The Importance of Diet for Uptake of Phthalates in Pregnant Women

The importance of diet for uptake of phthalates in pregnant women

Kostens betydelse för upptag av ftalater hos gravida kvinnor

Anna Roos

Fakulteten för hälsa, natur och teknikvetenskap Folkhälsovetenskap Examensarbete i folkhälsovetenskap I (magister) 15 HP Handledare: Carl-Gustaf Bornehag, Huan Shu Examinator: Carl-Gustaf Bornehag 2017-05-24

SAMMANFATTNING Bakgrund: Kemikalier med hormonstörande egenskaper (Endocrine Disruptor Chemicals) – EDCs, är ämnen som kan påverka det naturliga hormonsystemet hos människor och djur. Ftalater är industriproducerade kemikalier, flera av dem med misstänkt hormonstörande egenskaper. Ftalater är vanligt förekommande i många olika typer av produkter. De sprids till sin omgivning och förorenar miljön. De finns även i livsmedel. Genom att mäta biomarkörer i urin, blod, bröstmjölk och fostervatten kan man konstatera att både gravida kvinnor och foster är exponerade för ftalater. Detta är av stor oro då man vet att fosterstadiet är den period i livet då exponering för kemikalier med hormonstörande egenskaper är som mest kritiskt, på grund av negativa hälsoeffekter.

Syfte: Syftet med studien är att undersöka hur intag av mejeriprodukter, fett, kött och fisk påverkar urinnivåer av ftalater hos gravida kvinnor.

Metod: Urinprov analyserade för innehåll av ftalater från 1,670 kvinnor deltagande i SELMA-studien har använts för statistisk analys, tillsammans med enkätsvar angående kostvanor besvarade av de 1,670 kvinnorna i vecka 25 av graviditeten.

Resultat: Mejeriprodukter och fett: Kostintag av grädde, standardmjölk, färskost, margarin för matlagning, majonnäs och flytande margarin hade signifikant samband med högre nivåer av mono-n-butyl ftalat (MnBP) och mono-benzyl ftalat (MBzP) i urinen hos gravida kvinnor. Kött: Ett kostintag av bacon och påläggskorv hade significant samband med högre nivåer av mono-n-butyl ftalat (MnBP) och mono-benzyl ftalat MBzP) i urinen hos gravida kvinnor. Fisk: Kostintag av sill/makrill hade significant samband med högre nivåer av mono-n-butyl ftalat (MnBP) och mono-benzyl ftalat (MBzP) i urinen hos gravida kvinnor. Kostintag av rökt makrill/sill, “annan fisk”, och sötvattensfisk hade significant samband med högre nivåer av di-2-ethylhexyl ftalat (DEHP) metaboliter i urinen hos gravida kvinnor.

Slutsats: Gravida kvinnor i Sverige är exponerade för ftalater. Resultat från detta arbete indikerar att gravida kvinnor i Sverige får i sig ftalater genom ett kostintag av mejeriprodukter med högre fetthalt, fett, kött med högre fetthalt, och fisk. Resultatet är så kallat råresultat och vidare studier behövs för att komplettera dessa fynd.

Nyckelord: Kemikalier med hormonstörande egenskaper, kost, ftalat, graviditet, urinnivå

Roos A., 2017. Kostens betydelse för upptag av ftalater hos gravida kvinnor, Magisteruppsats i folkhälsovetenskap, Karlstad Universitet

ABSTRACT Background: Endocrine disruptor chemicals - EDCs are compounds which may interfere with the natural hormone system in humans and animals. Phthalates are industrial chemicals suspected of being EDCs. Phthalates are widely used in a wide range of consumer products. They have therefore become environmental contaminants and are present in food and drinks. By measuring biomarkers in urine, blood, breast milk, and amniotic fluid, it is shown that pregnant women and fetuses are exposed to phthalates. Exposure for phthalates in pregnant women are of great concern since it is known that the period when fetus is developing is the most critical period for exposure due to related health risks.

Aim: The aim of this study is to examine how intake of dairy, fat, meat or fish is related to urinary levels of phthalates in pregnant women.

Method: Urine samples analyzed for the content of phthalate metabolites from 1,670 women participating in the SELMA-study has been used for statistical analysis, together with data selected from questionnaires regarding diet answered by the 1,670 women in week 25 of pregnancy.

Results: Dairy and fat: Diet of cream, full fat milk, cream cheese, margarine for cooking, mayonnaise and liquid margarine for cooking was significantly associated with higher levels of mono-n-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP) in pregnant women. Meat: Diet of bacon and sausage cuts was associated with higher levels of mono-n-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP). Fish: Diet of herring/mackerel was associated with higher levels of mono-n-butyl phthalate (MnBP) and mono-benzyl phthalate (MBzP). Diet of smoked mackerel/herring, “other fish”, and freshwater fish was associated with higher levels of di-2-ethylhexyl phthalate (DEHP) metabolites in pregnant women.

Conclusion: Pregnant women in Sweden are exposed to phthalates. Results in the current work indicate that pregnant women are exposed to phthalates via intake of high fat dairy, fat, high fat meat, and fish. Results are crude and further studies are needed to complement these findings.

Keywords: Endocrine disruptor chemicals, diet, phthalate, pregnancy, urinary levels

Roos A., 2017. The importance of diet for uptake of phthalates in pregnant women, Thesis in public health sciences, Karlstad University

TACK Till Carl-Gustaf Bornehag & Huan Shu. För att jag fick ta del. För att ni har lärt mig massor. För ert tålamod då arbetet dragit ut på tiden. För att jag inte hade klarat detta utan er!

TABLE OF CONTENTS 1. BACKGROUND ...... 1

1.1 Chemicals with endocrine disrupting properties (EDCs) ...... 1

1.1.1 Phthalates ...... 1

1.1.2 EDCs in pregnant women ...... 3

1.1.3 The Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) - study ...... 4

1.2 Uptake of EDCs ...... 4

1.2.1 Phthalates in dairy, fat, meat and fish ...... 5

1.3 Question at issue ...... 5

1.4 Aim ...... 5

1.5 Expected use with this study ...... 6

2. METHODS ...... 6

2.1 Study population ...... 6

2.2 Urine collection and chemical analysis ...... 6

2.3 Food frequency questionnaire...... 7

2.4 Bio statistical analysis ...... 8

3. Ethical approval ...... 9

4. Results ...... 10

4.1 The study population ...... 10

4.2 Urinary levels of phthalate metabolites in pregnant women ...... 10

4.3 Descriptive data on food intake ...... 11

4.4 Association between dietary intake and urinary levels of phthalate metabolites ...... 12

5. Discussion ...... 16

5.1 Diet and uptake of phthalates in humans ...... 16

5.2 Method discussion ...... 19

5.3 Further studies ...... 20

6. Conclusion ...... 20

References ...... 21

Appendix 1 ...... 26

Appendix 2 ...... 31

1. BACKGROUND 1.1 Chemicals with endocrine disrupting properties All human depends on a healthy functioning endocrine system for development and bodily functions (Bergman et al., 2013). There are chemicals in our surroundings with endocrine disrupting properties (EDCs), meaning they may interact with the endocrine system in humans and animals with adverse health effects as a result. Endocrine disrupting chemicals are used in a wide range of commonly used products. Since these chemicals may migrate into the surrounding environment, they may also be found in food and drinks. Due to biomonitoring data of urine, blood, breast milk and amniotic fluid it is known that all humans are exposed to chemicals, some of them suspected to disrupt the endocrine system (Fromme et al., 2011; Frederiksen, Sorgensen, & Andersson, 2010; Wan et al., 2013; Wittassek, Koch, Angerer & Bruning, 2011).

1.1.1 Phthalates Phthalic acid esters (phthalates) are industrial chemicals suspected of being EDCs (Dodson, Nishioka, Standley, Perovich, Brody & Rudel, 2012). In table 1 five commonly used phthalates and their metabolites are presented. Phthalates (di-esters) are referred to as a parent compound, which is broken down in to metabolites (mono-esters or oxidized products) as described in table 1. Figure 1 describes the molecular formula and structure of 10 investigated phthalate metabolites (ChemSrc, n.d.).

Table 1. Description of phthalates, including abbreviations and CAS no. Parent compound Abb. CAS no Metabolite Abb. CAS no Diethyl Phthalate DEP 84-66-2 Mono-ethyl phthalate MEP 2306-33-4 Dibutyl Phthalate DBP 84-74-2 Mono-n-butyl phthalate MnBP 131-70-4 Butylbenzyl Phthalate BBzP 85-68-7 Mono-benzyl phthalate MBzP 2528-16-7 Mono-(2-ethylhexyl) phthalate MEHP 4376-20-9 Mono-(2-ethyl-5-hydroxylhexyl) phthalate MEHHP 40321-99-1 Di-2-ethylhexyl Phthalate DEHP 117-81-7 Mono-(2-ethyl-5-oxohexyl) phthalate MEOHP 40321-98-0 Mono-(2-ethyl-5-carboxypentyl) phthalate MECPP 40809-41-4 Mono-(4-methyl-7-hydroxyloctyl)phthalate MHiNP 936021-98-6 Di-isononyl Phthalate DiNP 68515-48-0 Mono-(4-methyl-7-oxo octyl)phthalate MOiNP 936022-00-3 Mono-(4-methyl-7-carboxyheptyl)phthalate MCiOP 936022-02-5

1 Figure 1. Description of molecular formula and structure of 10 phthalate metabolites.

MnBP: C12H14O4 MEP: C10H10O4 MHiNP: C17H24O5 MOiNP: C17H22O5 MCiOP: C17H22O6

MBzP: C15H12O4 MEHP: C16H22O4 MEHHP: C16H22O5 MEOHP: C16H20O5 MECPP: C16H20O6

Phthalates are widely used in a wide range of consumer products (Dodson et al., 2012). Based on molecular weight and chemical properties, they are divided into high- or low molecular weight phthalates. High molecular weight phthalates such as DEHP, BBzP, and DiNP are used in for example food packaging and food containers (Rudel et al., 2011; Tran & Miyake, 2017), ﬂooring and wallcovering. Low molecular weight phthalates, such as DEP and DBP are used in personal care products and coating of some medications (Tran & Miyake, 2017). Phthalates are also used in plastics, cleaning products, building materials (Bornehag, Lundgren, Weschler, Sigsgaard, Hagerhed-Engman, & Sundell, 2005), printings (on food packaging’s) (Jarosowa, 2006), PVC tubing within milking industry (Cao, 2010; Fierens, Holderbeke, Willems, Henauw & Sioen, 2012) and prepacked and processed food (Takaro et al., 2010).

As phthalates migrates into the surroundings they have become environmental contaminants, present all around us in indoor dust, air, water and in soil (Bergman et al., 2013; Langer et al., 2014). Several studies confirm that pregnant women are exposed to phthalates; Casas et al. (2011) used one spot urine samples from 120 pregnant women. Samples were analyzed for 11 phthalate metabolites. Result showed that phthalates (MECPP, MEHHP, MEOHP, and MEP) were detected in all urine samples (Casas et al., 2011). Ye et al. (2008) reported concentrations of phthalates in spot urine samples from 100 pregnant women. Those phthalates which are used also in this thesis were detected in 96-100 % of samples (Ye et al., 2008). The Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA)- study could identify metabolites from 5 phthalates in the urine of all 2,356

2 pregnant women conducting in the study (Shu et al., submitted). Several of the investigated phthalates are EDCs.

1.1.2 EDCs in pregnant women EDCs have been detected in amniotic fluid, indicating that these compounds are transferred from the pregnant women to fetus (Jensen et al., 2012; Mose, Mortensen, Hedegaard & Knudsen, 2007). This is a concern regarding health consequences for the unborn child (Bergman et al., 2013). If the pregnant woman is repetitive exposed to phthalates during pregnancy, it may lead to phthalates accumulation in the fetus. Mose et al. (2007) measured levels of eight different phthalates in five placentas, which were dually perfused. During perfusions, the concentration of phthalates (MEP, MnBP, and MEHP) increased in maternal and fetal chamber in all five perfusions (Mose et al., 2007). It is known that when fetus is developing is the most critical period for exposure to EDCs. It may affect the child’s health, also later in life (Bergman et al., 2013; Takaro, Diamond, Gobas, Otton & Shu, 2010). EDCs in pregnant women is more a health risk for the child, rather than the pregnant woman (Bergman et al., 2012). Effects caused of EDCs in adults are likely to decrease when the EDC is no longer present. That is unfortunately not the same with the unborn child. When fetus is growing, tissues are developing in periods. Exposure to EDCs during such a period may lead to changes in development. These changes are most often not visible when the baby is born. Instead they may show from when the baby is a few months old until adulthood. Depending on which tissue is developing, exposure to EDCs may have different effects. Some tissues continue developing when the child is born and during childhood (Bergman et al., 2012). If the mother is exposed to EDCs also after the baby is born she may continue to transfer EDCs to the child via mother’s milk (Fromme et al., 2011). Jahreis et al. (2017) found a significant association between exposure to MnBP in pregnant women, and increased risk of asthma in children up to 6 years old (Jahreis et al., 2017). Exposure to phthalates in pregnant women has also been investigated regarding association with obesity-related metabolic disturbances (Perng, Watkins, Cantoral, Mercado-García, Meeker, Téllez-Rojo & Peterson, 2017), neurodevelopmental disorders (Tran & Miyake, 2017) and anogenital distance (AGD) as a biomarker of prenatal androgen exposure, in newborns (Swan et al., 2015). Exposure of EDCs may also play a role in preterm birth and low birth weight of babies (Bergman et al., 2012; Polánska, Ligocka, Sobala & Hanke, 2016).

1.1.3 The Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA)- study The SELMA-study is a population-based, longitudinal pregnancy cohort study. The study is conducted in the Swedish county of Värmland. The county has a population of about 270,000. There are 16 municipalities of which Torsby is the largest by area. Karlstad is the biggest town. The study started in September 2007 and aims to follow mothers from early pregnancy until the children reach school age. The SELMA-study is a cooperation between Karlstad University, the county council of Värmland, Lund University and several international research teams. The overall aim with the project is to investigate the importance of maternal and early life exposure to environmental- and lifestyle factors, and the risk of developing asthma and allergy. Neurodevelopmental disorder and reproductive development are also investigated (Bornehag et al., 2012; Selmastudien n.d).

1.2 Uptake of EDCs Phthalates enters the body system through intake of foods and drinks, dermal contact and inhalation. These chemicals are then rapidly metabolized and excreted from the body (Jarosowa, 2006; Kato et al., 2004; Koch, Rossbach, Drexler & Angerera, 2003; Takaro et al., 2010). Phthalates can be measured in urine, blood, amniotic fluid and breast milk (Frederiksen et al., 2010; Fromme et al., 2011; Langer et al., 2014; Wan et al., 2013; Wittassek et al., 2011). Concentrations of phthalates in urine samples may vary due to intake of liquids etc. in the pregnant women. Creatinine adjusted urinary metabolite concentrations correlate better with concentrations in blood, serum, or plasma than the unadjusted concentrations. Creatinine adjustment involves dividing micrograms of phthalate per liter urine, with grams of creatinine per liter urine (Barr, 2005).

