Transparency data

TOX/2026/21 Draft Supplementary Report on the Effects of Calcidiol in the Maternal Diet

Published 25 June 2026

This is a paper for discussion. This does not represent the views of the Committee and should not be cited.

Introduction

1. In 2019, the Scientific Advisory Committee on Nutrition (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 such as COT would be consulted to carry out relevant risk assessments. Following publication of the 2022 Statement on the potential effects of excess vitamin D intake during preconception, pregnancy and lactation, SACN asked COT to also review the risks of alcidiol supplementation in the maternal diet. This was on the basis that alcidiol is a more bioavailable form of vitamin D2 and D3 and its availability on the market is increasing.

3. The Committee was subsequently presented with a discussion paper on alcidiol supplementation during preconception, pregnancy and lactation in May 2025( calcidiol supplementation during preconception, pregnancy and lactation TOX/2025/21). It concluded that there was no substantive difference between EFSA and ACNFP advice, with both identifying a safe intake level of 10 µg/day, and ACNFP additionally proposing a conservative upper intake level of 40 µg/day to account for potential misuse. Members agreed that estimated intakes did not reach levels of toxicological concern and were therefore not considered a risk (Draft Minutes of the 20th May 2025 COT Meeting). However, a number of limitations were noted, including that women during preconception, pregnancy and lactation are underrepresented in the evidence base, and further clarification and revisions were requested.

4. Members also raised several methodological and presentational issues. These included ensuring consistent reporting of dose units, providing the duration of all human studies cited, and clearly setting out the limitations of key studies (for example where data were unpublished or based on limited clinical observations).

5. In relation to exposure assessment, Members agreed with the overall conclusion that exposures were below levels of concern. However, they asked whether the assessment should include all forms of vitamin D to better reflect total intake, and whether scenarios could consider NHS dietary advice for pregnant women. Following discussion between the Secretariat, Chair and Deputy Chair, it was agreed that the assessment should remain focused on orally consumed alcidiol, as requested by SACN. While the implications of following NHS advice on exposure was considered, it was not taken forward, as many recommendations cannot be reflected in the available NDNS data (for example cooking practices, portion limits or product-specific distinctions). In addition, modifying or removing food groups could introduce bias and additional uncertainty without significantly affecting exposure estimates, particularly as dietary sources contribute only a small proportion of overall alcidiol exposure compared with supplements. It was therefore considered unlikely that such refinements would change the overall conclusions.

6. Following an auxiliary meeting with the COT Chair, Secretariat and rapporteurs, it was agreed that a position statement, supported by a supplementary report, should be developed. These documents would summarise the Committee’s conclusions and provide a clear account of the evidence base and key data gaps.

7. The draft position statement sets out the Committee’s overall conclusions on alcidiol and vitamin D in the maternal diet, drawing on previous COT outputs and the 2024 ACNFP assessment. It is intended to provide a concise, standalone summary of the Committees current position on the effects of alcidiol and vitamin D, including key considerations on risk, exposure and data gaps.

8. The supplementary report supports the position statement by setting out the underlying evidence on alcidiol. It provides a more detailed assessment of toxicology, exposure and risk characterisation, including human and animal data, derivation of health-based guidance values, and a summary of uncertainties.

9. Members are asked to consider both documents together. In particular, views are sought on whether the position statement accurately reflects the Committee’s conclusions, and whether the supplementary report provides sufficient supporting detail.

10. The supplementary report (Annex A) has been prepared incorporating Members’ comments and suggested revisions.

Questions on which the views of the Committee are sought

a) Are Members content with the content and structure of the supplementary report?

Secretariat

May 2026

TOX/2026/21 Annex A

Introduction

1. This paper is a supplementary report to the position statement and specifically addresses the effects of alcidiol supplementation in women during preconception, pregnancy and lactation. It summarises the key messages from the discussion paper on alcidiol in the maternal diet that was presented to the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) in 2025, with a particular focus on addressing identified data gaps (COT, 2025).

2. Previously, as part of the Scientific Advisory Committee on Nutrition (SACN) risk assessment on nutrition and maternal health, the COT reviewed vitamin D and whether excess exposure would pose a risk to maternal health (COT., 2022). Following publication of the Statement on the potential effects of excess vitamin D intake during preconception, pregnancy and lactation a request from SACN was made for the COT to also consider whether excess exposure to a vitamin D derivative called calcidiol may also pose a risk to maternal health. The request was made by SACN on the basis that calcidiol is a more potent form of vitamin D2 (ergocalciferol) and D3 (cholecalciferol), and its availability is increasing on the market.

3. The Committee has previously discussed calcidiol in the maternal diet (COT, 2025), during which the apparent discrepancy between levels reported as safe by EFSA (EFSA, 2021) and by ACNFP was clarified as a misinterpretation of the ACNFP Safety Assessment “Calcidiol (25‑hydroxycholecalciferol monohydrate) as a novel food for use in food supplements” (ACNFP, 2024). Following an auxiliary meeting involving the COT Chair, Secretariat and rapporteurs for the calcidiol discussion paper, it was agreed that a position statement signposting relevant previous work on vitamin D and calcidiol would be produced. This would be accompanied by a supplementary report providing an overview of calcidiol in the maternal diet, summarising the evidence on effects and risks, and highlighting data gaps.

Background

4. Calcidiol is a naturally occurring metabolite of vitamin D. It is an inactive precursor to the biologically active hormone 1,25-dihydroxyvitamin D (1,25(OH)2D) (Vieth, 2020). In the context of supplementation, however, alcidiol is considered a novel source of vitamin D3 (ACNFP, 2024). The supplemental form is chemically synthesised from cholestatrienol and is identical to endogenous 25-hydroxyvitamin D (25(OH)D) (Vieth, 2020; ACNFP, 2024). Calcidiol is marketed under several names, including alcidiol monohydrate, 25-hydroxycholecalciferol monohydrate (25(OH)D3 monohydrate) (EFSA, 2023), calcifediol or 25(OH)D; the latter two terms are most used in the context of supplementation (Biondi et al., 2017).

5. Calcidiol is generally assumed to be approximately 2.5 times more bioavailable than cholecalciferol (vitamin D3) (EFSA, 2023; ACNFP, 2024). Compared with cholecalciferol, calcidiol is more hydrophilic and has a shorter half-life (Navarro-valverde et al., 2016; Henríquez and Gómez de Tejada Romero, 2020; Donati et al., 2023). Supplementation with calcidiol results in a more rapid increase in circulating serum 25(OH)D levels (Navarro-Valverde et al., 2016; Maghbooli et al., 2021). This effect is attributed to differences in absorption and metabolism. Unlike vitamin D3, calcidiol does not require bile acids for intestinal absorption nor hepatic 25-hydroxylation, leading to faster and more efficient entry into the systemic circulation (EFSA, 2022).

6. Consistent with its higher bioavailability, alcidiol has been reported to be more effective than vitamin D3 at increasing serum 25(OH)D levels, such that lower doses are required to achieve equivalent circulating levels (Vieth., 2020; Pereda and Nishishinya., 2022; Stamp et al., 1977). However, the COT does not consider alcidiol to be intrinsically more potent than vitamin D3 as neither are the active form of vitamin D (i.e. 1,25(OH)2D). However, the COT does recognise that alcidiol’s greater bioavailability, means that an equivalent oral dose can result in higher serum 25(OH)D concentrations compared with vitamin D3 (COT., 2025).

