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ABSTRACT
ARTICLE HISTORY
Gasoline was described to induce many biochemical and physiological dysfunctions with
subsequent disturbance of health and development of many diseases. It was reported Received June 05, 2018
Accepted July 18, 2018
to induce health hazards through generating reactive oxygen species with subsequent
Published August 01, 2018
harmful effects on the normal body physiology. This work reviewed the previous experi-
mental studies conducted on animal models and aimed to assess the effect of exposure KEYWORDS
to gasoline through different routes on the different body systems and organs. The histo-
Gasoline; car fuel; health;
pathological impact of gasoline on the nervous, respiratory, reproductive, and immune histology; pathology;
system was reviewed. Adding to that the impact of exposure to gasoline on the skin, trachea; skin; experimental
liver, kidneys, blood, bone marrow, and genes was also reviewed. It is hoped that this animals
review will encourage and support the conduction of more rigorous studies aimed to
assess the impact of gasoline on the health and possibly help in optimizing the exposure
standards for gasoline and other hydrocarbon fuels.
Although there were many studies conducted on days showed same changes but at a much severe
the effects of exposure to gasoline on different body degree (See Fig. 1).
organs through different routes, some controversy The same research team was investigating the
existed about these effects in this study. There was a tracheal histopathological changes induced in
need to summarize and discuss the results of these guinea pigs by inhalation of gasoline vapor in labo-
studies in order to be helpful for research studies ratory conditions [10]. The findings were consistent
aiming to work on this research area. This article with those reported by Al-Saggaf et al. [9] following
aimed to review the previous experimental studies exposure of animals at the station (See Fig. 2).
conducted on animal models to assess the effect of
exposure to gasoline through different routes on Effect of Gasoline on the Skin
the different body systems and organs. This review
It was described that skin is exposed to gasoline
raised the research question “what were the effects
during its use in cleaning, handling contaminated
proved to be induced by gasoline of the different
soil or water, or accidentally if spoiled on it and
body organs and systems of the experimental ani-
finally, exposure of workers at gas stations. Upon
mal in the previous research studies?”
exposure to gasoline, some ingredients of it can
pass through the skin [11].
Effect of Gasoline on the Nervous System
Some researchers have described that the skin of
The effect of vapor condensate of baseline gasoline guinea pig exposed to car fuel containing gasoline
(BGVC) and Gasoline/methyl tert-butyl ether (G/ for 21 days has resulted in erythematous thicken-
MTBE) on the pups of Sprague-Dawley rats exposed ing, ulcerated, firmly adherent to the underlying
to 10,000 and 20,000 mg/m3 6 hours/day, 7 days/ tissue, and bled abundantly on removal [12,13].
week was studied by Gray et al. [8]. They reported Microscopically, the thickness of the whole epider-
no adverse neuropathology in F1 pups and their mal, keratin, and granular layer was significantly
study revealed no alterations in F1 offspring-ex- increased compared to the control. Focal elon-
posed BGVC or G/MTBE in brain length or width gation of the rete ridges and infected ulcerations
compared to the control. They added that “exposure were also observed. Upon examined by the electron
to these substances did not cause changes in glial microscope, ill-defined dermo-epidermal junction
fibrillary acidic protein levels in any brain region and an increase in intercellular spaces among the
examined indicated that none of these substances basal layer cells due to desmosomal disruption
induced gliosis in the brain regions examined” [8]. were observed. The spinous and granular cell lay-
ers showed marked cytoplasmic vacuolation and
Effect of Gasoline on the Respiratory System the latter showed a marked decrease in fibrillar
contents. The individual layers in the stratum cor-
Al-Saggaf et al. [9] have studied the effect of car
neum were increased in thickness and the regular
fuel on histological structure of trachea and lung of
desmosomal junctions disappeared compared with
guinea pigs exposed to inhalation of gasoline near
the control [13] (See Fig. 3).
