Toxicology
The Scientific Committee for Food of the European Union concluded in its opinion on the toxicology of
ochratoxin A, expressed on 17 September 1998:
" Ochratoxin A is a mycotoxin which possesses carcinogenic, nephrotoxic, teratogenic, immunotoxic and possibly
neurotoxic properties. It has also been linked to nephropathy in humans. Ochratoxin A may have a long half-life
in humans.
Ochratoxin A is carcinogenic in rodents. In conventional mutagenicity tests it is negative. However, recent data
from in vitro and in vivo tests using less conventional methods have provided evidence of the genotoxic
potential of ochratoxin A.
The Committee is aware that further studies are on-going to elucidate the mechanisms involved in ochratoxin
carcinogenicity.
Estimates of tolerable daily intake by other bodies, based on non-threshold mathematical modelling approaches
or a safety factor/threshold approach, have ranged from 1.2 to 14 ng/kg b.w./day.
The Committee notes that the higher figure of 14 ng/kg b.w./day was derived using nephrotoxicity as the
endpoint. However there is now an increasing concern about potential genotoxicity of ochratoxin A and its
mechanism of action as a carcinogen.
Therefore the Committee considers it would be prudent to reduce exposure to ochratoxin A as much as possible,
ensuring that exposures are towards the lower end of the range of tolerable daily intakes of 1.2-14 ng/kg
b.w./day which have been estimated by other bodies, e.g. below 5 ng/kg b.w./day."
→ source (external link)
There's also a table on the last table showing that Wheat and Rye may be of concern.
Now here's a report by the canadian food inspection agency
A total of 943 samples were analyzed for the presence of OTA and DON. These samples included 197 breakfast cereals, 139 wines, 130 beer, 98 infant formulae, 97 dried fruits, 96 wheat products (flour, bran, germ, cream of wheat), 93 infant cereals, 76 corn products (corn/tortilla chips, cornmeal, semolina), and 17 oat products (whole oats, oatmeal).
Sixty-seven percent of the samples (628/943) did not contain detectable levels of OTA. The 315 remaining samples that were found to have detectable levels of OTA were from all classes of products included in this survey. OTA levels ranged from 0.040 ppb (parts per billion) to 6.773 ppb. Overall, 99.2% of the samples tested for OTA were below the Canadian maximum levels proposed for OTA by Health Canada. Five samples of infant cereal, one sample of breakfast cereal, one sample of wheat flour, and one sample of wheat germ exceeded the proposed maximum levels for OTA. The OTA levels in these eight samples were assessed and appropriate follow-up actions were initiated that reflected the magnitude of the human health concern.
Less than half of the samples (388/943 or 41%) did not contain detectable levels of DON. DON was not detected in any of the wine or dried fruit samples. DON levels ranged from 1 ppb to 2060 ppb. There are no Canadian maximum levels established for DON in finished products so compliance could not be evaluated. However, the levels of DON considered elevated were reviewed, and appropriate follow-up actions were initiated that reflected the magnitude of the human health concern.
→ source (external link)
That proves wheat is of concern.
Now here's an interesting article from cornell(2005):
At what levels has OTA been found in food?
OTA has been found in food and beverages at both low and high levels in many countries. While the molds that produce OTA may be visible on contaminated commodities, no studies were found citing cases where OTA was detectable by taste or smell in food or beverages.
Most often, OTA occurs in food and beverages at levels detectable only by laboratory analysis. Data on the occurrence of OTA in food and beverages are not available for many commodities in many countries. The data that are available are often out of date and/or incomplete. It is also difficult to compare OTA levels between countries or between types of food. Some of the highest levels of OTA have been found in cereal grains in Eastern Europe. For example, in Poland OTA levels were found in rye flour at levels up to 5,410 micrograms OTA per kilogram food (5,410 µg/kg) (2.2 kg = 1 lb). OTA levels in barley in Czechoslovakia have been found to be as high as 3,800 µg/kg. The highest OTA levels elsewhere tend to be much lower. For example, studies have reported such high OTA levels as: 120 µg/kg in rye (Denmark), 442 µg/kg in peas and beans (Sweden), 360 µg/kg in coffee beans (US), and 200 µg/kg in corn (France).
In many countries studies continue to find much lower levels of OTA across a variety of commodities. The OTA levels described above are given only as examples of some of the highest levels that have been found. OTA is often not detected in food at all. Research continues in many places to better understand how much OTA is in food.
Does OTA survive cooking, baking and other food processing?
The effects of heating and cooking processes on OTA contamination have been found to vary greatly. In some studies, OTA has broken down from heating and cooking, but in other studies OTA remained in the final baked or cooked products. The most variable results come from studies of coffee roasting in which remaining OTA levels range from 0-100%, depending on roasting conditions, contamination levels and measurement methods used. Scientists are working to better understand the conditions under which OTA degrades or remains intact throughout food processing.