7. In their safety assessment of calcidiol as a novel food for use in food supplements, the ACNFP., (2024) considered whether administration of calcidiol might alter downstream metabolic pathways or interfere with the homeostatic regulation of circulating vitamin D metabolites. Based on data submitted by DSM Nutrition Ltd, the ACNFP concluded that there was no evidence to suggest that supplemental 25‑hydroxycholecalciferol would be metabolised differently from endogenous calcidiol derived from dietary vitamin D or cutaneous synthesis, nor that it would exert wider effects on feedback regulation, related metabolic pathways, or vitamin D homeostasis. Accordingly, the ACNFP concluded that calcidiol is chemically and biologically equivalent to endogenous vitamin D3 metabolites and does not pose a toxicological concern. Nevertheless, the limited amount of published evidence directly examining whether calcidiol supplementation disrupts normal regulation of vitamin D metabolism is identified as an area of uncertainty in this supplementary report.

Toxicity

Human studies

8. The existing toxicological data set for calcidiol during pre-conception, pregnancy and lactation is limited and the population of interest being assessed (i.e., pregnant and lactating women) are currently underrepresented.

9. To date there are no published human studies on the safety of calcidiol during preconception, pregnancy and lactation. Most of the clinical trials published are in individuals with vitamin D deficiency (defined as serum 25(OH)D levels being <30 ng/mL by various study authors), and in post-menopausal women (Quesada-Gomez, et al., 2023). This is due to calcidiol’s higher bioavailability (ACNFP, 2024) than vitamin D and potential treatment for vitamin D deficiency (Quesada-Gomez, et al., 2023). However, there are some clinical trials that have included women of child-bearing age and are discussed in the “Human studies in women of childbearing age” section of this report. Although these studies were not designed to assess outcomes in women during preconception, pregnancy or lactation, they provide useful information on dosing, pharmacokinetics and safety in a relevant population, which may help inform considerations regarding potential risks in maternal exposure in the absence of targeted data.

10 Studies conducted on groups outside the population of interest were presented to the COT in the calcidiol discussion paper (COT, 2025); however, it was concluded that they fell outside the scope of the present work. For completeness a summary of these studies is provided.

Human studies outside the population of interest

11. Evidence on the safety of calcidiol from human studies excluding women of childbearing age is limited but broadly consistent across a range of adult groups, including postmenopausal women, older men, and vitamin D–deficient individuals. Collectively, these studies indicate that calcidiol administration at low to moderate doses results in predictable increases in serum 25(OH)D concentrations, generally within predefined safety ranges, with few reports of clinically relevant adverse outcomes. Across studies, hypercalcaemia was not observed, and markers of calcium and phosphate homeostasis typically remained within normal reference ranges (COT., 2025).

12. Short- to medium-term randomised controlled trials (ranging from approximately 10 weeks to 6 months) administering daily doses between 5 and 60 µg/day, or equivalent weekly or monthly bolus regimens, consistently reported good tolerability (Bischoff-Ferrari et al., 2012; Cashman et al., 2012; Gonnelli et al., 2021; Graeff-Armas et al., 2020; Jetter et al., 2014; Minisola et al., 2017; Vaes et al., 2018). Adverse events, where reported, were infrequent, mild to moderate in severity (e.g., gastrointestinal symptoms or headache), and rarely considered treatment related. In several studies designed primarily to assess efficacy or pharmacokinetics rather than safety, serum calcium, urinary calcium excretion, creatinine, parathyroid hormone (PTH) and bone turnover markers showed no clinically significant changes (Bischoff-Ferrari et al., 2012; Cashman et al., 2012; Minisola et al., 2017; Occhiuto et. al., 2024; Gonnelli et al., 2021; Graeff-Armas et al., 2020). Increases in 25(OH)D concentrations tended to plateau with ongoing exposure, suggesting a degree of homeostatic regulation during continued supplementation.

13. Longer-term data (up to 12 months and, in one study, 2 years) in postmenopausal or clinically defined populations (e.g., osteoporosis or vitamin D deficiency) similarly reported no substantive safety concerns with dosing regiments equivalent to repeated monthly calcidiol 0.266 mg administration (Navarro Valverde et al., 2016; Pérez‐Castrillón et al., 2020; Occhiuto et. al., 2024). Observed serum 25(OH)D concentrations generally remained below thresholds associated with vitamin D toxicity. Only isolated cases of borderline hypercalciuria or transient elevations in 25(OH)D were reported, without clinical consequences. The EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) has previously considered that concentrations > 200 nmol/L (equivalent to 80 ng/mL) are unlikely to pose a risk of adverse health outcomes such as hypercalciuria, hypercalcaemia or nephrocalcinosis (EFSA., 2021); however, serum 25(OH)D is an exposure biomarker and is not used diagnostically to define vitamin D toxicity or adverse health outcomes.

14. Overall, although these studies do not address the population of interest (i.e., women during preconception, pregnancy and lactation), they provide supportive evidence suggesting that calcidiol is generally well tolerated in adult populations at commonly studied doses. However, the relevance of these findings to maternal and infant health is limited by differences in physiological status, dosing regimens, and study objectives, and therefore these data are included for completeness rather than to inform risk characterisation in the population of interest.

Human studies in women of childbearing age

15. In a phase I clinical trial that assessed the safety and efficacy of calcidiol in 101 participants, of whom 65 % were women, with a mean age of 29.8 years. Participants in the treatment group received calcidiol over a 4-month period, administered either monthly or every two weeks depending on their vitamin D deficiency. Participants with mild to moderate deficiency (defined as serum 25(OH)D of 10 to <20 ng/mL by study authors) received 0.266 mg calcidiol monthly (as soft capsules). Participants with severe deficiency (defined as serum 25(OH)D of <10 ng/mL) received 0.266 mg calcidiol every 2 weeks (Guerra López et al., 2024).

16. Safety results indicated that only one participant developed plasma 25(OH)D concentrations exceeding 60 ng/mL whose levels returned to approximately 10 ng/mL following discontinuation of calcidiol treatment. A total of 66 adverse events were reported by approximately one‑third of the study population (n = 36/101). Of these, nine adverse events were considered potentially related to treatment and were reported by 5 % of participants receiving monthly calcidiol. These events were of mild or moderate severity and included headache, non‑clinically relevant increases in parathyroid hormone (PTH), nausea, abdominal discomfort, decreased appetite and diarrhoea. Bone metabolism parameters, including serum calcium, PTH, phosphate, albumin and alkaline phosphatase (ALP), were monitored. Statistically significant differences were observed only for serum calcium and albumin, and only in the monthly calcidiol group when comparing baseline values with those at month 4. These changes were not associated with any clinically relevant impact on health status (Guerra López et al., 2024).

17. One case of pregnancy was reported in the placebo group at the end of the treatment period. Due to the participant’s vitamin D deficiency (serum 25(OH)D <15 ng/mL), calcidiol was prescribed by her obstetrician outside the study setting at a dose of 0.266 mg/month for 54 days. The study authors reported a normal delivery with no maternal or neonatal complications. Overall, the authors concluded that calcidiol was safe at the doses evaluated in this study (Guerra López et al., 2024).

