1. The Scientific Advisory Committee on Nutrition (SACN) last considered maternal diet and nutrition in relation to offspring health in its reports on ‘The influence of maternal, fetal and child nutrition on the development of chronic disease in later life’ (SACN, 2011) and on ‘Feeding in the first year of life’ (SACN, 2018). In the latter report, the impact of breastfeeding on maternal health was also considered. In 2019, SACN agreed to conduct a risk assessment on nutrition and maternal health focusing on maternal outcomes during pregnancy, childbirth and up to 24 months after delivery; this would include the effects of chemical contaminants and excess nutrients in the diet.
2. SACN agreed that, where appropriate, other expert Committees would be consulted and asked to complete relevant risk assessments e.g., in the area of food safety advice. This subject was initially discussed by the COT during the horizon scanning item at the January 2020 meeting with a scoping paper being presented to the Committee in July 2020. This included background information on a provisional list of chemicals proposed by SACN, which was subject to change following discussion by COT who would be guiding the toxicological risk assessment process: candidate chemicals or chemical classes can be added or removed as the COT considered appropriate. The list was brought back to the COT with additional information in September 2020 where it was agreed that papers on a number of components, including cadmium, should be prioritised for review.
3. The UK Health Security Agency (UKHSA), previously Public Heath England, have produced information for the general public on the risk of exposure to cadmium but there are currently no Government dietary recommendations for the maternal diet that relates to this metal.

4.             Cadmium (Cd) is a soft malleable metallic element that is silvery-white or bluish white in appearance and exists in various mineral forms. Early uses include the use of cadmium compounds as pigments with more recent uses being in rechargeable batteries and coatings for prevention of corrosion of iron and steel. Cadmium can be released into the environment by natural activities (e.g., volcanic activity, erosion and weathering), and anthropogenic activities such as mining, smelting and refining non-ferrous metals.

5.             In the non-smoking population, the diet is the main source of cadmium exposure (approximately 90%), with less than 10% of exposure being due to inhalation from ambient air and drinking water (EFSA, 2009). Cereals and vegetables (e.g., potatoes) are the main food sources that contribute to cadmium exposure with levels dependent on the usage of phosphate fertilisers where cadmium is present as a contaminant. The uptake of cadmium by plants is influenced by the pH of the soil, with a low pH enhancing uptake (Jarup et al. 1998). In animal products, the main sources of cadmium are the kidney and liver due to cadmium accumulation in these organs. 

6.             Smoking is the main non-dietary source of exposure of cadmium in smokers due to the accumulation of cadmium in the tobacco leaves via the soil and can lead to a similar internal exposure as that acquired from the diet (EFSA, 2009).

7.             There are no data that indicate cadmium is an essential micronutrient for animals, plants, or microorganisms (EFSA 2009, Khan et al., 2017).

8.             The assessment started with a review of the opinions of the European Food Safety Authority (EFSA), Joint FAO/WHO Expert Committee on Food Additives (JECFA), World Health Organisation (WHO) and the Agency for Toxic Substances and Disease Registry (ATSDR) were used. This was supplemented with a literature review conducted using PubMed and Scopus over the last 15 years. The list of search terms are provided in Appendix A.

Toxicokinetics

9.             The oral bioavailability of cadmium from food and water can range from 1-10%, rising to up to 20% in individuals with iron deficiency (ATSDR, 2012; Krajnc et al. 1987). Lower iron stores are more common in women of reproductive age, especially during pregnancy, compared to men (EFSA, 2009; Romano et al. 2016). An increase in gastrointestinal absorption of cadmium has also been shown to be associated with a low intake of nutrients such as zinc and calcium in animal studies (Reeves and Chaney, 2008). Absorption of cadmium via inhalation (5-50% of cadmium is inhaled) is dependent on the size of the particles with 50-60% of ultrafine particles through smoking being retained, the remainder being exhaled with the smoke (EFSA, 2009; WHO, 2000).

10.             Cadmium can be transported in the blood by erythrocytes and is subsequently taken up by the liver, where it stimulates the production of the cysteine-sulfur rich protein metallothionein (MT) to which it binds.

11.             Metallothionein modulates a number of biochemical processes which includes binding to a number of trace metals (including cadmium) and thereby protecting cells and tissue against heavy metal toxicity. Bound and conjugated forms of cadmium are not in themselves toxic, but the complexes release divalent cadmium which is responsible for the cellular toxicity (Jacobo-Estrada et al. 2017).  Metallothionein also plays a role in the homeostasis of essential metals such as zinc and copper and provides a protective function as an antioxidant against reactive oxygen species (ROS), as well as protecting against DNA damage (Thirumoorthy et al. 2011). Cadmium has a disruptive effect at the cellular level by inducing signal dysregulation, competing with Zn2+ and Ca2+ transport and disrupting transducting modules and second messengers (Jacob-Estrada et al. 2017; Thevenod, 2009).

12.             The cadmium-metallothionein (Cd-MT) complex is filtered through the glomerulus and reabsorbed by the proximal tubular cells (Yang and Shu, 2015; EFSA, 2009). In the human body, the biological half-life ranges from 10-35 years (EFSA, 2009; WHO, 2017).

13.             Most ingested cadmium is excreted in the faeces due to poor absorption. Excretion via the urine is dependent on the cadmium concentration in the blood and kidney. In non-occupational exposure, the adult mean urinary cadmium in urine in non-smokers is normally < 1 µg/g creatinine (SCOEL, 2017).

Acute toxicity

14.             Acute cadmium toxicity occurs mainly from inhalation in an occupational setting, however acute toxicity from oral exposure has been reported with lethal dose ranges between 350 mg to 8900 mg of elemental cadmium which correspond to doses of ≈ 5 to 130 mg/kg bw in a 70 kg adult, and acute fatal doses of 5 g (cadmium iodide) and 150 g (cadmium chloride) ( IPCS, 1992; EFSA, 2009).

Chronic toxicity

15.             In non-occupational exposure, chronic exposure to cadmium is of more concern. The kidney is the main target organ, although effects on the liver can also occur. Chronic exposure can result in proteinuria and loss of tubular function in the kidney, with urinary excretion of β2-microglobulin being used as a useful biomarker to detect tubular damage (EFSA, 2009). If detected early, damage from cadmium exposure may be reversed (Gao et al., 2016), but it may become irreversible and progress even once exposure has ceased (EFSA, 2009). As cadmium accumulates in the kidney, it blocks the renal synthesis of 1,25 dihydroxyvitamin D which is essential for calcium absorption and bone mineralization. Divalent cadmium has similar physicochemical properties to calcium ion and so disrupts the  calcium signalling cascade affecting the absorption of calcium increasing the levels of   calcium and phosphorus excreted in the urine. With the reduction of calcium, osteomalacia and osteoporosis can result. The symptoms of bone fractures and kidney dysfunction were diagnosed as Itai-Itai (ouch-ouch) disease, first described in Japan in areas where the diet consisted of cadmium contaminated rice (ATSDR, 2012; Umemura and Wako, 2006; Unsal et al. 2020). In a Swedish cohort study, dietary cadmium level >13 µg/day were shown to increase the risk of osteoporosis and fractures by 32% and 31%  respectively (Engstrom et al. 2012).