the station tanks for 30 and 90 days. They reported
These findings indicated that gasoline produced
that trachea of animals exposed to gasoline vapor
skin irritation as it possessed lipid solving prop-
for 30 days showed inflammatory cell infiltration,
erties [14]. This irritation could be induced by
mainly of lymphocytes and eosinophils, in the
“destructing the hydrophobic barrier produced by
mucosa and submucosa as well as significant reduc-
the lamellar bodies producing layers and, second,
tion in the number of goblet cells. Scanning electron
by a direct effect on cells of the epidermal kerati-
microscopic examination showed focal desquama-
nocytes stimulating the release of inflammatory
tion of epithelial cells together with loss and short-
cytokines such as interleukin-1α” [15]. Production
ening of cilia on some columnar epithelial cells. The
of reactive oxygen species free radicals, with the
lung alveoli of these animals showed focal inflam-
subsequent cytotoxicity, could be another mecha-
matory cell infiltrate, intra-alveolar hemorrhage,
nism behind gasoline-induced skin irritation [16].
and emphysematous changes in some areas while
Reese and Kimbrough [17] reported that gasoline
the bronchi and bronchioles showed sloughing of
increased cellular microsomal enzyme activity
their epithelial lining and hypertrophy of their mus-
with subsequent production of toxic metabolites of
cle layer. Animals exposed to gasoline vapor for 90
benzene.
Figure 1. “(A) Light microscopic sections of the trachea from the control group, and the group exposed to gasoline
vapor for 30 days at the station. (B) SM = Submucosa Eosinophils (thin arrow), inflammatory infiltrate (interrupted
arrow), di1ated gland (asterisk) and desquamated epithelium (white arrow). Lost cells (black thick arrows) and
goblet cells (arrow head (stained with Hematoxyline & Eosin). (C and D) Scanning electron microscopic sections
of the trachea from thecontrol group and the group exposed to gasoline vapor at the station. (E and F) Normal cilia
(thick black arrow), lost cilia (interrupted white arrow), short cilia (interrupted black arrow) goblet cells (thick
white arrow)” (cited after permission from Al-Saggaf et al. [13]).
Ahaghotu et al. [18] during their study on hair- most probably because of delipidization and pro-
less rats stated that xylene and tetramethyl benzene tein denaturation with subsequent loss of barrier
isomers (TMB) caused granulocyte infiltration, function and enhanced transepidermal water loss”
swelling of the epidermis, and widespread destruc- [18]. Gunasekar et al. [19] observed a rise in the
tion of stratum corneum, as well as increased number of mast cells and plasma cells at the epi-
expression of tumor necrosis factor in the skin dermal separation from the basement membrane
compared to control. They added that “gasoline and in the dermis which suggests immune reaction
led to disruption and separation of keratin layers, induced by TMB in hairless rats.
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Samar Alsaggaf
Figure 2. “Light microscopic sections of the lung of control animals (A–D) and animals exposed to gasoline vapor
for 30 days (E–H). AVL = alveoli, B = intrapulmonary bronchus, Bi = bronchiole, Od = edema. Pneumocyte type I
(white arrow head), Pneumocyte type II (black arrow head). Emphysema (Thick black arrow), lymphoid aggregation
(Hematoxyline & Eosin) (interrupted arrow)” (cited after permission from Al-Saggaf et al. [13]).
Effect of Gasoline on Reproductive System genital anomalies as well as fertility [20]. The sub-
chronic effect of gasoline and gasoline/oxygenate
Gasoline was reported to decrease seminal param-
on the reproductive system and offspring were
eters and affect semen quality and induce male
assessed [8]. When gasoline blended with oxygenate
Figure 3. “(A) Light micrograph of a section of back skin from control rat showing normal intact keratinocyte layers
as well as hair follicles in the dermis. (B) A section of back skin painted by gasoline for 3 weeks showing thickening
and separation of keratin (star), a marked increase in the granular layer (double head arrow), Hematoxyline & Eosin
×600. (C) Transmission electron microscope (TEM) micrograph of a section of back skin from control showing intact
epidermal cells. (D) TEM micrograph of a section of skin painted with gasoline showing marked alteration of both
basal (GSe) and spinous cell layers [stratum spinosum (SS)]. The nuclei showed irregular outlines (black arrow). The
cytoplasm of some cells contains irregular vacuoles (black interrupted arrow) and dark disrupted filaments (star).
(E) TEM micrograph SS of skin painted with gasoline showing that some cells become distorted and shrunken with
irregular or fragmented nuclei (white arrow). (F) TEM micrograph of skin painted with gasoline showing increased
keratin layers (white arrow), karyolysis of granular cell nuclei, and a coarse electron-dense substance within the
cytoplasm (interrupted white arrow) ×7,500” (cited after permission from Al-Saggaf et al. [9]).
diisopropyl ether (G/DIPE) and ethanol (G/EtOH) gland and in their relative weight to body weight,
administrated at “10,000 and 20,000 mg/m3 6 although there were no histopathological changes
hours/day, 7 days/week” to male Sprague-Dawley detected in these organs. They added that none
rats, they resulted in a rise in absolute weight of of these substances induced and macroscopic or
epididymis, prostate, seminal vesicles/coagulating microscopic changes in female reproductive organs
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Samar Alsaggaf
[8]. The observed adverse effect level was the Genotoxic Effect of Gasoline
highest level tested (20,000 mg/m3 for gasoline and
The cytogenetic studies of unadditized gasoline and
gasoline/oxygenate) as there are no alternations in
its blending streams did not reveal any changes in
fertility, sperm counts, estrus cycle, or developmen-
chromosome aberrations or positive micronucleus
tal parameters in pups [8]. In another study done by
findings in laboratory animals [28]. In a study, the
Tyl et al. [21], reduced pup weights during lactation
cytogenetic hazard of different gasoline included
was reported in a two-generation study with inha-
oxygenates was assessed by Schreiner et al. [29].
lation exposure of gasoline blended with oxygenate
The vapor condensates of gasoline with oxygen-
t-amyl methyl ether (G/TAME) at concentrations of
ate ethanol (G/EtOH), diisopropyl ether (G/DIPE),
1,040, 2,250, and 12,500 mg/m3.
and t-butyl alcohol (G/TBA) were negative in both
Inhalational exposure of pregnant Sprague-
micronucleus and sister chromatid exchange (SCE)
Dawley rats to gasoline alone, or gasoline blended
tests “indicating an absence of DNA perturbation or
with various ethers or alcohols (on gestation days
cytogenetic hazard from inhalation of these mate-
5–20 for 6 hours/day at different levels) do not
rials” [29]. They reported a significant increase
produce selective developmental toxicity in rats. It
in SCE in rats given BGVC alone or in female rats
is noticed that “A dose responsive maternal effects
given G/MTBE. Gasoline/t-amyl methyl ether (G/
included decreased maternal body weight and/or
TAME) induced increased SCE in both sexes at the
weight change, and reduced food consumption. No
highest dose only. Although DNA perturbation was
significant malformations were described in any
noticed for several samples, DNA damage was not
study” [22].
expressed as increased micronuclei in bone mar-
row cells [29].
Effect of Gasoline on Immune System
In another study, Trevisan et al. [30] conducted
In previous research studies, Jet propulsion fuel-8 a study aimed to assess the occurrences of chro-
was reported to be an immunotoxicant when mosomal abnormalities and SCE in workers of gas
inhaled [23], topically administrated to the skin stations. They could not observe the presence of
[24], or when given orally through gavage [25]. In benzene and its derivatives and did not observed
contrast to these studies, White et al. [26] found chromosomal destruction that may be associated
that exposure of the female rodent species B6C3F1 with the gas station activity in the worker.
mice and Crl:CD rats to jet fuel kerosene through
inhalation for “28 days at levels up to 2,000 mg/m3” Effect of Gasoline on Kidneys
did not suppress innate, humoral, or cell-mediated
The effect of subchronic exposure of Sprague-
immune functions. They added that there was no
Dawley rats to inhalation of BGVC and gasoline
significant effect detected in either species on body
combined with methyl tertiary butyl ether (G/
weights, spleen, or thymus weights and with a few
MTBE) at different concentrations “2,000, 10,000,
exceptions, spleen cell numbers and phenotypes
or 20,000 mg/m3 for 6 hours/day, 5 days/week
were also unaffected.
