4- Hazard quantification/Effects assessment

Table effect assessment

Species Doses NOEL LOEL Durati Effects Ref.

tested on
Mice 2,4,8 and 4 Rise to pre-mutagenic DNA http://mutage.oxfordjournals.org
15 mg/kg Weeks damage in resting splenocytes /content/25/1/57.full
bw/day
Swiss strain 2,3,7,8 1 1 year Amyloidosis and dermatitis http://www.chem.unep.ch/pops/
mice mg/kg ng/kg/da pops_inc/proceedings/bangkok/
bw/day y KIMURA.html

Rat Fo 1 Lower rate of conception and http://www.chem.unep.ch/pops/

generatio ng/kg/day lower birth weight and they pops_inc/proceedings/bangkok/
n: affect estrous cyce KIMURA.html
100
ng/kg/da
y

F1 and
F2
generatio
n: 1o
ng/kg/da
y
Rat 0,2,4 and 9 and lesions.mean body weight and www.vkm.no/dav/7b023a9623
8 ng/kg 15 survival were reduced in rats
 bw in month receiving 8mg furan/kg bw.
corn oil Non –neoplasmic liver lesions
were abundant in all rats
administered furan at all
doseswith highest toxicity in
the biliary tract in liver.
Rhesus 5 ng/kg 0.126 4 71% of 5 ng/kg and 86% of 25 http://www.chem.unep.ch/pops/
monkey and 25 ng/kg/day years nd/kg showed endometriosis pops_inc/proceedings/bangkok/
ng/kg for dose 5 KIMURA.html
ng/kg
Mice 5 ng/kg Single Supress antibody production http://www.chem.unep.ch/pops/
dose and causes change in pops_inc/proceedings/bangkok/
lymphocyte KIMURA.html
Marmosets 5 ng/kg Single Change in lymphocyte http://www.chem.unep.ch/pops/
dose subpopulation in the blood. pops_inc/proceedings/bangkok/
KIMURA.html
Mice 0.0, 0.03, 0.12 90 Liver weight were increased at file:///D:/2nd%20yr/toxi/net
0.12,0.5, mg/kg days 8.0 mg/kg BW dose in %20txi/Subchronic%20Oral
2.0 and BW/day female.Level of serum enzyme %20Toxicity%20Study%20of
8.0 mg/kg alanine transaminase %20Furan%20in
BW/ day representative of liver damage %20B6C3F1%20Mice.htm
were increased three fold at
highest dose. Histological
changes in liver were observed
at 2.0 and 8.0 mg/kg BW in
both sexes. Clinical parameters
were altered for the kidney
Male Rats 2,4 and 8 90 Toxicity in male reproductive Karacaoglu and Selmanoglu,
mg/kg/da days system i.e. Significant 2010
y to 3 or reduction in weight of seminal http://www.agrihunt.com/food-
4 weeks vesicle, decrease in industry/1356-furan.html
old male testosterone level, impairment
 rats in testis, epididymis and
prostrate gland, no effect on
sperm count and its
morphology while apotopic
cells in testis increase.
Rat 8 or 15 5 days Hepatocellular adenomas and US National Toxicological
mg/kg /week carcinomas Program (NTP)
BW for 2 http://www.agrihunt.com/food-
years industry/1356-furan.html
mice 0,4,8, General- 5 days General-Increase in serum Risk assessment of furan exposure
15,30 and 2.5mg/kg a level enzyme aminotransferase in the Norwegian population.
60mg/kg BW/day week and sorbitol dehydrogenase at
BW Chronic- for 13 8 and 15 mg/kg BW. Increase in
10.7 weeks dose dependent poliferation
mg/kg and apotopic index.
bw/day Sub chronic-final mean body
weight of male mice receiving
high dose were lower than
control mice. Absolute and
reative liver weight at two top
dose level (15 and 30) showed
dose dependent significant
increase in comparision to
control. A week dose
dependent incidence of liver
lesion was observed at 8
mg/kg BW in male mice and 15
mg/kg BW in femae mice and
increasing with dose , but
reached statistical significance
first at 30 mg/kg BW for both
sexes. Nearly all animals
 deveoped liver lesions at 30
and 60 mg/kg BW
(the conversion to one unit (e.g. ug/kg) is important to be able to pick out the critical effect and to compare exposure and critical
effect-levels in a later stage)

