Effects of ingestion of petroleum product (kerosene) on haematological parameters

Introduction

Fractional distillation of crude petroleum yield different fractions of petroleum products. Which are petrol, kerosene and diesel. These fractions of crude oil contain aliphatic, aromatic and a variety of branded saturated and unsaturated hydrocarbon (Anderson, Yu and Schmeizer, 1995). Large proportion of crude oil and other petroleum product are lipophilic in nature and biological membrane may therefore be the target sites where their adverse effects occur (Anozie and Onwurah, 2001).

Exposure to petroleum product through ingestion has been reported to have toxic effects on various organs and systems. Organs such as the hearts, lungs, skin and kidneys, while system such as the respiratory, immune and nervous system, resulting in various diseases and different forms of genotoxic, mutagenic, immunogenic, carcinogenic and neurogenic manifestation (Ross, 1996).

Petroleum product account for a large fraction of contamination at hazardous waste Sites, road side automobile mechanic whom have formed the wrong habits such as sucking of petrol with their mouth to wash their hands after work, also patients with sore throat are wrongly advised to lick sugar soaked in kerosene because it is claimed to cure sore throat (Chilcott and Chapd, 2007). Such acclaimed user occur with little or no care at all about it hazardous effect on health, which may result from accumulation of toxic Substances in them.

The metabolisms of aliphatic and aromatic hydrocarbons which are the major components of crude petroleum and petroleum products and even other xenobiotics result in generation of free radical species in various tissue (Achuba and Osakwe, 2003) free radicals are known to alter erythrocyte membrane as well as other cell membrane in red blood cell as a consequence of oxidative stress (Shakirov and Farkhudinov, 2000). Many compounds exert considerable dangerous influence on membrane integrity by direct contact with biomolecules, particularly the protein that constitute the architectural structure of plasma membrane (Anozie and Onwurah, 2001).

Petroleum products are used for various reasons by human beings at homes, in manufacturing and petrochemicals industries. The uses range from fuels for vehicles, cooking and lighting fuels in homes and outside homes, as chemical feedstock for industries as well as for therapeutic reasons (Hockabey, Wendy, VanCleave and Ostrander,1995). The daily use of petroleum product both in and outside petroleum industries may have effects on users, and those who work likely to be more affected their counterparts who do not work in these industries (Rothman, Li, Dosemeci and Marti,1996).

Conceptual framework

Kerosene, diesel and petrol are the most common constitute of petroleum product and they are all derived from the distillation of crude oil.

Kerosene is a liquid mixture of hydrocarbons (chain length C9-C16), produce by the distillation of Crude oil. It is important to note that kerosene is not a synonym for ‘’jet fuels’’ (which are distinct class of petroleum distillate product containing a range of chemical additives);

Diesel is a complex mixture of hydrocarbon produced by blending several fractions of crude oil distillate with brand specific chemical additives. The actual chemical composition of diesel varies widely according to the geographical source of crude oil, but generally comprises of C8 – C12   aliphatic hydrocarbon (boiling range 160-3600c) with up to 25% aromatic compounds. Diesel is defined as physical characteristic rather than chemical constituents (British Standard European Norm (BSEN, 2004).

Petrol is a complex mixture of aliphatic and aromatic hydrocarbon derived from blending fractions of crude oil with brand specific additives. The actual composition of petrol varies according to the source of crude oil, the manufacturing process and between batches. Examples of aromatic hydrocarbon are benzene, toluene, xylene and butadiene. Various concentrations are expressed as part per million (ppm), and refer to total hydrocarbon present. It should be noted that this conventional measure of concentration introduces a source error and should be considered at best an approximation, as the average molecular weight on which of part per  million (ppm) based.

Health effects of petroleum products

Prolonged dermal exposure to liquid, petrol or inhalation of vapour has been associated with renal dysfunction, attributed to liquid degeneration of proximal convoluted tubules and glomeruli (Master, 1991). The clinical manifestation includes haematuria, proteinuria and myoglobinuria. A late onset autoimmune glomerulonephrites is also described. Exposure to higher concentration of vapour is irritating to the eyes, respiratory track and skin. The critical health effect of petrol is chemical pneumonitis which arises from aspiration of liquid petrol or inhalation of petrol contaminated vomitius.

