International Journal of Research Studies in Medical and Health Sciences
Volume 5, Issue 7, 2020, PP 20-32
ISSN : 2456-6373

Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of
Boswellia Serrata Extract (Boswellin® Super)
Muhammed Majeed1, Sankaran Natarajan1, Sarang Bani1, Anjali Pandey1*, Prakriti Neupane2
1

Sami Labs Limited, #19/1, 19/2, I Main, II Phase, Peenya Industrial Area, Bangalore 560 058,
Karnataka, India
2
Clin World Private Limited, #19/1, 19/2, I Main, II Phase, Peenya Industrial Area, Bangalore 560
058, Karnataka, India*Corresponding Author: Anjali Pandey, Sami Labs Limited, #19/1, 19/2, I Main, II Phase, Peenya
Industrial Area, Bangalore 560 058, Karnataka, India
ABSTRACT
Boswellia serrata is a branching tree found abundantly in India, Boswellic acids extracted from resin ofplant is used in inflammatory conditions, arthritis and hyperlipidaemia. However, any supplement used forlong term use needs to be tested for potential mutagenicity and toxicity. Thus, we assessed the mutagenicityof Boswellia serrata extract by Mammalian Bone Marrow Chromosome Aberration Test and Mammalian
Bone Marrow Micronucleus Test and in vitro Bacterial Reverse Mutation Test. Further we assessed in vivo
toxicity by acute toxicity study and 90 days sub chronic toxicity study of Boswellia serrata extract. None of
the mutagenic assays showed any increase in mutagenicity above background. Also, the acute oral toxicity
and sub chronic toxicity study revealed that Boswellia serrata extract was not lethal to animals up to
2000mg/kg/day when observed for 14 days and 600mg/kg/day when observed for 90 days. Therefore, thesedata provide evidence that the Boswellia tested have no cytotoxic potency and are not mutagenic. Thus, ourfindings contribute to the risk assessment of preparations containing Boswellia serrata extract.
Keywords: Boswellia serrata extract, Mutagenicity, toxicity, Ames test, genotoxicity

INTRODUCTION
In Ayurvedic system of medicine, Boswellia
serrata is one of the ancient and mostappreciated herbs1. Boswellia serrata is abranching tree found abundantly in the dry
regions of India, Africa and Middle East.
Traditionally resin which is available under thebark of the tree, is used in various religious andsocio-cultural activities as incense and also invarious therapeutic purposes2-3.Resin, gum,
essential oils and terpenoids are the reported
chemical constituents of the exudate4.Boswellicacid, medicinally important terpenoids makes up
25-35% of the resin5-9. Boswellic acids arepentacyclic triterpenes, which may exist in an aconfiguration (geminal methyl groups at C-20)
or a bb configuration (vicinal methyl groups at
C-19/C-20). Furthermore, boswellic acids may
contain an oxo-moiety at C-11 and an acetyl
moiety at the C-3 OH group10.
Boswellia serrata extract (BSE) has been statedto have analgesic and psychopharmacologicaleffect from the non-phenolic extract and thealcohol extracted portion is effective inmanagement of inflammatory conditions,arthritis and hyperlipidaemia11.The major effectof the BSE is attributed by two boswellic acids
namely 11-keto-β-boswellic acid (KBA) andacetyl-11-keto-β-boswellic acid (AKBA). The
European Pharmacopoiea 6.0 includes these twoboswellic acids as markers to confirm thequality of the air-dried gum resin exudate of B.
serrata12.Further, β-boswellic acid, 11-keto-βboswellic acid and acetyl-11-keto-β-boswellicacid have been used in apoptosis of tumor cells,
specifically affected by leukemia or coloncancer6.
Though there are several studies on efficacy of
Boswellia serrata on various indications, safety
studies of the extract are very few or inadequate.
Also, Boswellia serrata extract is usuallyintended for long term use so potential
cytotoxic, genotoxic or mutagenic activity
testing of the extract is important. Further,mutagenicity tests help to reduce the genetic or
carcinogenetic hazards to humans as several
studies showed the connection between
mutagenicity and carcinogenicity13.In thepresent study, we have conducted the in vivo
acute toxicity study, 90 days sub chronic study,
Mammalian Bone Marrow Chromosome
Aberration Test and Mammalian Bone Marrow

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

Micronucleus Test and invitro Bacterial Reverse
Mutation Test of Boswellia serrata extract.

MATERIALS AND METHODS
Chemicals
Boswellia serrata extract(Boswellin® Super) isa standardized extract from the gum resin of B
serrata enriched to contain boswellic acids
namely β-Boswellic Acid, Acetyl-β-BoswellicAcid, 11-keto- β -Boswellic Acid and Acetyl11-keto- β -Boswellic Acid". It was manufactured
and supplied by Sami Labs limited Bangalore,
India. Salmonella typhimurium tester strains
TA98, TA100, TA1537, TA1535 and TA102
were obtained from Molecular Toxicology,
Inc.157, Industrial Park, Dr. Boone, NC 28607.
Animals
All animals used for the tests following described
were healthy adult. For the mammalian bonemarrow chromosome aberration test were used
12 mice and for the mammalian bone marrow
micronucleus test were used 25 mice. For theacute oral toxicity study were used 12 female
Wistar rats. For the dose range finding and main
study of the 90 days sub-chronic study wereused 28 Wistar rats of either sex and 55 Wistar
rats of either sex. Female animals used were
nulliparous
andnon-pregnant.Standard
propylene cage with stainless grill havingpelleted food and drinking water supply wereused to house the animals, three animals per
cage in air-conditioned room with adequate
fresh air supply (more than 12 air changes perhour) and autoclaved corn cob beddings. The
room temperature was maintained in between
19.60C to 23.70C and relative humidity of
50.30-65.60% with 12 h light and 12 h darkcycle during acclimatization, experimental
period and recovery period. All animals were
provided conventional laboratory rodent dietmanufactured by Nutrivet Life Sciences, Pune
and purified water was provided ad libitum.
Ethics
The institutional animal ethics committee(IAEC) had approved the protocol and animals
used in the individual protocols bearing
approval number sa-FORD_MAY_2015_21_
004, FORD_Sep_2015_23_037, sa-FORD_
JAN_ 2015_20_060 and sa-FORD_ JAN_2015_20_063 respectively for acute oral toxicity, 90
days sub-chronic study, Mammalian Bone
Marrow Chromosome Aberration Test andmammalian bone marrow micronucleus test
respectively. The study was conducted in the
CPSEA approved laboratory (reg. No. 1256/
bc/09/CPCSEA) in compliance of CPSEA
21