Who is exposed to OTA and how is exposure measured?
Many people around the world are exposed to OTA and many more have the potential to be exposed. The wide dispersal of food made possible by modern transportation and trade makes exposure more likely. It is not possible to know with certainty whether a population or an individual has been exposed without confirming exposure using one or more methods.
It is possible to verify exposure to OTA by directly measuring OTA levels in human blood, breast milk and some tissues. This is the most direct type of exposure measurement. OTA is metabolized slowly in the human body so it tends to remain present for several months or more allowing for measurement for a length of time after exposure. OTA has been found in human blood and breast milk in several European countries at levels sufficient to cause concern.
Exposure can also be estimated by measuring OTA levels in contaminated food that may have been consumed. Studies on some foods show that OTA levels often vary greatly from one batch of raw or processed food to the next. No comprehensive estimates currently exist on OTA levels in foods that comprise a typical American diet.
In some cases, exposure to OTA has also been estimated by sampling air and dust in households or workplaces, such as farms or food processing facilities, where OTA contamination is a suspected problem.
How much OTA is considered tolerable for people to ingest?
Several organizations in Europe have estimated tolerable levels of OTA exposure. These are levels of OTA that experts believe a person may ingest on a daily or weekly basis without harm over a lifetime. The Joint Expert Committee on Food Additives (JECFA) established the Provisional Tolerable Weekly Intake (PTWI) of 100 nanograms OTA per kilogram body weight per week (100 ng/kg bw/week) (1 billion ng=1 kg). This estimate is nearly equal to 14 nanograms per kilogram body weight per day (14 ng/kg bw/day), the upper limit of the range proposed by the European Commission Scientific Committee on Food (1.2-14 ng/kg bw/day).
Although these estimates are similar, there is still no worldwide consensus on what levels of OTA are considered tolerable for people to ingest. These guidelines are primarily meant to be used by scientists and regulatory agencies in their efforts in food safety protection. Intake guidelines are not intended to be used by consumers for calculating their personal intake levels.
→ source (external link)
To muddy the waters the book below(The Biology of Fungi Impacting Human Health - WA Shipton) cites a much larger tolerable limit, I think that was a typo.
"In experimental animals there is sufficient evidence to classify ochratoxin A as carcinogenic(spleen, liver, kidney), genotoxic(damages DNA), teratogenic (damages foetus), neurotoxic, immunosuppressiv and as having the ability to alter the skeletal structure in the developing animal. It also induces a variety of acute and subacute responses. Carcinogenicity in humans has not been established. Hence, it is classified as a Group 28 carcinogen. FAO/WHO suggest that a weekly intake of 100 ug/kg is tolerable. Infant cereals and foods have much lower tolerance levels -5 and 1ug/kg, respectively(Mazur & Kim 2006). However, the regulatory limits specified vary considerably (Table 3.2 - FAO 2004, Brera et. al. 2008).
But this website says a new limit, one that I didn't see in ncbi studies.
'OTA has been detected in human blood and breast milk, demonstrating dietary exposure. Daily intakes have been estimated at between 0.2 and 4.7 ng/kg bodyweight. In 2006, the European Food Safety Authority (EFSA) derived a tolerable weekly intake (TWI) of 120 ng/kg bodyweight for OTA in the diet, based on the latest scientific evidence.'
→ source (external link)
Lets then go to the EFSA website to see if that's true,
http://ec.europa.eu/...hratoxin_en.htm
The Scientific Committee on Food (SCF) adopted on 17 September 1998 an opinion that revised an earlier opinion of 22 September 1994 as regards toxicological safety of Ochratoxin A. In addition Scientific Co-operation report " Assessment of dietary intake of ochratoxin A by the population of EU Member States was published in January 2002.
