being f i t doesn’t deserv e all these
DESCRIPTION
Yousef Ahmad ShamsAldeen Faculty Of Pharmacy “saccharin & cancer “ Ajman university of science & technology A.U.S.T.N. Being f i t doesn’t deserv e all these. Contents. Objective Introduction What is saccharin Synthesis of saccharin F.D.A studies Arguments Studies follow up - PowerPoint PPT PresentationTRANSCRIPT
Yousef Ahmad ShamsAldeen
Faculty Of Pharmacy
“saccharin & cancer “ Ajman university of science & technology
A.U.S.T.N
Being fit doesn’t
deserve all these
Contents • Objective
• Introduction
• What is saccharin
• Synthesis of saccharin
• F.D.A studies
• Arguments
• Studies follow up
• Supporting commentaries
• The mechanism
• Urinary bladder transitional carcinoma
• Survey
• Recommendations
Introduction• Saccharin was discovered in 1879 by
a Russian chemist; Constantin Fahlberg at Johns Hopkin’s university .
• It is widely used from that date till today as an artificial sweetener as well as to keep their health away from the normal sucrose disadvantages such as ; weight gaining and hyperglycemia
What is saccharin?• Saccharin is an artificial
sweetener of 200 – 700 times sweeter than sucrose , used by those individuals suffering from diabetes , obesity and overweight or those going on diet
• It is white crystalline powder of molecular weight = 183.19gm/mloe with faint aromatic odour
• it has the following structure which is named by the IUPAC as 1,1-Dioxy-1,2-Benzoisothiazol-3-One
Synthesis of saccharin
F.D.A studies conclusions
• In renal system studying one of the authors said “ we have not seen like these lesions before “ regarding to the renal papillary lesions observation
• 3 main observations: Papillary lesions , venous thrombosis & renal pelvis hyperplasia
• In normal doses, the hyperplasic effect on renal pelvis is enough to be pre-neoplastic to transitional carcinoma of the urinary bladder.
Picture of F.D.A observations
Mammary glands saccharin was
carcinogenic for the mammary gland in both males and females
Vascular and hematopoietic system
• Lymphosarcoma ( malignant connective tissue tumour of lymphatic duct ) was observed in 5% saccharin ingested rats
Arguments
Comments F.D.A replication
" small number of rats with tumours "some stocks of un treated rats didn't develop these tumours , and the results indicated that saccharin in the probably large doses can develop carcinogenic effect as well as significant number of
tumours of the renal pelvic mucosa
"tumours were caused by stones in the urinary bladder "
Regarding to the studies results "the lesions in the urinary bladder preceded
the occurrence of stones but in no instance did the stones develop urinary
bladder tumours"
" tumours were caused due to parasites in Urinary bladder " ( nematode )*
" parasites were not recorded in the study in which the development of urinary
bladder tumours wasn't associated with stones bladder "
" tumours were recorded only at the highest doses "
At lower doses saccharin wasn't enough to reach the urinary bladder , while at
lower doses renal chronic renal diseases were recorded and
It is not necessary for tumours to develop at all dose levels in order to classify
the substance as carcinogenic N.B ; one female rat has developed a
urinary bladder tumour by being ingested 0.05% saccharin
"Tumours were caused by the impurity ; O-toluene sulphonamide not saccharin
"
More recent studies were applied by using a superbly purified saccharin , and animals developed tumours just as
they did in earlier studies
" tumours developing in bladder implantation and other studies were
irrelevant "
An F.D.A official stated that " bladder implantation should be considered as
an evaluation mechanism for saccharin carcinogenicity "
The tumours were anaplastic and undifferentiated
“Tumours were neither very malignant nor preceded by the development of pre
neoplastic lesions”
Tumours were diagnosed as carcinomas based upon morphological criteria, and they were more malignant than those
induced by cyclamate and were comparable with those induced by
other direct carcinogens On the other hands , hyperplasia observed
in the early 4 months of the study which then progressed into carcinoma
"Studies weren't well planned "Most of the studies were criticized by the National Academy of Science
Committee ;Control rats were given sodium carbonate
while treated rats were ingested with saccharin
" tumours were not developed in organs other than urinary bladder "
Tumours were observed chiefly in the Reproductive , haematopoietic , vascular
systems as well as lungs and squamous epithelium
Studies follow up… • saccharin was prohibited from being used
in food by the F.D.A regarding to the committee on human resource (17thof October 1977)
• F.D.A has announced that any saccharin beverages should be labelled with the following: "Use of this product may be hazardous to your health. This product contains saccharin, which has been determined to cause cancer in laboratory animals“
• But this label has been removed in 2000 not by the F.D.A but by the U.S congress because of heavy industrial lobbying
Supporting commentaries
• Saccharin is group 2B – possible carcinogen according to International Agency for Research and Cancer (IARC).