guidelines and OECD guidelines for testing ofchemicals 423, 408, 475, 474 and 471
respectively14-18.
Acute Oral Toxicity Study
The vehicle (0.5% Carboxy methyl cellulose)
was added to the weighed quantities of the test
item (300 and 2000 mg) slowly and mixed wellto make the formulations. It was then transferred
to calibrated measuring cylinders. The stock
concentrations of 30 and 200 mg/ml wereachieved by making up the volume to 10 ml in
the measuring cylinders. Formulation of the test
item was prepared fresh and unused volume wasdiscarded.
The test item was administered orally by gavage
as single dose using gavage needle number 14.
Dose was adjusted according to the body weight
which was measured on the dosing day andmaximum dose volume was 10ml/kg. Food wasgiven 3-5 hrs after dosing.
The dose given was 300mg/kg body weight,
2000mg/kg body weight and 2000mg/kg bodyweight in dose range finding study(G1) step I,
step II and main study(step III) respectively. All
the animals were observed for clinical signs of
toxicity and mortality at 30min, 1hr, 2hr, 3hr
and 4hr on the day one after dosing andthereafter once daily for clinical signs and twice
daily for mortality during the 14 days study
period. All the test animals were weighed on
day before the dose administration day 0 and on
day 7 and 14 during the study period.
90 Days Sub Chronic Toxicity Study
Five rats per sex per group were assigned to themain study group and five rats per sex wereassigned for recovery study group after
minimum 6 days of acclimatization. Rats wereadministered with dose of 0, 100, 200, 400 and
600 mg/kg body weight/day of test item toControl / control recovery (G1/G1R), Low dose
(G2), Mid dose (G3) and High dose / High doserecovery (G4/G4R) groups respectively in bothdose range finding study and main study.
All animals were observed twice daily (morningand evening) for morbidity and mortality,
throughout the acclimatization and study periods
for both Dose Range Finding Study (DRFS) andMain Study (DRMS). Clinical signs of animals
were observed before and after dose
administration on treatment day 1 and once
daily thereafter preferably at the same time each
day throughout the experimental and recovery
period. Detailed clinical examination was
conducted on day 1, day 7 and day 14 for dose
range finding study and was subjected on day 1

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

and weekly thereafter for main study.
Ophthalmological examination was conductedprior to exposure for all the animals and last
week of treatment for control and high dosegroup in dose range finding study. Whereas inmain study it was conducted prior to exposure
for all animals and on week 13th for main groupand week 17th for recovery group. For main
study,
functional
observation
battery/
neurobehavioral observation, sensory reactivity
to stimuli, assessment of grip strength, hind limb
foot splay and motor activity assessment were
performed in week 13th for main group animals
and in week 17th for recovery group animals.
Body weights were measured at start oftreatment, Day 7 and Day 14 and for Main Study,
animals were weighed during randomization, atstart of treatment and weekly thereafter, till theend of experimental period. Feed Consumption of
all animals were determined on Day 7 and Day 14
for Dose Range Finding Study and weekly once,
during the treatment and recovery period for Main
Study Clinical Pathology evaluation of all
surviving rats were performed on the termination
day, just prior to necropsy. Blood was collectedfrom retro orbital plexuses in vials without
anticoagulant for Clinical Biochemistry, 4.0%
EDTA for Haematology and 3.8% Sodium
Citrate for Coagulation factors just prior to or as
part of the procedure for euthanasia of theanimals. Clinical Pathological evaluations ofblood and serum were done as soon as possible,
after collection.
Urine sample was collected early morning
before blood sampling on the day of sacrifice.
Color, appearance and urine volume wererecorded by visual observation and otherparameters (blood/blood cell, bilirubin, Glucose,
Ketone, Leucocytes, nitrites, protein and pH)
were analysed using Auto Analyzer.
Complete internal and external examination was
done for animals and results were recorded.
Histopathological examination was carried out
on the preserved organs of control and high dosegroups rats.
Mammalian Bone Marrow Chromosome
Aberration Test
The mammalian in vivo chromosome aberration
test is used for the detection of structural
chromosome aberrations induced by test
compounds in bone marrow cells of animals,
usually rodents. A DRFS was conducted using
four groups vehicle (consisting of three maleand three female animals per group); and threetreatment groups. Vehicle control group was

administered orally with 0.5 % (w/v) carboxy
methylcellulose. The treatment groups treated at
the dose levels of 500, 1000 and 2000 mg of
Boswellia serrata Extract / kg body weight as
low, mid and high dose, respectively, via oralroute for two days treatments separated byapproximately 24h. Animals were administeredoral gavage with the test item or vehicle using
cannula. Positive control was administered byintraperitoneal route. The dose volume used was
10 ml/kg body weight. Cyclophosphamide
monohydrate was used as positive control at 50
mg/kg body weight dose level once on the dayof second dosing. Colchicine was injected to all
the animals intraperitoneally after final
treatment at dose level of 4 mg/kg body weight2 – 3 hours prior to sacrifice.
Samples of bone marrow were taken from boththe femurs between 22 - 24 hours following
final treatment. The cell suspension wascentrifuged at 1000 rpm for 10 min and thesupernatant was discarded. The pelleted cells
were re-suspended in approximately 5 mL
hypotonic solution (0.075 M KCl) and incubatedat 37 ± 2 ° C for 20 minutes.
After exposure to hypotonic solution, the cells
were centrifuged at 1000 rpm for 10 minutes atroom temperature and supernatant was
discarded. The residual cell pellet was mixed
with chilled Carnoy’s fixative for fixation ofcells. The cells were centrifuged again at 1000rpm for 10 minutes at room temperature andsupernatant was discarded. This fixation
procedure was repeated 2 times.
After centrifugation, this cell suspension was
dropped on a clean chilled slide by hanging drop
method and kept for air-drying. Two slides wereprepared from each animal. After drying, theslides were stained with 5 % Giemsa stain andmounted with DPX mount.
The Mitotic index was determined as-number ofdividing cells per 1,000 cells scored. Except for
range finding study, all slides were independently
coded before microscopic analysis. The slides
were scored for gaps, breaks, fragments,
deletions,exchanges
andchromosomal
disintegrations as structural chromosome
aberrations and 100 well spread metaphases per
animal were scored for chromosomal damage oncoded slides. The number of chromosome
aberration per metaphase was determined.
The individual mouse was observed daily during
the acclimatization period. With special
attention on the day of dosing (day 0) theexaminations were made during the first 30