If foods or drinks come in contact with phthalates during production, in industry, storing or processing such as cooking at home, phthalates might migrate into foodstuff and drinks. Still foodstuff may contain EDCs before being processed or packed, for example crops, meat, and fish which are exposed to EDCs from their environment (Cao, 2010; Fierens et al., 2012; Jarosowa, 2006; Montuori, Jover, Morgantini, Bayona & Triassi, 2008; Shu, 2010; Takaro et al., 2010). Studies have shown that we are exposed to phthalates, mostly DEHP and its

4 metabolites, via dietary intake of dairy, fat, meat and fish (Cao, 2010; Fierens et al., 2012; Schecter et al., 2013)

1.2.1 Phthalates in dairy, meat and fish Dairy: Phthalate metabolites (DEHP) is most commonly exposed to humans via dietary intake of fatty foods such as dairy (and meat) (Cao, 2010). Phthalates (DEHP) may be found in dairy in the whole milk chain, from farm to retail (Fierens et al., 2012). Removing dairy products from the diet may decrease levels of phthalate metabolites (MEP, MEOHP, and MEHHP) in urine (Ji, Lim Kho, Park & Choi, 2010).

Meat: Consumption of poultry has been shown to be associated with phthalate metabolites (metabolites of DEHP) in urine (Colacino, Harris & Schecter, 2010). Phthalates (DEHP) may be found in various meats and meat products (especially pork) (Schecter et al., 2013).

Fish: Phthalate metabolites (DEHP) may be found in fish (Schecter et al., 2013).

1.3 Question at issue It is known that pregnant women are exposed to phthalates via inhalation, dermal and dietary pathways (Bergman et al., 2012; Kato et al., 2004; Takaro et al., 2010). However, knowledge regarding specific food as sources for uptake is limited. Since maternal exposure is of concern regarding adverse health consequences for the unborn child, it is of importance to identify diets that is contributing to uptake of phthalates in pregnant women.

1.4 Aim The aim of this study is to examine how intake of dairy, fat, meat or fish is related to urinary levels of phthalates in pregnant women.

1.5 Expected use with this study Results from this study gives crude information regarding phthalate exposure from intake of dairy, fat, fish and meat. Complementary studies are needed to create evidence based dietary advices for pregnant women, in order to reduce uptake of phthalates.

2. METHODS 2.1 Study population Data is collected from pregnant women participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) –study (Bornehag et al., 2012). There are 25 antenatal care centers (ACCs) in Värmland. In Sweden, all pregnant women (99.9%) regularly visit an ACC during their pregnancy. The first appointment is around 10th week of pregnancy. All pregnant women visiting any of the 25 ACCs between September 2007 and March 2010 were invited to participate in the SELMA study. Women who planned to move outside Värmland, who had passed more than 22 weeks of pregnancy, or did not speak Swedish, were excluded. It was voluntary to participate in the study and the women were not prompted in any way. Of 6,658 women, 2,582 agreed to participate in the study (39%). Bornehag et al. (2012) found a self-selection bias in the SELMA-study when comparing those participating with those not participating. Data for example showed that those participating more frequently had asthma and allergy symptoms within their family. Mothers participating were also higher educated than those not participating. The authors mean that these findings indicate that the participating families do not fully represent the study population (Bornehag et al., 2012). Since the aim of current work is to investigate associations between dietary intake and phthalate metabolites in urine, such self-selection bias should not affect results. Using data from the SELMA-study provides a great opportunity to use valuable information regarding dietary intake and urinary levels of phthalates from a large study population of pregnant women. Of significant use when studying the importance of diet for uptake of phthalates in pregnant women.

2.2 Urine collection and chemical analysis Urinary samples analyzed for phthalates within the SELMA-study, from 1,670 women were used within this study. SELMA-women had handed their urine sample at the antenatal care center in week ten of pregnancy. Ahead of time they were instructed to use their first morning

6 void and to keep it in their refrigerator or below room temperature. Urine was then frozen (- 20°C) in a bio-bank at the central hospital in Karlstad (Bornehag et al., 2012).

“Aliquots of 0.2 mL of urine were added with 0.1 mL of ammonium acetate (pH 6.5) and 0.01 mL glucoronidase (E-coli) and thereafter incubated at 37°C in 30 min. Then 0.05 mL of a 50:50 (v:v) water and acetonitrile solution of labeled (3H or 13C) internal standards of all analyzed compounds were added and then analyzed by liquid chromatograph tandem mass spectrometry (LC-MS/MS). For the analysis of phthalate and phenol metabolites, a C18 column (2.1 mm i.d. x 50 mm, Genesis Lightn; Grace, Deerfield, IL, USA) was used prior to the injector to reduce the interferences of contaminants in the mobile phase. For analysis of phthalate metabolites, the samples were injected on a C18 column (1.5 μm, 2.0 mm i.d. x 30 mm VisionHT; Grace, Deerfield, IL, USA). The mobile phases were water and acetonitrile with 0.08% formic acid.” Analyze was performed in a laboratory at Lund University (Shu et al., 2014, pp. manuscript in preparation).

2.3 Food frequency questionnaire A food frequency questionnaire (FFQ) was used in mid pregnancy (25th week) in the SELMA-study (Selmastudien, n.d.). Questionnaires from 1,670 SELMA-women, for which there are urine analyzed, were used in the current study. The questionnaire includes questions on food, health and lifestyle. The instruction is to assess a mean dietary intake of the different foodstuffs. All data from the questionnaire used in the current work are shown in appendix 1. Questions regarding dairy, fat, meat and fish are for example:

Dairy: Question no 26: “How much do You drink/eat the following?” Possible alternatives regarding dairy are: skimmed milk/low-fat milk, semi-skimmed milk, full-fat milk, fruit yoghurt, low fat sour milk/low-fat yoghurt, semi-skimmed sour milk, sour milk/yoghurt, cream cheese-low fat, cream cheese, hard cheese-low fat, hard cheese, dessert cheese. Instruction: “1 glass = 2 dl, 1 cup = 1.5 dl. Fill in each line per day or per week”.

Fat: The questionnaire also contains questions regarding fat intake, both used for cooking, homemade dressing, on bread etc. For example, question no 30: “What types of fat do you usually use a) for cooking? b) in homemade dressing? (multiple choice possible). Possible

7 alternatives are butter/Bregott, liquid butter, olive oil, corn oil or sunflower oil, margarine for cooking, liquid margarine, rapeseed oil, other, none.

Meat: Question no 31 b) “How often on average do You eat the following? Fill in the number of times per month or per week or day, that means only one cross per line”. Possible answers for frequency are never, one-three times/month, one-two times/ week, three-four times/week or five-six times/week, once a day, two times/day or more than three times/day. The meat products in this question are beef, pork (sliced/in pot), meat of game animals, lamb, other meat, minced beef dishes, lean sausage, Falukorv sausage, other sausage, black pudding/blood sausage, liver/kidney, sliced meat such as ham or turkey, sausage cuts/salami, bacon/pork belly.

Fish: Question no 31 c) “How often on average do You eat the following?” Instruction: Fill in the number of times per month or per week or day, that means only one cross per line. Possible answers for frequency are never, one-three times/month, one-two times/ week, three- four times/week or five-six times/week, once a day, two times/day or more than three times/day. The fish/bird/egg products in this question are smoked mackerel/herring/others, herring/mackerel, salmon, cod/coalfish/saithe/fish fingers, tuna, freshwater fish, other fish, spawn/lump fish, caviar/Kalles, seafood/shrimps/crabs, chicken/other birds, eggs/omelets.

2.4 Bio statistical analysis All creatinine adjusted phthalate concentration from urine samples were log transformed for a more normal distribution. The log transformation made highly skewed distributions less skewed, which eased statistical analysis.

In the current work reported dietary intake of the different foodstuffs (dairy, fat, meat, fish) was divided into two groups; those who did consume that specific foodstuff, and those who did not consume that foodstuff. Data analyze was performed using SPSS version 21. Two sample t-test were conducted for the two groups (consuming vs. not consuming) for each phthalate metabolite level. A p-value less than 0.05 were used as a significant association between intake of foodstuff and levels of phthalates in urine. When analyzing results dairy was divided into full fat dairy and low fat dairy since results in current work indicated that

8 there were differences in impact on urinary levels of phthalates due to content of fat. Low fat dairy was here seen as dairy products with lower fat content than the origin product.

A ratio of geometric mean (RGM) was calculated by dividing log transformed mean concentrations of phthalate for those consuming, by log transformed mean concentrations of phthalate with those not consuming the specific foodstuff. A table was constructed for each phthalate metabolite inclosing p-value and RGM for each foodstuff (appendix 2). By analyzing RGM-values it was possible to see how intake of the different foodstuffs were affecting urinary levels of phthalates; If dietary intake of a specific foodstuff had for example a RGM=1.26 regarding urinary concentrations of a phthalate metabolite, those who ate that foodstuff had in mean 26 % higher log concentrations of investigated phthalate metabolite in their urine, compared to those who did not eat that foodstuff. If intake of that foodstuff was also significant associated with increased levels of investigated phthalate in urine, it was assessed that intake of that foodstuff is contributing to exposure of investigated phthalate in pregnant women.

3. Ethical approval The SELMA-study is approved by the Ethical committee in Uppsala, Sweden (Dnr 2007/062). The women participating in the SELMA-study, from whom data is used in current work, has during recruitment for the SELMA-study been informed of the overall aim with the project – to investigate associations between environmental exposure in early life, and incidence of asthma and allergy, and other chronical conditions, later in life (Selmastudien, n.d.). The aim of the current work is in line with the overall aim of the SELMA-study. Thereto no personal data of the SELMA-women has been used within the current work. Nevertheless, result from current study may cause anxieties and concern among public regarding chemicals in food and their investigated health consequences. Still, contributing with knowledge regarding dietary uptake of phthalates in pregnant women is important for public health and needs to be investigated.

4. RESULTS 4.1. The study population The 1,670 SELMA-women – for which there are both questionnaire data on food habits and urinary levels of phthalates, were all located in the county of Värmland in Sweden. Before the women got pregnant most of them (89.1 %) had a diet including meat and fish. 3.7 % of the women avoided meat but ate fish. 5.8 % avoided fish but ate meat. 1.3 % of the women were vegetarians eating dairy and egg. 0.1 % of the women were vegetarians eating dairy. 0.1 % of the women were vegans (Figure 2).

Figure 2. 1,670 SELMA-women’s diet before pregnancy.

Diet before pregnancy 100 89,1 % 90 80 70 60 50 40 30 20 3,7 % 5,8 % 10 1,3 % 0,1 % 0,1 % 0 Eat meat and Avoid meat, Avoid fish, eat Vegetarian Vegetarian Vegan fish eat fish meat eating dairy eating dairy and egg

Almost all (93.7 %) of the women had breakfast every day. Most women (83.2 %) had lunch every day (12.3 % had lunch several times a week). Most women (89.1 %) had dinner/supper every day (8.1 % had dinner/supper several times a week).

4.2 Urinary levels of phthalate metabolites in pregnant women Phthalate metabolites was identified in all 1,670 urine samples used in the current study. Limit of quantification (LOQ), minimum concentrations, percentiles and median concentrations for phthalate metabolites in urine samples are shown in table 2.

Table 2. Distribution of phthalate metabolites in urine of 1,670 pregnant women in the current study.

Metabolite/Compound %>LOQ Urine metabolites (ng/mL) N=1,670 SELMA-women

Min 25% Median 75% 95% MEP (DEP) 100.0 2.779 29,59 59.98 135,10 479.12 MnBP (MnBP) 100.0 3.025 41,19 69.82 112,13 226.28 MBzP (BBzP) 100.0 0.406 8,05 16.38 31,97 94.16 MEHP (DEHP) 99.6 0.139 2,05 3.65 6,50 15.97 MEHHP (DEHP) 100.0 0.862 9,36 16.21 26,81 66.48 MEOHP (DEHP) 99.9 0.468 6,30 11.03 18,35 43.14 MECPP (DEHP) 100.0 0.734 8,93 15.36 25,72 63.16 MHiNP (DiNP) 99.9 0.059 2,76 5.89 12,64 53.73 MOiNP (DiNP) 100.0 0.049 1,42 2.70 5,37 19.23 MCiOP (DiNP) 100.0 0.329 4,74 8.85 16,63 74.75

4.3 Descriptive data on food intake Answers to the food frequency questionnaire are described in detail in appendix 1. Tables were constructed for each phthalate metabolite with frequency and log mean for the two groups (consuming vs. not consuming) for each foodstuff, p-value, ratio and RGM values (appendix 2).

Dairy: SELMA-women preferred milk with lower fat content: Semi skimmed milk was the most frequently consumed milk; 66.9 % of the women drank semi skimmed milk on a daily basis. Low fat milk was preferred before full fat milk. When it comes to sour milk/yoghurt the women instead preferred full fat before low fat sour milk/yoghurt: 76 % of the women ate full fat sour milk/yoghurt and 60 % of the women ate full fat sour milk/yoghurt on a daily basis. 65.4 % of SELMA-women ate low fat sour milk/yoghurt and 42.9 % ate it daily (appendix 1, table A1, A3, A4).

Fat: Olive oil, liquid margarine and rapeseed oil was preferred for cooking among SELMA- women, before margarine or liquid butter: About half of the women used olive oil, and 24.7 % of the women used margarine for cooking (appendix 1, table A2).

Meat: Meat was commonly consumed among majority of SELMA-women: 94.9 % of the SELMA-women ate minced beef dishes, 91.6 % ate beef, 79.3 % ate pork, 85.8 % ate sliced meat, 78.1 % ate bacon, 81.7 % ate Falukorv sausage and 52.2 % of SELMA-women ate

11 sausage cuts. Least commonly consumed meat products were liver/kidney (4.7 %), lamb (12.8%), lean sausage, black pudding/blood sausage and meat of game (appendix 1, table A1, A4).

Fish: Cod/saithe/fishfingers, salmon and herring/mackerel was preferred among SELMA- women; 81.6 % ate cod/saithe/fishfingers, 72.9 % ate salmon, 63.8% ate herring/mackerel. A third of the SELMA-women reported consumption of “other fish”. 16.9 % of SELMA-women ate smoked mackerel/herring. 6.2 % of the SELMA-women reported that they ate freshwater fish (appendix 1, table A1).

4.4 Association between dietary intake and urinary levels of phthalate metabolites Table 3 below describes food items that were significantly associated with an increased level of phthalate metabolites in prenatal urine. Intake of these food items had a RGM higher than 1.05, meaning those who ate these foodstuffs had in mean 5% (or more) higher concentrations of investigated phthalate in their urine compared with those women who did not eat that specific foodstuff (appendix 2). Table 4 are describing foods that were associated with lower levels of phthalates in prenatal urine for those who ate, compared to those who did not eat that specific food. These foods had negative significant associations and low RGM values (<0.95) for marked phthalate (appendix 2.).

Table 3. Food items positively associated with an increased level of phthalate metabolites in prenatal urine among 1,670 pregnant women in SELMA.