18. No safety concerns were reported in a 16‑week randomised controlled trial involving 35 adults (aged ≥18 years) with vitamin D deficiency (defined as serum 25(OH)D ≤20 ng/mL) (Shieh et al., 2017). Participants received either vitamin D3 at 60 µg/day or calcidiol at 20 µg/day. Although both sexes were included, the distribution by sex was not reported. Serum calcium and urinary calcium excretion were selected as safety parameters, and no significant changes from baseline were observed. There were no reported cases of hypercalcaemia, hypercalciuria or nephrolithiasis. Serum PTH concentrations did not decrease significantly in either treatment group, which the authors attributed to low baseline PTH concentrations (40.1 ± 18.6 pg/mL (vitamin D3 group) vs 34.6 ± 13.9 pg/mL (calcidiol group)). Participants were asked about adverse events; however, details regarding the frequency and severity of these events were not reported (Shieh et al., 2017). It should be noted that participants in both this study and that of Guerra López et al. (2024) were vitamin D deficient at baseline, and responses may differ in individuals with adequate 25(OH)D status.

19. A study by Russo et al., (2011) investigated changes in serum 25(OH)D concentrations and calcium metabolism following calcidiol administration in 18 apparently healthy women aged 24–72 years, of whom 7 were premenopausal and 11 postmenopausal. Participants received oral calcidiol at a dose of 500 µg/month for 4 months. Although this study was not designed as a safety study, it is noteworthy due to its inclusion of apparently healthy women of childbearing age, none of whom had previously used vitamin D supplements or had acute or chronic conditions known to affect mineral metabolism or cause immobilisation. No safety concerns were reported (Russo et al., 2011).

20. Serum 25(OH)D concentrations increased significantly from baseline up to day 120 (P<0.001). However, increases followed a non‑linear pattern, and the change observed on day 3 was not statistically significant. Statistically significant increases in serum 1,25(OH)2D concentrations were also reported (P<0.05 and P<0.001), although these increases were marginal and non‑significant at days 60 and 120.

21. Statistically significant reductions in serum PTH concentrations compared with baseline were reported (P<0.001), consistent with the authors’ assertion that low 25(OH)D concentrations may result in compensatory increases in PTH.

22. The study authors reported no significant changes in serum calcium or phosphorus concentrations. A slight, asymptomatic increase in ionised calcium (1.35 mmol/L; upper limit of normal 1.33 mmol/L) was observed in one participant at days 20 and 60 (Russo et al., 2011).

23. Serum ALP, a biochemical marker of bone remodelling, was reported to decrease significantly from baseline at day 30. Urinary calcium and creatinine were assessed in 14 participants (including two premenopausal women) due to patient preference. Study authors reported that seven measurements slightly exceeded the upper limit of 4 mg/kg body weight, although individual values were not reported.

24. Study outcomes were not influenced by menopausal status. The study authors described the findings as “reassuring in terms of safety”, as increases in serum and urinary calcium were transient, inconsistent and not associated with reported adverse effects. The maximum observed serum 25(OH)D concentration was 81.6 ng/mL, which the authors stated was well below levels considered toxic. However, the authors emphasised that results should be regarded as preliminary due to the small sample size and limited duration of exposure and reiterated that the study was not designed to evaluate safety outcomes (Russo et al., 2011).

Animal studies

25. The following sub-chronic toxicity data obtained from primary research publications were also submitted to the ACNFP by DSM Nutritional Products Ltd in support of their application for calcidiol as a novel food for use in food supplements (ACNFP., 2024). It should be noted that these studies are proprietary and have not been published.

26. In a 14-day study, male rats were orally administered vitamin D3 at doses at 10-fold intervals from 0.65 - 6,500 nmol or calcidiol in Wesson oil at doses of 0.46 - 4,600 nmol/day. The average daily doses were estimated to be 2.3 - 22,750 µg/kg bw/day for vitamin D3 and 1.7 - 16,770 µg/kg bw/day, for calcidiol. Study authors reported “signs of excessive intake of vitamin D3” were observed at doses of vitamin D3 at 2,275 and 22,750 µg/kg bw/day and calcidiol at 16,770 µg/kg bw/day (Shepard and DeLuca, 1980). Death occurred in 9/10 rats administered vitamin D3 at 22,750 µg/kg bw/day. Other adverse effects included reduced plasma phosphorus concentrations, hypercalcaemia and greyish-white mottling of the kidneys (consistent with calcification) at doses of vitamin D3 at 2,275 µg/kg bw/day and calcidiol at 16,770 µg/kg bw/day (ACNFP., 2024 citing Shepard and DeLuca., 1980).

27. In a 90-day study conducted in line with OECD TG No. 408, male and female rats received oral doses of calcidiol equivalent to 0, 7, 20, 60 and 180 µg/kg bw/day in a powdered formulation. The formulation also contained antioxidant excipients of which many have biologically active potential which was not excluded given the absence of an excipient control. Mineralisation of the renal pelvis was observed in both sexes at doses of calcidiol of 20 µg/kg bw/day and above, and more specifically, 7 µg/kg bw/day in females. However, study authors did not consider this effect as adverse due to the absence of clinical chemistry findings indicating kidney dysfunction. Study authors therefore proposed an equivalent No Observed Adverse Effect Level (NOAEL) of calcidiol of 180 µg/kg bw/day (ACNFP, 2024 citing Thiel et al., 2007).

28. Further analysis of the histopathological findings from this study by Hard, (2014) concluded that mineralisation is more common in rats than any other species of laboratory animals. Also, the pattern of mineralisation observed is inconsistent with that of hypercalcaemia due to excess vitamin D3. Hard, (2014) attributed this inconsistency to the hygroscopic nature of the test substance and possibly the nature of excipients used in the study whose effects could not be excluded because of the lack of an excipient control in this study (ACNFP, 2024 citing Hard, 2014).

29. Based on the reported findings by Thiel et al., (2007), the ACNFP stated that “the mineralisation observed indicates disruption of kidney function at all doses in female rats and in all but the lowest dose in males. It is not, therefore, possible to derive a NOAEL from this study. If the lowest dose used, 7 μg/kg bw/day, which caused renal mineralisation in female rats only, is taken as a Lowest Observed Adverse Effect Level (LOAEL) this yields a margin of safety of 49 for a 70 kg adult ingesting 25-hydroxycholecalciferol at a dose of 10 mg/day or 21 for a 15 kg child taking 5 mg/day”. Ultimately, the ACNFP concluded that “given the human safety data provided, this provides sufficient reassurance for the use of 25-hydroxycholecalciferol at the proposed doses in humans” (ACNFP, 2024).

Genotoxicity

30. The ACNFP reported the genotoxicity data submitted by the applicant (DSM Nutritional Products Ltd) in their assessment on the safety of calcidiol as a novel food for use in food supplements. This included reverse mutation assays, in vitro mutagenicity tests, in vitro chromosome aberration tests and an in vivo micronucleus test, in line with OECD test guidelines No. 471, 490, 473 and 474 respectively.

31. The same studies were also assessed by EFSA in their opinion on the “Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU)2015/2283”. Based on these genotoxicity studies EFSA and the ACNFP concluded that calcidiol as a novel food was of no concern regarding genotoxicity (EFSA, 2021; ACNFP 2024).

Health based guidance values

32. For vitamin D, EFSA established a tolerable upper intake level (TUL) of 100 µg vitamin D/day, for adults (including pregnant and lactating women) and adolescents aged 11-17 years (EFSA, 2012). The TUL covers all sources of dietary intake. In 2023, EFSA reconfirmed this 100 µg/day TUL but expanded the definition to vitamin D equivalents (VDE) for the same population groups. EFSA proposed a factor of 2.5 for the conversion of calcidiol monohydrate into vitamin D3, for labelling purposes. The conversion factor reflects calcidiol’s greater potency in raising serum 25(OH)D concentrations compared with vitamin D3, at doses up to 10 μg/day (EFSA, 2023).