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)minutes continuously to assess the onset anddetermination of adverse effects and at
approximately 1, 2 and 4 hours afteradministration. Body weight of the individual
animal was observed and recorded on day 0, day
1 prior to dosing and on the day of bonemarrow collection.

methanol for 5 min and allowed to air dry for 15- 20 min. All the slides were stained with
Giemsa and May- Grunwald stain.
The proportion of immature among totalerythrocytes was determined for each animal bycounting a total of at least 200 erythrocytes.
Except for range finding study, all slides wereindependently coded before microscopic
analysis. At least 2000 erythrocytes per animal
were scored under 100X magnification for theincidenceof
micronucleatedimmature
erythrocytes.

The test item can be considered as positive if (i)There is dose-related increase in the relative
number of cells with chromosome aberrations;(ii) There is a clear increase in the number ofcells with aberrations in a single dose group at asingle sampling time. The test item can beconsidered as negative if it does not meet theabove criteria.
Mammalian Bone Marrow Micronucleus Test
The purpose of the micronucleus test is to
identify substances (liquid or solid) that cause
cytogenetic damage which results in theformation of micronuclei containing lagging
chromosome fragments or whole chromosomes.
After one-week acclimatization, a dose-finding
test was conducted using each of 12 male andfemale mice given Boswellia serrata extract(each 3 mice for three dose groups of 0, 500,
1000, or 2000 mg/kg bw/day, orally once a day)for 4 days. Boswellia serrata extract wasadministered once daily for two days by gavage
to 25 male mice (each 5 mice for 0, 500, 1000,
2000 mg/kg and a positive control) for the
micronucleus test. MMC (2 mg/kg bw/day innormal saline, only once on the final day of drug
administration)
wasadministeredbyintraperitoneal injection as a positive control.

Bacterial Reverse Mutation Test
Bacterial cell viability was determined bycolony forming units and the tester strain
attaining at least 1 x 109 bacterial cell/ml wereused in the assay. Based on the solubility test,
Dimethyl sulfoxide was selected as a vehicle forthe test item in the study.
Five concentrations of test item were tested intriplicate plates along with vehicle and positive
control. Since, there was no reduction in numberof revertant colonies and background lawn incytotoxicity assay up to the concentration 5000
µg/plate, the revertant count of TA98 andTA100 was directly incorporated fromcytotoxicity assay to Trial I for the tested
concentration from 312.5 to 5000 µg/platevehicle and positive controls in both presence
and absence of metabolic activation.
In Trial II, the assay was performed to confirm
the negative results. The tester strains TA1535,
TA1537, TA98, TA100 and TA102 were tested
only in the presence of S9 metabolic activation
system (10% v/v S9 mix) using plate
incorporation method. Five concentrations oftest item were tested in triplicate plates alongwith vehicle and positive controls.

A needle with syringe filled with fetal bovine
serum was inserted through the opening at thelower end of the femur bone to collect bonemarrow into the prelabelled tubes. The cellsuspension was centrifuged at approximately
1000 rpm for 10 minutes and the supernatant
was discarded. A small drop of the resuspended
cell pellet was smeared on a prelabelled slideand from each animal two slides were prepared.
The smeared slides were fixed in absolute

The reference mutagens used as positive
controls in each experiment with and without
metabolic activation were as per Table 1:

Table1. Concurrent positive controls included in the study
Positive Control

CAS No.

VehicleSodium azide
26628-22-8
Distilled water
2-Nitrofluorene
607-57-8 Dimethyl sulfoxide
9-Aminoacridine
90-45-9
Dimethyl sulfoxide
Mitomycin-C
50-07-7
Distilled water
2-Aminoanthracene 613-13-8 Dimethyl sulfoxide

Metabolic
Activation
Absence
Absence
Absence
Absence
Presence

StrainTA100, TA1535
TA98
TA1537
TA102
TA1537,TA1535,
TA102,TA100 and
TA98Concentration(µg/plate)
20
25
50
0.25
20

Key: CAS-Chemical Abstracts Service Registry Number, µg- microgram
23

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

Plate incorporation and preincubation methods
were conducted according to Maron and Ames
19
and OECD Guidelines for the Testing ofChemicals no. 471. Following the plate
incorporation method, 100 µL- Test Itemsolution at each dose level, vehicle control orreference mutagen solution (positive control),
500 µL- S9 mix (for test with metabolic
activation) or 0.1 mM Phosphate buffer (for test
without metabolic activation) and 100 µLBacterial suspension were mixed in a test tube
and 2 ml overlay agar (47 ± 2°C) was added toeach tube. The mixture was vortexed and poured
on to minimal agar plates. After solidification
the plates were incubated in an incubator for
48 hours at 37 ± 2°C.
After incubation, plates were observed forbackground lawn inhibition and counted forrevertant colonies. Conditions of the bacterial
background lawn was evaluated for evidence of
cytotoxicity.
The test substance was considered positive inbacterial reverse mutation assay when there isan increase at least a 2–fold increase in the mean
revertants per plate of at least one of these tester
strains over the mean revertants per plate of theappropriate vehicle control. This increase in themean number of revertants per plate must be
accompanied by a dose response (minimum of
2 to 3 concentrations) to increasing concentrationsof the test item for the tester strainsTA98,
TA100 and TA102 whereas for Tester Strains
TA1537 and TA1535 there should be at least a
3–fold increase in the mean revertant per plateof at least one of these tester strains over themean revertant per plate of the appropriate
vehicle control.
A test item for which the results do not meet theabove criteria is considered non-mutagenic inthis test.
Statistical Analysis
All the data was expressed in mean ± SD. In
sub-chronic toxicity study, Dunnett’s t-test wasapplied for all heterogeneous data, whereas
homogeneous data, which was analysed using
ANOVA and showing significance. In recovery
groups of main study, t-test was applied for all
homogeneous data, whereas heterogeneous data
was analysed by Mann Whitney’s test. A 95%
confidence level was used to determine
statistically significant differences.

