Registration Dossier

Administrative data

Description of key information

No data on the oral and inhalation are available or required given that the dermal route is the most plausible route of exposure to Heavy Fuel Oil Components.

Changes in haematological and clinical chemistry parameters and organ weight/s have been reported post dermal exposure to Heavy Fuel Oil Components. In general, alterations in serum cholesterol and blood urea nitrogen were recorded following administration of higher dermal doses accompanied by red cell, platelet, liver and thymus effects at lower treatment levels.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
1.06 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Decreased platelet count, increased relative liver weight (with histopathological change at higher treatments) in male rats and increased relative liver
weight in female rats.

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
subchronic
Species:
rat
Quality of whole database:
Skin irritation: Hyperkeratosis at treatment site observed in female rats

Additional information

Results from a series of GLP-compliant sub-acute studies of up to 28 days duration in rats and rabbits indicate the occurrence of treatment-related irritation in some, but not all, studies. Comparable findings were also observed following sub-chronic exposure and indicate that more extended exposure (i.e. 90 days versus 28 days) did not lead to any progression in severity of this effect (Feuston, 1994, 1997; ARCO, 1994d; Mobil, 1995a, 1994a,b, 1992e, 1985a, 1988l; API, 1985a, and Cruzan, 1986).

 

Systemic findings in the rat following 28 days repeated dermal exposure to Heavy Fuel Oil Components included decreased body weight, increased liver weight (sometimes with accompanying microscopic changes) and alterations in haematological and clinical chemistry parameters (ARCO, 1994c; 1993c; 1992ab-ag; 1990j; 1988c; 1987g,h; API, 1986a; 1983a). 28-day dermal exposure to Heavy Fuel Oil Components has also been demonstrated to adversely affect the liver of rabbits (API, 1980a-d).

 

Sub-acute no-effect levels for samples rich in cracked components (NOAEL = 1-10 mg/kg bw/d) were lower than those where non-cracked material predominated (NOAEL = 94-2350 mg/kg bw/d) but there were qualitative similarities in the type of systemic changes observed. Information is also available from rat sub-chronic dermal toxicity testing of two straight run samples and eight heavily cracked samples in the rat. Systemic findings included alterations in haematological parameters (RBC, HGB, HCT, platelets), clinical chemistry values (cholesterol, BUN) and organ weights (liver, thymus) with no clear relationship apparent between refining history and the resultant toxicological responses (i.e. common and consistent systemic findings were commonly present for both straight run and cracked samples). The red cell and platelet effects may have been secondary to bone marrow histopathology reported in rats following sub-chronic treatment with some Heavy Fuel Oil Components (e.g. heavy vacuum gas oil, heavy atmospheric gas oil, catalytic cracked heavy fuel oil, FCCU decant oil).

 

A systemic subchronic dermal NOAEL of 1.06 mg/Kg/day has been reported in a key study in male and female rats (ARCO, 1993a) while the NOAEL for local effects has been reported to be 53 mg/Kg/day in female rats in the same study. In another key but subacute study in rats (ARCO, 1993b), the systemic NOAEL was reported to be 1 mg/Kg/day in female rats and the LOAEL for local effects was reported to be 1 mg/Kg/day in both sexes of rats when the test material was applied undiluted.

 

Overall, there is sufficient evidence to indicate that Heavy Fuel Oil Components have a potential to cause systemic toxicity following repeated dermal exposure.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

One of 31 available studies

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

One of 31 available studies.

Repeated dose toxicity: dermal - systemic effects (target organ) cardiovascular / hematological: blood coagulation; digestive: liver

Justification for classification or non-classification

There is evidence to indicate that Heavy Fuel Oil Components have a potential to cause systemic alterations following repeated dermal exposure. Classification as STOT RE2- H373 is appropriate under the EU CLP Regulation (EC No. 1272/2008).