TOXICOLOGY:

ASCORBIC ACID:

Ascorbic acid is naturally found in vegetables and fruit, but can also
be artificially synthesized.
and it is very common to find it in multivitamin supplements.
most affected systems in case of toxic effects are gastrointestinal,
urinary, the haematological.
Studies:

ASCORBIC ACID: VIT C

6000mg

nausea, vomiting, diarrhea, flushing of

the face, headache, fatigue, and
disturbed sleep. Skin rashes were also
seen in the infants.

Long administration 3to

30gr day
1g at day for 3months

Diarrhea abdominal cramps , was

observed as a side effect

2g at day for 2eek

Supplementation of 200 mg of ascorbic

acid per day did not affect bacterial
killing by leukocytes. However, daily
intake of 2 g ascorbic acid for 2 weeks
significantly impaired bactericidal
activity

50mg at day in neanate

Oral supplementation of premature

infants with vitamin C is not associated
with evidence of increased erythrocyte
destruction, hyperbilirubinemia, or other
morbidity

Ascorbic acid did not significantly

influence the levels of serum
concentrations of cholesterol,
plasminogen activator activity,
plasminogen, fibrinogen, FR-antigen,
partial thromboplastin time, platelet
adhesiveness, alpha1-antitrypsin, or
alpha2-macroglobulin.

Vitamin C increases iron adsorption and

may be dangerous in patients with
hemochromatosis, thalassemia, or
sideroblastic anemia.
Ascorbic acid has induced hemolysis in
patients with glucose-6-phosphate
dehydrogenase deficiency

Many people believe vitamin C to be nontoxic and beneficial to health; therefore,

the vitamin is often taken in large amounts. There is no evidence suggesting that
vitamin C is carcinogenic or teratogenic or that it causes adverse reproductive
effects. Reviews of high vitamin C intakes have indicated low toxicity; adverse
effects have been reported primarily after very large doses (greater than 3 g/day).
Data show little increase in plasma steady state concentrations at intakes above
200 mg/day, and saturable intestinal absorption and renal tubular reabsorption data
suggest that overload of ascorbic acid is unlikely in humans. Possible adverse
effects associated with very high intakes have been reviewed and include: diarrhea
and other gastrointestinal disturbances, increased oxalate excretion and kidney
stone formation, increased uric acid excretion, pro-oxidant effects, systemic
conditioning ("rebound scurvy"), increased iron absorption leading to iron overload,
reduced vitamin B12 and copper status, increased oxygen demand, and erosion of
dental enamel
(1)(2)

CITRIC ACID:
in humans and animals citric acid it is very present, it is one of the
major intermediates of chemical reactions of the Krebs cycle.
Approximately in humans it produces about 2kg of citric acid daily
HUMAN EXPOSURE
Clinica
report

Clinical
report ,
various
sources
Clinical
report ,
various
sources
Reference
book
skin

SOURCE

CITRIC ACID

after ingesting a single dose of 25 g citric acid (approx. 417 mg/kg)

a young woman vomited and almost died

systemic effects after single exposure through i.v. transfusion of

large amounts of citrated blood: depletion of body calcium, effetcs
on blood composition, nausea, exacerbation, muscle weakness,
breathing difficulties up to cardiac arrest

systemic effects after repeated exposure through oral doses of

potassium citrate, either solid or dissolved in water: minor
gastrointestinal disturbances, diarrhoea, indigestion, nausea,
burning

excretion of citric acid in 82 adults ranges from 1.5 to 3.68 mmol/d

(total range 0.48.80 mmol/d) respectively from 290 to 707 mg/d
(total range 801,690 mg/d)

Acqueus Solutions 30% and 50%

Tests on
the animals of citric acid cause irritation,
ulceration on tissute

Eyes

citric acid applied for 24 hours

respectively a 2% aqueous
solution for 30 minutes found
severe and permanent injury to
rabbit eyes

Respyratori

Coughing is reported for guinea pigs

exposed for 30 minutes to
atmospheric citric acid
concentrations of 81 mg/m3

(aerosolised 6% solution). Coughing

was also produced in guinea pigs
exposed to 75 mg citric acid/ml as an
aerosol for 3 minutes. Citric acid
(concentration and application not
stated) caused brochoconstriction in
dogs with nonspecific airway
hyperreactivity.