In Mammalian Bone Marrow Chromosome
Aberration Test, occurrence of structural
chromosomal aberrations was evaluated byusing one-way analysis of variance. In
Mammalian Bone Marrow Micronucleus Test,
occurrence of micronuclei in test item treatedanimals to the results obtained for the vehicle
control group was evaluated using one way
Analysis of Variance (Dunnett's Method).

RESULTS
Acute Oral Toxicity Study
No mortality was observed in the animals of G1
and G2 treated with 300 and 2000 mg/kg bodyweight dose throughout the 14 days observation
period. The mean body weights of all theanimals of G1 and G2 (Step I, Step II, Step III
and Step IV) treated with 300 and 2000 mg/kg
body weight respectively, was observed withgain on day 7 and 14, as compared to day 0.No
external and internal gross pathological changes
were seen in all the animals of G1 (Step I and II)
and G2 (Step III and IV) treated with 300 and2000 mg/kg body weight respectively, duringterminal sacrifice.
90 Day Repeated Dose Oral Toxicity Study
No treatment related mortality/morbidity andchanges in clinical signs were observed up to
600 mg/kg body weight group and control ineither sex in Dose Range Finding (DRF) study
and up to 240 mg/kg body weight group andcontrol of Main Study.
No treatment related changes were noted inbody weight (Table 2), body weight gain
percentage and feed consumption up to 600
mg/kg body weight in either sex in Dose Range
Finding (DRF) study and up to 240 mg/kg bodyweight of Main Study. No treatment relatedchanges were noted in functional observational
battery/ neurobehavioral observation, foot splay,
grip strength and motor activity assessment.
There were no statistically significant changes
in the neurology, haematological parameters(Table 3), clinical chemistry (Table 4), and theurine parameters.
Visceral examination of the rats of control andother treated groups did not reveal any
pathological abnormality except size reductionin testis and epididymideswas observed in one
male rat of G4R group. The grosshistopathology showed no significant lesions inall dose groups and control group.

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)
Table2. Absolute organ weight -90 days sub chronic toxicity study of Boswellia serrata extract
Group (N)Dose (mg/Kg)
Organ (g)Body Weight (g)BrainAdrenals
TestesEpididymides
Ovaries with duct
UterusHeart
Liver
Kidneys
SpleenThymusG1 (10)G2 (10)G3 (10)060120Mean±SD
Mean±SD
Mean±SD
339.5±32.50
335.5±29.91
349.9±30.59
234.6±22.73
225.3±29.12
225.0±16.36
2.056±0.106
2.093±0.117
2.077±0.080
1.959±0.091
1.860±0.122
1.890±0.035
0.056±0.012
0.050±0.006
0.056±0.007
0.064±0.009
0.067±0.017
0.074±0.015
3.158±0.337
3.215±0.241
3.390±0.353
1.191±0.078
1.188±0.059
1.210±0.092
0.128±0.013
0.124±0.019
0.126±0.012
0.539±0.182
0.503±0.103
0.518±0.093
1.216±0.146
1.216±0.128
1.232±0.101
0.877±0.089
0.855±0.094
0.851±0.071
10.806±1.060 10.319±0.875 11.899±1.103
7.637±1.052
7.745±1.274
8.289±1.073
2.697±0.279
2.574±0.268
2.749±0.194
1.729±0.226
1.667±0.191
1.659±0.161
0.710±0.071 0.616↓*±0.069 0.684±0.154
0.531±0.107
0.559±0.140
0.585±0.192
0.286±0.087
0.270±0.044
0.233±0.084
0.236±0.048
0.210±0.030
0.232±0.047

G4 (10)240
Mean±SD
318.7±43.62
216.0±15.76
1.984±0.091
1.841±0.129
0.054±0.008
0.071±0.013
3.064±0.200
1.164±0.127
0.131±0.017
0.526±0.171
1.166±0.126
0.871±0.091
10.77±1.346
8.587±1.421
2.450±0.280
1.658±0.139
0.809±0.287
0.651±0.225
0.233±0.055
0.265±0.062

G1R (5)0
Mean±SD
389.2±33.42
243.0±15.46
2.155±0.092
1.861±0.080
0.051±0.007
0.059±0.011
3.256±0.304
1.331±0.108
0.108±0.012
0.466±0.099
1.197±0.129
0.950±0.137
12.172±2.170
7.950±0.721
2.788±0.308
1.627±0.092
0.721±0.273
0.495±0.095
0.249±0.051
0.145±0.028

G4R(5)
240
Mean±SD
377.4±43.10
238.20 19.59
2.091±0.121
1.891±0.067
0.047±0.009
0.064±0.013
2.821±1.174
1.175±0.390
0.117±0.011
0.518±0.189
1.260±0.108
0.937±0.130
12.657±1.672
8.796±0.876
2.794±0.129
1.844↑*±0.153
0.634±0.111
0.499±0.076
0.241±0.101
0.202±0.049

Keys: SD = Standard deviation, N = Number of animals in group, ↑* = Statistically significant increase (p <0.05), ↓*= Statistically significant decrease (p < 0.05).
Table3. Hematological parameters at 90 days sub-chronic toxicity study of Boswellia serrata extract
Group (N)G1 (10)G2 (10)
Dose (mg/kg)
060
Mean ± SD
Mean ± SD
Parameter Sex
M
8.16±0.35
8.28±0.64
RBC±(X
106/µl)F
8.34±0.43
8.29±0.22
M
36.84±2.25
37.42±2.99
HCT (%)
F
39.50±1.99
38.93±0.73
M45.11±1.6445.21±1.59
3MCV(µm )F
47.38±0.78
46.98±0.99
M13.93±0.82
14.10±0.93
HGB (g/dl)
F
15.11±0.60
15.04±0.29
M17.06±0.65
17.05±0.51
MCH (pg)F
18.13±0.38
18.17±0.36
M37.85±0.53
37.76±0.72
MCHC(g/dl)
F
38.28±0.56
38.69±0.54
M 405.40±71.13 474.00±90.22
PLT (X
103/µl)F 796.00±170.25 812.10±120.35
M
11.50±2.1212.38±2.48
WBC (X
103/µl)F
10.65±2.68
9.60±1.86
M
13.90±6.19
15.10±3.28
Neutrophil(%)
F
16.90±3.25
15.10±3.2885.20±6.20
84.10±3.45
Lymphocyte M(%)
F
81.30±3.40
84.10±3.45
M0.30±0.48
0.60±0.20
Monocyte(%)
F0.90±0.74
0.20↓*±0.42
M0.60±0.52
0.80±0.79
Eosinophil(%)
F
0.90±0.57
0.60±0.52M
0.00±0.00
0.00±0.00
Basophil (%)
F
0.00±0.00
0.00±0.00
M
22.60±2.9628.10±24.96
PT(sec.)F23.69±7.12
20.83±1.99
M30.75±3.00
22.70↓*±3.48
aPTT(sec.)
F
22.01±4.61
21.42±1.85

