

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 examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

See details on results

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

skin consisted of dry, scaly or thickened skin (treatment related)

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

skin changes - no reported changes to any other tissues examined

Histopathological findings: neoplastic:

not examined

Details on results:

Clinical observations:
[1] There was one incidental death in an animal receiving
200 mg/kg, on day 12. There was no evidence of systemic
toxicity other than reduced body weight gain in high dose
animals (see below). Treatment-related dermal changes were
noted in all groups (except controls), consisting of erythma
and oedema, cracked, flaky and/or leathery skin which was
assessed as moderate at 2000 mg/kg, slight to moderate at
1000 mg/kg and minimal at 200 mg/kg.

[2] Body weight changes.

Both males amd females receiving 2000 mg/kg lost weight in
the first week of study, resulting in overall statistically
lower body weight gain compared with controls over the
entire study. Body weight gain over the last 3 weeks of the
study was however normal, as were body weights and body
weight gain in the 2 lower dose groups. The effects on body
weight are attributed to the stress of the dosing procedure
during Week 1.

Laboratory findings:
No significant changes in blood chemistry or haematology.

Effects in organs:
Absolute and relative kidney weights were significantly
increased in males receiving 2000 mg/kg, while relative
kidney weight was decreased in females at this dose level.
Relative adrenal weights were increased in both males and
females at this dose level and in females at 200 mg/kg
(within historical control range and considered unlikely to
be related to treatment) and relative brain weight was also
increased in females at 2000 mg/kg (also unlikely to be
related to treatment). No microscopic findings were reported
that could be related to treatment, other than
histopathological effects in the skin and increased
granulopoiesis/cellularity of the bone marrow in 4 high-dose
males and 5 high-dose females. The histopathological
changes in the skin consisted of epidermal hyperplasia and
hyperkeratosis accompanied by inflammatory changes in the
dermis. No histopathological examination was carried out on
the skin of animals receiving 200 or 1000 mg/kg.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 200 mg/kg bw/day

Basis for effect level:

other: Local effect -skin irritation

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Reproductive toxicity: no adverse findings recorded during microscopic examination.