• Many other studies were achieved for saccharin and successfully proved the carcinogenicity of saccharin on human urinary bladder
The mechanism• Once the carbonyl
oxygen is ionized, in response to the resonance as well as to the lesser extent the sufonyl oxygen it will be highly neucleophilic that can attach to tissue proteins and causes destructions and mutations
Urinary bladder transitional carcinoma
• ranged from papillary to flat and non invasive to invasive and extremely differentiated ( grade I; papillary non invasive) to anaplastic aggressive cancers (grade III; invasive papillary or flat).
• death by obstruction of ureters rather than metastasis.
SurveyArtificial sweeteners users 65%
Checking the type of sweetener 45%
Knowing saccharin63.2%
Using saccharin specifically 16.85%
Not Knowing it's carcinogenic 83.14%
Using without knowing 13.8%
Knowing it's carcinogenic 17.2%
Knowing and using 2.3%
Using artificial sweeteners for subst.(% from users )
84.21%
For diabetic causes 14%
As diet regimen 49.12%
0.5 – 3 cachets ( % from users )84.8%
3-611.7%
6-103%
0
50
100
150
200
250
300
female checking knowingsaccharin
sacc.users don't know it'scarcinogenic
it's carcinogenic users and don'tknow
usersknowing
0
50
100
150
200
250
300
female sugar subs diabetic diet 0.5-3cachets 3-6 cachets 6-10 chachets
Artificial sweeteners users 60.17%
Checking the type of sweetener 37.17%
Knowing saccharin58.4%
Using saccharin specifically 18.6%
Not Knowing it's carcinogenic 84%
Using without knowing 15%
Knowing it's carcinogenic 16%
Knowing and using 2.6%
Using artificial sweeteners for subst.(% from users )
76.5%
For diabetic causes 32.35%
As diet regimen 42.64%
0.5 – 3 cachets ( % from users )69.1%
3-628%
6-104.4%
0
20
40
60
80
100
120
male checking knowingsaccharin
sacc.users don't know it'scarcinogenic
it's carcinogenic users and don'tknow
usersknowing
0
20
40
60
80
100
120
male sugar subs diabetic diet 0.5-3cachets 3-6 cachets 6-10 chachets
Our comments • It is carcinogenic as well as
teratogenic regarding to the studies • its application on the skin of the rats
in the presence of Croton oil can cause skin papillomas ( benign tumour of surface epithelium tissue ) since croton oil contains of skin promoter substances these are phorbol esters
• saccharin can lead to gain weight , which is of course opposite to the desire of these people going on diet
• sweetener saccharin activate a Cephalic Phase Insulin Release ( CPIR )when applied to the oral cavity only .
Recommendations • To take large amount of liquids
( water for instance ) if saccharin is ingested
• Regular users of saccharin are requested to take occasionally 3 days break from the chemical
• Pregnant women are not recommended to have saccharin
• To the manufacturers we said ; think about people health rather than their money !
• If it is necessary to have sweet beverages, it’s better to try better artificial sweeteners such as ( sucralose;600 times sweeter than sucrose & acesulfame potassium ; 200 times sweeter ) both are approved by F.D.A as safe products for normal and pregnant women.
Special thanks
• For all people who have helped me in this project;Family members, project supervisor, whith special thanks to Abdullah M.alkandari for his cooperation in getting the successful survey by the appreciated questionnaires.