Fuels, diesel, co-processed with hydrocarbons derived from thermally cracked waste plastics

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

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

Guideline:

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

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Fuels, diesel

EC Number:

269-822-7

EC Name:

Fuels, diesel

Cas Number:

68334-30-5

IUPAC Name:

Fuels, diesel

Constituent 2

Reference substance name:

Diesel

EC Number:

918-958-1

IUPAC Name:

Diesel

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.