(3)

ASPARTAME:
The FDA has established an ADI for aspartame of 50mg / kg / bw. Therefore,
current levels of use. Therefore, current use levels ofaspartame, even by high
users in special subgroups, remains well below ADI levels.
DIABETE**
ACUTE TOXICITY

SUBCRONIC TOXICITY

CHRONIC TOXICITY

CARCINOGENITY (by NTP National

Toxicology program)

studies with aspartame have been

conducted using oral and intraperiotoneal
exposure routes with mice, rats and
rabbits. No deaths or adverse effects
were reported with oral doses as high as
10,000 mg/kg.
no adverse effects due to aspartame
were reported in mice, rats, or dogs given
doses up to 13,000, 10,000, or 6,000
mg/kg bw/day, respectively
Chronic toxicity studies with aspartame,
and its decomposition products, have
been conducted in mice, rats, hamsters,
and dogs. The conclusions of these
studies were consistent in that no
adverse effect of aspartame was found
with doses up to 4,000 mg/kg bw/day
In all three studies, there were no tumors
attributed to exposure to aspartame in
either sex at any dose tested. In
conclusion, no evidence of
carcinogenicity was observed in these
transgenic mouse model studies with
dietary levels of aspartame equivalent to
7,500 mg/kg bw/day.

Human clinical studies with daily

doses of 75 mg/kg bw/day (more than
15 times the estimated daily average
intake and 1.5 times the established
ADI by the FDA) of aspartame for 24
weeks were not associated with any
significant changes in clinical
measures or adverse effects

Overall, the weight of the evidence

indicates that aspartame has no effect on
behavior, cognitive function, neural
function, or seizures in any of these
groups.

(4)(5)

BRILLANT BLU E E133:

The Panel estabilisched the new ADI for the brilliant blue is 6mg / kg
/ day, this value is based on NOAEL of 631mg/kg bw/ day from
crhonic studies of toxicology

ACUTE ORAL TOXICITY

The JECFA reported one oral acute

toxicity test. In this study Lu and Lavalle
(1964) found that the LD50 in rats was
higher than 2000 mg/kg bw.

SHORT TERM AND

SUBCHRONIC

The JECFA reported a study in mice after

feeding 1200 mg Brilliant Blue FCF over
19 days (approximately 60 mg Brilliant
Blue FCF/animal/day); no adverse effects
were observed.
. Five beagle dogs received a dietary
level of 2% Brilliant Blue FCF and 3 dogs
a 1% Brilliant Blue FCF dietary level for
one year. No clinical signs, gross
lesions or histological abnormalities
observed were attributable to

treatment, but no more details were

available (Hansen et al., 1966). The
Panel considered that the NOAEL is
2% in the diet, equivalent to 500
mg/kg bw/day.

GENOTOXICITY

Based on the available data, the Panel

considered that Brilliant Blue FCF is not
of concern with respect to genotoxicity

CHRONIC TOXICITY AND

CARCINOGENITY

Subcutaneous injections of 10 doses of 4

mg followed by 50 doses of 6 mg Brilliant
Blue FCF showed no tumour production
after 78 weeks in mouse (ICI, 1962). .
Standard haematological examinations
conducted on groups of 10 males and 10
females at week 13, 26 and 52 and on all
surviving mice at week 80 revealed no
consistent treatment related effects.. In
conclusion from the various studies
on the animals Brillant Blue FCF
dont show carcinogenic effects.

(6)

CARRAGEENAN:
A general overwev
Food aditive. It has no specific toxic effects and there are no human
studies, but might show toxic effects at very high doses, which are
not normally found in food. on animals we were esguiti some
chronic toxicity studies, carcinogenicity, acute, even by
administering high doses of carrageenan, but they have not
observed relevant data about the toxicity, even the NOAEL has not
been defined.
(7) (8)

LICORICE:
(Glycyrrhizin): One of the common colpicance of a big inttake of
licorice are hypertension , hypocalemia and quadryparesis after
prolungated haevy licorice intake; It is found in many foods and
beverages as a flavor enhancer / flavoring.
The FDA should start regulating the use of this substance and
create public awareness through the media about its health
hazards. (9)
.

NATURAL PEPPERMINT FLAVOR:

CORN STRATCH: