Registration Dossier

Administrative data

Description of key information

28-day repeated dose toxicity, dermal - Systemic NOAEL= 5 ml/kg, or approximately 3750 mg/kg (OECD TG 410 under occlusive conditions)

28-day repeated dose toxicity, inhalation - Systemic NOAEC=2050 ppm, or approximately  9840 mg/3 (OECD TG 412)

90-day repeated dose toxicity, inhalation - Systemic NOAEC>20,000 mg/m3. Local NOAEC = 10,000 mg/m3 (OECD TG 413).

Chronic toxicity, inhalation - Systemic NOAEC=292 ppm, or approximately 1400 mg/m3  (OECD 453)

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 402 mg/m³
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
375 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
total of 50 studies with gasoline or low boiling point naphthas covering sub-acite, sub-chronic and chronic exposure. No effects except for dermal irritaton at test application sites.

Additional information

Repeated exposure of rats by inhalation to unleaded gasoline and naphtha blending stocks produced very minor effects and only at the highest levels tested (20,000 – >30,000 mg/m3, depending on the specific levels tested). Typically the highest levels used in these tests are limited by safety consideration related to fire and explosion hazards. The various reported changes at the highest levels included body weight effects, organ weight changes, variations in hematologic parameters, and red nasal discharge although not all effects were found in all studies. The only pathological findings reported were changes in male rat kidneys associated with alpha-2u-globulin-induced renal nephropathy. When animals were held without treatment prior to sacrifice (i.e., recovery groups), the majority of these changes disappeared. In a study of unleaded gasoline in monkeys, no toxicologically important findings were apparent at the highest exposure level tested (approximately 7400 mg/m3).  The data from the naphtha blending stocks are very consistent with the data from gasoline itself.

The dermal studies indicate that gasoline has a very low potential for systemic toxicity as a consequence of dermal administration. However, repeated treatment at high levels can produce quite severe dermal effects at the application site.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

one of 5 studies investigating the nephrotoxic potential of light hydrocarbons. Alpha 2 u globulin induced nephropathy in the male rat is not a relevant health effect for humans

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

One of 22 studies investigating repeat dose toxicity following inhalation exposure for periods up to 2 yrs. The only consistent effect was alpha 2u nephropathy in male rats, an effect which is not relevant for human health.

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

Chronic dermal mouse study, support by 49 other repeat dose dermal studies in rats and mice covering sub-acute and sub-chronic exposure.

Justification for classification or non-classification

Many of the studies described in this section followed regulatory guidelines and many have been published in the scientific literature.  The data are sufficient for regulatory purposes, no additional testing is necessary. According to EU CLP regulation (EC No. 1272/2008), the classification for systemic toxicity is not warranted.