Registration Dossier

Toxicological information

Repeated dose toxicity: dermal

Currently viewing:

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
Study period:
1992-09-14 to 1993-07-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it was GLP compliant and was generally conducted according to OECD 411 guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 411 (Subchronic Dermal Toxicity: 90-Day Study)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity liquid hydrocarbon
Details on test material:
in the absence of measured data density assumed to be 835 kg/m3 (average for EU)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours a day, 5 days a week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.01, 0.1, or 1.00 mL/kg/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
Twenty
Control animals:
yes, sham-exposed

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
NOAEL
Effect level:
0.1 other: mL/kg/day
Sex:
male/female
Basis for effect level:
other: body weight; food consumption; haematology; clinical chemistry; histopathology

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The systemic LOAEL is 1.00 mL/kg/day (estimated to be 835 mg/kg/day) based on moderate dermal irritation accompanied by decreased body weight (males only), increased food consumption, changes in differential leukocyte counts, decreased albumin (and albumin/globulin ratio), and increased incidence of lymphoid hyperplasia of the auxilliary lymph node. The NOAEL is 0.1 mL/kg/day (estimated to be 83.5 mg/kg/day).
Executive summary:

In a 90-day dermal toxicity study, diesel fuel (Diesel 1) was applied to the shaved skin of twenty Sprague-Dawley rats/sex/dose at dose levels of 0, 0.01, 0.10, or 1.00 mL/kg bw/day, 6 hours/day for 5 days/week during a 90-day period.

 

There was moderate dermal irritation in the high-dose, slight dermal irritation in the mid-dose group, and very slight dermal irritation in the low-dose group. Body weight was decreased in high-dose males, but food consumption was increased in both sexes of the high-dose group. Changes in differential leukocyte counts, decreased albumin (and albumin/globulin ratio), and increased incidence of lymphoid hyperplasia of the auxilliary lymph node also occurred in the high-dose group and were considered to be secondary to the dermal irritation. The systemic LOAEL is 1.00 mL/kg/day (estimated to be 835 mg/kg/day) based on moderate dermal irritation accompanied by decreased body weight (males only), increased food consumption, changes in differential leukocyte counts, decreased albumin (and albumin/globulin ratio), and increased incidence of lymphoid hyperplasia of the auxilliary lymph node. No treatment-related effects were noted in examination of the weight of the testes and ovaries nor in the histopathology of the testis, ovary, prostate and uterus.

The NOAEL is 0.1 mL/kg/day (estimated to be 83.5 mg/kg/day).

 

This study received a Klimisch score of one and is classified as reliable without restrictions because it was GLP compliant and was generally conducted according to OECD 411 guidelines.