Parent compound -> DEP DBP BBzP DEHP DiNP Positive association and RGM>1.05 MEP MnBP MBzP MEHP MEHHP MEOHP MECPP MHiNP MOiNP MCiOP Cream FFD/V Full fat milk/day FFD/V FFD/V FFD/V Full fat sour milk/day FFD/V Margarine-for cooking FFD/V FFD/V Mayonnaise FFD/V FFD/V Cream cheese/week FFD/V FFD/V FFD/V FFD/V Liquid margarine-for cooking FFD/V Dessert cheese/week FFD/V Liquid butter- for cooking FFD/V Sausage cuts M Bacon M M Lamb M M M M M Low fat liver pate/week M Smoked mackerel/Herring/Others F Freshwater fish F F F F Other Fish F F F F Herring/mackerel F No fat in homemade dressing x x * FFD=Full fat dairy, V=Vegetable fats/Fats, M=Meat, F=Fish. Bold regarding FFD/V means the foodstuff; full fat dairy or vegetable fats/fats, which had a significant association with marked phthalate, since they are grouped together.

Dairy and fat: Full fat dairy and fat/vegetable fat were grouped together in table 3 and 4. As it is shown in table 3 intakes of several full fat dairy products were associated with increased levels of phthalate metabolites in prenatal urine, most often MnBP and MBzP. Those who ate full fat milk every day had in mean 10 % higher concentrations of DBP metabolites (MnBP) and in mean 15 % higher concentrations of BBzP metabolites (MBzP) than those who did not consume full fat milk every day (appendix 2.). There was no low-fat dairy associated with an increase of phthalate metabolites in urine. Instead, the consumption of low fat dairy products showed association with lower levels of phthalate metabolites in urine. For example, intake of low fat milk, low fat sour milk and semi skimmed sour milk were associated with lower levels of MBzP in urine compared with those who did not eat these foods. When it comes to fat, such as margarine, liquid margarine and mayonnaise, these foodstuffs were also associated with increased levels of MnBP and MBzP in urine. Those who ate margarine for cooking had in mean 12 % higher concentrations of DBP metabolites (MnBP) and in mean 26 % higher concentrations of BBzP metabolites (MBzP) in urine than those who did not consume margarine for cooking (appendix 2.). Still there were some vegetable high fat foods associated with lower levels of phthalates in prenatal urine; Olive oil for homemade dressing and olive

13 oil for cooking at home was associated with lower levels of MnBP and MBzP in urine (table 4).

Intake of full fat dairy products (cream cheese and dessert cheese) were also associated with higher levels of MOiNP and MCiOP in urine (table 3).

Meat: As it is shown in table 3 intakes of meat was associated with higher levels of phthalate metabolites in prenatal urine; bacon and sausage cuts were associated with higher levels of MnBP and MBzP. Those who ate bacon had in mean 7 % higher concentrations of MnBP and in mean 12 % higher concentrations of MBzP in their urine compared with those who did not consume bacon. There are also meat products in results with high RGM values (but no significant association). Meaning those women who ate these meat products had in mean higher concentrations of MnBP and MBzP in their urine compared to those who did not. These were mostly high fat meat products; Falukorv sausage and other sausage (appendix 2.).

Intake of lamb was associated with higher levels of DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP) in urine (table 3). Those who ate lamb had in mean 26 % higher concentrations of MEHP and 17-20 % higher concentrations of MEHHP, MEOHP, MECPP in their urine, compared to those who did not eat lamb (appendix 2.). There were several meat products with no significant association but high RGM-values for DEHP metabolites, meaning those who ate these foods had 5% (or more) higher concentrations of investigated phthalate in their urine compared with those women who did not eat that specific food. For example, sliced meat (MEHP, MEOHP), other meat (MEHHP, MEOHP) and liver/kidney (MEHHP, MEOHP, MECPP) (appendix 2).

Meats (lamb and low fat liver pate) were also associated with higher levels of MCiOP in prenatal urine (table 3).

There were no meats associated with decreased levels of phthalate metabolite in prenatal urine (Table 4).

Fish: As it is shown in table 3 intakes of fish was associated with higher levels of phthalates in prenatal urine; Intake of herring/mackerel was associated with higher levels of MBzP in

14 urine (Table 3). But as shown in table 4 there were other fish items associated with lower levels of MnBP and MBzP such as salmon, spawn, seafood.

Intake of smoked mackerel/herring, “other fish”, and freshwater fish were all associated with higher levels of DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP) in urine. The fish affecting urine concentrations of DEHP metabolites the most was freshwater fish. Those who ate freshwater fish had in mean 20-26 % higher concentrations of DEHP metabolites in their urine compared to those women who did not eat freshwater fish (appendix 2.). There were no fish products associated with decreased levels of DEHP metabolites in prenatal urine (Table 4). The only fish products with low RGM-values for DEHP metabolites were spawn and seafood, meaning those who ate these foods had 5% (or more) lower concentrations of investigated phthalate in their urine compared to those women who did not eat that specific food, although not significant (appendix 2).

There were no significant association between intake of fish and DiNP metabolites in urine. Still intake of spawn had high RGM for all three DiNP metabolites in urine (appendix 2).

Table 4. Food items negatively associated with an increased level of phthalate metabolites in prenatal urine among 1,670 pregnant women in SELMA.

Parent compound -> DEP DBP BBzP DEHP DiNP Negative association and RGM<0.95 MEP MnBP MBzP MEHP MEHHP MEOHP MECPP MHiNP MOiNP MCiOP Cottage cheese/day FFD/V Low fat cream cheese/day LFD Hard cheese/day FFD/V Full fat milk/day FFD/V Butter, Bregott-for cooking FFD/V FFD/V Olive oil-for cooking FFD/V FFD/V Olive oil-in homemade dressing FFD/V FFD/V Low fat creme fraiche LFD LFD LFD LFD Low fat sourmilk/yoghurt/day LFD Semi-skimmed sour milk/day LFD Liquid butter-for cooking FFD/V Low fat milk/day LFD Full fat fruit yoghurt/week FFD/V FFD/V Sour cream FFD/V FFD/V FFD/V Full fat sour milk/day FFD/V Herring/mackerel F Salmon F F Spawn F Seafood F Eggs/Omelets x x x * FFD=Full fat dairy, V=Vegetable fats/Fats, LFD=Low fat dairy, M=Meat, F=Fish. Bold regarding FFD/V means the foodstuff; full fat dairy or vegetable fats/fats, which had a significant association with marked phthalate, since they are grouped together.

5. DISCUSSION 5.1 Diet and uptake of phthalates in humans Dairy and fat: Results of the current work showed that intake of several full fat dairy products was associated with increased levels of phthalate metabolites in prenatal urine, most often MnBP and MBzP (table 3.). In opposite, the consumption of low fat dairy products showed association with lower levels of phthalate metabolites in urine (table 4.). When it comes to fat, such as margarine, liquid margarine and mayonnaise, intake of these foods was also associated with increased levels of MnBP and MBzP in urine (table 3.). Still, olive oil for homemade dressing and olive oil for cooking at home was associated with lower levels of MnBP and MBzP in urine (table 4.). Results of current work regarding increased levels of MnBP in urine due to intake of dairy is in line with Schechter et al. (2013), who found DBP in five of nine samples of dairy products other than milk in their study. Results in the current work regarding dairy and MnBP is also to in line with Fierens et al. (2012), even if Fierens et al. found phthalates in low fat dairy; Fierens et al. (2012) investigated phthalates in milk and dairy products, from farm to retail. Low-fat milk available in retail contained metabolites of

DnBP. Cheese available at retail contained metabolites of DnBP (Fierens et al., 2012). DnBP is metabolized into MnBP why presence of DnBP in dairy indicate exposure to MnBP. Results in current work also indicated that fat content in dairy products are decisive for concentrations of phthalate metabolites (MnBP and MBzP) in urine. Further, results showed that intake of fat was related to increased levels of MnBP and MBzP in urine. That was expected since phthalates are lipophilic. Still, vegetable oil, which is also fat, was negatively associated with concentrations of MnBP and MBzP in urine. Further studies are needed to look upon differences in phthalate exposure between animal fat and vegetable fat. Further studies may also include differences in processing and packaging for the different foodstuffs.

In the current work intake of full fat milk on a daily basis, was associated with increased levels of DEHP metabolites (MEHP) in urine (Table 3). There were no other significant association between intake of dairy and increased levels of DEHP metabolites in urine. Even if full fat milk were associated with increased levels of DEHP metabolites results of current work are not fully in line with other studies; Ji et al. (2010) did a pilot study (n=25) to see if a diet change affected urinary levels of phthalates. The participants changed from a mixed diet to a vegetarian diet for five days. Levels of phthalates was compared within an hour after start, and within two hours before end of program. The participants reported dietary intake via questionnaires. All phthalates analyzed were detected in all samples. Levels of phthalates (MEP, MEOHP, and MEHHP) decreased during the program. The study made by Ji et al. (2010) also showed that consumption of dairy increased urinary levels of phthalates (MEOHP and MEHHP) (Ji, Lim Kho, Park & Choi, 2010). Fierens et al. (2012) investigated phthalates in milk and dairy products, from farm to retail, and found phthalates (DEHP) in raw milk in the dairy factory’s cooling tank. Probably due to contaminated feed. Low-fat milk available in retail contained metabolites of DEHP. Phthalates (DEHP) was also found in butter packed in foil (Fierens et al., 2012). Even if result of the current work showed that intake of dairy (full fat milk) increased levels of DEHP metabolites in urine (table 3), there were more results indicating association between intake of dairy and lower levels of DEHP metabolites in urine (table 4), or no difference for DEHP metabolites in urine between those who consumed dairy and those who did not (appendix 2). Results of current work regarding dairy and DEHP metabolites is more in line with Serrano et al. (2014). They used data from the Infant Development and Environment Study (TIDES). A cohort study with an aim to investigate association between exposure to phthalates in pregnant women and infant reproductive development. Serrano et al. (2014) used data from food frequency questionnaire and urine

17 samples from 656 pregnant women from US. Women reported number of servings per week of peanut butter/nut butter, beef, seafood, poultry, other meats, spices, oils, fats, soy, and dairy. Their result showed that intake of dairy was associated with lower concentrations of DEHP metabolites in urine in pregnant women. According to the authors these results were highly unexpected since foodstuff with higher fat content may contain higher weight phthalates since they are more lipophilic, especially DEHP. The authors see a possible explanation in the rapid metabolism of phthalates. They thereby advocate urine sample collection 24-48 h after dietary report (Serrano et al., 2014). Weather the metabolism of phthalates play a role in results of current work needs further investigation.

Meat: Results of the current work showed that MnBP and MBzP in urine was more associated with intake of high fat meat/pork (table 3.). RGM values showed that women who ate high fat meat/pork products had in mean higher concentrations of MnBP and MBzP in their urine compared to those who did not (appendix 2.). When it comes to DEHP metabolites in urine, result in current work indicated that these phthalates are more related to intake of other meat/lean meat (table 3.). Dietary intake of lamb was the one meat product significant associated with higher levels of all four DEHP metabolites in urine. RGM values showed that women who ate meat products such as sliced meat, other meat, and liver/kidney had in mean higher concentrations of metabolites of DEHP in their urine compared to those who did not (appendix 2.). Results in current work for association between intake of meats (significant for lamb and high RGM for other) and phthalates in urine is to extent in line with Schecter et al. (2013) who examined phthalate concentrations in food. The different phthalates investigated were found in a range from 6% to 74%. DEHP was the most frequent phthalate in all foods tested except in beef. Pork had the highest concentration of total phthalates. Result in current work for association between pork and MnBP and MBzP, before pork and DEHP metabolites, is not in line with Colacino et al. (2010) who investigated associations between dietary intake of meat and phthalate concentrations in urine. They analyzed data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) and found that metabolites of DEHP were associated with the consumption of poultry (Colacino, Harris & Schecter, 2010). According to Cao (2010), DEHP is most commonly exposed to humans via dietary intake of fatty foods such as high fat meats. Still intake of several other high fat meats showed no association with DEHP metabolites in urine in the current study. Also the strong association between intake of lamb and all four DEHP metabolites in urine needs further investigation.

Fish: In the current work intake of herring/mackerel was associated with higher levels of MBzP in urine (table 3). Still there were other fish items associated with lower levels of MnBP and MBzP such as salmon, spawn, seafood (table 4). These results may indicate that fat content is decisive for content of phthalates since herring and mackerel are fish with higher fat content, and seafood has low fat content. Still salmon and spawn which were associated with lower levels of MnBP and MBzP are higher in fat content (Livsmedelsverket, n.d.), why further investigation is needed.

In the current work intake of fish was associated with higher levels of DEHP metabolites in prenatal urine; Smoked mackerel/herring, “other fish”, and freshwater fish were all associated with higher levels of DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP) in urine (table 3.). The fish affecting urine concentrations of DEHP metabolites the most was freshwater fish. Those who ate freshwater fish had in mean 20-26 % higher concentrations of DEHP metabolites in their urine compared to those women who did not eat freshwater fish (appendix 2.). Results in current work is in line with results from Colacino et al. (2010), who found associations between DEHP metabolites (MEHP) and fish consumption in their study. Results are also in line with Schecter et al, (2013) who tested foods for different phthalates and found that DEHP was most common and at the highest concentrations in fish (median concentrations of 86 ng/g).

5.2 Method discussion The questionnaire was answered by the SELMA-women fifteen weeks after urinary samples were collected. Phthalate metabolites analyzed within this study are rapidly metabolized and excreted through the body why urinary measurements of these compounds are best used to assess recent exposure. The questionnaire asks for the woman’s dietary intake during pregnancy. The instruction is to assess a mean dietary intake of the different foodstuffs. So, the answers were more reflecting dietary habits during pregnancy, rather than dietary intake for a specific day. Still it is possible that the pregnant women have changed their dietary habits during this period. This time lap may be a bias. It is also possible that SELMA-women were uncertain for example about the name of the fish they were consuming or whether it is marine or freshwater.

Analysis in current work was done without adjustment for potential confounders which is a limitation. Such confounding factors could be inhalation of household dust containing phthalates, PVC-flooring, or dermal contact with products containing phthalates etc. Neither was the result analyzed for dose-response associations.

5.3 Further studies Results from this study gives crude information regarding phthalate exposure from intake of dairy, fat, fish and meat. Complementary studies are needed to create evidence based dietary advices for pregnant women, in order to reduce uptake of phthalates. Results in the current work is based on differences between those consuming and those who don’t. Further studies may include a dose-response analysis to see if urinary levels of investigated phthalate are affected by higher or lower intake of different foodstuff. Analysis in current work is done without adjustment for potential confounders which is a limitation, and further studies should be controlled for confounders such as exposure for phthalates via inhalation and dermal contact. The long-term aim is to identify diets reducing uptake of phthalates in pregnant women.

6. Conclusion Pregnant women in Sweden are exposed to phthalates. Results in the current work indicate that pregnant women are exposed to phthalates via intake of high fat dairy, fat, high fat meat, and fish. Additionally, results indicate that fat content is decisive for uptake of phthalates. Still results are crude and further studies are needed to complement these findings.

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Appendix 1. Table A1. Distribution of answers on the food frequency questionnaire to 1,670 pregnant women in SELMA. Question: “How often on average do You eat the Following?”. Instruction: “Fill in the number of times per month or per week or per day, that means only one cross per line. Put a cross in the 0-box if you rarely or never eat the commodity.”

