International Journal of Toxicology

30(6) 662-670
A Preliminary 13-Week Oral Toxicity ª The Author(s) 2011
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Study of Ginger Oil in Male and Female DOI: 10.1177/1091581811419023
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Wistar Rats

Kottarapat Jeena1, Vijayastelter B. Liju1, and Ramadasan Kuttan1

Abstract
Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was
studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex
per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as
comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective
organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in
hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major
component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the
serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral
administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

Keywords
essential oil, oral administration, toxicity, Zingiber officinale

Introduction to 600 mg/kg per day.10 In the present study, we conducted a

Ginger, rhizome of Zingiber officinale Roscoe, is one of the
most widely used spices, belonging to the family Zingibera-
ceae. It is a common condiment in various foods and beverages
and mainly used to impart aroma and flavor.1 Ginger oil is
obtained by steam distillation of the rhizome of Z officinale.
This product possesses the aroma and flavor of the spice but
lacks the pungency.
Until recently, essential oils have been studied mostly for
their flavor and fragrance. Essential oils and their components
are now gaining worldwide interest because of their potential
multipurpose functional use.2 Antimicrobial, antifungal, and
radical-scavenging properties of spices and their essential oils
have been reported.3,4 Essential oils and some of their compo-
nents are also used as food preservers and for nutraceutical
applications.
A number of studies have been reported on the pharmaco-
logical properties of ginger oil. Ginger oil has been used in the
prevention and therapeutic management of nausea in general
anesthesia patients.5 It is also shown to have antiplatelet activ-
ity in vitro.6 It is also reported to suppress chronic adjuvant
arthritis induced in both the paw and knee of Sprague-Dawley
rats.7 The antinociceptive and immunomodulatory activities of
ginger oil have also been studied.8,9
Acute (single dosage) and subacute (30 days) oral toxicity
studies have shown the essential oil of ginger in Swiss albino
mice and Wistar rats to be nontoxic and nonadverse at doses up
subchronic toxicity study of the essential oil of ginger isolated
from Z officinale Roscoe in rats after oral administration at
concentrations of 100, 250, and 500 mg/kg per day once daily
for 13 consecutive weeks to assess the oral safety of ginger oil.
We have also analyzed the chemical composition of ginger oil
(test article) and separately for the presence of the ginger oil
components in the serum after oral dosing.
Materials and Methods
Ginger Oil
The essential oil isolated by steam distillation from the rhizome
of ginger was supplied by Kancore Ingredients Limited, Anga-
mali, Kerala, India (www.kancor.in). Ginger oil (Sample No.
GIO-91204) was supplied as a pale yellow to light amber
liquid. Ginger oil is stable up to 2 years. We used the same lot
in all the toxicity studies. Liquid paraffin oil (CAS No-8012-
95-1), which was used as the vehicle, was purchased from
Merck Specialities Private Limited, Mumbai, India.
1
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India
Corresponding Author:
Ramadasan Kuttan, Amala Cancer Research Centre, Amala Nagar, Thrissur,
Kerala 680 555, India
Email: amalacancerresearch@gmail.com
Jeena et al
Chemical Composition of Ginger Essential Oil
The composition of ginger oil prepared from fresh ginger
rhizomes was determined by gas chromatography (GC) and
GC-mass spectrophotometry (MS) techniques using a
Hewlett–Packard gas chromatograph (Model 6890) coupled
with a quadruple mass spectrometer (Model HP 5973) and a
HP-5MS capillary column (5% phenylmethylsiloxane; 30 m 
320U m  0.25U m) supplied by Hewlett-Packard, CA, USA.
The interphase, ion source, and selective mass detector tempera-
tures were maintained at 243 C, 230 C, and 150 C, respec-
tively. Helium was used as a carrier gas at a flow rate of 1.4
mL/min For the essential oil, the oven temperature was
programmed linearly at 60 C; then increased from 60 C to
243 C at a rate of 3 C/min.
Identification of Components
The components are identified using the National Institute of
Standards Technology (NIST) library search facility provided