33. The COT agreed with the TUL for vitamin D and VDE (COT., 2014; 2022; 2025). As discussed in the Statement on the potential effects of excess vitamin D intake during preconception, pregnancy and lactation, the COT noted that the TUL may not cover individuals who may be more vulnerable to adverse effects of vitamin D such as those with specific genetic predispositions (COT., 2022).

34. In EFSA’s scientific and technical assistance to the evaluation of the safety of calcidiol monohydrate as a novel food, EFSA concluded that safety had been established up to an intake of 10 µg/day for adolescents and adults, including pregnant and lactating women (EFSA., 2021). EFSA noted that this intake corresponds to 25 µg VDE/day when applying the proposed conversion factor of 2.5 for calcidiol monohydrate to vitamin D3 (EFSA., 2024).

35. EFSA based its conclusion on the safety of calcidiol monohydrate, under the proposed conditions of use and at intakes up to 10 µg/day, on the following considerations for adolescents and adults (including pregnant and lactating women) (EFSA., 2024):

I) “calcidiol monohydrate did not raise serum 25(OH)D concentrations above 107 nmol/L and did not increase the risk of hypercalcaemia, hypercalciuria or other adverse health effects at doses up to 10 μg/day in RCTs. The duration of the intervention ranged from 4 weeks to 12 months, depending on the study; and

II) conservative, total combined vitamin D intake estimates from calcidiol (NF + background diet) and vitamin D (highest P95) from the background diet (up to 70.2 and 78.5 μg/day for adolescents and adults, respectively) were well below the UL for adolescents and adults, including pregnant and lactating women (100 μg/day)”

36. The ACNFP agreed with EFSA’s conclusion that an intake of 10 µg/day of calcidiol monohydrate is safe. In addition, the ACNFP established an adjusted upper intake level of 40 µg/day for adults by applying the 2.5 conversion factor to the vitamin D TUL of 100 µg/day. This adjusted upper intake level was intended to account for foreseeable consumer misuse, given that calcidiol-containing products may be available over the counter and used without medical supervision (ACNFP, 2024). The COT agreed with both the level of calcidiol intake established as safe (10 µg/day) and the adjusted upper intake level of 40 µg/day (includes lactating and pregnant women).

Exposure

37. An exposure assessment was conducted for women of childbearing age in the UK which considered all dietary sources of calcidiol including foods and supplements. This was presented to the COT within the discussion paper on the effects of calcidiol supplementation during preconception, pregnancy and lactation at the May 2025 COT Meeting (COT, 2025). As this document constitutes a supplementary report, only a summary of the results is presented here; full methodological details and results of the exposure assessment are presented under Annex B and C.

38. Calcidiol, may be present in some foods of animal origin such as milk, butter, eggs, fish, meat and offal in the form of 25-hydroxycholecalciferiol (25(OH)D3) or 25-hydroxyergocalciferol (25(OH)D2). Calcidiol in the form 25(OH)D2 has been reported in whole milk, butter and in some meat and offal (Ovesen et al., 2003; Jakobsen and Saxholt, 2009).

39. Dietary exposure was estimated using consumption data for women of childbearing age (16–49 years) from the National Diet and Nutrition Survey (NDNS; Bates et al., 2014, 2016, 2020; Roberts et al., 2018), as the NDNS does not provide specific consumption data for pregnant or lactating women. Consumption estimates were generated for 11 food groups identified in EFSA’s 2021 opinion, “Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283”.

40. Supplements aimed at adults were identified using online sources which supplied calcidiol in doses ranging from 10 to 20 µg/day. No supplements containing calcidiol were identified that were specifically aimed at pregnant and breast-feeding women.

41. The highest estimated exposure to calcidiol from food sources alone was 1.1 µg/day. When intake from both food sources and calcidiol supplements was considered, the estimated minimum and maximum mean exposures ranged from 10 to 20 µg/day. The corresponding estimated minimum and maximum intakes at the 97.5th percentile were 11 and 21 µg/day, respectively.

Risk characterisation

42. The COT were in agreement with the proposed safe level of intake of 10 µg/day for adults (including lactating and pregnant women) (COT., 2025; EFSA., 2024). The COT were also in agreement with the additional TUL of 40 µg/day proposed by the ACNFP, in order to identify a level of intake that would be safe consumers (including lactating and pregnant women) were to go beyond the proposed intake of 10 µg/day (COT., 2025; ACNFP., 2024).

43. All calcidiol-containing supplements available on the market at the time did not exceed the ACNFP TUL of 40 µg/day. All supplements available on the market were at the level EFSA established as safe (i.e., up to 10 μg/day), with one exception, which exceeded the EFSA safe level by 2-fold.

44. The highest estimated exposures of calcidiol from food sources only, was 1.1 µg/day, which is significantly below the ACNFP TUL of 40 µg/day, and the level EFSA established as safe (i.e., up to 10 μg/day). For food and calcidiol supplements combined, maximum mean exposures of calcidiol exceeded the level EFSA established as safe (i.e., up to 10 μg/day) by 2-fold. The minimum 97.5th percentile intake marginally exceeded the level EFSA established as safe (i.e., up to 10 μg/day), whereas the maximum 97.5th percentile intake exceeded the level EFSA established as safe (i.e., up to 10 μg/day by 2.1-fold. However, all mean and 97.5th percentile chronic intakes of calcidiol from food and supplements combined were below the ACNFP TUL of 40 µg/day.

45. It should also be noted that supplements are likely to be the greatest contributor to calcidiol intake in women of childbearing age, whereas calcidiol intake from the food sources alone is low. Furthermore, not all women of child-bearing age consume supplements. Results from the most recent NDNS (years 9-11) report have shown that between 2016-2019 20 % of female respondents aged 19-64 years consume vitamin D supplements (Bates et al, 2020).

46. The COT concluded that estimated intakes were not reaching threshold levels and therefore were not of risk.

Uncertainties

47. The existing toxicological data set for calcidiol during pre-conception, pregnancy and lactation is limited and the target population being assessed are currently underrepresented. To date there are no published human studies on the safety of calcidiol during preconception, pregnancy and lactation. Most of the clinical trials published are in individuals with vitamin D deficiency (defined as serum 25(OH)D levels being <30 ng/mL by various study authors), and in post-menopausal women (Quesada-Gomez, et al., 2023). Although in their 2024 opinion EFSA acknowledged that bioavailability and safety data were lacking for pregnancy and lactating women but considered “the data available for adults were sufficient to cover these population groups” (EFSA., 2024).

48. There is limited published evidence specifically addressing whether calcidiol supplementation disrupts the normal homeostatic regulation of vitamin D metabolism. Available studies have predominantly focused on pharmacokinetics, serum 25(OH)D concentrations and downstream biomarkers (e.g., PTH), rather than directly evaluating potential effects on endogenous regulatory feedback mechanisms within the vitamin D pathway. Consequently, some uncertainty remains regarding the extent to which exogenous calcidiol supplementation may influence endogenous control processes, particularly under conditions of long-term or higher dose exposure. This evidence gap has previously been considered by the ACNFP., (2024) which concluded that calcidiol does not present a toxicological concern, based on the absence of evidence indicating disruption of normal homeostatic mechanisms. Overall, this uncertainty reflects a limitation in the available evidence base, not identification of adverse effects.

49. Individuals with a loss of function mutation in enzyme CYP24A1 are more likely to have higher circulating levels of calcidiol in their blood as this enzyme is responsible for the breakdown of calcidiol and 1,25(OH)2D (Jones et al., 2012) and are therefore more prone to the effects of excessive calcidiol exposure.

