EJECUCIÓN DE LOS SISTEMAS GENERALES

PCDD/Fs, generally referred as "dioxins", have been labeled as the most toxic man-made chemicals. The primary health concern used to be carcinogenicity. From the public health point of view, concern about cancer is justified; 50% of males and 33% of females in Sweden develop cancer during their lifetime (Sytyke 2013).

However, other PCDD/F health risks, such as developmental and reproductional disorders, immune function, and diabetes, are currently considered as potential and topical health risk end points (The National Academies Press, 2006).

Dioxins belong to groups of polychlorinated dibenzo-p-dioxins (PCDD) (picture 4) or polychlorinated dibenzofurans (PCDF). Congeners that have chlorines in positions 2, 3, 7, and 8 possess "dioxin-like" properties. The term dioxins is very often used to refer to sum of compounds (seven congeners of dioxins, ten furans and twelve PCBs). In 1990, WHO established TDI of 10 pg/kg bw for TCDD (WHO 1998). The toxicity of PCDD/F is mediated through the aryl hydrocarbon (AH) receptor. Binding to the AH receptor induces many genes, including cytochrome P450 1A1 enzyme which function to break down toxic compounds (Pohjanvirta 2009).

Studying the combined effects of different carcinogens is very complex. Also dioxin congeners vary greatly in toxicity and therefore the concept of toxic equivalence (TEQ) has been developed. This enables to sum up the toxicity of the whole group, and it has been used extensively in assessing both exposure and adverse health effects. They key concept in TEQ approach is called Toxic Equivalence Factor (TEF). For each dioxin congener, there is an assigned relative toxicity compared to the most potent dioxin congener 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), and the TEF values vary from 1 to 0.00003. Various sets of TEF values have been developed, e.g. WHO-TEF, Nordic TEF and international TEF or I-TEF but WHO-TEF approach is the most commonly used. The latest re-evaluation of TEF values was conducted by WHO in 2005. (Tuomisto et al. 2011)

Picture 4. General chemical structure of PCDDs.

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Dioxins are by-products of industrial processes. They remain in a stable form once released in the environment. Emissions have decreased during the last decades (EFSA 2005; Tuomisto et al. 2011). They are metabolized and excreted very slowly.

Half life is commonly used for describing how persistend substances are. Dioxins are lipophils and they bioaccumulate and become biomagnified in animals, and therefore dioxin congeners have long half-lives in humans, up to decades. This makes them different to MeHg which have much shorter half live, 72 days in aquatic systems (U.S.EPA 2001). Half life also relates to the lag in decline of concentrations in the environment. This means that dioxins persist in the environment much longer, which is also seen in the Baltic Sea. After controlling dioxin emissions there was a clear decline in the concentrations, but recently the decline has gradually leveled off (Hallikainen et al. 2011). Therefore, fish is still the biggest source of human exposure to dioxin in Finland, approximately 95% of dioxin exposure originates from fish (Kiviranta et al. 2004).

Since environmental concentrations are typically low, epidemiological evidence for dioxin almost exclusively comes from contamination incidents. The best-known dioxin accident took place in 1976 in Seveso, Italy, where a trichlorophenol production reactor in a chemical factory blew up and released kilogram quantities of TCDD to the environment. Chloracne was observed in about 200 persons but no other direct adverse health outcomes were noted. Individual variation was also remarkable, some individuals developed symptoms when their exposere was 1000 pg/g (in lipid) whereas some individuals were free from symptoms after exposed to more than ten times higher concentrations (Sytyke 2013). After 25 year follow-up, there was no health difference between the exposed and controls, including mortality and cancer incidence. However, changes in tooth development and decreased male offspring of persons exposed as small children were noted.

Several dioxin accidents of smaller scale have taken place, such as citrus pulp pellet incident in 1997 in Brazil, animal feed contamination incident in 2010 in Germany, hazardous waste site incident in 1979 in New York, and salvage oil incident in 1971 in Eastern Missouri (Tuomisto et al. 2011).

Regulations on PCDD/F

Table 5 shows diversity of dioxin guidance values in terms of concentration of dioxin in foodstuff and feed. The concentrations in the Baltic herring, the most dioxin-contaminated fish species in the Baltic Sea, typically range from 4 to 10 pg/g in fresh weight, and 20-30 pg/g in fat (Hallikainen et al. 2004). Finland and Sweden have been previously granted a derogation from the EU for selling fish exceeding the maximum concentrations of dioxins and PCBs (EY 1259/2011). In 2011 the derogation became permanent. The reason for the derogation is the evidence of large health benefits acquired from fish consumption. Table 6 presents TDI values per day, figures include dioxins and dioxin-like PCBs. There is a time trend moving into

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strickter TDIs. The TDIs in the table also fall pretty close together, only WHO 1990 is clearly higher than the other TDIs. Average population total intake of PCDD/F in 2005 in Finland was 54 pg/d WHO TEQ and respective intake of PCDD/F + dioxin-like PCBs 114 pg/d (WHO TEQ), which are under the maximal recommended intakes (Hallikainen et al. 2010). In 2005, the average intake of young women in Finland was estimated at 1.5 pg/kg bw/d (Kiviranta et al. 2005).

Table 5. Guidance values for dioxin concentration in foodstuff and in fish in the EU

Limit value Value

Food fish (EY 1259/2011) 3.5 pg/g fresh weight Food fish (including dioxin-like PCBs)

(EY 1259/2011)

6.5 pg/g

Meat and meat products (EY 1259/2011) 1-2.5 pg/g fat (WHO-PCDD/F-TEQ) Milk products (EY 1259/2011) 2.5 pg g/fat

(WHO-PCDD/F-TEQ) Hen eggs and egg products (EY

1259/2011)

2.5 pg/g fat (WHO-PCDD/F-TEQ) Oils and fats (EY 1259/2011) 0.75 pg/g fat

(WHO-PCDD/F-TEQ) Feed: Fish, other aquatic animals, their

products and by-products with the exception of fish oil (IP 2002)

1.25 ng/kg (WHO-PCDD/F-TEQ)

Feed: Fish oil (IP 2002) 6 ng/kg (WHO-PCDD/F-TEQ)

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human health effects and decision making Table 6. Maximal daily intakes of PCDD/F (WHO TEQ PCDD/F-PCB). (U.S.EPA 2009;

European Commission 2000)

Organization Value (pg/kg bw/d)

JECFA (2001) 2.3

WHO (1990) 10

WHO (1998) 1-4

Japan (1998) 4

Nordic countries (2000) 5

United Kingdom (2001) 2

Scientific Committee on Food (SCF) 2