According to the hazard assessment done on various animals, furan was found to have carcinogenic effect and liver is the main
target organ. Both rat and mice are susceptible to furan toxicity but rat is the most sensitive species. A dose dependent increase in
hepatocelluar adenomas and carcinomas were observed in rat and mice and an increase in the incidence of cholangiocarcinomas
was observed in rat liver. Cholangiocarcinomas in male and female rats are the most sensitive toxicological end point observed in
rodents. On the basis of available data, VKM considers that rat choangiocarcinomas may be revelant for human risk from furan.. In
mice, it was found that furan gives rise to premutagenic DNA damage in resting splenocytes with the dose 2, 4, 8 and 15 mg/kg
BW/day for 4 weeks. Similarly on other study of mice with single dose of 5 ug/kg, it was found that furan superess antibody
production and cause change in lymphocyte. Again when 0.0, 0.03, 0.12, 0.5. 2.0 And 8.0 mg/kg BW/day dose was given for 90
days, Noel level was found to be 0.12 mg/kg BW/day and the effects were most prevalent in female. Liver weight was increased at
8.0 mg/kg BW dose in female. Similarly level of serum enzyme alanine transaminase representative of liver damage were increased
three fold at highest dose. Histological changes in liver were observed at 2.0 and 8.0 mg/kg BW in both sexes. Clinical parameters
were altered for the kidney. On Swiss strain mice LOEL was found to be 1 ug/kg BW/day with doses 2,3,7,8 mg/kg BW/day tested
for 1 year and effect such as amyloidosis and dermatitis was observed.

Similarly on effect assessment on rat with dose of 100 ug/kg/day for Fo:generation and 10 ug/kg/day for F1:generation, NOEL was
observed to be 1ng/kg/day with the effect of lower rate of conception and lower birth weight which affect estrous cycle. On other
study in which dose of 0, 2, 4 and 8 ug/kg BW/day was given in corn oil for 9 and 15 month, effect was observed as lesions. Also
mean BW and survival rate were reduced in rat receiving 8 ug Furan/kg BW. Non-neoplasmic liver lesions were abundant in all rats
administered furan at all doses with toxicity in billiary tract in liver. Similarly on a study of 90 days performed in male rat with dose of
2, 4 and 8 mg/kg BW/ day to 3 or 4 weeks old male rat, effect as toxicity in male reproductive system i.e. Significant reduction in
weight of seminal vesicle, decrease in testosterone level, impairment in testis, epididymis and prostrate gland, no effect on sperm
count and its morphology while apotopic cells in testis increase were observed. Also the hepatocellular adenomas and carcinomas
were observed on the rat which were given furan dose of 8 or 15 mg/kg BW for 5 days/week for 2 years.
On the study done on Rhesus Monkey with dose 5 ng/kg BW/day and 25 ng/kg BW/day for 4 yrs, NOEL 0.126 ng/kg BW/day was
observed for furan level 5 ng/kg BW and 71% of rat wit dose 5ng/kg BW/day and 86% of rat with dose 25 ng/kg BW/day showed
endometriosis.

Also the effect such as change in lymphocyte sub-population in blood wa seen in Marmosets fed with single dose of 5 ng/kg
BW/day.

Also according to study done in mice by (Risk assessment of furan exposure in the Norwegian population.)
ADI =10.7*10^3 ug/kg BW/ day
=107 mg/kg BW/day

Where ADI=NOEL/ Safety Factor

Safety Factoor=100
 5- Exposure assessment
TABLE 1
(Based on VKM Norwegian Scientific Committee for food safety )