Rarely/never 1-3 times/month 1-2 times/week3-4 times/week 5-6 times/week 1 times/day 2 times/day 3+times/day MEAT no. no. no. no. no. no. no. Beef 141 439 842 203 8 5 1 Pork slices/in pot 346 631 600 48 4 4 1 Meat of game animals 1053 382 134 43 8 3 Lamb 1457 137 28 3 1 Other meat 1103 230 161 24 4 2 Minced beef dishes 86 210 1132 192 14 3 Lean Sausage 1159 307 118 4 Falukorv sausage 306 781 525 14 2 1 Other sausage 608 732 255 8 1 Black pudding/blood sausage 1131 437 57 2 1 Liver/kidney 1592 26 5 2 2 Sliced meat 237 348 496 363 90 71 28 2 Sausage cuts 798 425 285 83 18 12 5 1 Bacon 366 911 332 21 3 2 FISH Smoked mackerel/herring/others 1388 211 29 6 Herring mackerel 1065 503 55 13 1 Salmon 452 878 301 7 1 1 Cod/coalfish, saithe/fish fingers 308 906 419 6 1 1 Tuna 986 566 83 3 1 Freshwater fish 1567 55 7 1 Other fish 1119 384 90 3 2 Spawn 1386 235 5 Caviar (Kalles) 692 510 319 84 13 15 Seafood 461 992 180 5 2 Chicken/Other bird 89 479 961 110 7 2 Eggs/omelets 90 422 791 271 46 26 2 FAT/DAIRY Icecream 165 795 522 143 17 7 1 Mayonnaise light/fat free 1298 307 29 1 1 Mayonnaise 1104 455 71 6 1 Creme fraiche light/fat free 509 426 552 137 11 1 Creme fraiche 645 543 374 63 10 3 Cream 414 713 412 95 8 4 2 Cooking cream 346 491 630 154 18 3 Sour cream 739 738 146 10 2 2 Coffee cream 1564 57 7 4 1 2

Table A2. Distribution of answers on the food frequency questionnaire to 1,670 pregnant women in SELMA. Question: “What types of fat do You usually use? For cooking? In homemade dressing? (multiple choice possible)”

Fat for cooking: No. do not use: No. usually use: Butter, bregott 1175 489 Liquid butter 1263 401 Olive oil 835 828 Corn oil or sunflower oil 1421 242 Margarine for cooking 1258 406 Liquid margarine 979 685 Rape oil 1083 581 Fat in homemade dressing: No. do not use: No. usually use: Olive oil 825 830 Corn oil or sunflower oil 1536 118 Rape oil 1238 417 Other oil 1605 50 None 1261 394

Table A3. Distribution of answers on the food frequency questionnaire to 1,670 pregnant women in SELMA. Question: “How much do You drink/eat the following?” Instruction: If you do not drink/eat any of items fill in 0. 1 glass=2 dl, 1 cup=1.5 dl. Fill in each line per day or per week.

Quantity-> 0 0.5 0.75 1 1.5 2 2,3 2.5 3 3.5 3.75 4 4.5 5 6 7 7.5 8 9 Skimmed milk/Low-fat milk glass/d 995 1 115 4 107 2 49 15 7 4 Skimmed milk/Low-fat milk glass/w 618 1 27 35 1 34 15 15 7 7 3 1 Semi-skimmed milk glass/d 553 12 248 8 193 3 74 2 36 1 21 7 4 Semi-skimmed milk glass/w 313 49 1 92 1 74 42 37 18 39 1 6 4 Full-fat milk glass/d 1109 4 51 2 52 1 1 15 5 3 1 1 1 Full-fat milk glass/w 666 1 50 38 1 16 16 15 2 10 2 2 Fruit yoghurt glass/d 735 8 1 151 3 40 6 2 Fruit yoghurt glass/w 412 9 2 191 4 172 2 92 1 35 1 29 7 16 2 Low-fat sour milk/yoghurt glass/d 953 2 107 6 49 6 2 1 1 Low-fat sour milk/yoghurt glass/w 578 2 72 1 94 55 20 28 5 23 1 Semi-skimmed sour milk glass/d 1094 69 5 35 1 2 1 2 Semi-skimmed sour milk glass/w 701 39 1 39 13 1 16 23 8 8 1 Sour milk/yoghurt glass/d 668 6 1 180 15 66 1 17 4 3 2 3 Sour milk/yoghurt glass/w 401 1 2 126 2 157 2 99 1 47 1 42 19 24 3 1 Quantity-> 10 10.5 11 12 13 14 15 16 20 21 25 28 30 35 40 49 50 56 Skimmed milk/Low-fat milk glass/d Skimmed milk/Low-fat milk glass/w 7 2 9 3 2 1 Semi-skimmed milk glass/d 2 1 Semi-skimmed milk glass/w 21 2 3 11 5 2 2 4 1 2 1 1 1 1 Full-fat milk glass/d 1 Full-fat milk glass/w 3 7 2 1 1 1 1 Fruit yoghurt glass/d 1 Fruit yoghurt glass/w 3 2 1 1 Low-fat sour milk/yoghurt glass/d Low-fat sour milk/yoghurt glass/w 3 1 4 1 1 1 Semi-skimmed sour milk glass/d Semi-skimmed sour milk glass/w 3 2 1 Sour milk/yoghurt glass/d 1 Sour milk/yoghurt glass/w 9 1 1 6 1 2

Table A4. Distribution of answers on the food frequency questionnaire to 1,670 pregnant women in SELMA. Question: “How much do You drink/eat the following?” Instruction: If you do not drink/eat any of items fill in 0. 1 glass=2 dl, 1 cup=1.5 dl. Fill in each line per day or per week.

Quantity-> 0 0.25 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 6 6.5 7 8 9 Cottage cheese, kvarq tbsp/day 1019 1 7 1 14 3 6 2 Cottage cheese, kvarq tbsp/week 603 3 70 85 55 2 31 38 13 5 1 Cream cheese-low fat tbsp/d 1175 1 15 9 1 1 Cream cheese-low fat tbsp/w 766 1 29 26 15 1 10 5 2 1 1 Cream cheese tbsp/d 977 1 36 20 8 2 1 1 Cream cheese tbsp/w 621 4 114 97 42 1 32 17 4 4 2 Hard cheese-low fat slides/d 983 17 1 84 25 1 47 6 10 1 2 Hard cheese-low fat slides/w 652 6 27 12 27 23 20 5 5 1 Hard cheese slides/d 266 1 73 265 82 214 38 60 5 25 3 Hard cheese slides/w 182 13 38 31 70 62 62 24 37 3 Dessert cheese tbsp/d 1169 7 1 Dessert cheese tbsp/w 753 4 65 32 13 9 2 1 Liver pate-light tbsp/d 1221 7 2 1 1 1 1 Liver pate-light tbsp/w 795 12 13 5 7 7 3 Liver pate tbsp/d 632 4 64 2 55 1 20 10 2 3 Liver pate tbsp/w 380 1 3 170 202 110 2 74 58 26 9 10 Slice bread with butter/margarine/d 80 71 6 459 20 234 7 241 3 46 33 1 7 8 Slice bread with butter/margarine/w 50 1 7 1 15 10 38 19 22 23 23 8 Quantity-> 10 11 12 13 13.5 14 15 16 17 18 19 20 21 22 23 24 25 Cottage cheese, kvarq tbsp/day Cottage cheese, kvarq tbsp/week 22 2 1 2 3 Cream cheese-low fat tbsp/d Cream cheese-low fat tbsp/w 1 Cream cheese tbsp/d 1 Cream cheese tbsp/w 6 1 Hard cheese-low fat slides/d 1 1 Hard cheese-low fat slides/w 24 4 4 5 1 1 2 Hard cheese slides/d 16 2 4 1 Hard cheese slides/w 85 14 22 15 2 3 24 1 2 1 Dessert cheese tbsp/d Dessert cheese tbsp/w 1 Liver pate-light tbsp/d Liver pate-light tbsp/w 1 Liver pate tbsp/d 2 Liver pate tbsp/w 22 1 7 4 3 2 Slice bread with butter/margarine/d 1 1 1 Slice bread with butter/margarine/w 49 2 11 3 42 10 11 6 11 1 12 9 1 1 2 4 Quantity-> 27 28 30 32 33 35 40 42 43 45 56 58 60 63 70 84 Cottage cheese, kvarq tbsp/day Cottage cheese, kvarq tbsp/week 1 Cream cheese-low fat tbsp/d Cream cheese-low fat tbsp/w Cream cheese tbsp/d Cream cheese tbsp/w Hard cheese-low fat slides/d 1 Hard cheese-low fat slides/w 3 2 1 Hard cheese slides/d Hard cheese slides/w 10 11 1 2 1 3 1 1 1 1 Dessert cheese tbsp/d Dessert cheese tbsp/w Liver pate-light tbsp/d Liver pate-light tbsp/w Liver pate tbsp/d Liver pate tbsp/w 1 Slice bread with butter/margarine/d Slice bread with butter/margarine/w 1 7 7 2 1 5 2 1 1

Appendix 2. Tables below show associations between SELMA-women’s reported dietary intake of foods, and phthalates measured in their urine. Association’s marked light green has high RGM values, those marked darker green has high RGM values (>1.05) and significant associations. Association’s marked light red has low RGM values (<0.95), those marked darker red has low RGM values and significant negative associations.

Do not consume Does consume Foods in relation with MEP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Liquid butter- for cooking 1263 1,55 401 1,62 0,01 1,05 1,17 Low fat creme fraiche 509 1,54 1161 1,58 0,12 1,03 1,10 Falukorv sausage 306 1,54 1364 1,57 0,28 1,02 1,07 Eggs/Omelets 90 1,54 1580 1,57 0,56 1,02 1,07 Low fat sourmilk/yoghurt/week 578 1,55 1092 1,58 0,23 1,02 1,07 Low fat cream cheese/week 766 1,55 904 1,58 0,26 1,02 1,07 Other meat 1103 1,56 567 1,59 0,25 1,02 1,07 Pizza 327 1,55 1343 1,57 0,51 1,01 1,05 Cod/Saithe/Fishfingers 308 1,55 1362 1,57 0,56 1,01 1,05 Ice cream 165 1,55 1505 1,57 0,57 1,01 1,05 Low fat milk/week 618 1,56 1052 1,58 0,67 1,01 1,05 Cream cheese/week 621 1,56 1049 1,58 0,36 1,01 1,05 Semi-skimmed milk/week 313 1,56 1357 1,57 0,66 1,01 1,02 Low fat hard cheese/week 652 1,56 1018 1,57 0,55 1,01 1,02 Low fat liverpate/week 795 1,56 875 1,57 0,72 1,01 1,02 Liquid margarine-for cooking 979 1,56 685 1,57 0,73 1,01 1,02 No fat in dressing 1261 1,56 394 1,57 0,73 1,01 1,02 Spawn 1386 1,57 284 1,58 0,61 1,01 1,02 Fruit yoghurt/week 412 1,57 1258 1,57 0,97 1,00 1,00 Low fat sourmilk/yoghurt/day 953 1,57 717 1,57 0,93 1,00 1,00 Semi-skimmed sour milk/week 701 1,57 969 1,57 0,83 1,00 1,00 Sour milk/week 401 1,57 1269 1,57 0,88 1,00 1,00 Cottage cheese/week 603 1,57 1067 1,57 0,78 1,00 1,00 Dessert cheese/week 753 1,57 917 1,57 0,98 1,00 1,00 Beef 141 1,57 1529 1,57 0,95 1,00 1,00 Pork 346 1,57 1324 1,57 0,83 1,00 1,00 Minced beef dishes 86 1,57 1584 1,57 0,99 1,00 1,00 Lean sausage 1159 1,57 511 1,57 0,96 1,00 1,00 Other sausage 608 1,57 1062 1,57 0,97 1,00 1,00 Liver/kidney 1592 1,57 78 1,57 0,96 1,00 1,00 Sliced meat 237 1,57 1433 1,57 0,91 1,00 1,00 Sausage cuts 798 1,57 872 1,57 0,98 1,00 1,00 Tuna 986 1,57 684 1,57 0,99 1,00 1,00 Other fish 1119 1,57 551 1,57 0,8 1,00 1,00 Seafood 461 1,57 1209 1,57 0,97 1,00 1,00 Cocking cream 346 1,57 1324 1,57 0,98 1,00 1,00 Sour cream 739 1,57 931 1,57 0,8 1,00 1,00 Olive oil-for cooking 835 1,57 828 1,57 0,93 1,00 1,00 Corn-/sunfloweroil-for cooking 1421 1,57 242 1,57 0,99 1,00 1,00 Olive oil-in dressing 825 1,57 830 1,57 0,94 1,00 1,00 Corn-/sunfloweroil-in dressing 1536 1,57 118 1,57 0,96 1,00 1,00 Low fat milk/day 995 1,57 675 1,56 0,54 0,99 0,98 Full fat milk/week 666 1,57 1004 1,56 0,71 0,99 0,98 Sour milk/day 668 1,57 1002 1,56 0,64 0,99 0,98 Low fat hard cheese/day 983 1,57 687 1,56 0,47 0,99 0,98 Game 1053 1,57 617 1,56 0,62 0,99 0,98 Lamb 1457 1,57 213 1,56 0,82 0,99 0,98 Rape oil-in dressing 1238 1,57 417 1,56 0,62 0,99 0,98 Hard cheese/week 182 1,59 1488 1,57 0,45 0,99 0,95 Buttered bread/week 50 1,59 1620 1,57 0,8 0,99 0,95 Chicken/other bird 89 1,59 1581 1,57 0,57 0,99 0,95 Semi-skimmed milk/day 553 1,58 1117 1,56 0,5 0,99 0,95 Fruit yoghurt/day 735 1,58 935 1,56 0,33 0,99 0,95 Liver pate/day 632 1,58 1038 1,56 0,31 0,99 0,95 Salmon 452 1,58 1218 1,56 0,42 0,99 0,95 Caviar-"Kalles" 692 1,58 978 1,56 0,46 0,99 0,95 Cream 414 1,58 1256 1,56 0,46 0,99 0,95 Black pudding 1131 1,57 539 1,55 0,39 0,99 0,95 Smoked mackerel/herring/others 1388 1,57 282 1,55 0,44 0,99 0,95 Margarine-for cooking 1258 1,57 406 1,55 0,52 0,99 0,95 Liver pate/week 380 1,59 1290 1,56 0,17 0,98 0,93 Creme fraiche 645 1,59 1025 1,56 0,21 0,98 0,93 Semi-skimmed sour milk/day 1094 1,58 576 1,55 0,23 0,98 0,93 Cream cheese/day 977 1,58 693 1,55 0,16 0,98 0,93 Low fat liver pate/day 1221 1,58 449 1,55 0,26 0,98 0,93 Rape oil-for cooking 1083 1,58 581 1,55 0,21 0,98 0,93 Freshwater fish 1567 1,57 103 1,54 0,42 0,98 0,93 Buttered bread/day 80 1,61 1590 1,57 0,37 0,98 0,91 Bacon 366 1,6 1304 1,56 0,16 0,98 0,91 Dessert cheese/day 1169 1,58 501 1,54 0,09 0,97 0,91 Herring/mackerel 1065 1,58 605 1,54 0,09 0,97 0,91 Mayonnaise 1104 1,58 566 1,54 0,08 0,97 0,91 Other oil-in dressing 1605 1,57 50 1,53 0,49 0,97 0,91 Panncakes 323 1,61 1347 1,56 0,04 0,97 0,89 Low fat cream cheese/day 1175 1,58 495 1,53 0,02 0,97 0,89 Coffee cream 1564 1,57 106 1,52 0,19 0,97 0,89 Hard cheese/day 266 1,62 1404 1,56 0,03 0,96 0,87 Full fat milk/day 1109 1,59 561 1,53 0,01 0,96 0,87 Cottage cheese/day 1019 1,59 651 1,53 0,01 0,96 0,87 Butter, Bregott-for cooking 1175 1,59 489 1,52 0,01 0,96 0,85