with the data analysis software supplied along with GC-MS
system.
Animals
All animal experiments were conducted after getting prior per-
mission from Institutional Animal Ethics Committee (IAEC)
and per the instructions prescribed by the Committee for the
Purpose of Control and Supervision of Experiments on Ani-
mals (CPCSEA), Ministry of Environment and Forest, Govern-
ment of India, under the supervision of a certified veterinarian.
Young adult male and female Wistar rats weighing 140 to
220 g and aged 7 to 8 weeks old were purchased from Small
Animal Breeding Station, Kerala Agricultural University,
Mannuthy, Kerala, India. They were housed in the animal
facility of Amala Cancer Research Centre, in well-ventilated
polypropylene cages. Experiments in rats were started after
acclimatization for 1 week. The animals were divided into
5 groups (randomized by initial body weight) with each cage
containing 5 rats of the same sex. The housing environment
was maintained at a controlled temperature of 22 C + 2 C and
relative humidity 60% + 10% and provided 12-hour light/dark
cycles. Rats were fed with normal pelleted rat chow (Sai Durga
Feeds and Foods, Bangalore, India) and supplied with purified
water ad libitum. The composition of the feed administered is
as follows: Crude protein: 20% to 21%, ether extract: 4% to
5%, crude fiber: 4%, ash: 8%, calcium: 1.2%, phosphorous:
0.6%, nitrogen-free extract: 54%, mean energy (kcal/kg):
3600, pellet size: 12 mm.
Analysis of Ginger Oil Components in Serum
In a separate experiment, male Wistar rats aged 8 to 10 weeks
and weighing 180 to 190 g were used for the determination of
serum concentrations of ginger oil components. The animals
were fasted overnight with free access to water. Animals were
administered orally by gavage a single dose of 500 mg/kg body
663
weight of ginger oil dissolved in paraffin oil. Animals without
any treatment and those treated with paraffin oil served as
untreated and vehicle controls, respectively. Blood samples
were collected at 1 hour and 2 hours post dosing.
The blood samples were centrifuged at 4000g for 10 minutes
at room temperature. Serum was collected and 1 mL of serum
was extracted with 2 mL ethyl acetate. The ethyl acetate extract
was analyzed by gas chromatography analysis and checked for
ginger oil components as given below.
A fused silica capillary column with a stationary phase
equivalent to Carbowax 20 mol/L with a diameter 30 m 
0.32 mm and 1.0 mm film thickness was used for GC/MS
analysis. The sample volume used was 0.5 mL. Nitrogen was
used as carrier gas with linear flow velocity 25 cm/s. Tempera-
ture of the column was initially programmed at 150 C for
1 minute, and then increased at the rate of 10/min to a final
temperature of 280 C hold for 30 minutes. Flame ionization
detector was used to detect the peaks. zingiberene was used as
the reference standard.
Subchronic Toxicity Study
Experimental design and conduct. A total of 50 healthy rats, 25
male and 25 female, were acclimatized to laboratory conditions
and divided into 5 groups: each group consisting of 5 males and
5 females. The animals were divided as follows:
Group Treatment Number and Sex
I Untreated 5 males and 5 females
II Vehicle control (paraffin oil) 5 males and 5 females
III Ginger oil (100 mg/kg) 5 males and 5 females
IV Ginger oil (250 mg/kg) 5 males and 5 females
V Ginger oil (500 mg/kg) 5 males and 5 females
Ginger oil and paraffin oil was administered once daily in
the morning by oral gavage and continued for 13 weeks (6 d/
week). Ginger oil was dissolved in paraffin oil (500 mg/mL)
and administered to the rats at doses of 100, 250, and 500 mg/
kg/d. The highest dose of 500 mg/kg/d was selected based on
the therapeutic dose of ginger oil.10 The vehicle control ani-
mals were given paraffin oil (5 mL/kg); the untreated group did
not receive any treatment.
Observations of clinical signs were made at 10, 30, and 60
minutes after dosing during the first day and once daily there-
after for 91 days. The animals were monitored for clinical and
behavioral symptoms such as watery stool, immobility, neuro-
muscular problems, mortality, and any adverse reactions. The
body weight of each rat was recorded on day 0 and at 5-day
intervals throughout the course of the study and mean body
weights were calculated. The quantity of food and water con-
sumed by groups consisting of 5 rats were recorded every 5 days
and the food consumption per rat was calculated for all the
groups. After 13 weeks, the animals were sacrificed under light
ether anesthesia.
664 International Journal of Toxicology 30(6)