Food product Analytical method Mean furan High furan exposure Reference
exposure
Jarred baby food For 6 months old 0.18 0.45 Risk assessment of furan
infant (n=1220) (111) (44) exposure in the Norwegian
population .
Jarred baby food with For 6 months old 0.26 0.58 Risk assessment of furan
infant formula, milk infant (n=1220) (77) (34) exposure in the Norwegian
powder population .
Jarred baby food For 12 month infant 0.56 1.30 Risk assessment of furan
(n=1436) (36) (15) exposure in the Norwegian.
Jarred baby food with For 12 month infant 0.69 1.51 Risk assessment of furan
powder based porridge (n=1436) (29) (13) exposure in the Norwegian.
Can of jarred baby food For 2 years children 0.18 0.64 Risk assessment of furan
exposure in the Norwegian.
Can of jarred baby food For 2 years old 0.25 0.77 Risk assessment of furan
with canned fruits, children exposure in the Norwegian.
sweets
Breakfast cereals For 4 years old 0.03 0.11 Risk assessment of furan
children exposure in the Norwegian.
Breakfast cereals with For 4 years old 0.008 0.26 Risk assessment of furan
tomato juice, sweets children exposure in the Norwegian.
Consume coffee roasted For 18 to 70 years 0.33 0.81 Risk assessment of furan
ground old exposure in the Norwegian.
Consume coffee with For 18 to 70 years 0.34 0.82 Risk assessment of furan
vegetable old exposure in the Norwegian.
Coffee, chocolate For 18 to 70 years 0.27 0.77 Risk assessment of furan
old exposure in the Norwegian.

TABLE 2
(Based on food products )
Food Analytical method Concentrations Max Intake dose Reference
product in product (ug/kg bw)
Commercial Thermal With fruit:16.5 With fruit:0.07 National monitoring data (analysed as purchased in powder)
porridge degradation Without fruit:2.5 Without fruit:0.01
Jarred Heat treatment 9.2 <0.01 National monitoring data (analysed as purchased in powder)
tomato
sauce
Milk Heat treatment 5.6 0.03 EFSA database on furan level (2011)
product
(yoghurt,
cheese)
Jarred baby Heat treatment 38.7 0.18 EFSA database on furan level (2011)
food (meat
and
vegetable)
Baby food HS-GC-M 44.5 FDA, 2004
including HS-GC-M 4.16-40.4 Zoeller, et.al., 2004
can and jar
HS-GC-MS/HS- 42 EFSA,2010
SPME-GC-MS
HS-SPME-GC-MS 31.36 Liu & Tsai. 2010
SPME-GC-MS 29.9 Kim, et.al., 2009
SPME-GC-MS 31.93 Jestoi, et.al., 2009
Beer HS-GC-M 1.93 FAD, 2004

HS-GC-MS/HS- 3.3-5.2 EFSA,2010

SPME-GC-MS
HS-SPME-GC-MS 11.5 Liu & Tsai. 2010

Coffee
HS-GC-MS 38.57 FDA , 2004
HS-GC-MS/HS-
SPME-GC-MS 37- 3611 EFSA, 2010
HS-SPME-GC–MS Altaki, et al., 2011
 HS-SPME-GC-Ms 66.91 Liu & Tsai, 2010

HS-GC-MS 5.53 FDA ,2005

HS-GC-MS/HS-
SPME-GC-MS 02-May EFSA 2010

HS-SPME-GC-Ms 15.9 Liu & Tsai, 2010

Fruit Juices
SPME–GC-MS 3.51 Kim, et al., 2010

HS-GC-MS 11.32 FDA , 2004 , 2005

HS-SPME-GC-Ms 11.7 Liu & Tsai, 2010

Jam SPME–GC-MS 3 Kim, et al., 2010

HS-GC-MS 5.55 FDA 2004

HS-GC-MS/HS-
SPME-GC-MS 17-18 EFSA 2010
Fish
HS-SPME-GC-Ms 31.7 Liu &Tsai, 2010
HS-GC-MS 21.9 FDA, 2004 & 2005
HS-GC-MS 6.18 Zoeller, et al., 2004
HS-GC-MS/HS-
Can Fruit SPME-GC-MS 2.5 -9 EFSA , 2010
and HS-SPME-GC-Ms 11.7 Liu & Tsai, 2010
Vegetable
SPME–GC-MS 17.4 Kim, et al., 2010