Does not consume Does consume Foods in relation with MBzP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Margarine-for cooking 1258 0,8 406 0,9 0 1,13 1,26 Other oil-for dressing 1605 0,83 50 0,92 0,13 1,11 1,23 No fat in dressing 1261 0,81 394 0,89 0 1,10 1,20 Full fat milk/day 1109 0,81 561 0,87 0 1,07 1,15 Bacon 366 0,79 1304 0,84 0,03 1,06 1,12 Cream cheese/week 621 0,8 1049 0,85 0,03 1,06 1,12 Mayonnaise 1104 0,81 566 0,86 0,01 1,06 1,12 Liquid margarine-for cooking 979 0,81 685 0,86 0,01 1,06 1,12 Ice cream 165 0,79 1505 0,83 0,28 1,05 1,10 Pizza 327 0,8 1343 0,84 0,18 1,05 1,10 Falukorv sausage 306 0,8 1364 0,84 0,19 1,05 1,10 Sausage cuts 798 0,81 872 0,85 0,03 1,05 1,10 Freshwater fish 1567 0,83 103 0,87 0,28 1,05 1,10 Full fat milk/week 666 0,81 1004 0,84 0,19 1,04 1,07 Panncakes 323 0,81 1347 0,84 0,25 1,04 1,07 Herring/mackerel 1065 0,82 605 0,85 0,08 1,04 1,07 Coffee cream 1564 0,83 106 0,86 0,47 1,04 1,07 Corn-/sunfloweroil in dressing 1536 0,83 118 0,86 0,37 1,04 1,07 Eggs/omelets 90 0,81 1580 0,83 0,58 1,02 1,05 Other sausage 608 0,82 1062 0,84 0,27 1,02 1,05 Tuna 986 0,82 684 0,84 0,4 1,02 1,05 Low fat cream cheese/week 766 0,82 904 0,83 0,61 1,01 1,02 Cod/Saithe/Fishfingers 308 0,82 1362 0,83 0,64 1,01 1,02 Cream 414 0,82 1256 0,83 0,65 1,01 1,02 Sour cream 739 0,82 931 0,83 0,61 1,01 1,02 Cream cheese/day 977 0,83 693 0,84 0,56 1,01 1,02 Other Fish 1119 0,83 551 0,84 0,52 1,01 1,02 Semi-skimmed milk/day 553 0,83 1117 0,83 0,99 1,00 1,00 Low fat sourmilk/yoghurt/week 578 0,83 1092 0,83 0,99 1,00 1,00 Semi-skimmed sour milk/week 701 0,83 969 0,83 0,88 1,00 1,00 Sour milk/day 668 0,83 1002 0,83 0,71 1,00 1,00 Sour milk/week 401 0,83 1269 0,83 0,63 1,00 1,00 Cottage cheese/week 603 0,83 1067 0,83 0,82 1,00 1,00 Low fat hard cheese/week 652 0,83 1018 0,83 0,82 1,00 1,00 Dessert cheese/week 753 0,83 917 0,83 0,82 1,00 1,00 Low fat liver pate/week 795 0,83 875 0,83 0,64 1,00 1,00 Liver pate/day 632 0,83 1038 0,83 0,97 1,00 1,00 Liver pate/week 380 0,83 1290 0,83 0,84 1,00 1,00 Buttered bread/week 50 0,83 1620 0,83 0,95 1,00 1,00 Pork 346 0,83 1324 0,83 0,84 1,00 1,00 Game 1053 0,83 617 0,83 0,88 1,00 1,00 Black pudding 1131 0,83 539 0,83 0,8 1,00 1,00 Sliced meat 237 0,83 1433 0,83 0,88 1,00 1,00 Smoked mackerel/Herring/others 1388 0,83 282 0,83 0,95 1,00 1,00 Caviar-"Kalles" 692 0,83 978 0,83 0,72 1,00 1,00 Creme fraiche 645 0,83 1025 0,83 0,75 1,00 1,00 Rape oil-for cooking 1083 0,83 581 0,83 0,69 1,00 1,00 Rape oil-in dressing 1238 0,83 417 0,83 0,9 1,00 1,00 Semi-skimmed milk/week 313 0,84 1357 0,83 0,58 0,99 0,98 Low fat liver pate/day 1221 0,83 449 0,82 0,41 0,99 0,98 Lean sausage 1159 0,83 511 0,82 0,53 0,99 0,98 Hard cheese/day 266 0,85 1404 0,83 0,48 0,98 0,95 Hard cheese/week 182 0,85 1488 0,83 0,55 0,98 0,95 Minced beef dishes 86 0,85 1584 0,83 0,75 0,98 0,95 Fruit yoghurt/day 735 0,84 935 0,82 0,47 0,98 0,95 Low fat hard cheese/day 983 0,84 687 0,82 0,33 0,98 0,95 Liver/kidney 1592 0,83 78 0,81 0,73 0,98 0,95 Buttered bread/day 80 0,86 1590 0,83 0,52 0,97 0,93 Beef 141 0,86 1529 0,83 0,44 0,97 0,93 Chicken/Other bird 89 0,86 1581 0,83 0,45 0,97 0,93 Low fat milk/week 618 0,85 1052 0,82 0,2 0,96 0,93 Fruit yoghurt/week 412 0,85 1258 0,82 0,15 0,96 0,93 Semi-skimmed sour milk/day 1094 0,84 576 0,81 0,09 0,96 0,93 Cottage cheese/day 1019 0,84 651 0,81 0,16 0,96 0,93 Low fat cream cheese/day 1175 0,84 495 0,81 0,16 0,96 0,93 Dessert cheese/day 1169 0,84 501 0,81 0,27 0,96 0,93 Other meat 1103 0,84 567 0,81 0,22 0,96 0,93 Lamb 1457 0,83 213 0,8 0,21 0,96 0,93 Cocking cream 346 0,86 1324 0,82 0,18 0,95 0,91 Low fat sourmilk/yoghurt/day 953 0,85 717 0,81 0,06 0,95 0,91 Corn-/sunfloweroil-for cooking 1421 0,84 242 0,8 0,15 0,95 0,91 Spawn 1386 0,84 284 0,79 0,05 0,94 0,89 Seafood 461 0,87 1209 0,81 0,01 0,93 0,87 Low fat milk/day 995 0,85 675 0,79 0 0,93 0,87 Butter, Bregott-for cooking 1175 0,85 489 0,79 0,02 0,93 0,87 Low fat creme fraiche 509 0,88 1161 0,81 0 0,92 0,85 Liquid butter-for cooking 1263 0,85 401 0,78 0,01 0,92 0,85 Salmon 452 0,89 1218 0,81 0 0,91 0,83 Olive oil-for cooking 835 0,87 828 0,79 0 0,91 0,83 Olive oil-in dressing 825 0,88 830 0,78 0 0,89 0,79

Does not consume Does consume Foods in relation with MnBP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Margarine-for cookin 1258 1,5 406 1,55 0 1,03 1,12 Buttered bread/week 50 1,47 1620 1,51 0,21 1,03 1,10 Full fat milk/day 1109 1,5 561 1,54 0 1,03 1,10 Freshwater fish 1567 1,51 103 1,55 0,13 1,03 1,10 Bacon 366 1,49 1304 1,52 0,03 1,02 1,07 Eggs/Omelets 90 1,49 1580 1,52 0,41 1,02 1,07 Cream 414 1,49 1256 1,52 0,02 1,02 1,07 Sour milk/day 668 1,5 1002 1,53 0,02 1,02 1,07 Cream cheese/day 977 1,5 693 1,53 0,07 1,02 1,07 Mayonnaise 1104 1,5 566 1,53 0,03 1,02 1,07 No fat in dressing 1261 1,51 394 1,54 0,04 1,02 1,07 Sour milk/week 401 1,5 1269 1,52 0,38 1,01 1,05 Cream cheese/week 621 1,5 1049 1,52 0,03 1,01 1,05 Hard cheese/day 266 1,5 1404 1,52 0,46 1,01 1,05 Other sausage 608 1,5 1062 1,52 0,18 1,01 1,05 Creme fraiche 645 1,5 1025 1,52 0,14 1,01 1,05 Liver/kidney 1592 1,51 78 1,53 0,53 1,01 1,05 Herring/mackerel 1065 1,51 605 1,53 1,19 1,01 1,05 Other Fish 1119 1,51 551 1,53 0,17 1,01 1,05 Coffee cream 1564 1,51 106 1,53 0,48 1,01 1,05 Semi-skimmed milk/day 553 1,51 1117 1,52 0,39 1,01 1,02 Full fat milk/week 666 1,51 1004 1,52 0,32 1,01 1,02 Low fat cream cheese/week 766 1,51 904 1,52 0,28 1,01 1,02 Low fat hard cheese/day 983 1,51 687 1,52 0,8 1,01 1,02 Dessert cheese/day 1169 1,51 501 1,52 0,37 1,01 1,02 Low fat liver pate/day 1221 1,51 449 1,52 0,66 1,01 1,02 Panncakes 323 1,51 1347 1,52 0,55 1,01 1,02 Pizza 327 1,51 1343 1,52 0,53 1,01 1,02 Lamb 1457 1,51 213 1,52 0,82 1,01 1,02 Black pudding 1131 1,51 539 1,52 0,46 1,01 1,02 Sausage cuts 798 1,51 872 1,52 0,66 1,01 1,02 Smoked mackerel/Herring/Others 1388 1,51 282 1,52 0,55 1,01 1,02 Tuna 986 1,51 684 1,52 0,28 1,01 1,02 Sour cream 739 1,51 931 1,52 0,46 1,01 1,02 Rape oil-for cooking 1083 1,51 581 1,52 0,61 1,01 1,02 Low fat milk/week 618 1,51 1052 1,51 0,92 1,00 1,00 Low fat sourmilk/yoghurt/week 578 1,51 1092 1,51 0,94 1,00 1,00 Semi-skimmer sour milk/day 1094 1,51 576 1,51 0,98 1,00 1,00 Cottage cheese/day 1019 1,51 651 1,51 0,96 1,00 1,00 Low fat cream cheese/day 1175 1,51 495 1,51 0,92 1,00 1,00 Low fat hard cheese/week 652 1,51 1018 1,51 0,87 1,00 1,00 Dessert cheese/week 753 1,51 917 1,51 0,88 1,00 1,00 Low fat liver pate/week 795 1,51 875 1,51 0,9 1,00 1,00 Other meat 1103 1,51 567 1,51 0,95 1,00 1,00 Falukorv sausage 306 1,51 1364 1,51 0,85 1,00 1,00 Sliced meat 237 1,51 1433 1,51 0,67 1,00 1,00 Ice cream 165 1,51 1505 1,51 0,66 1,00 1,00 Other oil-dressing 1605 1,51 50 1,51 0,95 1,00 1,00 Low fat milk/day 995 1,52 675 1,51 0,54 0,99 0,98 Semi-skimmed milk/week 313 1,52 1357 1,51 0,78 0,99 0,98 Fruit yoghurt/day 735 1,52 935 1,51 0,33 0,99 0,98 Low fat sourmilk/yoghurt/day 953 1,52 717 1,51 0,49 0,99 0,98 Semi-skimmed sour milk/week 701 1,52 969 1,51 0,58 0,99 0,98 Cottage cheese/week 603 1,52 1067 1,51 0,6 0,99 0,98 Liver pate/day 632 1,52 1038 1,51 0,76 0,99 0,98 Liver pate/week 380 1,52 1290 1,51 0,64 0,99 0,98 Pork 346 1,52 1324 1,51 0,71 0,99 0,98 Game 1053 1,52 617 1,51 0,76 0,99 0,98 Lean sausage 1159 1,52 511 1,51 0,65 0,99 0,98 Cod/Saithe/Fishfingers 308 1,52 1362 1,51 0,71 0,99 0,98 Spawn 1386 1,52 284 1,51 0,62 0,99 0,98 Caviar-"Kalles" 692 1,52 978 1,51 0,45 0,99 0,98 Seafood 461 1,52 1209 1,51 0,39 0,99 0,98 Cocking cream 346 1,52 1324 1,51 0,46 0,99 0,98 Butter, Bregott-for cooking 1175 1,52 489 1,51 0,73 0,99 0,98 Liquid butter-for cooking 1263 1,52 401 1,51 0,61 0,99 0,98 Rape oil-in dressing 1238 1,52 417 1,51 0,52 0,99 0,98 Fruit yoghurt/week 412 1,53 1258 1,51 0,29 0,99 0,95 Buttered bread/day 80 1,53 1590 1,51 0,64 0,99 0,95 Corn-/sunfloweroil-for cooking 1421 1,52 242 1,5 0,55 0,99 0,95 Liquid margarine-for cooking 979 1,52 685 1,5 0,13 0,99 0,95 Minced beef dishes 86 1,54 1584 1,51 0,37 0,98 0,93 Hard cheese/week 182 1,53 1488 1,5 0,36 0,98 0,93 Olive oil-for cooking 835 1,53 828 1,5 0,07 0,98 0,93 Olive oil-in dressing 825 1,53 830 1,5 0,06 0,98 0,93 Corn-/sunfloweroil-in dressing 1536 1,52 118 1,49 0,44 0,98 0,93 Beef 141 1,55 1529 1,51 0,13 0,97 0,91 Salmon 452 1,54 1218 1,5 0,02 0,97 0,91 Low fat creme fraiche 509 1,54 1161 1,5 0,02 0,97 0,91 Chicken/Other bird 89 1,56 1581 1,51 0,12 0,97 0,89