Blood was collected by direct heart puncture method. A part of Table 1. Chemical Composition of Ginger Oil
the blood was collected in heparinized tubes and used for the
Number Compound (%)
determination of hematological parameters and the other part was
collected in nonheparinized tubes and used for serum chemistry 1. Camphene 5.138
analysis. Necropsy was performed in all animals in the presence 2. Sabinene 8.277
of a veterinary pathologist and observations were recorded. The 3. Isoborneol 1.136
organ weights were recorded as absolute values and their relative 4. a-Cubebene 0.749
5. a-Elemene 1.566
values (ie, percentage of the body weight) were calculated.
6. g-Elemene 0.576
7. Aromadendrene 0.336
Parameters Assessed 8. Germacrene 2.401
9. Ar-curcumene 15.353
Blood samples were analyzed for hematological parameters (total 10. beta-panasinsene 1.469
erythrocyte count [RBC], hemoglobin, platelet, and total and dif- 11. Zingiberene 31.080
ferential leukocyte counts). Total white blood cells were mea- 12. Beta bisabolene 13.809
13. a-Sesquiphellandrene 14.020
sured after diluting the blood in Turk fluid and counted using a
14. Verbenone 0.297
hemocytometer.11 For differential leukocyte count, blood smears 15. Elemol 0.446
were prepared on a clean glass slide, stained with Leishman stain 16. Thujopsene 1.036
and various types of cells were counted manually with a micro- 17. Silane 1.605
scope.12 Platelet count was determined by diluting the blood with 18. Franesol 0.702
Rees Ecker diluting fluid and counted using a hemocytometer.12
Total RBC count was measured by diluting the blood with Dacie
fluid and counted using a counting chamber.12 Hemoglobin con-
tent (Hb) was measured by cyanmethemoglobin (Drabkin)
method using the kit from Agappe Diagnostics, Thane, India.
Blood collected in nonheparinized tubes were centrifuged at
5000 rpm for 10 minutes. The clear serum obtained was used
for the following investigations: total bilirubin was determined
by Jendrassik-Diazotized sulfanilic acid method13; albumin
was determined based on its reaction with bromocresol green Figure 1. Structure of zingiberene, the major component present in
(binding method); and total protein concentration was deter- ginger oil.
mined by biuret method.14 Kidney function markers such as
creatinine and blood urea nitrogen were estimated by
Jaffe-Kinetic and urease-colorimetric method, respectively.15 from untreated, vehicle control, and animals treated with 500
Aspartate aminotransferase (AST) and alanine aminotransferase mg/kg per day of ginger oil were fixed in 10% neutral buffered
(ALT) were estimated by the IFCC (International Federation of formalin. Tissue sections were taken and stained with
Clinical Chemistry) kinetic method16 and alkaline phosphatase hematoxylin-eosin and observed under high power (40).
(ALP) by PNNP (p- nitrophenyl phosphate) hydrolysis method17
with kits supplied by Raichem Lifesciences Pvt. Ltd., Mumbai, Statistical Analysis
India, using a Merck Microlab300 Analyzer from Systronics Mean + standard deviation (SD) was calculated. Two separate
(India) Limited, Ahmedabad, India. Cholesterol and low- statistical analyses were conducted for evaluating data on rela-
density lipoprotein (LDL) was estimated using CHOD-PAP tive organ weights, lipid profile, hematology, and clinical
enzymatic method,18 and high-density lipoprotein (HDL) and chemistry parameters that is, the vehicle control group (paraf-
triglycerides by phosphotungistic precipitation and GPO-PAP fin oil treated) was compared with the untreated group and the
method, respectively.19 The kidney, liver, and lipid profile mar- ginger oil-treated groups were compared with the vehicle con-
kers were estimated using commercially available kits supplied trol (paraffin oil) group for both male and female rats sepa-
by Piramal Healthcare Limited, Navi Mumbai, India. Serum rately. One-way analysis of variance (ANOVA) followed by
sodium, potassium, and bicarbonate were estimated using Flame appropriate post hoc test (Dunnett multiple comparison test)
photometer 129 ion selective electrolyte analyzer supplied by using Graph pad in Stat software were used. Levels achieving
Piramal Healthcare Limited, Navi, Mumbai, India. Chloride was differences of P < .05 and P < .01 were considered significant.
estimated by mercurous thiocyanate method using a kit supplied
by Raichem Lifesciences Pvt. Ltd., Mumbai, India.
Results
Histopathological Examinations Composition of Ginger Oil
A portion of selected tissues such as liver, kidney, spleen, A number of compounds were identified by GC/MS analysis of
stomach, intestine, as well as cerebral cortex and cerebellum ginger essential oil and those components identified are given
Jeena et al 665

Figure 2. A, Gas chromatographic analysis of serum from control (paraffin treated) animals. B, Gas chromatographic analysis of serum from
ginger oil–treated animals at 2 hours. Serum was extracted with ethyl acetate successively and all the washings were pooled; 0.5 mL was injected
into the column. The retention time obtained was 12.8 to 13.7 minutes, which was same for the standard zingiberene.

in Table 1. The structure of the main sesquiterpene hydrocar-
bon (zingiberene) identified is shown in Figure 1.
Analysis of Ginger Oil in Serum
Ethyl acetate extract of the serum after dosing with ginger oil
showed the presence of several peaks at 12.8 to 13.7 minutes
in the 2-hour post dosing sample (Figure 2), which were not
seen in the serum of normal rats or serum of rats treated with
paraffin oil alone, indicating that ginger oil was absorbed and
detected in blood. The highest peak observed, peak 4, which
appeared at 12.8-minute retention time, was identified as
zingiberene.
Subchronic Toxicity Study
Subchronic administration of ginger oil at doses 100, 250, and
500 mg/kg per day did not produce any mortality. The animals
were healthy and no clinical signs of toxicity were noted. There
were no unusual changes in behavior or in locomotor activity
observed during the period of study. The 13-week
administration of ginger oil did not produce any decrease in
the body weight of male and female rats (Figure 3A and B).
Administration of ginger oil did not produce any difference
in the food consumption of male and female rats when
compared with vehicle control (Table 2). Similarly, the water
consumption pattern was also not altered in treated groups
when compared to vehicle control (data not shown). Watery
stool was observed in some animals in treated groups including
vehicle control, for the first 2 days and may be attributed to the
administration of paraffin oil, with resolution beginning on day
3. The average food intake was nearly 11 g/d for male rats and
9 g/d for female rats.
No abnormal changes were observed in the relative organ
weights of liver, kidney, spleen, lungs, brain, and stomach with
respect to body weight in ginger oil-treated animals when com-
pared to vehicle control animals (Table 3). Variations observed
between untreated and vehicle control groups are within the
normal variation in rats.20 At terminal sacrifice, necropsy
observations were unremarkable.
Administration of ginger oil did not produce any change in
the hematological parameters (hemoglobin, RBC counts,
666 International Journal of Toxicology 30(6)

Table 2. Mean Food Consumption at Week 1 and at Weeks 3, 6, 9,

and 12 in Rats During Subchronic Study

Food Consumptiona

Week 1 Week 3 Week 6 Week 9 Week 12

Males
Untreated 10.0 13.8 12.6 13.0 14.0
Vehicle control 8.4 11.8 12.2 12.0 11.8
100 mg/kg 10.8 13.6 13.8 11.0 10.6
250 mg/kg 8.2 10.4 13.6 11.6 12.4
500 mg/kg 9.6 13.2 11.0 10.4 11.4
Females
Untreated 9.4 8.4 7.8 8.0 9.2
Vehicle control 8.4 6.4 8.2 10.2 8.0
100 mg/kg 10.0 8.4 9.4 10.0 8.4
250 mg/kg 10.2 7.0 7.8 11.4 7.8
500 mg/kg 8.9 7.4 10.2 10.6 7.6
a
Consumption expressed as g/rat/d.

Figure 3. A, Effect of subchronic administration of ginger oil on body
weight of male rats. B, Effect of subchronic administration of ginger oil
on body weight of female rats.
platelet counts, and total and differential leukocyte counts) in
untreated, vehicle control, and ginger oil-treated rats (Table 4).
Subchronic administration of ginger oil did not produce any
significant changes in hepatic function parameters such as alka-
line phosphatase, total protein, albumin, and globulin content.
A slight increase in total bilirubin was observed in female rats
treated with ginger oil and a decrease in AST and ALT levels
(Table 5). The variations observed between untreated and vehi-
cle control groups even though significant were within the
normal range of serum values for rats.20
The renal function markers, blood urea and serum creati-
nine, did not show any variation in treated animals compared
to vehicle control (Table 6). There was no change in the levels
of serum electrolytes chloride, potassium, and bicarbonate.
An increase in the levels of sodium was observed in male rats
treated with 500 mg/kg per day ginger oil (Table 7). In the
absence of changes in chloride levels or similar changes in
females, this change was not considered biologically
significant.
A slight decrease (not significant) was observed in choles-
terol and triglycerides levels, but there was no change in HDL,
LDL, and very-LDL (VLDL) cholesterol, indicating that
administration of ginger oil for 13 weeks did not produce any
change in lipid profile (Table 8). These results indicated that
ginger oil did not adversely affect hepatobiliary function
involved in fat metabolism.
Histopathological Examinations
Histopathological examinations of the brain, kidney, spleen,
liver, stomach, and intestine did not show any pathological
lesions in the organs of animals treated with ginger oil
(Figure 4). Histopathological examination of the organs in the
untreated, vehicle control, and ginger oil-treated groups did not
show any differences.
Discussion
The main usage of essential oils lies in the flavoring of bev-
erages, confectionery, perfumery, and fragrance industries.21
However, essential oils have been reported to possess pharma-
cological properties and are being used for nutraceutical and
medicinal applications. The use of essential oils is also gaining
more consumer interest.
There are very few reports on the toxicity of ginger oil. A
35-day safety evaluation of ginger powder and that of a
patented ginger extract EV.EXT 33 has been reported.22,23 The
acute and subacute (30 days) toxicity profile of ginger oil has
also been reported.10 The current investigation describes a
detailed study on the subchronic (13 weeks) toxicity of ginger
oil using toxicological and pathological analysis.
The major component of ginger oil used in this study was
found to be zingiberene (31.08%). Our initial data on Wistar
rats after single oral (gavage) dose showed that oral gavage
administration of ginger oil yielded ginger oil components
especially zingiberene in serum 2 hours post dosing.
Our study showed that ginger oil did not cause toxicity in
rats after oral doses of up to 500 mg/kg per day. No mortality
was observed during the period of study. Ginger oil also did not
retard growth or affect food consumption, indicating normal
metabolism of the animals. No changes were observed in the
absolute or relative organ weights of liver, kidney, spleen,
stomach, and brain in ginger oil-treated rats compared with
vehicle control. Differences observed between the untreated
Jeena et al 667

Table 3. Effect of Subchronic Administration of Ginger Oil on Relative Organ Weighta