G3 (10)G4 (10)G1R (5)G4R (5)
120
240
0
240
Mean ± SD
Mean ± SD
Mean ± SD
Mean ± SD
8.18±0.38
8.02±0.91
9.68±0.48
7.48↓*±0.14
8.09±0.37
7.96±0.61
8.17±0.31
7.81±0.31
37.14±2.04
36.78±1.7844.16±2.4739.50↓*±0.80
38.36±1.92
39.96±2.2138.70±1.60
37.30±1.4945.41±2.05
46.41±6.07
45.64±3.3052.86↑*±1.8747.42±1.01
50.35±3.8547.32±1.0347.76±0.23
13.96±0.66
13.62±0.71
16.50±0.74
14.56↓*±0.43
14.54±0.77
14.82±0.82
14.90±0.46
14.40±0.37
17.09±0.68
17.14±1.69
17.08±1.06
19.50↑*±0.81
17.99±0.51
18.69±1.2218.24±0.43
18.44±0.40
37.66±0.47
37.05±1.1237.42±0.78
36.92±0.48
37.93±0.79
37.17↓*±1.1138.54±0.51
38.64±0.80
496.50±105.97 473.90±120.56 571.20±58.65 497.20↓*±33.28
729.70±87.39 647.80↓*±147.51 615.20±73.35 530.40±49.47
11.05±3.3513.61±4.78
16.08±4.6812.10±1.62
10.00±2.71
10.70±2.16
9.14±1.15
9.06±1.98
21.20↑*±3.6815.90±3.70
15.20±5.76
19.80±3.3516.70±2.2114.10±3.0318.60±6.80
17.40±5.90
77.50↓*±3.8482.90±3.67
83.20±5.63
78.20±4.02
81.80±2.8285.40↑*±3.20
80.40±7.73
81.20±6.14
0.42±0.48
0.40±0.52
0.80±0.84
0.60±0.55
0.70±0.48
0.30↓*±0.48
0.20±0.45
0.40±0.55
0.60±0.70
0.80±0.63
0.80±1.30
1.40±1.14
0.80±0.63
0.20↓*±0.42
0.80±0.84
1.00±0.71
0.00±0.00
0.00±0.00
0.00±0.00
0.00±0.00
0.00±0.00
0.00±0.00
0.00±0.00
0.00±0.00
22.19±4.54
21.58±7.02
18.02±0.40
19.42±2.01
20.51±3.69
21.05±3.81
21.25±0.63
20.61±1.54
22.51↓*±4.61
27.42±5.04
22.25±4.07
23.01±4.88
21.40±1.66
21.04±3.4219.37±2.50
18.16±3.31

Keys: SD = Standard deviation, N = Number of animals in group, ↑* = Statistically significant increase (p <0.05), ↓*= Statistically significant decrease (p < 0.05).

25

International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 202Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)
Table4. Clinical Biochemistry parameters at 90 days sub-chronic toxicity study
Group (N)Dose (mg/kg)
Parameter

G1 (10)0
Sex
Mean ±SD
M214.49±70.74
ALP (U/I)
F
96.73±25.74
M
61.30±13.55
ALT(U/I)
F
50.56±6.85
M
3.15±0.21
Albumin(g/dl)
F
3.34±0.24
M
152.26±22.95
AST(U/I)F
159.90±42.15
M
48.55±46.94
Bileacids(µmol/L)
F
20.02±13.62
M
52.12±13.52
Urea(mg/dl)
F45.31±8.33
M
9.72±0.22
Calcium(mg/dl)
F
9.94±0.26
M
45.47±11.75
Cholesterol(mg/dl)
F
47.96±7.26
M
0.58±0.04
Creatinine(mg/dl)
F
0.58±0.04
M
59.09±9.16
Glucose(mg/dl)
F76.54±14.81
0.14±0.04
Totalbilirubin(mg M/dl)F
0.13±0.05
M
7.09±0.22
Totalprotein(g/dl)
F
7.48±0.48
58.72±10.92
Triglyceride(mg/ M
F54.69±10.67dl)
6.26±0.55
Phosphorus(mg/ M
F
5.03±0.79dl)
M 2681.30±648.05
LD(U/I)F 2602.50±1123.84
M
2.17±0.37
GGT(U/I)F
2.42±0.34
M
567.70±124.54
CK(U/l)F
621.80±287.10
M
154.80±2.49
Na(mmol/l)
F
141.90±1.10
M
5.69±0.28K(mmol/l)F
5.16±0.55
M
111.30±2.00
Cl(mmol/l)
F103.70±1.42
M24.36±6.32
BUN(mg/dl)
F
21.17±3.89
M
3.95±0.38
Glob(g/dl)
F
4.14±0.36M
0.81±0.12
A/G–Calculated
F
0.81±0.08

G2 (10)60
Mean± SD
212.07±40.57
106.09±22.35
60.26±6.46
48.19±5.96
3.19±0.21
3.32±0.16
167.85±18.68
128.89±16.81
34.10±14.20
17.64±15.13
51.51±6.8844.13±4.94
9.96±0.15
9.85±0.24
53.26±10.34
54.46±8.37
0.60±0.04
0.58±0.03
68.82±7.33
69.03±8.55
0.16±0.02
0.12±0.03
7.56↑*±0.31
7.46±0.30
66.01±11.48
61.92±18.05
6.50±0.37
4.62±0.41

G3 (10)120
Mean ± SD
202.27±60.14
149.29±94.81
52.91±4.6152.26±10.60
3.17±0.21
3.22±0.36
150.01±22.82
148.85±27.88
31.06±14.93
13.92±7.4753.16±12.88
48.12±7.03
9.74±0.56
9.83±0.49
56.02±9.5947.45±12.63
0.58±0.04
0.60±0.05
62.04±7.40
66.78±7.55
0.13±0.02
0.10±0.02
7.38±0.34
7.38±0.57
62.72±11.34
49.43±12.28
6.25±0.61
5.54±0.75

