ABSTRACT
Lubricating oil base stocks (LOBs) are substances used in the manufacture of finished lubricants and greases. They are produced from residue remaining after atmospheric distillation of crude oil that is subsequently fractionated by vacuum distillation and additional refining steps. Initial LOB streams that have been produced by vacuum distillation but not further refined may contain polycyclic aromatic compounds (PACs) and may present carcinogenic hazards. In modern refineries, LOBs are further refined by multistep processes including solvent extraction and/or hydrogen treatment to reduce the levels of PACs and other undesirable constituents. Thus, mildly (insufficiently) refined LOBs are potentially more hazardous than more severely (sufficiently) refined LOBs. This article discusses the evaluation of LOBs using statistical models based on content of PACs; these models indicate that insufficiently refined LOBs (potentially carcinogenic LOBs) can also produce systemic and developmental effects with repeated dermal exposure. Experimental data were also obtained in ten 13-week dermal studies in rats, eight 4-week dermal studies in rabbits, and seven dermal developmental toxicity studies with sufficiently refined LOBs (noncarcinogenic and commonly marketed) in which no observed adverse effect levels for systemic toxicity and developmental toxicity were 1000 to 2000 mg/kg/d with dermal exposures, typically the highest dose tested. Results in both oral and inhalation developmental toxicity studies were similar. This absence of toxicologically relevant findings was consistent with lower PAC content of sufficiently refined LOBs. Based on data on reproductive organs with repeated dosing and parameters in developmental toxicity studies, sufficiently refined LOBs are likely to have little, if any, effect on reproductive parameters.
Subject(s)
Petroleum/toxicity , Toxicity Tests, Acute , Toxicity Tests, Chronic , Administration, Cutaneous , Administration, Inhalation , Administration, Oral , Animals , Carcinogens/toxicity , Female , Fetal Development/drug effects , Lethal Dose 50 , No-Observed-Adverse-Effect Level , Polycyclic Aromatic Hydrocarbons/analysis , Polycyclic Aromatic Hydrocarbons/toxicity , Pregnancy , RatsABSTRACT
Oral repeated-dose studies with low-viscosity mineral oils showed distinct species and strain differences, which are hypothesized to be due to differences in bioavailability, with Fischer 344 rats being more susceptible than Sprague-Dawley rats or dogs. Sensitive analytical methodology was developed for accurate measurement of low levels of mineral hydrocarbons and applied in single-dose toxicokinetics studies in rats and humans. Fischer 344 rats showed a 4-fold higher AUC(0-∞) and consistently higher blood and liver concentrations were found than Sprague-Dawley rats. Hepatic mineral hydrocarbon concentration tracked the blood concentration in both strains, indicating that blood concentrations can serve as functional surrogate measure for hepatic concentrations. In human volunteers receiving 1mg/kg body weight of low-viscosity white oil, all blood concentrations of mineral hydrocarbons were below the detection limit. Comparison with threshold blood concentrations associated with NOAELs in both rat strains, indicate that the margin-of-exposure is at least 37-fold. Using an internal dose metric rather than applied dose reduces the uncertainty around the temporary ADI considerably since it intrinsically accounts for intra- and inter-species differences. The current data support replacement of the temporary ADI of 0.01 mg/kg/day by a (permanent) ADI of at least 1.0mg/kg/day for low- and medium-viscosity mineral oils.
Subject(s)
Mineral Oil/pharmacokinetics , Mineral Oil/toxicity , Adult , Animals , Area Under Curve , Female , Gas Chromatography-Mass Spectrometry/methods , Humans , Hydrocarbons/blood , Liver/drug effects , Liver/metabolism , Liver/pathology , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Rats , Rats, Inbred F344 , Rats, Sprague-Dawley , Species Specificity , Young AdultABSTRACT
Early subchronic and chronic inhalation toxicology studies on various petroleum mineral oils and formulated lubricants supported the ACGIH TLV of 5 mg/m(3) for mineral oil mist. Additional subchronic studies with aerosolized mineral base oils and lubricants during the last 15 years demonstrated that exposures to aerosols of mineral base oils (often >100 mg/m(3)) resulted mainly in concentration-related accumulation in the lung of alveolar macrophages laden with oil droplets. Inflammatory cells were observed with higher aerosol concentrations, consistent with the clinical literature from highly exposed workers. These pulmonary changes appeared to be a nonspecific response to the presence of deposited aerosol. Studies on sensory irritation during exposures of lab animals to mineral oils indicate possible effects only with very high aerosol concentrations. Coupled with changes in refining to remove carcinogenic polynuclear aromatic hydrocarbons from mineral oils several decades ago, this information indicates that current aerosols of mineral oils have a profile of low toxicity from acute to long-term exposures. Available information suggests that additives in some formulated products and/or maintenance of mineral-based metalworking fluids may play a much more significant role in potential health effects.