Group Liver Spleen Lungs Kidney Brain Stomach

Male
Untreated 3.37 + 0.31 0.42 + 0.12 0.38 + 0.12 0.73 + 0.06 0.49 + 0.04 0.50 + 0.06
Controlb 4.07 + 0.49c 0.32 + 0.01 0.56 + 0.06d 0.73 + 0.02 0.75 + 0.02d 0.62 + 0.03d
100 mg/kg 2.83 + 0.40 0.26 + 0.03 0.52 + 0.03 0.64 + 0.04 0.49 + 0.06 0.46 + 0.02
250 mg/kg 3.43 + 0.38 0.25 + 0.07 0.59 + 0.07 0.84 + 0.05 0.60 + 0.08 0.56 + 0.05
500 mg/kg 3.70 + 0.26 0.30 + 0.03 0.49 + 0.03 0.65 + 0.13 0.55 + 0.06 0.51 + 0.07
Female
Untreated 4.17 + 0.65 0.28 + 0.05 0.76 + 0.12 0.92 + 0.07 0.79 + 0.07 0.66 + 0.06
Controlb 3.95 + 0.19 0.25 + 0.05 0.72 + 0.06 0.88 + 0.05 0.82 + 0.12 0.70 + 0.32
100 mg/kg 3.43 + 0.19 0.23 + 0.02 0.72 + 0.18 0.87 + 0.07 0.84 + 0.12 0.75 + 0.11
250 mg/kg 3.94 + 0.49 0.28 + 0.09 0.84 + 0.22 0.86 + 0.06 0.92 + 0.17 0.68 + 0.09
500 mg/kg 4.41 + 0.54 0.22 + 0.03 0.74 + 0.11 0.92 + 0.06 0.81 + 0.14 0.74 + 0.08
a
Values are mean + standard deviation (SD) of 5 animals/group and expressed as the organ weight/100 g of body weight.
b
Paraffin oil
c
P < .05; significant when compared to normal.
d
P < .01; significant when compared to normal.

Table 4. Effect of Subchronic Administration of Ginger Oil on Hematological Parametersa

Group Hb (g/dL) RBC (106) Platelet (106) WBC (mm3)

Male
Untreated 14.78 + 1.18 8.43 + 0.53 621.6 + 23.2 9250 + 127.4
Controlb 15.32 + 0.68 7.92 + 0.21 658.8 + 22.2 9679 + 159.2
100 mg/kg 14.99 + 1.21 8.65 + 0.28 647.4 + 27.9 9332 + 368.4
250 mg/kg 15.79 + 0.97 7.52 + 0.43 633.2 + 42.5 10752 + 382.8
500 mg/kg 15.68 + 1.21 8.32 + 0.41 669.4 + 33.1 10653 + 475.5
Female
Untreated 13.84 + 0.29 6.78 + 0.61 526.6 + 25.8 7658 + 291.2
Controlb 13.67 + 0.48 6.87 + 0.61 572.2 + 41.1 7479 + 255.6
100 mg/kg 14.57 + 1.83 6.65 + 0.85 591.2 + 43.8 7019 + 595.8
250 mg/kg 13.21 + 0.76 6.50 + 0.14 566.2 + 40.9 7160 + 405.2
500 mg/kg 12.99 + 1.87 7.70 + 0.58 554.4 + 40.6 7276 + 439.5
Abbreviations: Hb, hemoglobin; RBC, red blood cell; WBC, white blood cell; SD, standard deviation.
a
Values are mean + SD of 5 animals/group.
b
Paraffin oil.

Table 5. Effect of Subchronic Administration of Ginger Oil on Liver Function Testa

Group Total Bilirubin (mg/dL) ALT (U/L) AST (U/L) ALP (U/L) Total Protein (g/dL) A:G Ratio

Male
Untreated 0.20 + 0.09 127.2 + 27.2 243.0 + 63.0 238.6 + 100.6 8.0 + 0.5 0.7:1 + 0.4
Controlb 0.40 + 0.17c 150.0 + 33.8 187.2 + 73.2 253.2 + 15.2 6.9 + 0.5 1.2:1 + 0.2
100 mg/kg 0.27 + 0.12 74.8 + 15.2 83.4 + 10.2 128.6 + 30.8 8.5 + 0.8 0.8:1 + 0.1
250 mg/kg 0.59 + 0.16 90.0 + 12.6 69.6 + 9.7 259.2 + 11.8 6.5 + 0.6 1.0:1 + 0.3
500 mg/kg 0.57 + 0.12 94.4 + 7.8 56.2 + 8.2 290.2 + 7.6 7.1 + 0.3 1.0:1 + 0.1
Female
Untreated 0.41 + 0.30 64.0 + 14.6 194.4 + 43.1 284.0 + 40.6 7.0 + 0.3 1.0:1 + 0.3
Controlb 0.17 + 0.04d 160.4 + 12.9d 202.0 + 60.9 286.6 + 38.9 7.6 + 0.3 1.1:1 + 0.1
100 mg/kg 0.37 + 0.05e 68.4 + 18.0 64.8 + 13.7 127.8 + 14.7 7.5 + 0.3 1.0:1 + 0.1
250 mg/kg 0.48 + 0.21f 93.6 + 18.5 54.6 + 11.9 92.6 + 5.4 6.5 + 0.8 1.3:1 + 0.4
500 mg/kg 0.42 + 0.09e 108.6 + 54.6 57.6 + 11.1 111.2 + 20.0 6.0 + 0.6 1.3:1 + 0.2
Abbreviations, ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; A:G, albumin-to-globulin ratio; SD, standard deviation.
a
Values are mean + SD of 5 animals/group.
b
Paraffin oil.
c
P < .05; significant when compared with normal.
d
P < .01; significant when compared with control.
e
P < .05; significant when compared with control.
f
P < .01; significant when compared with control.
668 International Journal of Toxicology 30(6)

Table 6. Effect of Subchronic Administration of Ginger Oil on Renal and vehicle control groups may be attributed to animal
Function Testa variation in the groups which may not be treatment related.
Blood Urea Serum
The variations, even though significant in some cases, were
Group Nitrogen (mg/dL) Creatinine (mg/dL) found to be within the normal range reported in Wistar rats.20
There was also no significant change in hematological
Male parameters between the vehicle control and treated groups.
Untreated 81.8 + 9.4 0.70 + 0.19 Administration of ginger oil at the concentration studied did
Controlb 72.6 + 3.7 0.56 + 0.05
not produce any elevation of ALP, AST, and ALT levels when
100 mg/kg 86.6 + 10.4 0.32 + 0.16
250 mg/kg 64.6 + 2.2 0.64 + 0.07 compared to the vehicle control. However, when untreated
500 mg/kg 62.2 + 1.5 0.58 + 0.09 animals were compared with vehicle control, AST and ALT
Female were found to be slightly higher which was not significant in
Untreated 87.0 + 4.1 0.50 + 0.07 males but significant in females. Reasons for the increased
Controlb 78.2 + 6.8 0.56 + 0.05 activity in these animals are not known at present. Similarly,
100 mg/kg 84.0 + 11.4 0.40 + 0.12 the renal markers, serum creatinine and urea levels, were also
250 mg/kg 65.4 + 5.5 0.54 + 0.23
not altered compared with the vehicle control. An increase was
500 mg/kg 67.4 + 4.4 0.57 + 0.05
observed in serum sodium electrolyte levels in males, but there
a
Values are mean + standard deviation (SD) of 5 animals/group. were no toxic effects on kidney as illustrated by other renal
b
Paraffin oil. parameters and supported by the histopathology of kidney.

Table 7. Effect of Subchronic Administration of Ginger Oil on Serum Electrolytesa

Group Bicarbonate (mEq/L) Sodium (mEq/L) Potassium (mEq/L) Chloride (mEq/L)