16.             Levels of urinary cadmium of the order of 1 µg/g of creatinine have been associated with a decrease of bone density with increasing risk of fractures in women and height loss in men (Kazantzis, 2004). During pregnancy, absorption of cadmium is enhanced due to physiological changes which ensure the nutritional needs of mother and fetus and it can directly interfere with the metabolism of calcium and decrease vitamin D synthesis in the kidneys, which leads to increased absorption and body burden of cadmium (Al-Saleh et al. 2011; Kazantzis, 2004; Young and Cai, 2020).

Genotoxicity

17.          Although not directly genotoxic, cadmium has the potential to induce DNA damage, micronuclei, chromosomal aberrations, sister chromatid exchange (SCE) and genetic mutations (ATSDR, 2012; EFSA, 2009). The mechanisms associated with this indirect affect include increased ROS formation, DNA repair inhibition, reduction in cell growth and resistance to apoptosis, and epigenetic changes in DNA methylation (Hartwig et al. 2020).

Carcinogenicity

18.          Cadmium and its compounds were reviewed in 2012 by IARC who classified them as Group 1 (carcinogenic to humans) as there was sufficient evidence that cadmium and its compounds caused lung cancer and positive associations of cadmium with the risk of kidney and prostate cancer (IARC, 2012).

19.          A statistically significant increased risk of lung cancer from inhalation exposure was originally associated with occupational exposure to cadmium, however it has now also been shown in the general population with no occupational exposure from inhalation (Nawrot et al. 2015, Satarug et al. 2017).  A synergistic effect between smoking, occupational exposure and renal cancer was indicated and it was suggested that additional factors other than cadmium may have been contributing via the cigarette smoke (Kolonel, 1967). Associations have also been reported in in vivo studies which show an increase in cancers of the bladder and prostate, however, in human studies there are inconsistencies in the results (IARC, 2012; Nordberg et al. 2018).

20.          Cohort studies have suggested that dietary exposure to cadmium below the levels suggested by EFSA and JECFA show an increased risk of breast cancer and osteoporosis in post-menopausal women. However, an EC Joint Research Council report (EC, 2007) concluded that there is currently no evidence that cadmium acts as a carcinogen following oral exposure (cited by EFSA, 2009).

Reproductive and developmental toxicity

21.          Cadmium accumulates in the placenta with lower levels being detected in the maternal and cord blood (Roles et al. 1978; Osman et al. 2000; Gundacker et al. 2012). Accumulation is associated with placental necrosis, loss of function and reduction in trophoblast cell proliferation (Thompson and Bannigan 2008; Banerjee et al. 2020; Cerrillos et al. 2019).

22.          Metallothionein is produced in the placenta as a protective barrier against cadmium entering the fetus. However, this can disrupt zinc homeostasis in the placenta by displacing the zinc in the metallothionein complex with cadmium (Casserta et al. 2013; Espart et al. 2018). Cadmium has been shown to interfere with endocrine hormone synthesis which is linked to fetal growth impairment by interfering with placental steroidogenesis in vitro (Unsal et al. 2020; Caserta et al. 2013; Everson et al. 2017). Cadmium also inhibits 11-β-hydroxysteroid dehydrogenase (11-β-HSD2) activity which has been linked to intrauterine growth restriction in in vitro and human studies (Ebrahim et al. 2015; Kippler et al. 2012).  

23.          During gestation there is a larger demand for iron which is required for fetal development, this is mediated by the Divalent Metal Transporter-1 (DMT-1) in the intestine and the placenta. If iron stores begin to be depleted, cadmium transport is facilitated by DMT-1 (Jacob-Estrada et al. 2017).

24.          In utero exposure to cadmium is associated with changes in DNA methylation which can alter the epigenetic mechanisms affecting fetal development and genomic expression (Banerjee et al. 2020; Dharmadasa et al. 2017). The DNA methylation appears to have different effects dependent on the sex of the fetus, with positive correlation with hypermethylation of SALL1 genes with cadmium exposure for boys and negative correlation of hypomethylation of SIAH3, HS3ST4 and TP53TG1 genes for girls (Kippler et al. 2013; Banerjee et al. 2020).

25.          Adverse birth outcomes linked with blood and urine  biomarkers of cadmium exposure and cadmium levels in placental samples at birth can include low birth weight, smaller head circumference, low Apgar score, crown-heel lengths and neurobehavioural developmental effects (Tung et al. 2022; Guo et al. 2017).

26.          In a birth cohort study by Guo et al. (2017) (n = 1073 mother-newborn pairs) from an agricultural population in China, the results showed that the cadmium concentration in cord blood was significantly negatively associated with ponderal index at birth (this assesses the ratio of a person’s length to weight). No association was shown between urinary cadmium concentrations and ponderal index.

27.          Placental samples (n=192) from participants in the RICHS cohort study (Tung et al. 2022) showed an association between increased cadmium concentrations in the placenta (mean cadmium 4.56 ng/g) and an increase in adverse neurobehavioural outcomes. It was assumed that most of the cadmium was obtained from the diet, although no dietary information was obtained from the cohort and there was a relatively low prevalence of women who smoked during pregnancy (10.2%).

28.          In contrast, the MOCEH cohort study based in Korea (Shah-Kulkarni et al. 2020) showed no significant association with prenatal cadmium exposure (levels of 1.40, 1.52 and 0.68 µg/L in early pregnancy, late pregnancy and cord blood respectively) and the mental development index or the psychomotor development index in infants at 6 months of age.

29.          Adverse maternal effects linked to cadmium exposure include pre-eclampsia, proteinuria, renal dysfunction and micronutrient deficiency (Liu et al. 2019; Osario-Yanez et al. 2016). An association has also been reported between cadmium exposure and hypertension in pregnant women smokers (n= 9), although it is unclear what components in the smoke are causing the hypertension or if there were any synergistic effects with the cadmium (Kosanovic et al. 2002). Animal studies have shown that pregnant animals were more sensitive to the toxic effects of cadmium in comparison to non-pregnant ones with pregnant rats showing similar effects to those seen in human pre-eclampsia including blood in the urine and later development of visceral congestion, pulmonary and haemorrhagic oedema, (Chisolm and Handorf, 1987). However, in one human study (Osorio-Yanez et al. 2016) high levels of urinary cadmium were not reported in those that developed pre-eclampsia, with no observed statistically significant differences in urinary cadmium concentrations among women who reported smoking during pregnancy (n=43), former smokers (n= 130) and never smokers (n= 441).

30.          There is inconsistency in the available epidemiological data with some studies suggesting that cadmium and its compounds can lead to an increased risk of cancer, pre-eclampsia and affecting birth weights of new-borns, while others show no effect (Nordberg et al. 2018; Menai et al. 2021; IARC, 2012).