50. An additional uncertainty may include background exposure from UVB radiation. However, exposure to UVB radiation is unlikely to result in adverse serum 25(OH) levels, even when consuming dietary intakes of calcidiol, due to an inbuilt mechanism in the skin. SACN, 2016 stated that “prolonged sunlight exposure does not lead to excess production of cutaneous vitamin D”. This is “because endogenously produced pre-vitamin D3 and vitamin D3 are photolyzed to inert compounds” (SACN, 2016), thus preventing conversion into its primary metabolite; 25(OH)D, (i.e., calcidiol) (ACNFP., 2024; Pérez-López et al., 2015). SACN also stated that “Vitamin D3 is produced endogenously from 7-dehydrocholesterol (7-DHC) in the skin of humans and animals by the action of sunlight containing UVB radiation (wavelength 280- 315 nm) or by artificial UVB light. The 7-DHC in the epidermis is converted to pre-vitamin D3, which reaches a maximum concentration in the skin within a few hours (Holick et al., 1980)” (SACN, 2016). Consequently, the possibility of vitamin D intoxication via UV exposure was not considered further.

51. The NDNS does not specifically include data for pregnant and lactating women, so women of child-bearing age (i.e. 16-49 years) were used as a proxy for these consumer groups in the exposure assessment. There is limited information on how dietary patterns may differ between these groups; consequently, estimated exposures from food sources may be either over‑ or underestimated. However, this uncertainty is not expected to alter the overall conclusions on risk from calcidiol, as exposure from supplements is much greater than that from food.

Conclusions

52. Calcidiol (25‑hydroxyvitamin D (25(OH)D)) is the primary circulating metabolite of vitamin D and the immediate precursor to the biologically active hormone 1,25‑dihydroxyvitamin D, responsible for regulating calcium and phosphate homeostasis. When administered as a supplement, calcidiol is chemically and biologically equivalent to endogenously produced 25(OH)D derived from dietary vitamin D or cutaneous synthesis. Compared with cholecalciferol (vitamin D3), calcidiol is more hydrophilic and does not require hepatic 25‑hydroxylation, resulting in more rapid absorption and a faster rise in circulating serum 25(OH)D concentrations.

53. The principal adverse effects associated with excessive vitamin D or calcidiol exposure arise from sustained elevations in circulating vitamin D metabolites, leading to disruption of calcium homeostasis, notably hypercalcaemia and hypercalciuria, with potential downstream effects on renal function, soft‑tissue calcification and, in severe cases, nephrocalcinosis. Calcidiol is not considered intrinsically more toxic than vitamin D3, as neither represents the biologically active hormone; however, calcidiol’s greater bioavailability means that equivalent oral doses may result in higher serum 25(OH)D concentrations. This characteristic has been explicitly accounted for in the derivation of health‑based guidance values through the application of conversion factors and conservatively derived upper intake levels.

54. In line with the ACNPF and EFSA, the COT agreed with the proposed safe level of intake of 10 µg/day calcidiol for adults (including pregnant and lactating women). The COT were also in agreement with the additional TUL of 40 µg/day proposed by the ACNFP, in order to identify a level of intake that would be safe if consumers were to go beyond the proposed intake of 10 µg/day (including pregnant and lactating women). This was considered a possibility by the ACNFP as the product is available over the counter and would be used without medical supervision. This clarified that there was no difference between the EFSA and ACNFP advice on Tolerable Upper Levels (COT., 2025).

55. The available human evidence indicates that calcidiol supplementation produces predictable, dose‑related increases in circulating serum 25(OH)D concentrations and is generally well tolerated in adult populations at the doses studied. Randomised and controlled studies conducted outside the population of interest (women during preconception, pregnancy and lactation) have administered daily calcidiol doses ranging from approximately 5 to 60 µg/day, as well as intermittent regimens equivalent to monthly doses of 266 µg (equivalent to ~9 µg/day). Across these studies, which typically were at or above the EFSA recommended safe intake level of 10 µg/day, few adverse effects were reported, and clinically relevant disturbances of calcium or phosphate homeostasis were uncommon. Evidence from studies including women of child‑bearing age is more limited but similarly does not identify safety concerns at monthly doses of 266 µg calcidiol, although these studies were not designed to assess safety.

56. The exposure assessment (Annex B) estimates that for women of childbearing age, the highest estimated exposures of calcidiol from food sources only, was 1.1 µg/day, which is significantly below the ACNFP TUL of 40 µg/day and the level EFSA established as safe (i.e., up to 10 μg/day). When considering exposure estimates from food and supplements combined, maximum mean exposures of calcidiol exceeded the level EFSA established as safe (i.e., up to 10 μg/day) by 2-fold. The minimum 97.5th percentile intake marginally exceeded the level EFSA established as safe (i.e., up to 10 μg/day), whereas the maximum 97.5th percentile intake exceeded the level EFSA established as safe by 2.1-fold.  However, all mean and 97.5th percentile chronic intakes of calcidiol from food and supplements combined were below the ACNFP TUL of 40 µg/day. Supplements are the greatest contributor to calcidiol exposure in these population groups. Furthermore, not all women of child-bearing age take supplements, it has been estimated that 20 % of females aged 19-64 years take vitamin D supplements. Overall, the COT conclude that exposure from calcidiol supplements and calcidiol from food sources in healthy pregnant and lactating women are unlikely to result in significant exceedances of the ACNFP TUL and the level EFSA established as safe.

57. Risk cannot be excluded in women who are sensitive to vitamin D toxicity and may develop hypercalcaemia at lower vitamin D intakes than the general population. These sensitive groups include individuals with chronic kidney disease, granulomatous diseases (e.g., sarcoidosis), certain lymphomas, hyperparathyroidism or baseline hypercalcaemia, hypoparathyroidism treated with active vitamin D (1,25(OH)2D), and rare genetic disorders of vitamin D metabolism (e.g., loss‑of‑function mutations in CYP24A1).

58. The COT acknowledged that there are gaps in the toxicological evidence base for calcidiol, most notably the limited availability of data directly relevant to the population of interest. To date, there are no published human studies specifically designed to assess the safety of calcidiol during preconception, pregnancy or lactation. Consequently, risk assessment for these life stages necessarily relies on data from other adult populations and established understanding of vitamin D metabolism, and would benefit from additional relevant data should such information become available in the future.

Questions on which the views of the Committee are sought

a) Are Members content with the content and structure of the supplementary report?

List of Abbreviations and Technical terms

Abbreviations / Technical terms	Definition
1,25(OH)2D	1,25-dihydroxyvitamin D
25(OH)D	25-hydroxyvitamin D
25(OH)D2	25-hydroxyergocalciferol
25(OH)D3	25-hydroxycholecalciferiol
ACNFP	Advisory Committee on Novel Foods and Processes
ALP	Alkaline phosphatase
bw	Bodyweight
COT	Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment
EC	European Commission
EFSA	European Food Safety Authority
FSA	Food Standards Agency
FSS	Food Standards Scotland
HBGV	Health Based Guidance Value
kg	Kilograms
LOAEL	Lowest Observed Adverse Effect Level
mg	Milligram
ng	Nanogram
nmol	Nanomole
NOAEL	No Observed Adverse Effect Level
OECD	Organization for Economic Cooperation and Development
pg	Picogram
PTH	Parathyroid hormone
RCT	Randomised Clinical Trial
SACN	Scientific Advisory Committee on Nutrition
TUL	Tolerable Upper Intake Level
UL	Upper level
VDE	Vitamin D equivalent

References

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TOX/2026/21 Annex B

1. Annex B provides the full exposure assessment for calcidiol, as presented to the COT within the 2025 discussion paper on the effects of calcidiol supplementation during preconception, pregnancy and lactation.

