HAZARDS IDENTIFICATION

I. TOXICOKINETICS

ABSORPTION
Inhalation Exposure
 Indirect evidence from case reports of gasoline sniffers
 Increases in blood, urinary lead levels, as well as the characteristic neurological signs –
indicators of exposure
 Gasoline – mixture
o Pattern of absorption following inhalation varies for the individual components
 Higher blood/gas coefficients, higher rate of absorption
o Xylene
o Benzene
o Toluene
 Lower coefficients
o Cyclohexane
o Ethane
o Ethylene
Oral Exposure
 Absorption is believed to be relatively complete because of the high lipophilicity of the
hydrocarbon compounds, large surface area of the gastrointestinal tract, and the long
resident time in the tract

Dermal Exposure
 Dermal absorption of hydrocarbon solvents is known to be low relative to the oral route
Aromatic hydrocarbons are expected to have higher skin penetration than the aliphatic
hydrocarbons
o Benzene

DISTRIBUTION
Inhalation Exposure
 Elevated blood levels of hydrocarbons
o Benzene, toluene, pentane, hexane
o Detected in the blood samples collected from Wistar rats immediately after
exposure to 5,000ppm gasoline vapor after 30mins
 Lead concentrations were slightly elevated in the blood
 Triethyl lead, inorganic lead, metabolites of tetraethyl lead may accumulate in the brain
and produce encephalopathy and slowed nerve conduction

Oral Exposure
 Liver (663ppm), gastric wall (324 ppm), and lungs (457ppm)
o Had highest gasoline concentrations
  Brain (44.2), Bile (59), kidney (51.5)
 Conc in the blood from brain (29.4), lungs (132), heart (51.5
 Elevated blood levels of hydrocarbons such as benzene, toluene, pentane, and hexane

Dermal Exposure
 No studies

METABOLISM
 Not known, expected interacting gasoline components may affect metabolic products
formed
 Organic tetraethyl lead (was a component of gasoline)
o Converted to triethyl lead (liver)
o Water-soluble metabolite can accumulate in the brain
 Can be further broken down to inorganic lead

EXCRETION
 No specific data on the elimination of gasoline
 Varies because of the metabolism of gasoline components by hepatic enzymes
 Benzene, toluene, xylene metabolites
o Excreted primarily in the urine
 Inorganic lead eliminated in urine
 Urinary phenol (benzene) elevated in pump workers (40mg/L from normal <20mg/L)
 Estimated t1/2 – 16.9 hours

II. TOXICODYNAMICS

Nephropathy (Male wistar rats)

 Metabolite or one of its constituents (metabolite of 2,4,4-trimethyl-w-pentanol TMPOH)
binds to alpha2u-globulin
 Complex is reabsorbed in the proximal tubule (TMPOH-alpha2u-globulin complex),
difficult to catabolize
 Phagocytized by lysosomes within the tubule cells
 Lysosomes burst  induce toxicity and cell death
 Accumulation of casts and hyperplastic events

Liver Tumor Induction

 Antiestrogenic effects of unleaded gasoline is the possible underlying mechanism in
female mouse