31.          A tolerable weekly intake (TWI) for cadmium was established by the EFSA CONTAM panel in 2009. EFSA noted that the reproductive effects of cadmium, based on the available epidemiology at that time, were uncertain and considered cadmium to be primarily toxic to the kidneys. Hence, the TWI of 2.5 µg/kg bw was based on renal effects. To determine a BMDL5 of 1 µg/g of creatinine, a meta-analysis was conducted between urinary cadmium and urinary β-2-microglobulin as the tubular damage biomarker. An elevated level of β-2-microglobulin of 4 µg/g of creatinine with an adjustment factor of 3.9, accounting for the inter-individual variation of urinary cadmium resulted in the BMDL5 of 1 µg/g creatinine. To enable 95% of the population to have a urinary concentration below 1 µg/g of creatinine by the age of 50, it was calculated that the daily intake of cadmium should not exceed 0.36 µg cadmium/kg bw or 2.5 µg cadmium/kg bw per week (EFSA, 2009).

32.             At the 33^rd meeting, the Joint FAO/WHO Committee on Food Additives (JECFA) established a Provisional Tolerable Weekly Intake (PTWI) of 7 µg/kg bw in 1988. In 2011, JECFA (73^rd meeting) re-assessed cadmium and established a Provisional Tolerable Monthly Intake (PTMI) of 25 µg/kg bw (equivalent to 0.8 µg/kg bw/day), reflecting the long half-life of cadmium and the bioaccumulation in the kidney. Urinary excretion of > 5.24 µg of cadmium per gram of creatinine indicated a sharp increase in β-2-microglobulin (JECFA, 2011). At its 91st meeting in 2021, JECFA calculated national estimates of total dietary exposure to cadmium and compared these to the PTMI established in 2011. Estimates ranged from 0.6 µg/kg bw per month (2.6% of PTMI) in adults in Mali to 24 µg/kg bw per month (96% of PTMI) in children (aged 4-11) in China. It was noted that there were high percentiles occasionally above the PTMI, but on average it was between 20 and 60% of the PTMI. UK and EU data were considered in this analysis but it is unknown where in the range these would have fallen (JECFA 2021).

33.               In 2011, following JECFA’s re-evaluation, EFSA compared the different approaches used by the EFSA CONTAM Panel and JECFA to determine a health-based guidance value (HBGV). EFSA concluded that the choice of toxicodynamic function played an important role on the outcome (EFSA 2011a) and that the TWI determined by the CONTAM Panel should be maintained “to ensure a high level of protection of consumers, including subgroups of the population such as children, vegetarians or people living in highly contaminated areas”. Nevertheless, they also acknowledged that some subgroups could exceed both the JECFA PTMI and the CONTAM Panel TWI (EFSA 2011b).

Sources of cadmium exposure

Human breast milk

Human breast milk

34.             Human breast milk has previously been discussed in the COT statement on cadmium in the infant diet (COT, 2018). Cadmium intake in the average and high level exclusively breast-fed UK infants from 0 to < 6 months ranged between 11 – 68% of the EFSA TWI of 2.5 µg/kg bw/week. The highest total exposure to cadmium in the infant diet was found in solid food for 12 - <60 month old children which constituted up to 260% of the EFSA TWI of 2.5 µg/kg bw/week (0.36 µg/kg bw/day). Although there was an exceedance, it was not expected to remain at this level over the decades of bioaccumulative exposure considered by EFSA in setting the HBGV.  The Committee concluded that there was no major concern, however efforts to minimise the levels of cadmium in the environment should continue.

Food

35.             Cadmium levels have been measured in the composite food samples of The Total Diet Study (TDS) (Bates et al. 2014, 2016; Roberts et al. 2018). The highest exposure to cadmium came from the food groups miscellaneous cereals, potatoes, and bread.

36.             In a Swedish birth cohort study, the maternal diets with high intakes of vegetables, root vegetables, nuts, grains and rice were significantly associated with higher erythrocyte and urinary cadmium levels, whereas red meat consumption had an inverse association (Gustin et al. 2020). High accumulation of cadmium has also been reported in rice where it is a staple food in Asia and it was shown that females had a higher elevated body burden of cadmium (Simmons et al. 2005; Kippler et al. 2007; Geng and Wang, 2019).

Drinking water

37.             Drinking water can be contaminated with cadmium due to leaching from corroded/galvanized pipes or solder used within taps and water heaters (WHO, 2011). In areas with high cadmium pollution, well water may also be affected, with cadmium levels in excess of 25 µg/L (WHO, 2000; Lauwerys et al. 1990) being reported.

38.             Directive 2003/40/EC specifies a maximum level of cadmium in natural mineral waters of 3.0 µg/L and equivalent UK legislation. The EU adopted the revised Drinking Water Directive ((EU) 2020/2184) which came into force at the start of 2021, which upheld the set value of 5.0 µg/L of Directive 98/83/EC on the quality of water intended for human consumption.

39.             Levels of cadmium in drinking water in 2020 were published for England and Wales (99^th percentile 0.23 µg/L, no mean data available), Scotland (mean and 97.5^th percentile 0.02 and 0.06 µg/L respectively) and Northern Ireland (mean and 97^th percentile 0.038 and 0.04 µg/L respectively) by the Drinking Water Inspectorate and the Drinking Water Quality Regulator (DWQR) for Scotland and Northern Ireland Water respectively.

Environmental

Dust

40.             Cadmium dust includes various cadmium compounds including cadmium chloride and cadmium oxide which is formed when moist air oxidises the cadmium (Pohanish 2017; IPCS,1992). The cadmium levels in dust were determined by ICP-OES with a median concentration of <0.30 µg/g. Although the concentrations were low in environmental samples, urine samples in a study conducted in Western Australia by Hinwood et al. (2013) showed elevated levels. It was suggested that these higher levels of cadmium were linked to the participants eating fish and not taking iron/folic acid supplements, while those participants who used iron and folic acid supplements showed an association with decreased cadmium levels. Other factors that could affect the levels of cadmium were economic status and the geographical location in Western Australia.

Soil

41.             Cadmium occurs naturally in the Earth’s crust, is commonly found in association with zinc ores and is is also associated with atmospheric pollution (e.g., volcanic eruptions and emissions from smelting) and phosphate fertilisers. The Soil Guideline Value for residential soils adopted a total concentration of 10 mg/kg for cadmium which is above the concentration found in most soils (Rawlins et al. 2012; Environment Agency, 2009).The summary statistics reported for the principal domain for England and Wales were a normal background concentration (NBC) of 1.0 mg/kg (n = 4418) and 1.4 mg/kg (n = 681) respectively.