Exposure assessment

Occurrence of calcidiol in food

2. Calcidiol, may be present in some foods of animal origin such as milk, butter, eggs, fish, meat and offal in the form of 25-hydroxycholecalciferiol (25(OH)D3) or 25-hydroxyergocalciferol (25(OH)D2). Calcidiol in the form 25-hydroxyergocalciferol has been reported in whole milk, butter and in some meat and offal (Ovesen et al., 2003; Jakobsen and Saxholt, 2009).

3. Occurrence of calcidiol in 11 food sources was reported in EFSA’s 2021 paper ‘Safety of calcidiol monohydrate produced by chemicals synthesis as a novel food pursuant to Regulation (EU)2015/2283’. These levels have been summarised and can be found in Table 1.

Table 1. Foods containing calcidiol (Adapted from page 11 of Safety of calcidiol monohydrate produced by chemical synthesis as a novel food pursuant to Regulation (EU) 2015/2283).

Food	Form of calcidiol	Concentration (µg /kg)
Semi-skimmed milk	25-hydroxycholecalciferol	0.042
Whole milk	25-hydroxyergocalciferol	0.031
Butter	25-hydroxycholecalciferol,	0.96
Butter	25-hydroxyergocalciferol	0.58
Egg yolks	25-hydroxycholecalciferol	5 – 12
Salmon flesh	25-hydroxycholecalciferol	1.1
Raw trout	25-hydroxycholecalciferol	2.2
Pork cuts	25-hydroxycholecalciferol	0.7 – 1.4
Pork rind	25-hydroxycholecalciferol	3.4
Pork liver	25-hydroxycholecalciferol	4.8
Cow Kidney	25-hydroxycholecalciferol	5.1 – 9.8
Beef Liver	25-hydroxyergocalciferol	1.7

Food consumption 

4. The following exposure assessments for calcidiol in food are based on consumption data from the National Diet and Nutrition Survey (NDNS) (Bates et al., 2014, 2016, 2020; Roberts et al., 2018); however, it is important to note that the NDNS does not provide data for pregnant or lactating women. Therefore, data presented below are based on women of childbearing age (16-49 years) and consumption data may not be entirely representative of the maternal diet, specifically in liver food groups due to National Health Service (NHS) recommendations that pregnant women should not consume liver or liver products (NHS, 2024). Evidence suggests that some foods and nutrients may be under-reported to a greater extent than others, and some may be overreported, but there is no information available on the level to which different foods are misreported in the NDNS in this group.

5. Consumption data were generated for all 11 food groups in Table 1 including both whole foods and recipes; these data can be found in Annex C. Table A1 provides acute consumption data and Table A2 provides chronic consumption data. Both tables summarise the mean and 97.5th percentile consumption per food group, for women of childbearing age.

Milk

6. A search within the recipes database of the NDNS (Bates et al., 2014, 2016, 2020; Roberts et al., 2018) was conducted to retrieve both semi-skimmed milk, whole milk, and recipes containing milk which had been recorded in the survey. Other types of milk were excluded as this search was conducted based on the food groups described in Table 1.

Butter

7. Calcidiol has been detected in butter as both 25-hydroxycholecalciferol and 25-hydroxyergocalciferol (EFSA, 2021). Consumption data were retrieved for butter and recipes containing butter.

Egg Yolk

8. Both whole egg and yolk only consumption was included from the NDNS database to ensure that all egg yolk consumers were included. Foods containing egg white only were excluded from the assessment. The egg yolk makes up approximately 29.3% of the edible portion of a medium egg, and 28.7% of a large egg. The NDNS database does not specify the use of large or medium eggs therefore the figure was rounded to 29% (DH, 2012) and applied to whole eggs foods to give estimates for consumption specifically of egg yolks.

Salmon

9. Foods containing salmon in the NDNS database do not specify with or without skin, however the assumption has been made that recipes represent salmon flesh.

Trout

10. Due to a low number of consumers of trout in the NDNS database, an ‘all fish’ food group was used as proxy based on the assumption that trout is eaten in similar quantities to other types of fish such as cod and haddock.

11. It is important to note that whilst levels of calcidiol were detected in raw trout, both canned and cooked fish and fish recipes were used within this exposure assessment as raw trout data were not available within the NDNS.

Pork

12. Calcidiol is present in in pork cuts, pork rind, and pork liver as 25-hydroxycholecalciferol. The NDNS database was used to retrieve recipes containing varying forms of pork meat including pork belly, pork loin, sausages and bacon. Within the database, pork crackling was used to represent consumption of pork rind.

Beef kidney

13. Due to a low number of consumers of beef kidney in the NDNS database, an ‘all kidney’ food group was used as proxy based on the assumption that kidney from animals such as lamb and pork would be consumed similarly.

Beef Liver

14. For women of childbearing age, within the NDNS database there are no consumers of beef liver, therefore an ‘all liver’ food group was used as proxy based on the assumption that liver from animals such as chicken and lamb would be consumed similarly.

Exposure estimates from food

15. An exposure assessment was conducted using food groups and occurrence levels presented in Table 1 only. A summary of exposure estimates for each food at its corresponding occurrence level of calcidiol can be found in Table 2 and 3. Table 2 provides acute exposure estimates to calcidiol from food, and Table 3 provides chronic exposure estimates, for women of childbearing age. In these tables, acute and chronic exposures are presented for both mean and 97.5th percentile groups on a per person and per kilogram bodyweight basis.

Table 2: Estimated acute exposure to Calcidiol from food for women of childbearing age (16-49 years). 

Food Groups	Type of Calcidiol	Level(s) detected (µg /kg)	Number of consumers	Mean  (ug/person/day) *	P97.5 (ug/person/day) *	Mean (ug/kg bw/day) *	P97.5 (ug/kg bw/day) *
Semi-skimmed milk	25-hydroxycholecalciferol	0.042	2083	0.0085	0.026	0.00013	0.00041
Whole milk	25-hydroxyergocalciferol	0.031	1333	0.0041	0.017	0.000063	0.00026
Butter	25-hydroxycholecalciferol	0.96	1736	0.015	0.049	0.00023	0.00074
Butter	25-hydroxyergocalciferol	0.58	1736	0.0092	0.029	0.00014	0.00045
Egg yolk	25-hydroxycholecalciferol	5.0 - 12.0	2128	0.17- 0.41	0.46 -1.1	0.0025 - 0.0061	0.0072 - 0.017
Salmon	25-hydroxycholecalciferol	1.1	375	0.087	0.22	0.0013	0.0036
Trout	25-hydroxycholecalciferol	2.2	168	0.17	0.52	0.0026	0.0082
Pork cuts	25-hydroxycholecalciferol	0.7 - 1.4	1406	0.049 - 0.099	0.15 - 0.3	0.00072 - 0.0014	0.0021- 0.0044
Pork rind	25-hydroxycholecalciferol	3.4	69	0.053	0.21	0.00079	0.003
Pork liver	25-hydroxycholecalciferol	4.8	68	0.096	0.26	0.0013	0.0034
Cow Kidney	25-hydroxycholecalciferol	5.1 - 9.8	17**	0.077 - 0.15	0.14 - 0.27	0.0011 - 0.0021	0.0022 - 0.0042
Beef Liver	25-hydroxyergocalciferol	1.7	96	0.063	0.21	0.00093	0.0036

*Rounded to 2 s.f.