G4 (10)240
Mean ± SD
193.15±70.78
144.62↑*±29.37
64.19±10.29
50.75±10.15
3.10±0.18
3.26±0.18
179.07±43.14
145.63±25.64
38.75±21.93
17.36±15.35
60.52±9.32
53.69±12.43
9.50±0.36
9.68±0.42
53.32±8.4954.27±11.33
0.60±0.05
0.57±0.05
63.23±7.13
69.79±11.48
0.12±0.04
0.11±0.03
7.65↑*±0.26
7.76±0.43
61.30±8.13
50.20±13.84
6.58±0.56
5.55±0.52

G1R (5)0Mean ± SD
140.84±29.96
91.14±36.58
59.48±3.6451.88±6.95
3.24±0.14
3.70±0.22
108.40±8.24203.64±42.79
5.96±2.03
10.44±5.78
32.00±2.2842.60±6.82
9.71±0.14
10.34±0.31
52.16±6.56
56.78±9.85
0.65±0.03
0.51±0.04
107.80±18.44
71.94±21.57
0.12±0.01
0.15±0.03
7.44±0.12
7.71±0.36
57.04±15.33
54.20±5.58
5.59±0.55
5.07±0.49

2626.00±939.77 2607.90±648.65
1758.60±593.03 1974.10±684.28

2961.40±1392.65
1972.60±984.31

1037.40±200.53 1091.80±322.80
2597.6±967.9 3164.60±765.60

2.57±0.71
2.55±0.32
598.10±347.72
379.10±120.75
152.20±1.48141.30±1.25
5.79±0.45
5.10±0.34
109.90±1.66
103.10±1.10
24.07±3.2220.62±2.31
4.37±0.36
4.14±0.27
0.74±0.09
0.80±0.07

2.60±0.52
2.62±0.47
4.11±4.18
3.29↑*±0.34
519.10±170.59 475.70±166.29
391.70±172.32 289.10↓*±100.40
150.50↓*±1.90151.90±0.74
146.60↑*±1.58 147.80↑*±1.55
5.73±0.46
5.64±0.31
5.15±0.21
5.06±0.69
108.20↓*±1.55
110.10±1.10107.80↑*±1.81 108.00↑*±2.1624.84±6.02
28.28±4.35
22.49±3.28
25.09±5.81
4.21±0.44
4.55↑*±0.28
4.16±0.29
4.50±0.48
0.76±0.11
0.68±0.07
0.78±0.08
0.74±0.09

2.23±0.58
1.93±0.28
244.20±53.31
512.0±207.7
143.40±0.89
145.0±1.0
4.80±0.16
4.88±0.16
104.60±1.14106.6±0.89
14.95±1.06
19.91±3.19
4.19±0.21
4.02±0.22
0.77±0.07
0.92±0.06

G4R (5)240
Mean ± SD
138.72±29.62
82.22±11.61
46.08↓*±3.4845.80±6.80
3.28±0.15
3.54±0.20
103.92±20.04
181.88±38.25
8.08±4.11
7.30±2.81
32.46±2.5443.22±2.37
9.71±0.28
10.12±0.26
60.66±16.88
54.36±11.25
0.59↓*±0.01
0.47±0.02
90.26±8.43
62.42±6.46
0.12±0.02
0.16±0.06
7.25±0.25
7.64±0.34
60.02±12.59
56.04±8.62
5.58±0.79
5.88±1.00

2.05±0.74
2.33±0.36
225.60±65.51
462.80±83.16
144.60±1.52145.00±2.55
5.22↑*±0.26
4.94±0.52
105.60±1.52
106.20±2.5915.17±1.19
20.20±1.11
3.96±0.14
4.10±0.25
0.83±0.03
0.860.07

Keys: SD = Standard deviation, N = Number of animals in group, ↑* = Statistically significant increase (p <0.05), ↓*= Statistically significant decrease (p < 0.05).

Mammalian Bone Marrow Chromosome
Aberration Test of Boswellia serrata Extract
In dose range finding study and in main study,
animals (male and female) treated with 500,
1000 and 2000 mg of Boswellia serrata Extract/kg body weight, positive control (50 mg/kg
body weight cyclophosphamide monohydrate)
and 0.5 % (w/v) Carboxymethyl Cellulose(vehicle control) appeared normal, no mortality
observed, throughout experimental period.
The body weight of the animals was within therange of commonly recorded for this strain andage. Mean and Standard deviation for individual
animal body weight on the day of dosing were
within the range.
No bone marrow toxicity i.e. no significant
decrease in the mitotic index was observed intreatment groups (treated at the dose levels of
500, 1000 and 2000 mg of Boswellia serrata
Extract / kg body weight) when compared toconcurrent vehicle control group (Table 5 and 6).
No significant increase in number of structural
chromosomal aberrations was observed in either
male or female animals treated at the dose levels

International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 202026

Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)of 500, 1000 and 2000mg of Boswellia serrata
Extract /kg body weight when compared toconcurrent vehicle control group(Table 7).
Significant increase in number of structural
chromosomal aberrations was observed inpositive control group, treated with 50 mg of
Cyclophosphamide monohydrate / kg bodyweight when compared to concurrent vehicle
control group, which represent the sensitivity oftest system to positive control (Table 7).

Table5. Mitotic index after Boswellia administration-Dose Range Finding StudyGroup

Dose Level(mg/kg B.wt)

G1

0

G2

500

G3

1000

G4

2000

Sex

Mitotic Index
Mean
5.40
5.10
5.63
5.00
5.37
4.97
5.67
5.03

M
F
M
F
M
F
M
F

SD
0.36
0.30
0.67
0.30
0.31
0.21
0.42
0.31

Key: mg = milligram, kg = kilogram, b. wt = Body weight SD= Standard Deviation
Table6. Mitotic index after Boswellia administration-Main StudyGroup

Dose Level(mg/kg B.wt)

G1

0

G2

500

G3

1000

G4

2000

G5
(PC)

50 #

Sex

Mitotic Index
Mean
5.11
4.62
4.76
4.91
5.17
4.80
5.04
4.83
4.69
4.94

M
F
M
F
M
F
M
F
M
F

Key: mg = milligram, kg = kilogram, b. wt = Body#
= Cyclophosphamide monohydrate, PC = Positive control
Table7. Summary Data on Chromosome Aberrations Main Study
Group
No.