HS-GC-MS 14.9 FDA, 2006 & 2008

HS-GC-MS/HS-
SPME-GC-MS 15-18 EFSA 2010
Cereals and
cereals
product HS-SPME-GC-Ms 34.2 Liu & Tsai, 2010

HS-GC-MS 29.05 FDA, 2004

HS-SPME-GC-Ms 6.42 Liu and Tsai, 2010

Sport and
Nutritional
drink SPME–GC-MS 7.23 Kim, et al., 2010
HS-GC-MS 25.03 US FDA 2004, 2005, 2006, and 2008
Miscellaneo HS-GC-MS NC Zoeller, et al., 2004
us food HS-GC-MS/HS-
including SPME-GC-MS EFSA 2010
soup,broth,
HS-SPME-GC-Ms 54.8 Liu & Tsai, 2010
sauce,
vinegar etc. SPME–GC-MS 20.2 Kim, et al., 2010

HS-GC-MS 4.35 FDA ,2005, 2006 & 2008

Meat and
meat HS-GC-MS/HS-
products SPME-GC-MS 17-19 EFSA 2010

HS-GC-MS 12.46 FDA, 2004

Milk HS-GC-MS/HS-
products SPME-GC-MS 5 to 6 EFSA ,2010
Infant HS-GC-M 11.3 FAD, 2004
Formula
HS-GC-MS/HS- 0-2.5 EFSA,2010
SPME-GC-MS
 HS-SPME-GC-MS 12.35 Liu & Tsai. 2010

According to Table 1 for -6, -12, and -24 months main source of exposure is jarred baby food. Similarly, for 4 , 9, and 13 years
major food source containing furan is breakfast cereals . In adults, Furan exposure is coffee. The highest furan exposure was
calculated for 12 months infant . VKM(Vitenskapls komiteen for Mattrygghet) considers that current exposure to furan in all
Age group particularly on infant and children is of health concern.

When exposure assessment of furan was done in various food product on various places , its concentration was found
different. On commercial porridge, furan level was found to be 16.5 ug with fruit and 2.5ug without fruit and maximum
intake dose was found to be 0.07 ug/kg BW with fruit and 0.01 ug/kg BW without fruit. Similarly concentration of furan on
Jarred tomato sauce was found to be 9.2 with maximum dose intake <0.01 ug/kg BW.

According to EFSA database on furan level (2011), furan on milk product was found to be 5.6 whereas its max intake was
found as 0.3 ug/kg BW and on Jarred baby food, it was calculated as 3.87 and maximum concentration was found as 0.18
ug/kg BW.

On the basis of various studies on baby food including can and jar, furan level varies as 44.4 ug(FAD,2004), 4.16-40.4 ug
(zoeller,et.al.,2004), 42 ug (EFSA,2010), 31.36 ug(Liu and Tsai, 2010), 29.9 ug (kim,et.al.,2009), 31.93 ug(Jestoi,et.al.,2009).
Similarly concentration of furan on beer was found as 1.93 ug(FAD,2004) ,3.3-5.2 ug(EFSA,2010) , 11.5 ug(Liu and Tsai,
2010) . and on that of coffee was found as 38.57 ug(FAD,2004) ,37-36.11 ug (EFSA,2010), 66.91 ug (Liu and Tsai, 2010).
Also the concentration of furan on fruit juice and jam was studied as 5.53 ug (FAD,2004), 15.9 ug (Liu and Tsai, 2010), 3.51
ug (kim,et.al.,2009) , and 11.32 ug(FAD,2004) , 11.7 ug(Liu and Tsai, 2010) ,3 ug(kim,et.al.,2009) respectively. Concentration
of furan on fish was found to be 5.55 ug(FAD,2004) ,17-18 ug(EFSA,2010) ,31.7 ug(Liu and Tsai, 2010), and on can fruit
and vegetable it was found as 21.9 ug (FAD,2004 and 2005),6.18 ug(zoeller,et.al.,2004) , 2.5-9 ug(EFSA,2010) , 11.7 ug(Liu
and Tsai, 2010) ,17.4 ug(kim,et.al.,2009) . Its concentration on cereal and cereal product was found as 14.9 ug(FAD,2006
and 2008) ,15-18 ug (EFSA,2010) ,34.2 ug(Liu and Tsai, 2010) . Concentration on sport and nutritional drink was found as
29.05 ug(FAD,2004) , 6.42 ug (Liu and Tsai, 2010),7.23 ug(kim,et.al.,2009) . Also concentration on meat and meat product
was found to be 4.35 ug(FAD,2005, 2006 and 2008) , 17-19 ug (EFSA,2010) and on milk product, it was found to be 12.46
ug(FAD,2004) , 5-6 ug (EFSA,2010) and on infant formula, it was found to be 11.3 ug (FAD,2004),0-2.5 ug (EFSA,2010) ,
12.35 ug (Liu and Tsai, 2010) .