** Consumption or exposure estimates made with a small number of consumers may not be accurate. Where the number of consumers is less than 60, this should be treated with caution and may not be representative for a large number of consumers.

Table 3: Estimated chronic exposure to Calcidiol from food for women of childbearing age (16-49 years). 

Food Groups	Type of Calcidiol	Level(s) detected (µg /kg)	Number of consumers	Mean  (ug/person/day) *	P97.5 (ug/person/day) *	Mean  (ug/kg bw/day) *	P97.5 (ug/kg bw/day)*
Semi-skimmed milk	25-hydroxycholecalciferol	0.042	2083	0.0048	0.017	0.000071	0.00024
Whole milk	25-hydroxyergocalciferol	0.031	1333	0.002	0.01	0.000031	0.00016
Butter	25-hydroxycholecalciferol	0.96	1736	0.0066	0.024	0.0001	0.00038
Butter	25-hydroxyergocalciferol	0.58	1736	0.004	0.014	0.00006	0.00023
Egg yolks	25-hydroxycholecalciferol	5.0 - 12.0	2128	0.066 - 0.16	0.2 - 0.47	0.00098 - 0.0024	0.0032- 0.0076
Salmon	25-hydroxycholecalciferol	1.1	375	0.025	0.059	0.00037	0.00098
Trout	25-hydroxycholecalciferol	2.2	168	0.047	0.16	0.0007	0.0022
Pork cuts	25-hydroxycholecalciferol	0.7 - 1.4	1406	0.016 - 0.033	0.057 - 0.11	0.00024 - 0.00048	0.00089 - 0.0018
Pork rind	25-hydroxycholecalciferol	3.4	69	0.015	0.053	0.00022	0.00079
Pork liver	25-hydroxycholecalciferol	4.8	68	0.028	0.09	0.0004	0.0013
Cow Kidney	25-hydroxycholecalciferol	5.1 - 9.8	17**	0.02 - 0.038	0.038 - 0.073	0.00027 - 0.00052	0.00055 - 0.001
Beef Liver	25-hydroxyergocalciferol	1.7	96	0.017	0.06	0.00026	0.00092

*Rounded to 2 s.f.

** Consumption or exposure estimates made with a small number of consumers may not be accurate. Where the number of consumers is less than 60, this should be treated with caution and may not be representative for a large number of consumers.

Milk 

16. Acute exposure estimates derived for 25-hydroxycholecalciferol in semi-skimmed milk at a concentration of 0.042 µg/kg are 0.0085 µg/day and 0.026 µg/day mean and 97.5th percentile values, respectively. Chronic exposure estimates are 0.0048 µg/day and 0.017 µg/day mean and 97.5th percentile values, respectively.

17. Acute exposure estimates derived for 25-hydroxyergocalciferol in whole milk at a concentration of 0.031 µg/kg are 0.0041 µg/day and 0.017 µg/day mean and 97.5th percentile values, respectively. Chronic exposure estimates are 0.002 µg/day and 0.01 µg/day mean and 97.5th percentile values respectively.

Butter

18. Calcidiol in butter was detected as 25-hydroxyergocalciferol at a concentration of 0.58 µg/kg and as 25-hydroxycholecalciferol at a concentration of 0.96 µg/kg and.

19. At a concentration of 0.58 µg/kg acute exposures were 0.0092 µg/day and 0.029 µg/day mean and 97.5th percentile values, respectively. At a concentration of 0.96 µg/kg, acute exposure estimates are 0.015 µg/day and 0.049 µg/day mean and 97.5th percentile values, respectively.

20. Chronic exposure estimates at a concentration of 0.58 µg/kg are 0.004 µg/day and 0.014 µg/day mean and 97.5th percentile values, respectively. At a concentration of 0.96 µg/kg, exposure estimates are 0.0066 µg/day and 0.024 µg/day mean and 97.5th percentile values, respectively.

Egg yolk

21. In egg yolk, 25-hydroxycholecalciferol was detected at a range of 5.0 to 12 µg/kg. Acute exposure estimates range from 0.17 to 0.41 µg/day and 0.46 to 1.1 µg/day mean and 97.5th percentile values, respectively. Chronic exposure estimates range from 0.066 to 0.16 µg/day and 0.2 to 0.47 µg/day mean and 97.5th percentile values, respectively. The highest exposure to calcidiol from food was noted from egg yolks.

Salmon

22. Acute exposure estimates to 25-hydroxycholecalciferol in salmon at a level of 1.1 µg/kg are 0.087 µg/day and 0.22 µg/day mean and 97.5th percentile values, respectively. Chronic exposure estimates are 0.025 µg/day and 0.059 µg/day mean and 97.5th percentile values, respectively.

Pork

23. 25-hydroxycholecalciferol was detected at a range of 0.7 to 1.4 µg/kg in pork cuts, 3.4 µg/kg in rind (crackling), and 4.8 µg/kg in pork liver.

24. Acute mean exposures range from 0.049 to 0.099 µg/day in pork cuts, 0.053 µg/day in rind (crackling), and 0.096 µg/day in pork liver. Acute exposure estimates at the 97.5th percentile range from 0.15 to 0.3 µg/day in pork cuts, 0.21 µg/day in rind (crackling), and 0.26 µg/day in pork liver.

25. Chronic mean exposures range from 0.016 to 0.033 µg/day in pork cuts, 0.015 µg/day in rind (crackling), and 0.028 µg/day in pork liver. Chronic exposure estimates at the 97.5th percentile range from 0.057 to 0.11 µg/day in pork cuts, 0.053 µg/day in rind (crackling), and 0.09 µg/day in pork liver.

Beef

26. 25-hydroxycholecalciferol was detected in beef kidney at a range of 5.1 to 9.8 µg/kg, whilst 25-hydroxyergocalciferol was detected at a level of 1.7 µg/kg in beef liver.

27. Acute mean exposures range from 0.077 to 0.15 µg/day in beef kidney, and 0.063 µg/day in beef liver. Acute exposure estimates at the 97.5th percentile range from 0.14 to 0.27 µg/day in beef kidney, and 0.21 µg/day in beef liver.

28. Chronic mean exposures range from 0.02 to 0.038 µg/day in beef kidney, and 0.017 µg/day in beef liver. Chronic exposure estimates at the 97.5th percentile range from 0.038 to 0.073 µg/day in beef kidney, and 0.06 µg/day in beef liver.

Total exposure estimates from food sources

29.  Estimated total exposures to calcidiol from 11 food sources (Table 1), in women aged 16-49 years, are presented in Tables 3 and 4 below.  Due to a range of occurrence values for some food groups, these data have been presented as minimum and maximum exposure estimates. Exposure data from food sources containing calcidiol will be compared to the ACNFP TUL of 40 µg/day and the level EFSA established as safe (i.e. up to 10 μg/day.

Table 3. Estimated total acute exposure to calcidiol from food sources (excluding supplements) in women aged 16-49 years.

Total calcidiol exposure** (food sources)	Mean (µg/person/day) *	P97.5 (µg/person/day) *	Mean (µg/kg bw/day)*	P97.5 (µg/kg bw/day)*
Minimum	0.19	0.5	0.0028	0.008
Maximum	0.4	1.1	0.006	0.017

*Rounded to 2 s.f.

** Determined from a distribution of consumption of any combination of categories, rather than by summation of the respective individual mean / 97.5th percentile consumption value for each of the 11 food categories.

30. Women of childbearing age are estimated to have minimum acute calcidiol exposures of 0.19 and 0.5 µg/day for mean and 97.5th percentile consumption, respectively. Maximum acute exposures are 0.4 and 1.1 µg/day for mean and 97.5th percentile consumption, respectively.

Table 4. Estimated total chronic exposure to calcidiol from food sources (excluding supplements) in women aged 16-49 years.

Total calcidiol exposure** (food sources)	Mean (µg/person/day) *	P97.5 (µg/person/day) *	Mean (µg/kg bw/day)*	P97.5 (µg/kg bw/day)*
Minimum	0.082	0.24	0.0012	0.0038
Maximum	0.17	0.52	0.0025	0.0081

*Rounded to 2 s.f.

**Determined from a distribution of consumption of any combination of categories, rather than by summation of the respective individual mean / 97.5th percentile consumption value for each of the 11 food categories.

31. Women of childbearing age are estimated to have minimum chronic exposures of calcidiol at 0.082 and 0.24 µg/day mean and 97.5th percentile values, respectively. Maximum expsoures are 0.17 and 0.52 µg/day mean and 97.5th percentile values, respectively.

Exposure estimates from supplements

32. Calcidiol is currently available in supplemental form and may be used in future food fortification (Guo et al., 2017). Calcidiol is present in supplements in the form of calcifediol or 25(OH)D (Biondi et al., 2017).

33. Supplements aimed at adults were identified using online sources which supplied calcidiol in doses ranging from 10 to 20 µg/day. No supplements containing calcidiol were identified that were specifically aimed at pregnant and breast-feeding women.

34. Estimate calcidiol exposures from calcidiol-containing supplements are presented in Table 5. These exposure estimates assume that a 70.3 kg female between the ages of 16 to 49 consumes the supplement at the recommended dose for adults. The bodyweight of 70.3 kg was determined as the mean bodyweight of all females of childbearing age (16 to 49 years) within years 1-11 of the NDNS database.

35. The limited number of calcidiol-containing supplements available on the market are presented in Table 5, some of which are not available in the UK, but are able to be ordered online from international stores.

Table 5. Calcidiol exposure estimates for women of childbearing age consuming calcidiol-containing supplements.*

Supplement	Calcidiol concentration per serving (µg)	Serving size (tablets/day)	Calcidiol exposure (µg/kg bw/day)**
VitamoreD - Vitamin D3 as Calcifediol	10	1	0.14
D.velop Tablets Adult	20	2	0.28
D.velop Gummies Adult	10	2	0.14
Bioclinic Naturals Opti Active D	10	1	0.14
Vitamin D DPrev Active	10	1	0.14

*based on a bodyweight of 70.3kg.

** Rounded to 2 s.f.

36. The supplements listed in Table 5 are generally aimed at adults although it should be noted that pregnant women may consume these supplements as many individuals are unaware of their pregnancy at the time and may consume calcidiol-containing supplements that are of higher potency than vitamin D2 and D3 supplements.

37. The estimated calcidiol exposures from calcidiol-containing supplements range from 10 to 20 µg/day, which is equivalent to 0.14 to 0.28 µg/kg bw/day.

Total exposure estimates from food and supplements combined

38. Total exposure estimates to calcidiol from food and supplement sources combined in women aged 16-49 years are presented in Tables 6 and 7 below. For acute exposure estimates, total exposure from food sources (Table 2) was summed with exposure data from dietary supplements (Table 5). For chronic exposure estimates, total exposure from food sources (Table 4) was summed with exposure data from dietary supplements (Table 5).

39. To calculate the minimum total exposures in Tables 6 and 7, the lowest supplement exposure (10 µg/person/day or 0.14 µg/kg bw/day) was summed with the minimum exposures from food (Tables 4 and 5) for both mean and 97.5th percentile consumption. To calculate the maximum total exposures as seen in Tables 6 and 7, the highest supplement exposures from Table 5 (20 µg/person/day or 0.28 µg/kg bw/day) were summed with the maximum exposures from food (Tables 3 and 4) for both mean and 97.5th percentile consumption.

Table 6. Estimated total acute calcidiol exposure from food sources combined with supplements in women aged 16-49 years.

Total calcidiol exposure (food + supplements)	Mean (ug/person/day)*	P97.5 (ug/person/day)*	Mean (μg/kg bw/day)*	P97.5 (μg/kg bw/day)*
Minimum	10	11	0.14	0.15
Maximum	20	21	0.29	0.3

*Rounded to 2 s.f.

40. Minimum total acute calcidiol exposures from all dietary sources including supplements, for women aged 16-49 years, are 10 µg/day and 11 µg/day for mean and 97.5th percentile consumption, respectively. Maximum total acute exposures from all dietary sources including supplements are 20 µg/day and 21 µg/day mean and 97.5th percentile, respectively.

Table 7. Estimated total chronic calcidiol exposure from food sources combined with supplements in women aged 16-49 years.

Total calcidiol exposure (food + supplements)	Mean (ug/person/day)*	P97.5 (ug/person/day)*	Mean (μg/kg bw/day)*	P97.5 (μg/kg bw/day)*
Minimum	10	10	0.14	0.14
Maximum	20	21	0.28	0.29

*Rounded to 2 s.f.

41. Minimum total chronic calcidiol exposure from all dietary sources including supplements amongst women aged 16-49 years is 10 µg/day for both mean and 97.5th percentile groups. Maximum total chronic exposures from all food sources are 20 µg/day and 21 µg/day mean and 97.5th percentile values, respectively. Exposure to calcidiol from dietary sources are minor relative to exposure from supplements.

TOX/2026/21 Annex C

1. The data presented in the tables below are based on consumers of foods reported in the NDNS ((Bates et al., 2014, 2016; 2018, 2020).

Table A1: Estimated acute consumption of foods containing Calcidiol for women of childbearing age (16-49 years).

Food Groups	No. of consumers	Mean Consumption (g/person/day) *	97.5	Mean Consumption (g/kg bw/day) *	P97.5
Semi-skimmed milk	2083	200	620	3	9.7
Whole milk	1333	130	560	2	8.5
Butter	1736	16	51	0.24	0.77
Egg yolk	2128	34	93	0.5	1.4
Salmon	375	79	200	1.2	3.3
Trout	168	78	240	1.2	3.7
Pork cuts	1406	70	210	1	3.1
Pork rind	69	16	62	0.23	0.89
Pork liver	68	20	53	0.28	0.7
Cow Kidney	17**	15	27	0.21	0.43
Beef Liver	96	36	120	0.54	2.1

*Rounded to 2 s.f.

** Consumption or exposure estimates made with a small number of consumers may not be accurate. Where the number of consumers is less than 60, this should be treated with caution and may not be representative for a large number of consumers.

Table A2: Estimated chronic consumption of foods containing Calcidiol for women of childbearing age (16-49 years).

Food Groups	No. of consumers	Mean (g/person/day) *	P97.5	Mean (g/kg bw/day) *	P97.5
Semi-skimmed milk	2083	110	400	1.7	5.7
Whole milk	1333	65	330	1	5
Butter	1736	6.9	25	0.1	0.4
Egg yolk	2128	13	39	0.2	0.63
Salmon	375	22	54	0.34	0.89
Trout	168	22	73	0.3	1
Pork cuts	1406	23	81	0.34	1.3
Pork rind	69	4.3	15	0.064	0.23
Pork liver	68	5.8	19	0.084	0.27
Cow Kidney	17**	3.9	7.4	0.054	0.11
Beef Liver	96	10	35	0.15	0.54

*Rounded to 2 s.f.

** Consumption or exposure estimates made with a small number of consumers may not be accurate. Where the number of consumers is less than 60, this should be treated with caution and may not be representative for a large number of consumer.