Male
Untreated 22.6 + 4.6 139.2 + 11.4 6.46 + 0.66 96.0 + 19.2
Controlb 21.8 + 3.1 163.2 + 10.4c 7.50 + 0.43 108.8 + 16.24
100 mg/kg 22.4 + 1.3 138.0 + 13.0 6.08 + 0.11 104.6 + 4.22
250 mg/kg 20.2 + 1.9 151.8 + 7.10 6.16 + 0.92 103.6 + 5.18
500 mg/kg 20.8 + 1.9 179.8 + 12.2d 6.00 + 0.67 110.6 + 5.18
Female
Untreated 21.6 + 3.2 153.2 + 7.2 6.66 + 0.50 118.6 + 13.35
Controlb 21.4 + 3.2 136.8 + 21.9 7.40 + 0.47 111.2 + 7.22
100 mg/kg 20.6 + 2.7 132.2 + 3.70 5.38 + 0.38 97.2 + 3.03
250 mg/kg 19.8 + 1.3 136.8 + 13.5 5.50 + 0.85 103.0 + 5.70
500 mg/kg 20.8 + 2.1 142.8 + 4.5 6.18 + 0.26 100.6 + 7.30
a
Values are mean + standard deviation (SD) of 5 animals/group.
b
Paraffin oil.
c
P < .05; significant when compared with normal.
d
P < .05; significant when compared with control.

Table 8. Effect of Subchronic Administration of Ginger Oil on Lipid Profilea

Group Cholesterol (mg/dL) Triglycerides (mg/dL) HDL (mg/dL) LDL (mg/dL) VLDL (mg/dL)

Male
Untreated 80.4 + 4.7 132.6 + 5.8 36.2 + 2.2 18.0 + 3.4 26.2 + 1.3
Controlb 82.2 + 6.9 129.4 + 21.1 38.0 + 3.6 18.6 + 2.3 25.6 + 4.2
100 mg/kg 87.6 + 4.7 108.2 + 11.3 42.0 + 4.2 24.2 + 2.4 21.2 + 2.3
250 mg/kg 67.2 + 3.0 103.6 + 14.7 45.4 + 9.8 18.6 + 1.6 20.2 + 3.0
500 mg/kg 74.2 + 4.8 116.8 + 5.8 32.0 + 3.7 19.4 + 2.1 22.8 + 1.1
Female
Untreated 87.4 + 3.6 166.6 + 28.4 37.6 + 2.1 16.8 + 3.1 33.0 + 5.9
Controlb 87.0 + 4.0 141.6 + 10.5 42.6 + 3.5 16.6 + 1.7 27.8 + 2.2
100 mg/kg 86.6 + 3.2 148.2 + 3.7 36.6 + 1.5 20.8 + 2.8 29.2 + 0.8
250 mg/kg 76.4 + 6.9 117.2 + 19.2 32.6 + 3.6 20.6 + 2.7 23.2 + 4.1
500 mg/kg 71.2 + 2.3 115.0 + 11.0 31.4 + 2.1 17.2 + 1.9 22.6 + 2.3
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; VLDL, very LDL.
a
Values are mean + SD of 5 animals/group.
b
Paraffin oil.
Jeena et al 669

Figure 4. Histopathological analysis of organs from normal, vehicle control (paraffin oil treated) and ginger oil (500 mg/kg body weight). A,
Liver. B, kidney. C, cerebral cortex. D, spleen. E, stomach. F, intestine.
670
Reasons for the increase in serum sodium may warrant further
investigation. The decrease in the levels of total cholesterol and
triglycerides may indicate its possible hypolipidemic activity
which needs further investigation. Histopathology of liver, kid-
ney, brain, stomach, spleen, lungs, and intestine also showed
normal architecture.
Ginger powder at a very high dose of 2 g/kg was shown to
slightly reduce the relative weight of the testes (11.5%).22 But
there were no changes in the relative weight of testes with
subacute (35 days) administration of ginger powder up to
1000 mg/kg per day.22 In the present study, testes were not
further evaluated as there were no obvious changes observed
at necropsy. Ginger powder did not change any other biochem-
ical and hematological parameters. Our findings in the current
study are also consistent with earlier results obtained in the 30-
day subacute toxicity study of ginger oil.10 These results con-
firmed that ginger oil is not toxic to male and female rats
following subchronic oral administrations of up to 500 mg/kg
per day (no observed adverse effect level [NOAEL]).
Acknowledgment
We are thankful to Mr Shankar Iyer, New Udaya Pharmacy and Labora-
tory, Cochin, Kerala, India, for doing gas chromatographic analysis.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: funded by
Spices Board, Cochin, Kerala, India [NO.MD/M & H/01/08-09].
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