Dose Level(mg/kg B.wt)

G1
(VC)
G2

0
500

G3

1000

G4

2000

G5
(PC)

50#

Sex
M
F
M
F
M
F
M
F
M
F

SD
0.45
0.28
0.33
0.45
0.41
0.37
0.39
0.27
0.26
0.45

weightSD=% Structural Aberrations
Including Gaps
Excluding Gaps
Mean ± SD
Mean ± SD
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.20 ± 0.45
0.20 ± 0.45
0.00 ± 0.00
0.00 ± 0.00
7.20 ± 0.45
6.80 ± 0.84
7.60 ± 1.14
6.60 ± 0.55

Standard

Deviation,

Numerical
Aberrations
Mean ± SD
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00
0.00 ± 0.00

Key: mg = milligram, kg= kilogram, b.wt = Body weight, M = Male, F = Female, SD= Standard Deviation, # =Cyclophosphamide monohydrate, VC = Vehicle control, PC = Positive control

Mammalian Bone Marrow Micronucleus
Test of Boswellia serrata Extract in Mice
All the animals of vehicle control, treatment(treated at the dose levels of 500, 1000 and 2000
mg of Boswellia serrata Extract /kg body weight)
and positive control groups were observed to benormal throughout experimental period.
No toxicity to bone marrow (i.e. significant
decrease in the P/E ratio) was observed in any of
the treatment groups (treated at the dose levels
27of 500, 1000 and 2000 mg of Boswellia serrata
Extract mg /kg body weight), when compared toconcurrent vehicle control group.
No statistically significant increase in number ofmicronucleated polychromatic erythrocytes (%MNPCE) was observed in either male or female
animals treated at the dose levels 500, 1000 and2000 mg of Boswellia serrata Extract mg/kg
body weight when compared to concurrent
vehicle control group in both DRF study andmain study (Table 8 and 9).

International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 2020

Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

Statistically significant increase in number ofmicronucleus (% MNPCE) was observed inpositive control group (treated with 50 mg of

Cyclophosphamide monohydrate
weight) in main study (Table 9).

/kg

body

Table8. Proportion of Immature Erythrocytes among Total Erythrocytes (dose range finding study)
Group
G1

Dose (mg/kg b. wt)
0 (VC)

G2

500

G3

1000

G4

2000

Sex
M
F
M
F
M
F
M
F

Mean P/E
0.568
0.601
0.552
0.538
0.579
0.544
0.542
0.542

Key: mg =milligram, kg = kilogram, b. wt = body weight, M = Male, F = Female, PCE = Polychromatic
Erythrocytes, E = Total Number of Erythrocytes, P/E = Ratio of Polychromatic Erythrocytes to Total Number ofErythrocytes.
Table9. P/E Ratio and Mean and SD of % Micronucleated Polychromatic Erythrocytes (MNPCE) (Main Study)
Group
No.

Dose (mg/kg
b.wt)

G1

0 (VC)

G2

500

G3

1000

G4

2000

G5

50 (PC)Sex

P/E% MNPCE

M
F
M
F
M
F
M
F
M
F

0.5516
0.54140.53360.52080.52740.5244
0.52660.531
0.5198
0.535

0.00
0.00
0.00
0.00
0.19
0.00
0
0.174
11.63811.4

No. of
MNPCE/Group
0
0
0
0
1
0
0
1
62
57

MNPCE
Mean
SD
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.00
0.20
0.45
0.00
0.00
0.00
0.00
0.20
0.45
12.40
1.14
11.40
1.82

Key: mg =milligram, kg = kilogram, b. wt = body weight, PCE = Polychromatic Erythrocytes, NCE =Normochromatic Erythrocytes, P/E = Ratio of Polychromatic Erythrocytes to Total Number of Erythrocytes,
MNPCE = Micronucleated Polychromatic Erythrocytes, PC = positive control (Cyclophosphamide
monohydrate), VC = Vehicle control, SD = Standard Deviation.

with respect to dose concentration in all thetester strains. In the all the tester strains, slight
precipitation was observed at highest tested in
the presence of metabolic activation system(Figure 2 and 3).

Bacterial Reverse Mutation Test of Boswellia
serrata Extract
Trial I: In all the tester strains, there was noincrease in the number of revertant colonies andno background lawn reduction up to the highest
tested concentration i.e 5000 µg/plate, whencompared to vehicle control (Figure 1).

There was no reduction in background lawn in
the all the tested concentrations up to 5000
µg/plate in the presence of metabolic activation
when compared to vehicle control plates.

Trial II: The spontaneous revertant colonies
were within the acceptable range and did notshow any increase in revertant colony count

Trial I - Dose Response Curve without Metabolic activation
350.00

Revertant Count

300.00250.00200.00TA1537
TA1535150.00TA98
TA100

100.00

TA102
50.00
0.00
312.5

625

1250

2500

5000

Concentration (µg/plate)Figure1. Bacterial Reverse Mutation Test of Boswellia serrata Extract; Dose response curve Trial I
International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 202028

Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)
Trial I - Dose Response Curve with Metabolic activation
350.00

Revertant Count

300.00250.00TA1537200.00TA1535150.00TA98
TA100

100.00

TA102
50.00
0.00
312.5

625

1250

2500

5000

Concentration (µg/plate)Figure2. Bacterial Reverse Mutation Test of Boswellia serrata Extract; Dose Response Curve Trial II
Trial II - Dose Response Curve with metabolic activation
350.00

Revertant Count

300.00250.00TA1537200.00TA1535150.00TA98
TA100

100.00

TA102
50.00

0.00
128

320

800

2000

5000

Concentration (µg/plate)Figure3. Bacterial Reverse Mutation Test of Boswellia serrata Extract; Dose response curve trial II – withmetabolic activation

DISCUSSION
Boswellia serrata a traditional medicinal herb isknown to have Boswellic acids as major
constituents in its gum extract20.A lot of preclinical and clinical studies has been conducted
to evaluate its efficacy in the indications likeosteoarthritis, crohn’s disease, autoimmuneencephalitis and many other inflammatory
conditions11. The present study aimed to study
the mutagenicity of Boswellia serrata extract interms of bacterial reverse mutation test, bacterial
chromosome aberration test, micronucleus test,
and in vivo safety by acute and sub chronic
toxicity study.
As bone marrow is a highly vascularized tissue
and can be readily isolated and processed due torapidly cycling cells, it has been used as thestandard to test the mutagenic hazards in various
animal model21. In this study, all the animals
were found to be normal, and no bone marrow
toxicity was observed with the Boswellia
29

serrata extract. Also, number of structural
chromosomal aberrations didn’t increasesignificantly inall animals treated with
Boswellia serrata Extract when compared toconcurrent vehicle control group and positive
control group.
The Ames test detects the point mutations
including substitution, addition or deletion of
one or multiple DNA base pair using aminoacid-requiring strains of S. typhimurium and E.
coli22.In this study, the tester strains TA98,
TA100, TA1537, TA1535 and TA102 weretreated with test item, in the presence (5 % and
10 % v/v S9 Mix) and absence of metabolic
activation did not show background bacterial
lawn inhibition compared to vehicle control
groups. There was no dose-related increase in
the number of revertant colonies observed in thetester strains treated with test item, both in thepresence and absence of metabolic activation. In
S9 efficiency check, the number of increasing
revertant colonies was not observed in positive

International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 2020

Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

control plates of 2-aminoanthracene in absenceof metabolic activation when compared withpresence of metabolic activation, whichindicates efficiency of S9 fraction.
In all the tester strains, the frequency of the
spontaneous revertant colonies in vehicle
control was within the acceptable range ofhistorical control data. The positive controls
used in the study exhibited significant increasein the mean number of revertant frequency
respective to their strains when compared tovehicle control, indicating the sensitivity of thespecific mutagens and confirmed function of
metabolic activation system.
Micronucleus assay is the most reliable in vivo
assay to assess the induction of chromosomal
aberration which is main endpoint ofmutagenicity hazard identification and risk
assessment23. Boswellia serrata treated groupwhen compared to concurrent vehicle control
group in both DRF study and main study didn’t
show statistically significant increase in numberofmicronucleus.
Whereasstatisticallysignificant increase in number of micronucleus
was observed in positive control group.
In single dose acute oral toxicity study, it was
found that up to 2000mg/kg body weight ofBoswellia serrata extract didn’t show any
morbidity and mortality.
In 90 day repeated dose toxicity study, allhematological parameters in animals of different
treated groups of both the sex were comparable
to control group, except statistically significant
change was observed in Neutrophils, Lymphocyte,
aPTT, MCHC, Platelets, Eosinophils andMonocytes in different dose treated group whencompared to control group of main study andrecovery groups. The observed variations inhematological parameters were considered to be of
no toxicological significance and a minimal innature and occurred in the absence of clear dose
related response.
At the end of treatment and recovery period,
statistically significant change was observed inparameters like Total Protein, Chloride,
Potassium, Sodium, ALP,GGT and Creatinine
kinase in few animals of different dose groupwhich was considered as an incidental andwithout clear dose related distribution in either
male or female rats. These alterations have nobiological impact on the individual animal andfurther it is not evidenced by variations in organ
weight and histopathological observations.
Hence it could be considered as an incidental

finding and not incurred due to administration of
the test item.
There were no treatment-related changes inurine parameters in both the sexes of treated andtreatment free groups at the end of treatment andrecovery period. All of the physical,
biochemical and microscopic parameters ofurine in treated rats were well comparable tocontrol group rats. External examination of all
male and female rats of control and all treatedgroups did not reveal any abnormality ofpathological significance. Visceral examinationof the rats of control and other treated groups
did not reveal any pathological abnormality.
Absolute and relative weight of organs oftreated group rats of either sex did not differ
significantly when compared to the respective
control group ratsat the end of treatment period.
Few minor variations without clear dose related
distribution was observed viz., statisticallysignificant decrease were observed in absolute
splenic weight in male rats treated at 60 mg/kg
as compared to control group, statisticallysignificant increased were noted in relative
weight of liver treated at 120, 240 mg/kg infemales as compare to control group in bothmain and recovery group animals.
External examination of all male and female rats
from control and all treated groups including
recovery groups did not reveal any abnormalityof pathological significance. Visceral examinationof the rats from control and other treated groups
did not reveal any pathological abnormality
except size reduction in testes was observed in
one male rat of G4R group.
Microscopic examination of control group andrats treated at 240 mg/kg revealed varying
degree of pathological changes in different
organs. Lesions observed in liver, kidneys,
lungs, aorta, heart, colon, thymus, trachea,
adrenal gland, skin of high dose treated groupare well comparable with respective control
group rats and exhibited no dose relationship.
Greaves, 2007 opined that laboratory animals
develop testicular atrophy spontaneously and it
may be seen sporadically, therefore, observed
atrophic lesion of testis and epididymides can beconsidered as spontaneous. All the observed
lesions are minimal to mild in nature. Further
these observed lesions are commonly observedin rodents during toxicological studies24-26.
Hence, occurrence of these lesions could beconsidered as spontaneous or incidental innature.

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Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of Boswellia Serrata Extract (Boswellin® Super)

CONCLUSION
Our result shows that Boswellia serrata extract
is non-mutagenic from Bacterial reverse phasemutation assay, bone marrow chromosomal
aberration test and bone marrow micronucleus
test. Single dose acute oral toxicity study up to
2000mg/kg body weight of Boswellia serrata
extract didn’t show any mortality. 90 days subchronic study of Boswellia serrata extract up to
the dose of 600mg/kg did not show any adverse
effect and can be concluded that 600mg/kg
repeated dose in the experimental animals issafe and can be considered as ―No Observed
Adverse Effect Level‖ (NOAEL) under theexperimental
condition
applied.
Thus,
Boswelliaserrata extract remains unclassified
under the hazard category as per Globally
Harmonized Classification System (GHS).

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Citation: Muhammed Majeed et al., “Mutagenic, Genotoxic and Sub Chronic Oral Safety Analysis of
Boswellia Serrata Extract (Boswellin® Super)”, International Journal of Research Studies in Medical and
Health Sciences. 2020; 5(7): 20-32.

Copyright: © 2020 Muhammed Majeed et al., This is an open-access article distributed under the terms of
the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction inany medium, provided the original author and source are credited.

International Journal of Research Studies in Medical and Health Sciences V5 ● I7 ● 202032