for 13 weeks” was previously studied by Clark et
In a more recent study conducted by White et
al. [31]. They reported that both male and female
al. [27], they reported that “exposing the female
rats exposed to the BGVC and G/MTBE at all levels
Sprague-Dawley rats to BGVC, G/MTBE, G/TAME,
showed “eosinophilic hyaline granules within the
and gasoline with t-butyl alcohol (G/TBA) 6
cytoplasm of renal proximal convoluted tubular
hours/day, 5 days/week for 4 weeks did not alter
epithelial cells in a dose-dependent manner. Most
the humoral immune response as evaluated in
10,000 and 20,000 mg/m3 exposed males also had
the immunoglobulin M (IgM) antibody-forming
evidence of tubular regeneration. Several animals
cell response to the T-dependent antigen sheep
among each of these exposure groups had corti-
erythrocytes.” Spleen weight, spleen cell number,
comedullary intraluminal tubular granular casts.
or IgM antibody production did not show any sig-
Mallory-Heidenhain staining of renal tissue of
nificant changes when assessed. They added that
male rats showed red staining of granular material
the humoral immune response was significantly
within the proximal tubular epithelium. Minimal
depressed after exposure to the three vapor con-
staining was apparent in control males and slight to
densates: G/EtOH and G/DIPE at the 20,000 mg/m3
moderate staining was present in exposed female
dose and G/ethyl tertiary butyl ether at the 10,000
animals” [31].
and 20,000 mg/m3 doses.
Figure 4. “(A) Photomicrograph of liver exposed to gasoline fume for 3 hours (T3). Hematoxyline & Eosin (H&E)
×400: showing extensive distorted histoarchitecture, shrinkage/degenerating/hepatocytes (yellow arrows), pykno-
tism (purple arrow), and dilated central vein (red arrow). (B) Photomicrograph of liver exposed to gasoline fume for
5 hours (T4). H&E ×100: showing extensive distorted histoarchitecture, degenerated endothelium (green arrow);
dilated sinusoids (blue arrows), and central vein (red arrow); chromatolytic hepatocytes (yellow arrows) and pyk-
notic cells (purple arrows)” (cited after permission from Owagboriaye et al. [7]).
www.ejmjih.com 39
Samar Alsaggaf
hoped that this review will encourage and support microscopic study under laboratory conditions.
the conduction of more rigorous studies aimed to J Anim Vet Adv 2009; 8(11):2118–24.
assess the impact of gasoline on the health and pos- [11] Goh CL, Soh SD. Occupational dermatoses in
sibly help in optimizing the exposure standards for Singapore. Contact Dermatitis 1984; 11:288–93.
[12] Monteiro Riviere N, Inman A, Riviere J. Effects of
gasoline and other hydrocarbon fuels. Performing
short-term high-dose and low-dose dermal expo-
a future review on the clinical effects of exposure sure to Jet A, JP-8 and JP-8 +100 jet fuels. J Appl
to gasoline through different routes on the human Toxicol 2001; 21:485–94.
body is recommended. Not only that, but studies of [13] Al-Saggaf SM, Ali SS, Ayuob NN, Abdel-Hamid GA,
the possible protection against this reported patho- Al-Jahdali NH. Light and scanning microscopic
logical effect of gasoline on different body system study of the effect of car fuel (Gasoline) inhalation
are encouraged in order to help find solutions for on Gninea pig respiratory system at station. Res J
such problem. Med Sci 2010; 4(1):38–47.
[14] Welss T, Basketter DA, Schroder KR. In vitro skin
References irritation: facts and future. State of the art review
[1] Ritchie GD, Still KR, Alexander WK, Nordholm AF, of mechanisms and models. Toxicol In Vitro 2004;
Wilson CL, Rossi J 3rd, et al. A review of the neuro- 18:231–43.
toxicity risk of selected hydrocarbon fuels. J Toxicol [15] Effendy I, Loffler H, Maibach HI. Epidermal cyto-
Environ Health B Crit Rev 2001; 4(3):223–312. kines in murine cutaneous irritant responses.