Lets then see the paper cited,
Recommendations for maximum exposure The Joint FAO/WHO Expert Committee on Food Additives (JEFCA), on the basis of the nephrotoxicity of OA, proposed a provisional tolerable weekly intake (PTWI) for OA of 0.1 mg/kg body mass (equivalent to 14 ng/kg body mass/day) (11). However on the basis of carcinogenity data, The Working Group of the Nordic Council of Ministers proposed a maximum tolerable daily intake of 5 ng/kg bw of toxin (12), similar to the provisional tolerable daily intake (PTDI) established by the Canadian authority (1.2 - 5.7 ng/kg bw) (13). In 1998, taking into account the SCOOP data, the Scientific Committee for Food of the European Commission suggested that it was prudent to reduce exposure to OA as much as possible, “ensuring that exposures are towards the lower end of the range of tolerable daily intakes of 1.2-14 ng/kg bw/day which have been estimated by other bodies, e.g. below 5 ng/kg bw/day” (14)
Nothing wrong here, same said in the FAO/WHO recommendations. But in the same page from EFSA I cited above there's this:
In addition, the European Food Safety Authority (EFSA) has adopted an opinion on ochratoxin A in food on 4 April 2006. The conclusions of the opinion were confirmed in a statement issued by EFSA in 2010
The statement from 2010 says,
The risks for consumers associated with the dietary exposure to ochratoxin A have been evaluated by the previous Scientific Committee on Food (EC, 1996, 1998), the Joint FAO/WHO expert Committee on Food Additives (JECFA) in 1991 (FAO/WHO, 1991), 1995 (FAO/WHO, 1995) and 2001 (FAO/WHO, 2001) as well as more recently by European Food Safety Authority’s (EFSA) Panel on Contaminants in the Food Chain (CONTAM Panel) which adopted its opinion on ochratoxin A in food on the 4th of April 2006 (EFSA, 2006). The outcome of the EFSA opinion was a threshold-based approach using the lowest observable effect level of 8 microgram per kg bodyweight (b.w.) for early markers of renal toxicity in pigs (the most sensitive animal species) and applying a composite uncertainty factor of 450 for the uncertainties in the extrapolation of experimental data derived from animals to humans as well as for intra-species variability. Based on this assessment, a tolerable weekly intake of 120 ng/kg b.w. was derived for ochratoxin A.
120ng/kg per week translates to ~17.14 ng/kg per day. If the WHO/FAO recommends 5ng/kg this one sets the safe side at more than the triple. For an average person of 70kg 1199.8 ng per day. 45ng from the most dangerous brewer's yeast found in germany still doesn't seem as dangerous, even if you triple the dosage(90g).
It's also important to note what was said in the abstract( the summary says the same):
The European Food Safety Authority (EFSA) was asked by the European Commission to assess recent scientific information on the toxicity of ochratoxin A and, if necessary, to update its opinion on ochratoxin A in food adopted on 4 April 2006 by the Scientific Panel on the Contaminants in the Food Chain (CONTAM Panel). Five publications, most of which were from one research group, were submitted to the European Commission. The CONTAM Panel noted that four of these publications address the possible co-exposure to ochratoxin A and aristolochic acid of the human population in areas previously identified as having a higher prevalence of Balkan Endemic Nephropathy, the etiology of which has not yet been established, and the pathologies related to these two substances. In addition, a new method of analysis for multiple mycotoxins was presented in one of the papers, including data from breakfast cereals from the French retail market. The links to the respective abstracts are provided in the Appendix. The CONTAM Panel acknowledged the additional scientific information presented in the publications provided by the requestor. The Panel concluded that the nature of the information provided by these papers was not relevant to the overall assessment of the risks related to food contamination with the mycotoxin ochratoxin A, and as a consequence neither contradicts nor changes the conclusions drawn in the EFSA’s opinion on ochratoxin A in food. An update of the opinion on ochratoxin A, on the basis of the submitted papers, is therefore not necessary.
They said that an update was not necessary, but they did change the upper daily limit.
Interestingly enough is this paper, that I cited before, that is from 2010 and still cites the WHO/FAO recommendations:
A tolerable daily intake (TDI value) of 5 ng OTA/kg bw/day is recommended by the World Health Organization since it has toxic effects and is found in human blood [80,89,90,91] and in breast milk [80,92,93,94], thus proving human exposure. Furthermore, it is recommended that OTA levels in food and feed should be reduced as much as technologically possible.
This one from 2012 reviews all previous upper daily limits established and sets out a new one(a good read, very throughout):
Assuming the other uncertainty factors discussed above (i.e., intraspecies, LOAEL or no observed adverse-effect level or Benchmark dose, subchronic to chronic) remained the same, use of five as the new interspecies uncertainty factor would result in TDI values of 53 ng/ kg body weight/day and 15.6 ng/kg body weight/day, in place of the TDI values reported by EFSA (2006)and Kuiper-Goodman et al. (2010), respectively. Also, although the conservative default in risk assessment is to assume that the human is the most sensitive species for any toxicant, there are no data for humans to suggest a greater sensitivity to OTA than for pigs.
It also mentions the WHO/FAO recommendation:
A tolerable daily intake (TDI value) of 5 ng OTA/kg bw/day is recommended by the World Health Organization since it has toxic effects and is found in human blood [80,89,90,91] and in breast milk [80,92,93,94], thus proving human exposure. Furthermore, it is recommended that OTA levels in food and feed should be reduced as much as technologically possible.
Now I had limited my searched to articles from 2012 up to now. More than 10 pages appeared. Seems to be a hot topic among researches.
Edited by Busaum, 12 September 2015 - 01:23 AM.