6- Risk characterization/ quantification

In rodents, the liver is the main target organ for furan toxicity. Three concepts are fundamental to understanding the limitations
of Dietary assessment, habitual consumption, validity and precision (Living stone and Black, 2003) . It is well known that
cancer development in rodents and humans can be different, and that the interpretation of results from rodents to human
health risk can be difficult. Normally, cancer development in rodents is used as indicator test. It means to say that the chemical
causing cancer on rodents may be potential carcinogen in humans. Cancer in bile duct of rodents known to be malignant
cancer in human. Rat and human differ in respect that rat do not have gall bladder while human have. It is expected that
children can be susceptible for development of tumors as a result of expoaure to chemicals acting through a mutagenic mode
of action.
According to hazard assessment, ADI of the furan on human was found to be 1284.51 ug/kg BW/day w.r.t the experiment done
on mice. The NOEL on mice was found to be 10.7 mg/kg BW/day. Similarly, the NOEL level of furan and its effect on other
animals were studied and the results were found to be different in accordance to different studies. However in most of the
cases, effect was seen in liver and Furan was also found to be carcinogenic. Along with this it also affected the life
expectancy , reproduction, respiratory system and other function of body. Exposure of furan is found mainly on thermally
processed food product. Its exposure on commercial porridge, milk product, jarred baby food, tomato sauce, beer, infant
formula, sport and nutritional drink, fish and fish product etc were studied on various experiments and the concentration and
exposure of furan was different on different studies.
Exposure of furan was not very high in comparision to the effect level. Margin of exposure was considerably low which
indicates that the risk factor of furan is low on the human population.

7- Risk classification/qualification

Authority Year Type of limit Target Value Margin of Safety Reference

Norwegian 2012- NOEL=10.7 Norweign Commercial With fruit:18350.19722 Risk assessment of furan
scientific 09-20 *10^3 ug/kg populatio porridge: exposure in the Norwegian
Committee for BW/day for n with Without fruit: population.
Food Safety dose of 5 fruit:0.07 128451.3806
ug/kg Without
BW/day fruit:0.01
Milk 42817.12685
product:
0.03
Jarred baby 7136.187808
food: 0.18

According to the study of the Norwegian scientific Committee for Food Safety on the topic Risk assessment of furan exposure
in the Norwegian population, margin of safety of furan on different food product was found to be different and the result also
concluded that risk of furan was low in that region and Norweign population were not susceptible to the furan toxicity. ADI of
furan according to the study was found to be about 1284.513806 and margin of safety for Commercial porridge: with fruit was
found to be 18350.197 and that for without fruit was found to be 128452.3806, that for milk product was found to be
42817.12685 and for jarred baby food was found to 7136.187808. hence it can be concluded that risk factor of furan on the
target population is low.

Health and Safety factors :-

1 If not handled properly, Furan is a potentially hazardous chemical for industrial use .
2 the concentration of Furan in the atmosphere should be kept to a minimum , and skin contact with liquid furan should be
avoided.
3 It is recommended that workers with any abnormal circulatory, gastro-intestinal tract, or liver condition should not be exposed
to furan.
4 Too much jarred foods to infant should be avoided.
5 Too much use of roasted coffee to adult should strictly prohibited .
6 Furan is mostly due to contamination of food with food for instance if roasted coffee is feed along with chocolate. So,
recommendation from dietician or Nutritionist is most .

HAVE SAFE FOOD AND STAY HEALTHY

keyruntiwari

The end 