Ingestion of diesel or acute exposure to vapour may lead to general signs of intoxication such as mild central nervous system [CNS] with symptoms such as dizziness, headache, nausea and vomiting. Skin exposure to diesel may result in dermatitis [Conservation of Clean Air and Water in European(CONCAWE) (1996)]. Skin exposure to kerosene may result in dermatitis through the extraction of endogenous skin lipids. Ingestion of kerosene or acute exposure to vapour may lead to general signs of intoxication such as mild central nervous system (CNS) such as dizziness, headache, nausea and vomiting. Whilst kerosene is considered a direct acting dermal, carcinogen chronic skin exposure may result in turmourgenesis.

Kinetics and metabolism effects of petroleum products

As kerosene is a mixture of chemicals there is no definitive absorption, distribution, metabolism and excretion (ADME) data. Individual components of kerosene are known to undergo dermal absorption (Singe,2003) and kerosene is absorbed following pulmonary exposure. The extent of dermal and pulmonary absorption is close and time dependent (Bebarta,2004). Limited number of metabolism studies suggested that kerosene efficiently removed from the circulation by the liver and lungs.

Petrol is a complex mixture of hydrocarbons so there is no definitive absorption, distribution, metabolism and excretion (ADME) data available for animals or humans. The onset of local or systemic effect following dermal, oral and inhalation exposure indicate that these are all potential routes of entry for petrol vapour or liquid. Petrol exposure alter hepatic enzyme activity in rats and human (Priestly,1981), Dermal exposure to petrol can be retrospectively identified following solvent extraction of

Hydrocarbon from the skin.

Diesel is a mixture of chemicals, there is no definitive absorption, distribution, metabolism and excretion (ADME) data available for either animals or humans. The onset of local or systemic effects following dermal, oral or pulmonary indicates that these are all potential routes of absorption of diesel (International Agency for the Research on Cancer, 1989).

Sources and route of exposure

The main route of exposure to kerosene causing toxicity is via inhalation during ingestion (aspiration). Acute, oral exposure may occur from accidental or intentional ingestion. Inhalation of kerosene may occur through occupational exposure to petrochemical and aviation sectors, from the use of commercially available products such as paints and insecticides, via accidents release e.g. road traffic incident or through substance abuse. Contaminated water may represent a substantial aspiration risk during whole body immersion (swimming or near drowning).

Domestic exposure to diesel is uncommon, although limited skin exposure may occur whilst refueling domestic vehicles and pulmonary exposure may result from ingestion of liquid during manual siphoning. Leakage of diesel unto hot engine manifolds may liberate a respirable aerosol of micrometer sized diesel particles (Wilson, 2001). Occupational exposure may potential occur during manual filling within the petrochemical industry. Repair of diesel engine, where diesel is used as a cleaning agent,

Diesel accounted for all spillage resulting from road traffic incidents in the UK during 2003 and 42% of all significant, pollution incidents for the same period.

Petrol contains mixture of volatile hydrocarbons and so inhalation is the most common form of exposure (Short, 1997). Petrol vapour can reach supra-lethal concentrations in confined ventilated areas, although such exposures are rare. It is generally considered that dermal absorption of petrol does not contribute significantly to systemic signs of toxicity. Accidental ingestion of petrol by adult is often the result of siphoning petrol tanks where as the incidence of petrol ingestion in children is relatively low.

Health effects of acute/single exposure of petroleum products on human

The health effect of acute / single exposure of petroleum product on human are as follows;

General Toxicity

The acute health risks involved in handling and using petrol are minimal provided that the products are used in accordance with appropriate health and safety practices. The main health effect associated with petrol exposure is chemical pneumonitis, following ingestion. Vascular endothelial damage of the liver, lung, kidney and spleen has been described following severe intoxication with associated renal lipid degeneration confined mainly to the proximal tubules (Holder,1974). A rare complication of petrol Intoxication maybe cardiac amhythia and ventricular fibrillation, attributed to increased myocardial sensitivity to endogenous catecholamine’s (Litovitz,1988).

The main hazard associated with diesel is chemical pneumonitis that may arise following aspiration of vomitus (ingestion) or inhalation of aerosol during manual siphoning (International Programmme on Chemical Safety,1996).

The acute health risks involved in handling and using kerosene are minimal provided that the products are used in accordance with current safety practices. The main hazard associated with kerosene is chemical pneumonitis resulting from aspiration of vomitus following ingestion (National Poison Information Service, 2003) or inhalation of kerosene liquid or contaminated water. A rare complication of kerosene intoxication may be cardiac arrhythmia and ventricular fibrillation attributed to increased

Myocardial sensitivity to endogenous catecholamine’s (Bebarba,2004).

Inhalation

It has been suggested that the concentration of petrol vapour is the primary determinant of acute toxicity rather than duration of exposure (Iron,1961). This assumption is based on exposure of less than 30mins and relate to one study of three dogs dosed with different petrol product. Petrol

Vapour  is readily detectable by most individual at concentration below 1 to 2 parts per million (ppm) (Whittemore,1983), although prior exposure within 24hours or chronic, occupational exposure may increase the olfactory  threshold in sufficient concentration (>10,000ppm),petrol may act as an anaesthetic, sometimes resulting in immediate loss of consciousness following inhalation effects on central nervous system are readily apparent above 900 (ppm) within a few minutes, the morbidity of which resembles alcohol intoxication (dizziness, excitement and incoordination).

It has been stated that inhalation of diesel vapour may lead to central nervous system (CNS), respiratory depression and cardiac arrhythmias. However there is no specific case study to confirm these effects; it is assumed that the presence of low molecular weight hydrocarbon in diesel is sufficient to contribute to such signs of toxicity (Powell, 2001).Most clinical instances of myocardial sensitization occur following exposure to volatile solvent such as those found in adhesive lighter fluid, nail polish remover and aerosol propellants. Diesel vapours at 37 predominantly contain C10+hydrocarbon. Direct aspiration of diesel is a secondary source of pulmonary exposure that may lead to chemical pneumonitis, a delayed onset and potential fatal lung disorder characterized by cyanosis, dyspnoea and chest x-ray opacities.

Whilst kerosene vapour may be mildly irritating to the respiratory system, exposure is not likely to be fatal as the low volatility of kerosene, limits air concentrations to below 100mg/m-3, which is the approximate no observable adverse effect level (NOAEL) in several animal species (Rhode, 1995). However, exposure within a confined space at elevated temperature may induce narcotic effects such as narcolepsy, cataplexy and confusion. Inhalation of water contaminated with kerosene may occur when swimming, and has been associated with exogenous lipoid pneumonia. Spray application may result in exposure to high concentration of kerosene aerosol, which may provoke signs of pulmonary irritation such as coughing and dyspnoea, in addition to mild central nervous system (CNS) depression.

Ingestion

Following oral intake of diesel, the signs are generally stated which include nausea, vomiting, diarrhoea, irritation of the aero-digestive and gastro intestinal tracts (GIT). In one reported case of intentional poisoning, chemical pneumonitis was observed which may have been due to aspiration of vomitus (Fabre,1983).

Ingestion of petrol may cause acute generalized signs of gastro-intestinal tracts (GIT) irritation including nausea, vomiting colic and diarrhoea. The relatively low oral toxicity of petrol is Comparable to that of other petrochemical products such as kerosene. Ingestion of 7.5g/kg-1  has been reported to be the lethal dose in adult humans in the absence of pulmonary effect caused by aspiration of ingested petrol (Machle,1941). A critical delayed health effect associated with petrol with ingestion of petrol is chemical pneumotitis, resulting from aspiration of petrol during the swallowing process following emesis.

Signs of oral kerosene poisoning include diarrhoea, nausea and vomiting. Approximately 30-50% of children presenting with suspected kerosene ingestion as asymptomatic. Death following oral exposure is normally associated with aspiration of vomit rather than systemic toxicity.

Dermal/ocular exposure

Acute dermal exposure of diesel may result in local irritation such as erythema and prvritis which is generally more severe than that seen with other middle distillate products. The incorporation of additive may augment dermal sensitivity to diesel. It has been suggested that the inclusion of visible markers may increase the self-perceived dermal irritancy of diesel (Wahlberg, 1995). Eye exposure to diesel may cause transient pain and hyperaemia. Diesel is generally considered to be less irritating to the eyes than other middle distillate fuels such as kerosene and petrol.

Kerosene is a mild, transient ocular irritant that may produce conjunctivitis, hyperaemia and lacrimation. Acute dermal exposure may result in local irritation [erythema,pruritis] a small proportion of individual (<5%)  may exhibit hypersensitivity to kerosene, and skin contact may result in burn like injuries (Varsano, 1992).

Mild ocular irritation may follow prolong 8hrs exposure to low concentration (140ppm) of petrol vapour or short 30minutes exposure to vapour above 200ppm. More pronounced signs of ocular toxicity (lacrimation) occur above concentrations of 1000ppm (Davis,1960). The substance causing eye irritation was distilled from gasoline at extremely low temperature and in very small amounts. Petrol ‘’burns’’ resemble scalding, with an initial erythema leading to blister formation. Prolonged dermal exposure between 45 minutes-12 hours  may lead to partial or full thickness burn with associated loss of epidermis and coagulation necrosis (brown, yellow, gold).

Neurotoxicity

Diesel is known to contain a number of potentially neurotoxic substances and exposure to other mild distillate fuels has resulted in neurotoxic chemicals including drowsiness, neurasthenia and decreased sensorimotor speed.

Petrol contains number of potentially neurotoxic chemicals including n-hexane, benzene, butadiene, toluene, ethylbenzene, xylene and trimethyl pentane. Historically, lead (as tetraethyl lead TEL) has been identified as the principal component of petrol responsible for neurological deficits following intentional (recreational) inhalation or massive acute exposure.

Acute exposure to kerosene in human has been associated with a variety of central nervous system (CNS) effects including irritability, restlessness, ataxia, drowsiness, convulsions, coma and death, these are generally considered to be secondary effects resulting from hypoxia (Farwana,1981).

Delayed effects following an acute exposure

There is a limited evidence to suggest that long term pulmonary residual effects may occur following chemical pneumotitis. These effects are considered minor and are of unknown clinical relevance to kerosene (Henry, 2001).

Limited evidence to suggest that long term pulmonary residual effects may occur following chemical pneumonitis as a result of aspiration induced pneumonitis; these chronic effects are of unknown clinical relevance to diesel (Seymour, 2001).

There is a limited evidence to suggest that long term pulmonary residual effects may occur following chemical pneumonitis as a result of aspiration induced pneumonitis; the effect of which are of unknown clinical relevance to petrol. A variety of delayed, neurological deficits have historically been associated with the acute inhalation of petrol vapour including peripheral neuritis, impairment  of memory paresthesia, ataxis and epilepsy (Machle,1941).

Animal and in-vitro data

General toxicity

The oral toxicity of diesel is relatively low in rats. Diesel was reported as been non irritating to the eyes but severely irritating to the skin of rabbits. No death was reported following acute dermal exposure to 5g/kg-1 in rats study (International Agency for the Research on Cancer,1989).

The acute toxicity of petrol in a variety of animal species is broadly consistent with that reported in humans being predominantly associated with central nervous system (CNS), pulmonary and renal effects.

The oral toxicity of kerosene in a variety of laboratory animals is of the order 20-30g/kg-1. Intra-tracheal dosing of kerosene liquid which models the aspiration of vomit in humans result in substantial increase in toxicity and is consistent with known human health effects.

Health effects of chronic/ repeated exposure to petroleum production human

The health effects of chronic/repeated exposure on human are as follows;

General toxicity

The most common health effects associated with chronic/repeated kerosene exposure is dermatitis which may be associated with insufficient use of personal protective equipment (PPE) in occupational environments. Lung effects such as dyspnoea have been reported but tend to be associated with high level exposures (Still, 2003). It is conceivable that similar lung and skin effects may be observed in some individuals following a single, acute exposure.

Chronic or repeat exposure to diesel may result in dermatitis although there is some evidence to suggest that hyperkeratosis may be common feature of regular contact with diesel (International Programme on Chemical Safety, 1996). Under normal industrial or domestic use, dermal contamination is the most likely exposure scenario.

Dysfunction of the central nervous system is the predominant  pathological condition associated with chronic exposure to high levels such effects arising from frequent recreational exposure (sniffing or huffing) have been extensively documented. There is currently insufficient evidence  to unequivocally link chronic (occupational) exposure to petrol with other pathological conditions, this may be because petrol chemical workers are potentially expose to a wide range of chemicals in addition to other confounding factors (International Agency for the Research on Cancer, 2002). Whilst there is a known association between chronic petrol exposure and renal cancer in rats, there is currently no evidence to link petrol exposure and renal cancer in humans, it is generally accepted that the susceptibility of rats are mediated via a specific protein which is absent in other mammals (Johnson, 1990).

Inhalation

There is a limited to suggest that chronic exposure to long chain hydrocarbon mixture may be associated with tightness of chest and breathing difficulties, although a review of the duration and extent of exposure in such circumstances was not reported. In some cases, a lorry driver was exposed to an unknown concentration of diesel vapour over ten days’ period signs and symptoms including abdominal cramps, nausea, vomiting, acute renal failure, anaemia and thrombocytopenia (Power, 1964)

Ingestion

Chronic oral exposure to kerosene is unlikely to arise under normal circumstances and there is currently no human data on the chronic effects of kerosene ingestion in humans.

Chronic, oral exposure to diesel is unlikely to arise under normal circumstances and there is currently no data available on the chronic effects of diesel injection in humans.

Dermal/ocular exposure

There is no report on the effects of chronic ocular exposure to diesel in humans .Chronic skin exposure to kerosene is known to cause dermatitis.

Neurotoxicity

Long term exposure to low concentration of kerosene have been reported to produce non-specific central nervous system effects such as nervousness, loss of appetite and nausea that is not related to hypoxia (Ritchie, 2001).

Genotoxicity

An increase in cytogenetic changes Chromosomal aberrations in peripheral lymphocyte and bone marrow micronuclei has been reported in a limited study of workers exposure to a mixture of kerosene, bunker fuel, white spirit and xylene (Gullbery, 1981). However the mixed exposure precludes any specific conclusions and the result do not correlate with the effects of kerosene only exposure in animals.

At relatively high concentrations (1000-2500 ppm) in cell culture medium, petrol was mutagenic in drosophila  melanogaster. Negative result were reports in an in vivo bone marrow assay for clastinogenicity in the rat. A report of positive result being obtained using the unscheduled DNA synthesis (UDS) assay; limited studies in vitro (essentially only one dose level used) gave a positive result using rat.

Carcinogenicity

Epidemiological have not demonstrated a statistically significant link between cancer and occupational exposure to petrol. However, the IARC has classified petrol as possibly carcinogenic to humans mainly on the basis that there was inadequate evidence for the carcinogenicity in humans but there was limited evidence for carcinogenicity in experimental animals.

An excess of lung cancer was seen large cohort of Japanese exposure to kerosene, diesel oil, crude petroleum and mineral oil. Three case control studies found an association between lung cancer and use of kerosene stoves for cooking among women in Hong Kong; however no distinction was made between exposure to kerosene and exposure to its combustion products. There is inadequate evidence to classify kerosene as a human carcinogen and limited evidence for the carcinogenicity of kerosene to experimental animals.

Reproductive and developmental toxicity

Current evidence indicates that kerosene does not have a measurable effect on human reproduction or development. This is in accordance to animal studies (Koschier, 1999).

No reports specifically pertaining to the human reproductive or developmental toxicity of petrol were identified. The NOAEL for productive toxicity in a two generation rat study was reported to be 20,000mg/m-3 (Gonnet, 2001) petrol is not classified under chemical hazard information and packaging supply (CHIPS) regulations as a reproductive or developmental hazard.

There is currently information concerning the effect of diesel exposure on human reproduction and development. Exposure to diesel is not an indication for invasive prenatal diagnostic tests or termination of pregnancy (National Poison Information Service, 2005).

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