Does not consume Does consume Foods in relation with MEHP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Lamb 1457 0,14 213 0,24 0 1,71 1,26 Liver/kidney 1592 0,15 78 0,23 0,07 1,53 1,20 Freshwater fish 1567 0,15 103 0,23 0,04 1,53 1,20 Coffee cream 1564 0,15 106 0,22 0,07 1,47 1,17 Sliced meat 237 0,12 1433 0,16 0,15 1,33 1,10 Smoked mackerel/Herring/Others 1388 0,15 282 0,2 0,02 1,33 1,12 Full fat milk/day 1109 0,14 561 0,18 0,01 1,29 1,10 Other Fish 1119 0,14 551 0,18 0,03 1,29 1,10 Buttered bread/day 80 0,13 1590 0,16 0,48 1,23 1,07 Eggs/Omelets 90 0,13 1580 0,16 0,55 1,23 1,07 Sausage cuts 798 0,14 872 0,17 0,17 1,21 1,07 Caviar-"Kalles" 692 0,14 978 0,17 0,5 1,21 1,07 Other meat 1103 0,15 567 0,18 0,1 1,20 1,07 Mayonnaise 1104 0,15 566 0,18 0,11 1,20 1,07 Corn-/sunfloweroil-in dressing 1536 0,15 118 0,18 0,45 1,20 1,07 Sour milk/day 668 0,14 1002 0,16 0,28 1,14 1,05 Hard cheese/day 266 0,14 1404 0,16 0,32 1,14 1,05 Bacon 366 0,14 1304 0,16 0,51 1,14 1,05 Cod/Saithe/Fishfingers 308 0,14 1362 0,16 0,28 1,14 1,05 Cream cheese/day 977 0,15 693 0,17 0,16 1,13 1,05 Lean sausage 1159 0,15 511 0,17 0,29 1,13 1,05 Herring/mackerel 1065 0,15 605 0,17 0,15 1,13 1,05 Butter, Bregott-for cooking 1175 0,15 489 0,17 0,38 1,13 1,05 Corn-/sunfloweroil-for cooking 1421 0,15 242 0,17 0,56 1,13 1,05 Rape oil-for cooking 1083 0,15 581 0,17 0,24 1,13 1,05 No fat in dressing 1261 0,15 394 0,17 0,34 1,13 1,05 Full fat milk/week 666 0,15 1004 0,16 0,35 1,07 1,02 Low fat sourmilk/yoghurt/day 953 0,15 717 0,16 0,57 1,07 1,02 Semi-skimmed sour milk/day 1094 0,15 576 0,16 0,82 1,07 1,02 Cream cheese/week 621 0,15 1049 0,16 0,69 1,07 1,02 Low fat hard cheese/day 983 0,15 687 0,16 0,8 1,07 1,02 Dessert cheese/day 1169 0,15 501 0,16 0,78 1,07 1,02 Beef 141 0,15 1529 0,16 0,78 1,07 1,02 Pork 346 0,15 1324 0,16 0,78 1,07 1,02 Falukorv sausage 306 0,15 1364 0,16 0,58 1,07 1,02 Black pudding 1131 0,15 539 0,16 0,64 1,07 1,02 Salmon 452 0,15 1218 0,16 0,8 1,07 1,02 Creme fraiche 645 0,15 1025 0,16 0,79 1,07 1,02 Cream 414 0,15 1256 0,16 0,5 1,07 1,02 Semi-skimmed milk/day 553 0,16 1117 0,16 0,9 1,00 1,00 Sour milk/week 401 0,16 1269 0,16 0,94 1,00 1,00 Cottage cheese/day 1019 0,16 651 0,16 0,92 1,00 1,00 Low fat cream cheese/day 1175 0,16 495 0,16 0,97 1,00 1,00 Low fat liver pate/day 1221 0,16 449 0,16 0,98 1,00 1,00 Liver pate/day 632 0,16 1038 0,16 0,99 1,00 1,00 Minced beef dishes 86 0,16 1584 0,16 0,88 1,00 1,00 Tuna 986 0,16 684 0,16 0,97 1,00 1,00 Chicken/Other bird 89 0,16 1581 0,16 0,99 1,00 1,00 Cocking cream 346 0,16 1324 0,16 0,98 1,00 1,00 Other oil-in dressing 1605 0,16 50 0,16 0,99 1,00 1,00 Low fat cream cheese/week 766 1,56 904 1,54 0,81 0,99 0,95 Buttered bread/week 50 0,17 1620 0,16 0,86 0,94 0,98 Light milk/day 995 0,16 675 0,15 0,49 0,94 0,98 Fruit yoghurt/day 735 0,16 935 0,15 0,69 0,94 0,98 Low fat sourmilk/yoghurt/week 578 0,16 1092 0,15 0,59 0,94 0,98 Semi-skimmed sour milk/week 701 0,16 969 0,15 0,55 0,94 0,98 Cottage cheese/week 603 0,16 1067 0,15 0,59 0,94 0,98 Low fat hard cheese/week 652 0,16 1018 0,15 0,55 0,94 0,98 Game 1053 0,16 617 0,15 0,77 0,94 0,98 Other sausage 608 0,16 1062 0,15 0,58 0,94 0,98 Liquid butter-for cooking 1263 0,16 401 0,15 0,66 0,94 0,98 Margarine-for cooking 1258 0,16 406 0,15 0,69 0,94 0,98 Olive oil-in dressing 825 0,16 830 0,15 0,68 0,94 0,98 Low fat milk/week 618 0,17 1052 0,15 0,44 0,88 0,95 Dessert cheese/week 753 0,17 917 0,15 0,18 0,88 0,95 Low fat liver pate/week 795 0,17 875 0,15 0,26 0,88 0,95 Liver pate/week 380 0,17 1290 0,15 0,3 0,88 0,95 Olive oil-for cooking 835 0,17 828 0,15 0,24 0,88 0,95 Spawn 1386 0,16 284 0,14 0,46 0,88 0,95 Rape oil-in dressing 1238 0,16 417 0,14 0,38 0,88 0,95 Semi-skimmed milk/week 313 0,18 1357 0,15 0,31 0,83 0,93 Fruit yoghurt/week 412 0,18 1258 0,15 0,18 0,83 0,93 Panncakes 323 0,18 1347 0,15 0,2 0,83 0,93 Seafood 461 0,18 1209 0,15 0,13 0,83 0,93 Liquid margarine-for cooking 979 0,17 685 0,14 0,25 0,82 0,93 Hard cheese/week 182 0,19 1488 0,15 0,16 0,79 0,91 Pizza 327 0,19 1343 0,15 0,1 0,79 0,91 Ice cream 165 0,19 1505 0,15 0,29 0,79 0,91 Low fat creme fraiche 509 0,18 1161 0,14 0,05 0,78 0,91 Sour cream 739 0,18 931 0,14 0,03 0,78 0,91

Does not consume Does consume Foods in relation with MEHHP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Freshwater fish 1567 0,76 103 0,86 0,01 1,13 1,26 Lamb 1457 0,76 213 0,83 0,01 1,09 1,17 Other Fish 1119 0,75 551 0,8 0 1,07 1,12 Coffee cream 1564 0,77 106 0,81 0,26 1,05 1,10 Caviar-"Kalles" 692 0,75 978 0,78 0,09 1,04 1,07 Butter, Bregott-for cooking 1175 0,76 489 0,79 0,09 1,04 1,07 No fat in dressing 1261 0,76 394 0,79 0,27 1,04 1,07 Liver/kidney 1592 0,77 78 0,8 0,4 1,04 1,07 Corn-/sunfloweroil-in dressing 1536 0,77 118 0,8 0,35 1,04 1,07 Buttered bread/day 80 0,75 1590 0,77 0,55 1,03 1,05 Cod/Saithe/Fishfingers 308 0,75 1362 0,77 0,32 1,03 1,05 Full fat milk/day 1109 0,76 561 0,78 0,14 1,03 1,05 Other meat 1103 0,76 567 0,78 0,42 1,03 1,05 Sausage cuts 798 0,76 872 0,78 0,32 1,03 1,05 Herring/mackerel 1065 0,76 605 0,78 0,19 1,03 1,05 Mayonnaise 1104 0,76 566 0,78 0,32 1,03 1,05 Rape oil-for cooking 1083 0,76 581 0,78 0,28 1,03 1,05 Smoked mackerel/Herring/Others 1388 0,77 282 0,79 0,34 1,03 1,05 Full fat milk/week 666 0,76 1004 0,77 0,61 1,01 1,02 Hard cheese/day 266 0,76 1404 0,77 0,59 1,01 1,02 Buttered bread/week 50 0,76 1620 0,77 0,79 1,01 1,02 Sliced meat 237 0,76 1433 0,77 0,51 1,01 1,02 Bacon 366 0,76 1304 0,77 0,56 1,01 1,02 Cream 414 0,76 1256 0,77 0,6 1,01 1,02 Black pudding 1131 0,77 539 0,78 0,46 1,01 1,02 Low fat sourmilk/yoghurt/day 953 0,77 717 0,77 0,72 1,00 1,00 Low fat sourmilk/yoghurt/week 578 0,77 1092 0,77 0,71 1,00 1,00 Sour milk/day 668 0,77 1002 0,77 0,99 1,00 1,00 Sour milk/week 401 0,77 1269 0,77 0,93 1,00 1,00 Cream cheese/day 977 0,77 693 0,77 0,72 1,00 1,00 Cream cheese/week 621 0,77 1049 0,77 0,86 1,00 1,00 Low fat hard cheese/day 983 0,77 687 0,77 0,85 1,00 1,00 Dessert cheese/day 1169 0,77 501 0,77 0,9 1,00 1,00 Liver pate/day 632 0,77 1038 0,77 0,73 1,00 1,00 Game 1053 0,77 617 0,77 0,93 1,00 1,00 Lean sausage 1159 0,77 511 0,77 0,97 1,00 1,00 Salmon 452 0,77 1218 0,77 0,92 1,00 1,00 Spawn 1386 0,77 284 0,77 0,85 1,00 1,00 Ice cream 165 0,77 1505 0,77 0,97 1,00 1,00 Creme fraiche 645 0,76 1025 0,76 0,39 1,00 1,00 Corn-/sunfloweroil-for cooking 1421 0,77 242 0,77 0,95 1,00 1,00 Olive oil-in dressing 825 0,77 830 0,77 0,85 1,00 1,00 Low fat milk/week 618 0,78 1052 0,77 0,56 0,99 0,98 Cottage cheese/week 603 0,78 1067 0,77 0,44 0,99 0,98 Low fat cream cheese/week 766 0,78 904 0,77 0,57 0,99 0,98 Pork 346 0,78 1324 0,77 0,69 0,99 0,98 Falukorv sausage 306 0,78 1364 0,77 0,68 0,99 0,98 Seafood 461 0,78 1209 0,77 0,54 0,99 0,98 Eggs/Omelets 90 0,78 1580 0,77 0,86 0,99 0,98 Cocking cream 346 0,78 1324 0,77 0,66 0,99 0,98 Cottage cheese/day 1019 0,77 651 0,76 0,62 0,99 0,98 Low fat cream cheese/day 1175 0,77 495 0,76 0,46 0,99 0,98 Low fat liver pate/day 1221 0,77 449 0,76 0,39 0,99 0,98 Tuna 986 0,77 684 0,76 0,52 0,99 0,98 Margarine-for cooking 1258 0,77 406 0,76 0,57 0,99 0,98 Rape oil-in dressing 1238 0,77 417 0,76 0,55 0,99 0,98 Beef 141 0,79 1529 0,77 0,41 0,97 0,95 Low fat milk/day 995 0,78 675 0,76 0,31 0,97 0,95 Semi-skimmed milk/day 553 0,78 1117 0,76 0,23 0,97 0,95 Semi-skimmed sour milk/day 1094 0,78 576 0,76 0,24 0,97 0,95 Semi-skimmed sour milk/week 701 0,78 969 0,76 0,38 0,97 0,95 Low fat hard cheese/week 652 0,78 1018 0,76 0,34 0,97 0,95 Dessert cheese/week 753 0,78 917 0,76 0,31 0,97 0,95 Low fat liver pate/week 795 0,78 875 0,76 0,23 0,97 0,95 Olive oil-for cooking 835 0,78 828 0,76 0,43 0,97 0,95 Liquid margarine-for cooking 979 0,78 685 0,76 0,14 0,97 0,95 Hard cheese/week 182 0,8 1488 0,77 0,28 0,96 0,93 Semi-skimmed milk/week 313 0,79 1357 0,76 0,16 0,96 0,93 Fruit yoghurt/day 735 0,79 935 0,76 0,09 0,96 0,93 Fruit yoghurt/week 412 0,79 1258 0,76 0,04 0,96 0,93 Liver pate/week 380 0,79 1290 0,76 0,11 0,96 0,93 Panncakes 323 0,79 1347 0,76 0,18 0,96 0,93 Pizza 327 0,79 1343 0,76 0,17 0,96 0,93 Other sausage 608 0,79 1062 0,76 0,14 0,96 0,93 Liquid butter-for cooking 1263 0,78 401 0,75 0,25 0,96 0,93 Low fat Creme fraiche 509 0,8 1161 0,76 0,02 0,95 0,91 Sour cream 739 0,79 931 0,75 0,04 0,95 0,91 Minced beef dishes 86 0,82 1584 0,77 0,19 0,94 0,89 Chicken/Other bird 89 0,82 1581 0,77 0,19 0,94 0,89 Other oil-in dressing 1605 0,77 50 0,71 0,22 0,92 0,87