Air

42.             Cadmium can be released into the atmosphere by anthropogenic sources and occurs mainly as fine respirable particles in particulate matter (<10 µm). The Fourth Daughter Directive (2004/107/EC) set the target value for cadmium as 5 ng/m³. Using the data collated by the UK Air Information Resource for 2020 the air exposure measurements of cadmium for England and Wales ranged from 0.062 to 0.725 ng/m³ and 0.057 to 1.382 ng/m³  respectively (Home - Defra, UK)

43.          It has been estimated that one cigarette contains between 0.2 and 1.0 µg of cadmium and although advised not to smoke tobacco products while pregnant, those mothers that continue to smoke during their pregnancy have been shown to have higher cadmium levels in comparison to non-smoking mothers (Ebrahim and Ashtarinezhad, 2015). Chao et al. (2014) sampled human milk samples during the four stages of lactation and found that the highest levels were found in colostrum, thus infants of smoking mothers were exposed to more cadmium than those with non-smoking mothers. Second-hand smoke can also lead to a 2-fold higher exposure to cadmium in comparison to unexposed women (Stone et al. 2021).

44.          The COT have previously considered the potential toxicological risks from electronic cigarettes (E(N)NDS) and the effects on bystanders of secondary emissions (COT, 2018; 2019). The emissions from the electronic cigarettes differ from cigarette smoke (which is a well-known health hazard), with those from the electronic cigarette comprising the residual particulates/vapour exhaled from the user. The aerosols from these devices were evaluated for metals (including cadmium) by liquid phase extraction and ICP-MS.

45.             The National Diet and Nutrition Survey Rolling Programme (NDNS) and Total Diet Study does not include pregnant or lactating women, therefore the data for women of childbearing age (Bates et al. 2014, 2016; Roberts et al., 2018) were used as a surrogate to estimate cadmium exposure from food.  Childbearing age was taken to be 16-49 years of age. Caution must be taken when using these data as they may not be entirely representative of the maternal diet.

46.             The mean cadmium exposure from the total diet of women of childbearing age ranged between 0.12 – 0.21 µg/kg bw/day and the 97.5^th  percentile of 0.21-0.37 µg/kg bw/day. Combining the data obtained for England and Wales for drinking water with the TDS data, the exposure assessment of the TDS on the highest 97.5^th percentile for water, had a minimal effect on total exposure derived from all foods in the TDS.

47.               The food groups providing the highest cadmium exposures were miscellaneous cereals, potatoes, and bread. As stated above, high intakes of rice can occur, especially in certain groups, but there are no separate concentration data for cadmium in rice in the TDS. Although the TDS data can be used for exposure in specific sub populations (e.g. vegetarian or ethnic origin), the data sets are small and therefore not sufficiently robust to provide separate, statistically reliable exposure estimates in these sub-populations. (Appendix B). It should be noted that pregnant women are advised to eat a variety of different foods to ensure the correct amount of nutrients are being consumed. This includes bread, potatoes, breakfast cereals and rice (NHS, 2020). Therefore, pregnant women may have a different diet in comparison to non-pregnant females considered in the TDS.

48.             COT have previously concluded that the EFSA TWI of 2.5 µg/kg bw/week for cadmium was an acceptable value to use for risk assessment, following EFSA’s rigorous statistical review of the derivation of its HBGV compared with that of JECFA.

49.             Based on the TDS data, the cadmium intake based on bread for women of child-bearing age was 6.1% and 15% of the EFSA TWI daily amount at the mean and 97.5^th percentile, respectively.

50.             The mean and 97.5^th percentile cadmium intake based on the TDS data for miscellaneous cereals for women of child-bearing age were 8.9% and 26% respectively of the EFSA TWI.

51.             The mean total intake of cadmium from potatoes for women of maternal age was 6.4% of the EFSA TWI with the 97.5th percentile of 19%.

52.             The total daily exposure from food for women of maternal age showed a percentage of the EFSA TWI of 22% to 58% and the 97.5^th percentile between 58 and 100%.

53.             The amount of cadmium detected in the soil in the principal domains were at the limit of detection and not further assessed.

54.             Exposure to high levels of cadmium during pregnancy has been associated with adverse effects such as hypertension, pre-eclampsia, micronutrient deficiency in the mother, and adverse birth outcomes for the fetus. Hypertension has also been reported in animal studies showing pregnant animals are more sensitive to the toxicological effects of cadmium in comparison to non-pregnant animals, while pre-eclampsia has been observed in mice with high blood concentrations of cadmium.

55.             As cadmium accumulates within the body, previous exposures will determine the body burden so, for example, it should be noted that women who give up smoking while pregnant will still carry a higher body burden of cadmium than women who have never smoked.

56.             Food is the main source of cadmium for non-smoking women of maternal age who have never smoked. In this assessment, breads, miscellaneous cereals, and potatoes make the highest dietary contribution to cadmium exposure. Cadmium intake via other routes such as water, soil, and dust only contribute a small amount to total exposure. Taking the total amount of exposure from the TDS, the mean percentage and 97.5th percentile when compared to the EFSA TWI of 2.5 µg/kg bw/week were 22-58% and 58-100% respectively.

57.             Overall, cadmium in the maternal diet does not appear to be a health concern.

58.             However, consumption was based on data from women of childbearing age and therefore may not be fully representative of the maternal diet, leading to an under/overestimation of the actual exposure. However, it should be noted that use of the 97.5^th percentile is a conservative approach in relation to the HBGV, as it is unlikely that every commodity consumed would be in the 97.5^th percentile.

COT

November 2022

Statement Number 05/22

Agency for Toxic Substances and Disease Registry (ATSDR), (2012). Toxicological Profile for Cadmium. Available at: Toxicological Profile for Cadmium (cdc.gov).

Al-Saleh, I., Shinwari, N., Mashhour, A., Mohamed, G.E.D., Rabah, A. (2011). Heavy Metals (Lead, Cadmium and Mercury) in Maternal, Cord Blood and Placenta of Healthy Women. International Journal of Hygiene and Environmental Health. 214: 79-101. Available at: Heavy metals (lead, cadmium and mercury) in maternal, cord blood and placenta of healthy women - PubMed (nih.gov).

Banerjee, S., Suter, M.A., & Aagaard, K.M. (2020). Interactions Between Environmental Exposures and the Microbiome: Implications for Fetal Programming. Current Opinion in Endocrine and Metabolic Research. 13: 39-48. Available at: Interactions between environmental exposures and the microbiome: Implications for fetal programming - ScienceDirect.

Bates, B.; Lennox, A.; Prentice, A.; Bates, C.; Page, P.; Nicholson, S.; Swan, G. (2014) National Diet and Nutrition Survey Results from Years 1, 2, 3 and 4 (combined) of the Rolling Programme (2008/2009 – 2011/2012) Available at: Main heading (publishing.service.gov.uk).

Bates, B.; Cox, L.; Nicholson, S.; Page, P.; Prentice, A.; Steer, T.; Swan, G. (2016) National Diet and Nutrition Survey Results from Years 5 and 6 (combined) of the Rolling Programme (2012/2013 – 2013/2014) Available at: Main heading (publishing.service.gov.uk).

Bernard, A., & Lauwerys, R. (1986). Present Status and Trends in Biological Monitoring of Exposure to Industrial-Chemicals. Journal of Occupational and Environmental Medicine, 28(8): 558-562. Available at: Present status and trends in biological monitoring of exposure to industrial chemicals - PubMed (nih.gov).

Caserta, D., Graziano, A., Lo Monte, G., Bordi, G., Moscarini, M. (2013). Heavy Metals and Placental Fetal-Maternal Barrier: A Mini-Review on the Major Concerns. Eur Rev Med Pharmaco Sci. 17: 2198-2206. Available at: Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns - PubMed (nih.gov).

Cerrillos, L., Fernádez, R., Machado, M.J., Morillas, I., Dahiri, B., Paz, S., Gonzalez-Weller, D., Gutiérrez, A., Rubio, C., Hardisson, A., Moreno, I., Fernández-Palaćin, A. (2019). Placental Levels of Metals and Associated Factors in Urban and Sub-Urban Areas of Seville (Spain). Journal of Trace Elements in Medicine and Biology.54: 21-26. Available at: Placental levels of metals and associated factors in urban and sub-urban areas of Seville (Spain) - PubMed (nih.gov).

Chao, H., Guo, C., Huang, C., Chen, P., Li, H., Hsiung, D., Chou, Y. (2014). Arsenic, Cadmium, Lead, and Aluminium Concentrations in Human Milk at Early Stages of Lactation.  Pediatrics and Neonatology, 55: 127-134. Available at: Arsenic, Cadmium, Lead, and Aluminium Concentrations in Human Milk at Early Stages of Lactation - ScienceDirect.

COT (Committee on Toxicity on Chemicals in Food, Consumer Products and the Environment) (2019). Potential toxicological risks from electronic nicotine (and non-nicotine) delivery systems (E(N)NDS – e-cigarettes). Paper 9: Bystander exposure. Available at: E(N)NDS paper4 aerosol toxicity (food.gov.uk).

COT (Committee on Toxicity on Chemicals in Food, Consumer Products and the Environment) (2018). Statement on Potential Risks from Cadmium in the Diet of Infants Aged 0 to 12 Months and Children Aged 1 to 5 Years.  Available at: cotstatementoncadmium.pdf (food.gov.uk).

COT (Committee on Toxicity on Chemicals in Food, Consumer Products and the Environment) (2018). Potential toxicological risks from electronic nicotine (or non-nicotine) delivery systems (e-cigarettes). Paper 2: Exposure to metals present in the aerosol of electronic nicotine (or non-nicotine) delivery systems. Available at: tox2018-15.pdf (nationalarchives.gov.uk).

DEFRA (Department for Environment Food and Rural Affairs) (2012a). Technical Guidance Sheet on Normal Levels of Contaminants in English Soils: Cadmium. Technical Guidance Sheet No. TGS06. Available at: Science Search (defra.gov.uk).

DEFRA (Department for Environment for Food and Rural Affairs) (2013). Technical Guidance on Normal Levels of Contaminants in Welsh Soil: Cadmium. British Geological Survey (Keyworth, Nottingham) and DEFRA (London). R & D Project SP1008. Available at: Science Search (defra.gov.uk).

Dharmadasa, P., Kim, N., Thunders, M. (2017). Maternal Cadmium Exposure and Impact on Foetal Gene Expression Through Methylation Changes. Food and Chemical Toxicology, 109: 714-720. Available at: Maternal cadmium exposure and impact on foetal gene expression through methylation changes - PubMed (nih.gov).

Ebrahim, K., & Ashtarinezhad, A. (2015). The Association of Amniotic Fluid Cadmium Levels with the Risk of Preeclampsia, Prematurity and Low Birth Weight.  Iranian Journal of Neonatology. 6(2):1-6. Available at: [PDF] The Association of Amniotic Fluid Cadmium Levels with the Risk of Preeclampsia, Prematurity and Low Birth Weight | Semantic Scholar.

EC (European Commission) (2007). European Union Risk Assessment Report. Cadmium Metal and oxide. CAS No: 7440-43-9. EINECS No: 231-152-8. Available at:  European Union Risk Assessment Report (europa.eu).

EFSA (2009). Cadmium in food. Scientific Opinion of the Panel on Contaminants in the Food Chain. The EFSA Journal 980: 1-139. Available at: Cadmium in food ‐ Scientific opinion of the Panel on Contaminants in the Food Chain - - 2009 - EFSA Journal - Wiley Online Library.

EFSA (2011a). Comparison of the Approaches Taken by EFSA and JECFA to Establish a HBGV for Cadmium. EFSA Journal, 9(2): 2006. Available at: Comparison of the Approaches Taken by EFSA and JECFA to Establish a HBGV for Cadmium | EFSA (europa.eu).

EFSA (2011b). Statement on Tolerable Weekly Intake for Cadmium. EFSA Panel on Contaminants in the Food Chain (CONTAM). EFSA Journal, 9(2): 1975. Available at : Statement on tolerable weekly intake for cadmium | EFSA (europa.eu).

Engström, A., Michaëlsson, K., Vahter, M., Julin, B., Wolk, A., Åkesson, A. (2012). Associations Between Dietary Cadmium Exposure and Bone Mineral Density and Risk of Osteoporosis and Fractures Among Women. Bone,50: 1372-1378. Available at: Associations between dietary cadmium exposure and bone mineral density and risk of osteoporosis and fractures among women - ScienceDirect.

Environment Agency (EA) (2009). Using Soil Guideline Values. Available at: Microsoft Word - 090323 SGV Introduction final.doc (publishing.service.gov.uk).

Espart, A., Artime, S., Tort-Nasarre, G., Yaya-Varȯn, E. (2018). Cadmium Exposure During Pregnancy and Lactation: Materno-Fetal and Newborn Repercussions of Cd(II), and Cd-Metallothionein Complexes. Metallomics.10: 1359-1367. Available at: Cadmium exposure during pregnancy and lactation: materno-fetal and newborn repercussions of Cd(ii), and Cd&#x2013;metallothionein complexes (rsc.org).

Everson, T.M., Kappil, M., Hao, K., Jackson, B.P., Punshon, T., Karagas, M.R., Chen, J., Marsit, C.J. (2017). Maternal Exposure to Selenium and Cadmium, Fetal Growth, and Placental Expression of Steroidogenic and Apoptotic Genes. Environmental Research. 158: 233-244.  Available at: Maternal exposure to selenium and cadmium, fetal growth, and placental expression of steroidogenic and apoptotic genes - PubMed (nih.gov).

Filippini, T., Torres, D., Lopes, C., Carvalho, C., Moreira, P., Naska, A., Kasdagli, M., Malavolti, M., Orsini, N., Vinceti, M. (2020). Cadmium Exposure and Risk of Breast Cancer: A Dose-Response Meta-Analysis of Cohort Studies. Environment International.142: 105879.  Available at: Cadmium exposure and risk of breast cancer: A dose-response meta-analysis of cohort studies - PubMed (nih.gov).

Gao Y, Zhang Y, Yi J, Zhou J, Huang X, Shi X, Xiao S, Lin D. (2016). A Longitudinal Study on Urinary Cadmium and Renal Tubular Protein Excretion of Nickel– Cadmium Battery Workers After Cessation of Cadmium Exposure. International Archives of Occupational and Environmental Health. 89(7): 1137– 1145. Available at: A longitudinal study on urinary cadmium and renal tubular protein excretion of nickel-cadmium battery workers after cessation of cadmium exposure - PubMed (nih.gov).

Geng, H., & Wang, L. (2019). Cadmium: Toxic Effects on Placental and Embryonic Development. Environmental Toxicology and Pharmacology. 67: 102-107. Available at: Cadmium: Toxic effects on placental and embryonic development - ScienceDirect.

Grioni, S., Agnoli, C., Krogh, V., Pala, V., Rinaldi, S., Vinceti, M., Contiero, P., Vescovi, L., Malavolti, M., Sieri, S. (2019). Dietary Cadmium and Risk of Breast Cancer Subtypes Defined by Hormone Receptor Status: A Prospective Cohort Study. International Journal of Cancer. 144: 2153-2160. Available at: Dietary cadmium and risk of breast cancer subtypes defined by hormone receptor status: A prospective cohort study - PubMed (nih.gov).

Gundacker, C., & Hengstschläger, M. (2012). The Role of the Placenta in Fetajkll Exposure to Heavy Metals. Wien Med Wochenschr. 162/9-10: 201-206. Available at: The role of the placenta in fetal exposure to heavy metals - PubMed (nih.gov).

Guo, J., Wu, C., Qi, X., Jiang, S., Liu, Q., Zhang, J., Cao, Y., Chang, X., Zhou, Z. (2017). Adverse Associations Between Maternal and Neonatal Cadmium Exposure and Birth Outcomes. Science of the Total Environment, 575: 581-587. Available at: Adverse associations between maternal and neonatal cadmium exposure and birth outcomes - ScienceDirect.

Gustin, K., Barman, M., Stråvik, M., Levi, M., Englund-Ögge, L., Murray, F., Jacobsson, B., Sandberg, A., Sandin, A., Wold, A.E., Vahter, M., Kippler, M. (2020). Low-Level Maternal Exposure to Cadmium, Lead and Mercury and Birth Outcomes in a Swedish Prospective Birth-Cohort. Environmental Pollution, 265: 114986. Available at: Low-level maternal exposure to cadmium, lead, and mercury and birth outcomes in a Swedish prospective birth-cohort - PubMed (nih.gov).

Hartwig, A., Arand, M., Epe, B., Guth, S., Jahnke, G., Lampen, A., Martus, H., Monien, B., Rietjens, I.M.C.M., Schmitz-Spanke, S., Scriever-Schwemmer, G., Steinberg, P., Eisenbrand, G. (2020). Mode of action-based risk assessment of genotoxic carcinogens. Archives of Toxicology 94:1787-1877. Available at: Mode of action-based risk assessment of genotoxic carcinogens (nih.gov).

Hinwood, A.L., Callan, A.C., Ramalingam, M., Boyce, M., Heyworth, J., McCafferty, P., Odland, J.Ø. (2013). Cadmium, Lead and Mercury Exposure in Non Smoking Pregnant Women. Environmental Research, 126: 118-124. Available at: Cadmium, lead and mercury exposure in non smoking pregnant women - ScienceDirect.

International Agency for Research on Cancer(IARC)(2012). Arsenic, Metals, Fibres, and Dusts Volume 100 C A Review of Human Carcinogens. IARC Monographs on the Evaluation of Carcinogenic Risks: 121-141. Available at: IARC Publications Website - Arsenic, Metals, Fibres, and Dusts .

International Programme on Chemical Safety (IPCS). 1992. Cadmium. Poisons Information Monograph. PIM 089. Available at : Cadmium (PIM 089) (inchem.org) .

Jacobo-Estrada, T., Santoyo-Sánchez, M., Thévenod, F., Barbier, O. (2017). Cadmium Handling, Toxicity and Molecular Targets Involved During Pregnancy: Lessons from Experimental Models. Int J Mol Sci.  18(7): 1590. Available at: Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models - PubMed (nih.gov).

Jarup, L., Berglund, M., Elinder, C. G., Nordberg, G., Vahter, M. (1998). Health Effects of Cadmium Exposure – a review of the literature and a risk estimate. Scandinavian Journal of Work, Environment & Health, Vol 24, Supplement 1, pp 1-51. Available at: Health effects of cadmium exposure – a review of the literature and a risk estimate on JSTOR .

JECFA (Joint FAO/WHO Expert Committee on Food Additives) (2011). Evaluation of Certain Food Additives and Contaminants. WHO Technical Report Series, 960. Available at: Evaluation of certain food additives and contaminants: seventy-third report of the Joint FAO/WHO Expert Committee on Food Additives.

JECFA (Joint FAO/WHO Expert Committee on Food Additives) (2021). An Overview of JECFA 91^st Evaluation on Cadmium. Available at: PowerPoint Presentation (fao.org).

Julin, B., Wolk, A., Bergkvist, L., Bottai, M., Åkesson, A. (2012). Dietary Cadmium Exposure and Risk of Postmenopausal Breast Cancer: A Population-Based Prospective Cohort Study. Cancer Res. 72(6): 1459-66. Available at: Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study - PubMed (nih.gov).

Kazantzis, G. (2004). Cadmium, Osteoporosis and Calcium Metabolism. Biomaterials, 17(5): 493-8. Available at: Cadmium, osteoporosis and calcium metabolism - PubMed (nih.gov).

Khan, M.A., Khan, S., Khan, A., Alam, M. (2017). Soil Contamination with Cadmium, Consequences and Remediation Using Organic Amendments. Science of The Total Environment 601-602: 1591-1605.  Available at: Soil contamination with cadmium, consequences and remediation using organic amendments - PubMed (nih.gov).

Kippler, M., Ekström, E., Lönnerdal, B., Goessler, W., Åkesson, A., El Arifeen, S., Persson, L., Vahter, M. (2007). Influence of Iron and Zinc Status on Cadmium Accumulation in Bangladeshi Women. Toxicology and Applied Pharmacology,22(2): 221-226. Available at: Influence of iron and zinc status on cadmium accumulation in Bangladeshi women - ScienceDirect.

Kippler, M., Ekström, K., Mlakar, S.J., Bottai, M., Ahmend, S., Hossain, M.B., Raqib, R., Vahter, M., Broberg, K. (2013). Sex-Specific Effects of Early Life Cadmium Exposure on DNA Methylation and Implications for Birth Weight. Epigenetics, 8(5): 494-503. Available at: Sex-specific effects of early life cadmium exposure on DNA methylation and implications for birth we (tandfonline.com).

Kippler, M., Tofail, F., Gardner, R., Rahman, A., Hamadani, J.D., Bottai, M., Vahter, M. (2012). Maternal Cadmium Exposure During Pregnancy and Size at Birth: A Prospective Cohort Study. Environmental Health Perspectives, 120(2): 284-289. Available at: Maternal cadmium exposure during pregnancy and size at birth: a prospective cohort study - PubMed (nih.gov).

Kolonel, (1967). Association of Cadmium with Renal Cancer. Cancer, 37:1782-1787. Available at: Association of cadmium with renal cancer (wiley.com).

Kosanovic, M., Jokanovic, M., Jevremovic, M., Dobric, S., Bokonjic, D. (2002). Maternal and Fetal Cadmium and Selenium Status in Normotensive and Hypertensive Pregnancy. Biological Trace Element Research, 89: 97-103. Available at: Maternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancy - PubMed (nih.gov).

Krajnc, E.I., Van Gestel, C.A.M., Mulder, H.C.M. (1987). Integrated criteria document. Cadmium-Effects. Appendix. National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands (Report no. 758476004).

Lane,W., & Morel, F.M. (2000). A Biological Function For Cadmium in Marine Diatoms. Proc. Nat. Acad. Sci. 97: 4627-4631. Available at: A biological function for cadmium in marine diatoms - PMC (nih.gov).

Lauwerys, R., Amery, A., Bernard, A>, Bruaux, P., Buchet, J., Claeys, F., De Plaen, P., Ducoffre, G., Fagard, R., Lijnen, P., Nick, L., Roles, H., Rondia, D., Saint-Remy, A., Sartor, F., Staessen, J.  (1990). Health Effects of Environmental Exposure to Cadmium: Objectives, Design and Organization of the Cadmibel Study: A Cross-Sectional Morbidity Study Carried Out in Belgium from 1985 to 1989. Environmental Health Perspectives, 87: 283-289. Available at: A biological function for cadmium in marine diatoms - PMC (nih.gov).  

Liu,T., Zhang, M., Guallar, E., Wang, G., Hong, X., Wang, X., Mueller, N.T. (2019). Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort. Journal of the American Heart Association, 20;8(16). Available at: Trace Minerals, Heavy Metals, and Preeclampsia: Findings from the Boston Birth Cohort - PubMed (nih.gov). 

Menai, M., Heude, B., Slama, R., Forhan, A., Sahuquillo, J., Charles, M., Yazbeck, C. (2012). Association Between Maternal Blood Cadmium During Pregnancy and Birth Weight and the Risk of Fetal Growth Restriction: The EDEN Mother-Child Cohort Study. Reproductive Toxicology, 34: 622-627. Available at: Association between maternal blood cadmium during pregnancy and birth weight and the risk of fetal growth restriction: the EDEN mother-child cohort study - PubMed (nih.gov).  

Nair, A.R., DeGheselle, O., Smeets, K., Van Kerkhove, E., Cuypers, A. (2013). Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)? Int. J. Mol. Sci.14: 6116-6143. Available at: Cadmium-Induced Pathologies: Where Is the Oxidative Balance Lost (or Not)? - PubMed (nih.gov).

Nawrot, T.S., Martens, D.S., Hara, A., Plusquin, M., Vangronsveld, J., Roles, H.A., Staessen, J.A. (2015). Association of Total Cancer and Lung Cancer with Environmental Exposure to Cadmium: The Meta-Analytical Evidence. Cancer Causes & Control, 26: 1281-1288. Available at: Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence - PubMed (nih.gov).

NHS (2020) Have a healthy diet in pregnancy. Available at: Have a healthy diet in pregnancy - NHS (www.nhs.uk).

Nordberg, G.F., Bernard, A., Diamond, G.L., Duffus, J.H., Illing, P., Nordberg, M., Bergdahl, I.A., Jin, T., Skerfving, S. (2018). Risk Assessment of Effects of Cadmium on Humand Health (IUPAC Technical Report). Pure and Applied Chemistry, 90(4): 755-808. Available at: Risk assessment of effects of cadmium on human health (IUPAC Technical Report) (degruyter.com).

Osman, K., Åkesson, A., Berglund, M., Bremme, K., Schütz, A., Ask, K., Vahter, M. (2000). Toxic and Essential Elements in Placentas of Swedish Women. Clinical Biochemistry. 33(2): 131-138. Available at: Toxic and essential elements in placentas of swedish women - ScienceDirect.

Osorio-Yañez, C., Gelaye, B., Miller, R.S., Enquobahrie, D.A., Baccarelli, A.A., Qiu, C., Williams, M.A. (2016). Associations of Maternal Urinary Cadmium with Trimester-Specific Blood Pressure in Pregnancy: Role of Dietary Intake of Micronutrients. Biol Trace Elem Res. 174(1): 71-81. Available at: Associations of Maternal Urinary Cadmium with Trimester-Specific Blood Pressure in Pregnancy: Role of Dietary Intake of Micronutrients - PMC (nih.gov).

Pohanish, R.P. 2017. Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens, Seventh Edition. William Andrew, Oxford, Oxfordshire, UK.

Rawlins, B.G., McGrath, S.P., Scheib, A.J., Breward, N., Cave, M., Lister, T.R., Ingham, M., Gowing, C., Carter, S. (2012). The Advanced Soil Geochemical Atlas of England and Wales. Available at: Advanced_Soil_Geochemical_Atlas_of_England_and_Wales.pdf (nerc.ac.uk).

Reeves, P.G., & Chaney, R.L. (2008). Bioavailability as an Issue in Risk Assessment and Management of Food Cadmium: A Review. Science of the Total Environment. 398: 13-19. Available at: Bioavailability as an issue in risk assessment and management of food cadmium: A review - ScienceDirect.

Roberts, C.; Steer, T.; Maplethorpe, N.; Cox, L.; Meadows, S.; Page, P.; Nicholson, S.; Swan, G. (2018) National Diet and Nutrition Survey Results from Years 7 and 8 (combined) of the Rolling Programme (2014/2015 – 2015/2016) Available at: National Diet and Nutrition Survey (publishing.service.gov.uk).

Roels, H., Hubermont, G., Buchet, J.P., Lauwerys, R. (1978). Placental Transfer of Lead, Mercury, Cadmium, and Carbon Monoxide. Environmental Research. 16: 236-247. Available at: Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. III. Factors influencing the accumulation of heavy metals in the placenta and the relationship between metal concentration in the placenta and in maternal and cord blood - PubMed (nih.gov).

Romano, M.E., Enquobahrie, D.A., Simpson, C., Checkoway, H., Williams, M.A. (2016). Maternal Body Burden of Cadmium and Offspring Size at Birth. Environmental Research. 147: 461-468. Available at: Maternal body burden of cadmium and offspring size at birth - ScienceDirect.

SACN (2011) The influence of maternal, fetal and child nutrition on the development of chronic disease later in life. Available at: SACN_Early_Life_Nutrition_Report.pdf (publishing.service.gov.uk).