[2] Zahlsen I, Tri-Tugaswati A. Review of air pollution J Appl Toxicol 2000; 20:335–41.
and its health impact in Indonesia. Environ Res [16] Keogh BP, Allen RG, Pignolo R, Horton J, Tresini M,
1993; 63:95–100. Cristofalo VJ. Expression of hydrogen peroxide and
[3] Carlos JSP, Donna M. Human mercury exposure and glutathione metabolizing enzymes in human skin
adverse health effects in the Amazon: a review. Cad fibroblasts derived from donors of different ages.
Saúde Pública 2008; 24(4):503–20; doi:10.1590/ J Cell Physiol 1996; 167:512–22.
S0102-311X2008001600004 [17] Reese E, Kimbrough RD. Acute toxicity of gasoline
[4] Murray RK. Metabolism of xenobiotics. In: Janet and some additives. Environ Health Perspect 1993;
F, Jim R, Janene MO (eds.), Harper’s illustrated 101(Suppl 6):115–31.
biochemistry. 26th edition, The McGraw-Hill [18] Ahaghotu E, Babu RJ, Chatterjee A, Singh M. Effect
Companies, Inc., New York, NY pp 626–32, 2003. of methyl substitution of benzene on the percu-
[5] Rahman S, Sultana S. Chemopreventive activity of taneous absorption and skin irritation in hairless
glycyrrhizin on lead acetate mediated hepatic oxi- rats. Toxicol Lett 2005; 159(3):261–71.
dative stress and its hyperproliferative activity in [19] Gunasekar PG, Rogers JV, Kabbur MB, Garrett CM,
Wistar rats. Chemo Biol Intera 2006; 60(1):61–9. Brinkley WW, McDougal JN. Molecular and histo-
[6] Chi N. 8 occupational health hazards in oil and gas logical responses in rat skin exposed to m-xylene.
industry that you must know (part 1). Available J Biochem Mol Toxicol 2003; 17:92–4.
via http://oilandgasmanpowerprovider.blogspot. [20] De Jager C. Reduced seminal parameters break-
com/2015/10/occupational-health-hazards-in- throughs in andrology associated with environ-
oil-and-gas-industry.html (Accessed 27 July 2017). mental DDT exposure and p, p0-DDE concentration
[7] Owagboriaye FO, Dedeke GA, Aladesida AA, in men in Chiapas, Mexico: a cross-sectional study.
Bamidele JA, Olooto WE. Assessment of the effect J Androl 2006; 27(1):16–27.
of gasoline fume on stress hormones, antioxidant [21] Tyl RW, Myers CB, Marr MC, Fail PA, Seely JC, Elswick
status and lipid peroxidation in albino rat. J King B, et al. Two-generation reproductive toxicity study
Saud Univ Sci 2016; 30(3):393–99; doi:10.1016/j. of inhaled tertiary amyl methyl ether (TAME) vapor
jksus.2016.11.002 in CD rats. J Appl Toxicol 2003; 23(6):397–410.
[8] Gray TM, Steup D, Roberts LG, O’Callaghan JP, [22] Roberts LG, Gray TM, Trimmer GW, Parker RM,
Hoffman G, Schreiner CA, et al. Health assessment Murray FJ, Schreiner CA, et al. Health assessment of
of gasoline and fuel oxygenate vapors: reproduc- gasoline and fuel oxygenate vapors: developmental
tive toxicity assessment. Regul Toxicol Pharmacol toxicity in rats. Regul Toxicol Pharmacol 2014; 70(2
2014; 70(2 Suppl):S48–57; doi:10.1016/j. Suppl):S69–79; doi:10.1016/j.yrtph.2014.05.009
yrtph.2014.04.014 [23] Harris DT, Sakiestewa D, Titone D, He X, Hyde J,
[9] Al-Saggaf SM, Ali SS, Ayuob NN, Batawi AH, Mujalled Witten M. JP-8 jet fuel exposure suppresses the
MI. Histological study on the effect of gasoline on immune response to viral infections. Toxicol Ind
guinea pig epidermis: can flavonoid extract reverse Health 2008; 24:209–16.
this effect? Egypt J Histol 2011; 34:156–65.. [24] Ramos G, Limon-Flores AY, Ullrich SE. Dermal expo-
[10] Al-Saggaf SM, Shaker S, Ayuob NN, Al-Jahdali NH, sure to jet fuel suppresses delayed-type hypersen-
Abdel-Hamid GA. Effect of car fuel (Gasoline) inha- sitivity: a critical role for aromatic hydrocarbons.
lation on Trachea of Guinea pig: light and scanning Toxicol Sci 2007; 100:415–22.
[25] Keil DE, Dudley AC, EuDaly JG, Dempsey J, stations. Environ Monit Assess 2014; 186(4):2195–
Butterworth L, Gilkeson GS, et al. Immunological 204; doi:10.1007/s10661-013-3529-0
and hematological effects observed in B6C3F1 [31] Clark CR, Schreiner CA, Parker CM, Gray TM,
mice exposed to JP-8 jet fuel for 14 days. J Toxicol Hoffman GM. Health assessment of gasoline and
Environ Health A 2004; 67:1109–29. fuel oxygenate vapors: subchronic inhalation
[26] White KL Jr, DeLorme MP, Beatty PW, Smith MJ, toxicity. Regul Toxicol Pharmacol 2014; 70(2
Peachee VL. Jet fuel kerosene is not immunosup- Suppl):S18–28; doi:10.1016/j.yrtph.2014.07.003
pressive in mice or rats following inhalation for 28 [32] Owagboriaye FO, Dedeke GA, Ashidi JS, Aladesida
days. J Toxicol Environ Health A 2013; 76(13):778– AA, Olooto WE. Hepatotoxicity and genotoxicity of
97; doi:10.1080/15287394.2013.819307 gasoline fumes in albino rats. Beni-Suef Univ J Basic
[27] White KL, Peachee VL, Armstrong SR, Twerdok LE, Appl Sci 2017; 6:253–9.
Clark CR, Schreiner CA. Health assessment of gas- [33] Poon R, Yagminas A, Singh A, Valli VE, Chu I. Short
oline and fuel oxygenate vapors: Immunotoxicity term oral toxicity of gasohol in female rats. J Appl
evaluation. Regul Toxicol Pharmacol 2014; Toxicol 2001; 21(6):461–7.
70:S43–7. [34] Uboh FE, Ekaidem IS, Ebong PE, Umoh IB. The
[28] US EPA. Gasoline blending streams category assess- hepatoprotective effect of vitamin A against gaso-
ment document. 2008. Available via http://www. line vapor toxicity in rats. Gastroenterol Res 2009;
petroleumhpv.org/~/media/PetroleumHPV/ 2(3):162–7.
Documents/2008_aug21_gasoline_catanalysis_ [35] Uboh FE, Eteng MU, Ebong PE, Umoh IB.
final_category_assess_doc.pdf (Accessed 27 July Vitamins A and E reverse gasoline vapors-in-
2017). duced hematotoxicity and weight loss in female
[29] Schreiner CA, Hoffman GM, Gudi R, Clark CR. Health rats. Toxicol Ind Health 2010; 26(9):559–66;
assessment of gasoline and fuel oxygenate vapors: doi:10.1177/0748233710373080
micronucleus and sister chromatidexchange eval- [36] Abubakar MB, Abdullah WZ, Sulaiman SA, Ang
uations. Regul Toxicol Pharmacol 2014; 70(2 BS. The effects of exposure to petrol vapours on
Suppl):S29–34; doi:10.1016/j.yrtph.2014.05.014 growth, haematological parameters and oxidative
[30] Trevisan P, da Silva JN, da Silva AP, Rosa RF, Paskulin markers in sprague-dawley male rats. Malays J Med
GA, Thiesen FV, et al. Evaluation of genotoxic effects Sci 2015; 22(1):23–31.
of benzene and its derivatives in workers of gas
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