Does not consume Does consume Foods in relation with MEOHP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Freshwater fish 1567 0,6 103 0,69 0,01 1,15 1,23 Lamb 1457 0,59 213 0,67 0 1,14 1,20 Other Fish 1119 0,59 551 0,63 0,02 1,07 1,10 Butter, Bregott-for cooking 1175 0,59 489 0,63 0,07 1,07 1,10 Liver/kidney 1592 0,6 78 0,64 0,32 1,07 1,10 Coffee cream 1564 0,6 106 0,64 0,22 1,07 1,10 Buttered bread/day 80 0,58 1590 0,61 0,48 1,05 1,07 Full fat milk/day 1109 0,6 561 0,63 0,06 1,05 1,07 Corn-/Sunfloweroil-in dressing 1536 0,6 118 0,63 0,31 1,05 1,07 Buttered bread/week 50 0,58 1620 0,6 0,7 1,03 1,05 Hard cheese/day 266 0,59 1404 0,61 0,41 1,03 1,05 Sliced meat 237 0,59 1433 0,61 0,42 1,03 1,05 Sausage cuts 798 0,59 872 0,61 0,28 1,03 1,05 Bacon 366 0,59 1304 0,61 0,53 1,03 1,05 Cod/Saithe/Fishfingers 308 0,59 1362 0,61 0,53 1,03 1,05 Caviar-"Kalles" 692 0,59 978 0,61 0,11 1,03 1,05 Creme fraiche 645 0,59 1025 0,61 0,27 1,03 1,05 Other meat 1103 0,6 567 0,62 0,29 1,03 1,05 Smoked mackerel/Herring/Others 1388 0,6 282 0,62 0,32 1,03 1,05 Herring/mackerel 1065 0,6 605 0,62 0,23 1,03 1,05 Mayonnaise 1104 0,6 566 0,62 0,21 1,03 1,05 Rape oil-for cooking 1083 0,6 581 0,62 0,25 1,03 1,05 No fat in dressing 1261 0,6 394 0,62 0,2 1,03 1,05 Full fat milk/week 666 0,6 1004 0,61 0,46 1,02 1,02 Sour milk/day 668 0,6 1002 0,61 0,69 1,02 1,02 Cream cheese/day 977 0,6 693 0,61 0,74 1,02 1,02 Cream cheese/week 621 0,6 1049 0,61 0,65 1,02 1,02 Low fat hard cheese/day 983 0,6 687 0,61 0,79 1,02 1,02 Black pudding 1131 0,6 539 0,61 0,49 1,02 1,02 Cream 414 0,6 1256 0,61 0,6 1,02 1,02 Lean sausage 1159 0,6 511 0,6 0,87 1,00 1,00 Sour milk/week 401 0,6 1269 0,6 0,95 1,00 1,00 Dessert cheese/day 1169 0,6 501 0,6 0,96 1,00 1,00 Liver pate/day 632 0,6 1038 0,6 0,92 1,00 1,00 Game 1053 0,6 617 0,6 0,99 1,00 1,00 Spawn 1386 0,6 284 0,6 0,97 1,00 1,00 Corn-/Sunfloweroil-for cooking 1421 0,6 242 0,6 0,86 1,00 1,00 Margarine-for cooking 1258 0,6 406 0,6 0,97 1,00 1,00 Olive oil-in dressing 825 0,6 830 0,6 0,94 1,00 1,00 Low fat milk/day 995 0,61 675 0,6 0,43 0,98 0,98 Low fat milk/week 618 0,61 1052 0,6 0,61 0,98 0,98 Low fat sourmilk/yoghurt/day 953 0,61 717 0,6 0,75 0,98 0,98 Low fat sourmilk/yoghurt/week 578 0,61 1092 0,6 0,76 0,98 0,98 Semi-skimmed sourmilk/week 701 0,61 969 0,6 0,33 0,98 0,98 Cottage cheese/day 1019 0,61 651 0,6 0,68 0,98 0,98 Cottage cheese/week 603 0,61 1067 0,6 0,43 0,98 0,98 Low fat cream cheese/day 1175 0,61 495 0,6 0,56 0,98 0,98 Low fat cream cheese/week 766 0,61 904 0,6 0,73 0,98 0,98 Low fat hard cheese/week 652 0,61 1018 0,6 0,42 0,98 0,98 Dessert cheese/week 753 0,61 917 0,6 0,4 0,98 0,98 Low fat liver pate/week 795 0,61 875 0,6 0,3 0,98 0,98 Pork 346 0,61 1324 0,6 0,58 0,98 0,98 Falukorv sausage 306 0,61 1364 0,6 0,78 0,98 0,98 Salmon 452 0,61 1218 0,6 0,87 0,98 0,98 Tuna 986 0,61 684 0,6 0,53 0,98 0,98 Eggs/Omelets 90 0,61 1580 0,6 0,84 0,98 0,98 Ice cream 165 0,61 1505 0,6 0,93 0,98 0,98 Cocking cream 346 0,61 1324 0,6 0,58 0,98 0,98 Semi-skimmed milk/day 553 0,62 1117 0,6 0,26 0,97 0,95 Panncakes 323 0,62 1347 0,6 0,24 0,97 0,95 Pizza 327 0,62 1343 0,6 0,26 0,97 0,95 Other sausage 608 0,62 1062 0,6 0,26 0,97 0,95 Seafood 461 0,62 1209 0,6 0,28 0,97 0,95 Semi-skimmed sourmilk/day 1094 0,61 576 0,59 0,25 0,97 0,95 Low fat liver pate/day 1221 0,61 449 0,59 0,45 0,97 0,95 Liquid butter-for cooking 1263 0,61 401 0,59 0,24 0,97 0,95 Olive oil-for cooking 835 0,61 828 0,59 0,21 0,97 0,95 Rape oil-in dressing 1238 0,61 417 0,59 0,51 0,97 0,95 Semi-skimmed milk/week 313 0,63 1357 0,6 0,19 0,95 0,93 Hard cheese/week 182 0,63 1488 0,6 0,34 0,95 0,93 Liver pate/week 380 0,63 1290 0,6 0,16 0,95 0,93 Beef 141 0,63 1529 0,6 0,35 0,95 0,93 Fruit yoghurt/day 735 0,62 935 0,59 0,11 0,95 0,93 Sour cream 739 0,62 931 0,59 0,08 0,95 0,93 Liquid margarine-for cooking 979 0,62 685 0,59 0,1 0,95 0,93 Fruit yoghurt/week 412 0,63 1258 0,59 0,04 0,94 0,91 Low fat creme fraiche 509 0,63 1161 0,59 0,02 0,94 0,91 Minced beef dishes 86 0,65 1584 0,6 0,22 0,92 0,89 Chicken/Other bird 89 0,65 1581 0,6 0,24 0,92 0,89 Other oil-in dressing 1605 0,61 50 0,55 0,33 0,90 0,87

Does not consume Does consume Foods in relation with MECPP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Freshwater fish 1567 0,73 103 0,82 0,01 1,12 1,23 Lamb 1457 0,73 213 0,8 0 1,10 1,17 Liver/kidney 1592 0,73 78 0,78 0,2 1,07 1,12 Other Fish 1119 0,72 551 0,76 0,05 1,06 1,10 Corn-/Sunfloweroil-in dressing 1536 0,73 118 0,77 0,14 1,05 1,10 Coffee cream 1564 0,73 106 0,76 0,34 1,04 1,07 Butter, Bregott-for cooking 1175 0,73 489 0,76 0,07 1,04 1,07 Full fat milk/week 666 0,72 1004 0,74 0,22 1,03 1,05 Caviar-"Kalles" 692 0,72 978 0,74 0,26 1,03 1,05 Creme fraiche 645 0,72 1025 0,74 0,27 1,03 1,05 Full fat milk/day 1109 0,73 561 0,75 0,19 1,03 1,05 Smoked mackerel/Herring/Others 1388 0,73 282 0,75 0,42 1,03 1,05 Rape oil-for cooking 1083 0,73 581 0,75 0,16 1,03 1,05 Sour milk/week 401 0,73 1269 0,74 0,48 1,01 1,02 Low fat cream cheese/week 766 0,73 904 0,74 0,86 1,01 1,02 Cream cheese/week 621 0,73 1049 0,74 0,54 1,01 1,02 Low fat hard cheese/day 983 0,73 687 0,74 0,9 1,01 1,02 Low fat hard cheese/week 652 0,73 1018 0,74 0,91 1,01 1,02 Hard cheese/day 266 0,73 1404 0,74 0,86 1,01 1,02 Other meat 1103 0,73 567 0,74 0,54 1,01 1,02 Black pudding 1131 0,73 539 0,74 0,82 1,01 1,02 Sliced meat 237 0,73 1433 0,74 0,6 1,01 1,02 Sausage cuts 798 0,73 872 0,74 0,37 1,01 1,02 Herring/mackerel 1065 0,73 605 0,74 0,4 1,01 1,02 Salmon 452 0,73 1218 0,74 0,75 1,01 1,02 Cod/Saithe/Fishfingers 308 0,73 1362 0,74 0,73 1,01 1,02 Mayonnaise 1104 0,73 566 0,74 0,56 1,01 1,02 Cream 414 0,73 1256 0,74 0,75 1,01 1,02 Margarine-for cooking 1258 0,73 406 0,74 0,96 1,01 1,02 No fat in dressing 1261 0,73 394 0,74 0,43 1,01 1,02 Buttered bread/day 80 0,73 1590 0,73 0,97 1,00 1,00 Buttered bread/week 50 0,73 1620 0,73 0,99 1,00 1,00 Bacon 366 0,73 1304 0,73 0,93 1,00 1,00 Spawn 1386 0,73 284 0,73 0,94 1,00 1,00 Olive oil-in dressing 825 0,73 830 0,73 0,93 1,00 1,00 Rape oil-in dressing 1238 0,73 417 0,73 0,95 1,00 1,00 Low fat milk/week 618 0,74 1052 0,73 0,93 0,99 0,98 Low fat sourmilk/yoghurt/day 953 0,74 717 0,73 0,58 0,99 0,98 Low fat sourmilk/yoghurt/week 578 0,74 1092 0,73 0,93 0,99 0,98 Semi-skimmed sour milk/week 701 0,74 969 0,73 0,65 0,99 0,98 Sour milk/day 668 0,74 1002 0,73 0,93 0,99 0,98 Cottage cheese/day 1019 0,74 651 0,73 0,37 0,99 0,98 Cottage cheese/week 603 0,74 1067 0,73 0,81 0,99 0,98 Low fat cream cheese/day 1175 0,74 495 0,73 0,47 0,99 0,98 Cream cheese/day 977 0,74 693 0,73 0,84 0,99 0,98 Dessert cheese/day 1169 0,74 501 0,73 0,73 0,99 0,98 Dessert cheese/week 753 0,74 917 0,73 0,94 0,99 0,98 Low fat liver pate/week 795 0,74 875 0,73 0,72 0,99 0,98 Liver pate/day 632 0,74 1038 0,73 0,76 0,99 0,98 Game 1053 0,74 617 0,73 0,69 0,99 0,98 Lean sausage 1159 0,74 511 0,73 0,67 0,99 0,98 Tuna 986 0,74 684 0,73 0,46 0,99 0,98 Ice cream 165 0,74 1505 0,73 0,88 0,99 0,98 Olive oil-for cooking 835 0,74 828 0,73 0,26 0,99 0,98 Corn-/Sunflower-for cooking 1421 0,74 242 0,73 0,82 0,99 0,98 Semi-skimmed milk/day 553 0,75 1117 0,73 0,12 0,97 0,95 Liver pate/week 380 0,75 1290 0,73 0,42 0,97 0,95 Panncakes 323 0,75 1347 0,73 0,26 0,97 0,95 Pork 346 0,75 1324 0,73 0,46 0,97 0,95 Falukorv sausage 306 0,75 1364 0,73 0,27 0,97 0,95 Seafood 461 0,75 1209 0,73 0,18 0,97 0,95 Eggs/Omelets 90 0,75 1580 0,73 0,64 0,97 0,95 Cocking cream 346 0,75 1324 0,73 0,33 0,97 0,95 Low fat milk/day 995 0,74 675 0,72 0,27 0,97 0,95 Semi-skimmed sour milk/day 1094 0,74 576 0,72 0,16 0,97 0,95 Low fat liver pate/day 1221 0,74 449 0,72 0,32 0,97 0,95 Liquid butter-for cooking 1263 0,74 401 0,72 0,39 0,97 0,95 Semi-skimmed milk/week 313 0,76 1357 0,73 0,15 0,96 0,93 Fruit yoghurt/week 412 0,76 1258 0,73 0,05 0,96 0,93 Pizza 327 0,76 1343 0,73 0,11 0,96 0,93 Fruit yoghurt/day 735 0,75 935 0,72 0,16 0,96 0,93 Other sausage 608 0,75 1062 0,72 0,07 0,96 0,93 Sour cream 739 0,75 931 0,72 0,04 0,96 0,93 Liquid margarine-for cooking 979 0,75 685 0,72 0,11 0,96 0,93 Hard cheese/week 182 0,77 1488 0,73 0,11 0,95 0,91 Beef 141 0,77 1529 0,73 0,14 0,95 0,91 Low fat Creme fraiche 509 0,76 1161 0,72 0,03 0,95 0,91 Minced beef dishes 86 0,8 1584 0,73 0,9 0,91 0,85 Chicken/Other bird 89 0,8 1581 0,73 0,07 0,91 0,85 Other oil-in dressing 1605 0,74 50 0,67 0,19 0,91 0,85

Does not consume Does consume Foods in relation with MHiNP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Minced beef dishes 86 0,21 1584 0,34 0,06 1,62 1,35 Beef 141 0,25 1529 0,34 0,08 1,36 1,23 Sliced meat 237 0,28 1433 0,34 0,14 1,21 1,15 Cocking cream 346 0,28 1324 0,34 0,07 1,21 1,15 Bacon 366 0,29 1304 0,34 0,16 1,17 1,12 Lamb 1457 0,32 213 0,37 0,27 1,16 1,12 Spawn 1386 0,32 284 0,37 0,16 1,16 1,12 Cream cheese/week 621 0,3 1049 0,34 0,1 1,13 1,10 Pork 346 0,3 1324 0,34 0,2 1,13 1,10 Dessert cheese/week 753 0,31 917 0,35 0,1 1,13 1,10 Low fat liver pate/week 795 0,31 875 0,35 0,18 1,13 1,10 Ice cream 165 0,3 1505 0,33 0,5 1,10 1,07 Full fat milk/week 666 0,31 1004 0,34 0,21 1,10 1,07 Low fat sourmilk/yoghurt/week 578 0,31 1092 0,34 0,29 1,10 1,07 Semi-skimmed milk/week 701 0,31 969 0,34 0,14 1,10 1,07 Low fat milk/day 995 0,32 675 0,35 0,21 1,09 1,07 Full fat milk/day 1109 0,32 561 0,35 0,31 1,09 1,07 Low fat hard cheese/day 983 0,32 687 0,35 0,29 1,09 1,07 Low fat liver pate/day 1221 0,32 449 0,35 0,41 1,09 1,07 Black pudding 1131 0,32 539 0,35 0,3 1,09 1,07 Corn-/Sunfloweroil-in dressing 1536 0,33 118 0,36 0,57 1,09 1,07 Panncakes 323 0,31 1347 0,33 0,46 1,06 1,05 Chicken/Other bird 89 0,31 1581 0,33 0,73 1,06 1,05 Fruit yoghurt/day 735 0,32 935 0,34 0,46 1,06 1,05 Low fat sourmilk/yoghurt/day 953 0,32 717 0,34 0,4 1,06 1,05 Low fat cream cheese/week 766 0,32 904 0,34 0,41 1,06 1,05 Cream cheese/day 977 0,32 693 0,34 0,58 1,06 1,05 Dessert cheese/day 1169 0,32 501 0,34 0,53 1,06 1,05 Other sausage 608 0,32 1062 0,34 0,52 1,06 1,05 Sausage cuts 798 0,32 872 0,34 0,37 1,06 1,05 Other Fish 1119 0,32 551 0,34 0,52 1,06 1,05 Liquid margarine-for cooking 979 0,32 685 0,34 0,34 1,06 1,05 Low fat milk/week 618 0,32 1052 0,33 0,73 1,03 1,02 Low fat hard cheese/week 652 0,32 1018 0,33 0,7 1,03 1,02 Liver pate/week 380 0,32 1290 0,33 0,58 1,03 1,02 Falukorv sausage 306 0,32 1364 0,33 0,7 1,03 1,02 Salmon 452 0,32 1218 0,33 0,81 1,03 1,02 cream 414 0,32 1256 0,33 0,55 1,03 1,02 Semi-skimmed sour milk/day 1094 0,33 576 0,34 0,71 1,03 1,02 Sour milk/week 401 0,33 1269 0,33 0,84 1,00 1,00 Cottage cheese/w 603 0,33 1067 0,33 0,81 1,00 1,00 Low fat cream cheese/day 1175 0,33 495 0,33 0,95 1,00 1,00 Liver pate/day 632 0,33 1038 0,33 0,83 1,00 1,00 Pizza 327 0,33 1343 0,33 0,93 1,00 1,00 Liver/kidney 1592 0,33 78 0,33 0,99 1,00 1,00 Herring/mackerel 1065 0,33 605 0,33 0,87 1,00 1,00 Tuna 986 0,33 684 0,33 0,83 1,00 1,00 Caviar-"Kalles" 692 0,33 978 0,33 0,82 1,00 1,00 Mayonnaise 1104 0,33 566 0,33 0,8 1,00 1,00 Coffee cream 1564 0,33 106 0,33 0,99 1,00 1,00 Liquid butter-for cooking 1263 0,33 401 0,33 0,88 1,00 1,00 Rape oil-for cooking 1083 0,33 581 0,33 0,9 1,00 1,00 Olive oil-in dressing 825 0,33 830 0,33 0,82 1,00 1,00 Semi-skimmed milk/week 313 0,34 1357 0,33 0,8 0,97 0,98 Fruit yoghurt/week 412 0,34 1258 0,33 0,75 0,97 0,98 Hard cheese/day 266 0,34 1404 0,33 0,66 0,97 0,98 Hard cheese/week 182 0,34 1488 0,33 0,73 0,97 0,98 Cod/Saithe/Fishfingers 308 0,34 1362 0,33 0,58 0,97 0,98 Cottage cheese/day 1019 0,33 651 0,32 0,7 0,97 0,98 Lean sausage 1159 0,33 511 0,32 0,53 0,97 0,98 Freshwater fish 1567 0,33 103 0,32 0,79 0,97 0,98 Butter, Bregott-for cooking 1175 0,33 489 0,32 0,74 0,97 0,98 Corn-/Sunfloweroil-for cooking 1421 0,33 242 0,32 0,69 0,97 0,98 Rape oil-in dressing 1238 0,33 417 0,32 0,57 0,97 0,98 No fat in dressing 1261 0,33 394 0,32 0,75 0,97 0,98 Low fat creme fraiche 509 0,34 1161 0,32 0,61 0,94 0,95 Sour cream 739 0,34 931 0,32 0,34 0,94 0,95 Olive oil-for cooking 835 0,34 828 0,32 0,25 0,94 0,95 Semi-skimmed milk/day 553 0,35 1117 0,32 0,28 0,91 0,93 Seafood 461 0,35 1209 0,32 0,37 0,91 0,93 Creme fraiche 645 0,35 1025 0,32 0,31 0,91 0,93 Game 1053 0,34 617 0,31 0,19 0,91 0,93 Margarine-for cooking 1258 0,34 406 0,31 0,42 0,91 0,93 Smoked mackerel/Herring/Others 1388 0,33 282 0,3 0,36 0,91 0,93 Other meat 1103 0,34 567 0,3 0,14 0,88 0,91 Sour milk/day 668 0,36 1002 0,31 0,04 0,86 0,89 Other oil-in dressing 1605 0,33 50 0,28 0,44 0,85 0,89 Buttered bread/day 80 0,39 1590 0,33 0,33 0,85 0,87 Buttered bread/week 50 0,46 1620 0,32 0,13 0,70 0,72 Eggs/Omelets 90 0,48 1580 0,32 0,01 0,67 0,69

Doest not consume Does consume Foods in relation with MOiNP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Minced beef dishes 86 -0,08 1584 0 0,18 0,00 1,20 Spawn 1386 -0,01 284 0,05 0,07 -5,00 1,15 Sliced meat 237 -0,04 1433 0,01 0,2 -0,25 1,12 Cocking cream 346 -0,04 1324 0,01 0,9 -0,25 1,12 Cream cheese/week 621 -0,03 1049 0,02 0,03 -0,67 1,12 Lamb 1457 -0,01 213 0,04 0,13 -4,00 1,12 Liver/kidney 1592 0 78 0,04 0,39 ######## 1,10 Beef 141 -0,04 1529 0 0,31 0,00 1,10 Dessert cheese/week 753 -0,02 917 0,02 0,01 -1,00 1,10 Low fat liver pate/week 795 -0,02 875 0,02 0,14 -1,00 1,10 Coffee cream 1564 0 106 0,03 0,48 ######## 1,07 Full fat milk/week 666 -0,02 1004 0,01 0,09 -0,50 1,07 Semi-skimmed sour milk/week 701 -0,02 969 0,01 0,11 -0,50 1,07 Low fat cream cheese/week 766 -0,02 904 0,01 0,16 -0,50 1,07 Bacon 366 -0,02 1304 0,01 0,37 -0,50 1,07 Cream 414 -0,02 1256 0,01 0,29 -0,50 1,07 Full fat milk/day 1109 -0,01 561 0,02 0,2 -2,00 1,07 Dessert cheese/day 1169 -0,01 501 0,02 0,35 -2,00 1,07 Low fat liver pate/day 1221 -0,01 449 0,02 0,32 -2,00 1,07 Black pudding 1131 -0,01 539 0,02 0,28 -2,00 1,07 Other Fish 1119 -0,01 551 0,02 0,31 -2,00 1,07 Ice cream 165 -0,02 1505 0 0,57 0,00 1,05 Low fat milk/day 995 -0,01 675 0,01 0,45 -1,00 1,05 Fruit yoghurt/day 735 -0,01 935 0,01 0,47 -1,00 1,05 Low fat sourmilk/yoghurt/day 953 -0,01 717 0,01 0,38 -1,00 1,05 Low fat sourmilk/yoghurt/week 578 -0,01 1092 0,01 0,39 -1,00 1,05 Cream cheese/day 977 -0,01 693 0,01 0,34 -1,00 1,05 Low fat hard cheese/day 983 -0,01 687 0,01 0,34 -1,00 1,05 Mayonnaise 1104 -0,01 566 0,01 0,43 -1,00 1,05 Liquid margarine-for cooking 979 -0,01 685 0,01 0,32 -1,00 1,05 Low fat cream cheese/day 1175 0 495 0,01 0,76 ######## 1,02 Liquid butter-for cooking 1263 0 401 0,01 0,81 ######## 1,02 Corn-/Sunfloweroil-in dressing 1536 0 118 0,01 0,8 ######## 1,02 Low fat milk/week 618 -0,01 1052 0 0,72 0,00 1,02 Semi-skimmed milk/week 313 -0,01 1357 0 0,83 0,00 1,02 Low fat hard cheese/week 652 -0,01 1018 0 0,58 0,00 1,02 Hard cheese/day 266 -0,01 1404 0 0,73 0,00 1,02 Hard cheese/week 182 -0,01 1488 0 0,77 0,00 1,02 Liver pate/week 380 -0,01 1290 0 0,61 0,00 1,02 Panncakes 323 -0,01 1347 0 0,53 0,00 1,02 Pork 346 -0,01 1324 0 0,7 0,00 1,02 Fruit yoghurt/week 412 0 1258 0 0,93 ######## 1,00 Semi-skimmed milk/day 1094 0 576 0 0,74 ######## 1,00 Sour milk/week 401 0 1269 0 0,9 ######## 1,00 Cottage cheese/week 603 0 1067 0 0,84 ######## 1,00 Liver pate/day 632 0 1038 0 0,78 ######## 1,00 Other sausage 608 0 1062 0 0,81 ######## 1,00 Sausage cuts 798 0 872 0 0,81 ######## 1,00 Tuna 986 0 684 0 0,99 ######## 1,00 Freshwater fish 1567 0 103 0 0,94 ######## 1,00 Chicken/Other bird 89 0 1581 0 0,93 ######## 1,00 Rape oil-for cooking 1083 0 581 0 0,86 ######## 1,00 Olive oil-in dressing 825 0 830 0 0,79 ######## 1,00 Cottage cheese/day 1019 0 651 -0,01 0,68 ######## 0,98 Lean sausage 1159 0 511 -0,01 0,69 ######## 0,98 Herring/mackerel 1065 0 605 -0,01 0,75 ######## 0,98 Butter, Bregott-for cooking 1175 0 489 -0,01 0,65 ######## 0,98 Corn-/Sunfloweroil-for cooking 1421 0 242 -0,01 0,66 ######## 0,98 No fat in dressing 1261 0 394 -0,01 0,79 ######## 0,98 Pizza 327 0,01 1343 0 0,63 0,00 0,98 Falukorv sausage 306 0,01 1364 0 0,78 0,00 0,98 Salmon 452 0,01 1218 0 0,75 0,00 0,98 Cod/Saithe/Fishfingers 308 0,01 1362 0 0,76 0,00 0,98 Caviar-"Kalles" 692 0,01 978 0 0,67 0,00 0,98 Semi-skimmed milk/day 553 0,01 1117 -0,01 0,4 -1,00 0,95 Game 1053 0,01 617 -0,01 0,4 -1,00 0,95 Other meat 1103 0,01 567 -0,01 0,4 -1,00 0,95 Low fat Creme fraiche 509 0,01 1161 -0,01 0,44 -1,00 0,95 Creme fraiche 645 0,01 1025 -0,01 0,54 -1,00 0,95 Sour cream 739 0,01 931 -0,01 0,41 -1,00 0,95 Smoked mackerel/Herring/Others 1388 0 282 -0,02 0,47 ######## 0,95 Sour milk/day 668 0,02 1002 -0,01 0,14 -0,50 0,93 Seafood 461 0,02 1209 -0,01 0,2 -0,50 0,93 Margarine-for cooking 1258 0,01 406 -0,02 0,38 -2,00 0,93 Rape oil-in dressing 1238 0,01 417 -0,02 0,33 -2,00 0,93 Other oil-in dressing 1605 0 50 -0,04 0,47 ######## 0,91 Olive oil-for cooking 835 0,02 828 -0,02 0,09 -1,00 0,91 Buttered bread/day 80 0,06 1590 0 0,3 0,00 0,87 Buttered bread/week 50 0,09 1620 0 0,26 0,00 0,81 Eggs/Omelets 90 0,15 1580 -0,01 0,01 -0,07 0,69

Does not consume Does consume Foods in relation with MCiOP P-Value Ratio RGM Freq. Log-Mean Freq. Log-Mean Minced beef dishes 86 0,43 1584 0,51 0,11 1,19 1,20 Dessert cheese/week 753 0,48 917 0,54 0,01 1,13 1,15 Lamb 1457 0,5 213 0,56 0,05 1,12 1,15 Beef 141 0,46 1529 0,51 0,16 1,11 1,12 Sliced meat 237 0,47 1433 0,52 0,19 1,11 1,12 Cocking cream 346 0,47 1324 0,52 0,08 1,11 1,12 Semi-skimmed sourmilk/week 701 0,48 969 0,53 0,03 1,10 1,12 Cream cheese/week 621 0,48 1049 0,53 0,04 1,10 1,12 Low fat liver pate/week 795 0,48 875 0,53 0,02 1,10 1,12 Spawn 1386 0,5 284 0,55 0,11 1,10 1,12 Panncakes 323 0,48 1347 0,52 0,19 1,08 1,10 Low fat cream cheese/week 766 0,49 904 0,53 0,09 1,08 1,10 Liver/kidney 1592 0,51 78 0,55 0,31 1,08 1,10 Ice cream 165 0,48 1505 0,51 0,33 1,06 1,07 Low fat milk/week 618 0,49 1052 0,52 0,13 1,06 1,07 Full fat milk/week 666 0,49 1004 0,52 0,07 1,06 1,07 Low fat sourmilk/yoghurt/week 578 0,49 1092 0,52 0,14 1,06 1,07 Low fat hard cheese/week 652 0,49 1018 0,52 0,13 1,06 1,07 Liver pate/week 380 0,49 1290 0,52 0,33 1,06 1,07 Pork 346 0,49 1324 0,52 0,26 1,06 1,07 Salmon 452 0,49 1218 0,52 0,39 1,06 1,07 Low fat milk/day 995 0,5 675 0,53 0,16 1,06 1,07 Low fat sourmilk/yoghurt/day 953 0,5 717 0,53 0,11 1,06 1,07 Low fat liver pate/day 1221 0,5 449 0,53 0,23 1,06 1,07 Liquid margarine-for cooking 979 0,5 685 0,53 0,2 1,06 1,07 Full fat milk/day 1109 0,5 561 0,52 0,53 1,04 1,05 Fruit yoghurt/day 735 0,5 935 0,52 0,25 1,04 1,05 Semi-skimmed sourmilk/day 1094 0,5 576 0,52 0,36 1,04 1,05 Cottage cheese/week 603 0,5 1067 0,52 0,3 1,04 1,05 Low fat hard cheese/day 983 0,5 687 0,52 0,24 1,04 1,05 Dessert cheese/day 1169 0,5 501 0,52 0,35 1,04 1,05 Black pudding 1131 0,5 539 0,52 0,36 1,04 1,05 Fruit yoghurt/week 412 0,5 1258 0,51 0,67 1,02 1,02 Sour milk/week 401 0,5 1269 0,51 0,55 1,02 1,02 Falukorv sausage 306 0,5 1364 0,51 0,8 1,02 1,02 Other sausage 608 0,5 1062 0,51 0,69 1,02 1,02 Bacon 366 0,5 1304 0,51 0,54 1,02 1,02 Cream 414 0,5 1256 0,51 0,57 1,02 1,02 Low fat cream cheese/day 1175 0,51 495 0,52 0,64 1,02 1,02 Other Fish 1119 0,51 551 0,52 0,55 1,02 1,02 Corn-/Sunfloweroil-in dressing 1536 0,51 118 0,52 0,79 1,02 1,02 Semi-skimmed milk/week 313 0,51 1357 0,51 0,87 1,00 1,00 Cottage cheese/day 1019 0,51 651 0,51 0,89 1,00 1,00 Cream cheese/day 977 0,51 693 0,51 0,76 1,00 1,00 Liver pate/day 632 0,51 1038 0,51 0,92 1,00 1,00 Lean sausage 1159 0,51 511 0,51 0,9 1,00 1,00 Sausage cuts 798 0,51 872 0,51 0,82 1,00 1,00 Herring/mackerel 1065 0,51 605 0,51 0,77 1,00 1,00 Cod/Saithe/Fishfingers 308 0,51 1362 0,51 0,85 1,00 1,00 Chicken/Other bird 89 0,51 1581 0,51 0,99 1,00 1,00 Mayonnaise 1104 0,51 566 0,51 0,97 1,00 1,00 Butter, Bregott-for cooking 1175 0,51 489 0,51 0,82 1,00 1,00 Liquid butter-for cooking 1263 0,51 401 0,51 0,98 1,00 1,00 Corn-/Sunfloweroil-for cooking 1421 0,51 242 0,51 0,95 1,00 1,00 Rape oil-for cooking 1083 0,51 581 0,51 0,85 1,00 1,00 Olive oil-in dressing 825 0,51 830 0,51 0,87 1,00 1,00 Hard cheese/day 266 0,52 1404 0,51 0,76 0,98 0,98 Hard cheese/week 182 0,52 1488 0,51 0,7 0,98 0,98 Caviar-"Kalles" 692 0,52 978 0,51 0,66 0,98 0,98 Low fat creme fraiche 509 0,52 1161 0,51 0,55 0,98 0,98 Smoked mackerel/Herring/Others 1388 0,51 282 0,5 0,66 0,98 0,98 Tuna 986 0,51 684 0,5 0,54 0,98 0,98 Freshwater fish 1567 0,51 103 0,5 0,86 0,98 0,98 Coffee cream 1564 0,51 106 0,5 0,89 0,98 0,98 No fat in dressing 1261 0,51 394 0,5 0,81 0,98 0,98 Semi-skimmed milk/day 553 0,52 1117 0,5 0,3 0,96 0,95 Game 1053 0,52 617 0,5 0,29 0,96 0,95 Creme fraiche 645 0,52 1025 0,5 0,57 0,96 0,95 Sour cream 739 0,52 931 0,5 0,59 0,96 0,95 Olive oil-for cooking 835 0,52 828 0,5 0,3 0,96 0,95 Rape oil-in dressing 1238 0,51 417 0,49 0,35 0,96 0,95 Pizza 327 0,53 1343 0,5 0,31 0,94 0,93 Seafood 461 0,53 1209 0,5 0,24 0,94 0,93 Other meat 1103 0,52 567 0,49 0,1 0,94 0,93 Margarine-for cooking 1258 0,52 406 0,49 0,25 0,94 0,93 Buttered bread/day 80 0,55 1590 0,51 0,43 0,93 0,91 Sour milk/day 668 0,53 1002 0,49 0,07 0,92 0,91 Other oil-in dressing 1605 0,51 50 0,44 0,17 0,86 0,85 Buttered bread/week 50 0,61 1620 0,51 0,16 0,84 0,79 Eggs/Omelets 90 0,63 1580 0,5 0,02 0,79 0,74