SACN (2018) Feeding in the first year of life. Available at: SACN_report_on_Feeding_in_the_First_Year_of_Life.pdf (publishing.service.gov.uk).

Satarug, S., Vesey, D.A., Gobe, G.C. (2017). Current Health Risk Assessment Practice for Dietary Cadmium: Data from Different Countries. Food and Chemical Toxicology, 106: 430-445. Available at: Current health risk assessment practice for dietary cadmium: Data from different countries - PubMed (nih.gov).

Scientific Committee on Occupational Exposure Limits (SCOEL). SCOEL/OPIN/336 Cadmium and its inorganic compounds. Available at: SCOEL/OPIN/336 cadmium and its inorganic compounds - Publications Office of the EU (europa.eu).

Shah-Kulkarni, S., Lee, S., Jeong, K.S., Hong, Y., Park, H., Ha, M., Kim, Y., Ha, E. (2020). Prenatal Exposure to Mixtures of Heavy Metals and Neurodevelopment in Infants at 6 Months. Environmental Research, 182: 109122. Available at: Prenatal exposure to mixtures of heavy metals and neurodevelopment in infants at 6 months - ScienceDirect.

Simmons, R.W., Pongsakul, P., Saiyasitpanich, D., Klinphoklap, S. (2005). Elevated Levels of Cadmium and Zinc in Paddy Soils and Elevated Levels of Cadmium in Rice Grain Downstream of a Zinc Mineralized Area in Thailand: Implications for Public Health. Environ Geochem Health, 27 (5-6): 501-11. Available at: Elevated levels of cadmium and zinc in paddy soils and elevated levels of cadmium in rice grain downstream of a zinc mineralized area in Thailand: implications for public health - PubMed (nih.gov).

Srivastava, N., Spielman, S. J., Morrison, S. M., Moore, E. K. (2020). Geological Factors Impacted Cadmium Availability and Use as an Alternative Cofactor for Zinc in the Carbon Fixation Pathways of Marine Diatoms. School of Earth & Environment Faculty Scholarship. 47. Available at: Geological Factors Impacted Cadmium Availability and Use as an Alternative Cofactor for Zinc in the Carbon Fixation Pathways of Marine Diatoms. School of Earth & Environment Faculty Scholarship.

Stone, J., Sutrave, P., Gascoigne, E., Givens, M.B., Fry, R.C., Manuck, T.A. (2021). Exposure to Toxic Metals and Per- and Polyfluorolkyl Substances and the Risk of Preeclampsia and Preterm Birth in the United States: A Review.  Amer J Obstet Gynecol MFM, 3: 100308. Available at: Exposure to toxic metals and per- and polyfluoroalkyl substances and the risk of preeclampsia and preterm birth in the United States: a review - PubMed (nih.gov).

Thevenod, F. (2009). Cadmium and Cellular Signaling Cascades: To Be or Not To Be? Toxicology and Applied Pharmacology, 238: 221-239. Available at: Cadmium and cellular signaling cascades: to be or not to be? - PubMed (nih.gov).  

Thirumoorthy, N., Sunder, A. S., Kumar, K.T.M., Kumar, M.S., Ganesh, G.N.K., and Chatterjee, M. (2011). A Review of Metallothionein Isoforms and their Role in Pathophysiology. World Journal of Surgical Oncology, 9: 54. Available at: A Review of Metallothionein Isoforms and their Role in Pathophysiology - PMC (nih.gov).

Thompson, J. and Bannigan, J. (2008). Cadmium: Toxic effects on the reproductive system and the embryo. Reproductive Toxicology, 25: 304-315. Available at: Cadmium: toxic effects on the reproductive system and the embryo - PubMed (nih.gov).  

Tung, P.W., Burt, A., Karagas, M., Jackson, B.P., Punshon, T., Lester, B., Marsit, C.J. (2022). Association Between Placental Toxic Metal Exposure and NICU Network Neurobehavioral Scales (NNNS) Profiles in the Rhode Island Child Health Study (RICHS). Environmental Research, 204: 111939. Available at: Association between placental toxic metal exposure and NICU Network Neurobehavioral Scales (NNNS) profiles in the Rhode Island Child Health Study (RICHS) - ScienceDirect.

Umemura, T., and Wako, Y. (2006). Pathogenesis of Osteomalacia in Itai-Itai Disease. J Toxicol Pathol: 69-74. Available at: en (jst.go.jp).

Unsal, V., Dalkiran, T., Çiçek, M., Kölükçü, E. (2020). The Role of Natural Antioxidants Against Reactive Oxygen Species Produced by Cadmium Toxicity: A Review. Adv Pharm Bull, 10(2): 184-202. Available at:  The Role of Natural Antioxidants Against Reactive Oxygen Species Produced by Cadmium Toxicity: A Review (nih.gov).

Vahter, M., Åkesson, A., Lidén, C. (2002). Metals and Women’s Health. Environmental Research, 88(3): 145-155. Available at: Metals and women's health - PubMed (nih.gov).

WHO (2000). Chapter 6.3 Cadmium. Air Quality Guidelines – Second Edition. WHO Regional Office for Europe, Copenhagen, Denmark. Available at : Microsoft Word - 6.3-Cadmium.doc (who.int).

WHO (2011). Cadmium in Drinking Water. WHO/SDE/WSH/03.04/80/Rev/1. Available at: Microsoft Word - Fourth Edition Cadmium final 14 June 2011.doc (who.int).

WHO (2017). Guidelines for Drinking-Water Quality, 4^th Edition, Incorporating the 1^st Addendum. Available at: Guidelines for drinking-water quality, 4th edition, incorporating the 1st addendum (who.int).

Yang, H., & Shu, Y. (2015). Cadmium Transporters in the Kidney and Cadmium-Induced Nephrotoxicity. Int. J. Mol. Sci. 16: 1484-1494. Available at: Microsoft Word - ijms-66989-for publish (nih.gov).

Yoshida M, Ohta H, Yamauchi Y, seki Y. (1993). Age dependent changes in metallothionein levels in liver and kidney of the Japanese. Biological Trace Element Research 63: 167 – 175.

Zhang, M., Luo, J., Zhang, C., Cao, H., Xia, B., Hu, G. (2017). Alterations in Antioxidant Function and Cell Apoptosis in Duck Spleen Exposed to Molybdenum and/or Cadmium. J Vet Sci, 18(2): 193-200. Available at: Alterations in antioxidant function and cell apoptosis in duck spleen exposed to molybdenum and/or cadmium - PubMed (nih.gov).

An analysis of the ethnicity and vegetarian status of all consumers of bread, miscellaneous cereals and potatoes exposed to cadmium was carried out. The results were compared with high consumers (above the mean and  97.5^th percentile exposure) (Tables 1, 2 and 3).

Table B1. Ethnicity and vegetarian status of women exposed to cadmium from bread.

Table B2. Ethnicity and vegetarian status of women exposed to cadmium from miscellaneous cereals

Table B3. Ethnicity and vegetarian status of women exposed to cadmium from potatoes.