Summary

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

Key endpoints covered

66.             EFSA, HRB and CADTH address the three key endpoints under consideration, with ANSES focusing on neurodevelopmental and thyroid effects and NTP confined to neurodevelopment and cognition.

Databases

67.             PubMed/Medline would seem a good starting point for an updated literature search as this features in all of the key expert group reviews.

68.             Other databases used by multiple expert groups: Embase (NTP, HRB and CADTH), Web of Science (WoS; EFSA and NTP), and the Cochrane library (HRB and CADTH), while NTP was the only expert group to address Chinese database searching.

Literature search date

69.             ANSES and EFSA searches covered the period up to early 2024 (or late 2023 in the case of the targeted EFSA searches), while NTP searches were generally up to 2020 (children’s IQ searches were updated to October 2023), and HRB and CADTH covered up to 2021 and 2017 (or 2018), respectively.

Chemical search terms

70.             The EFSA list of chemical search terms seems to be the most comprehensive, though other expert groups (e.g. NTP) include unique terms.

71.             The TRACE list specifies relevant fluoride chemicals (e.g. simple salts) for potential inclusion in the search strategy. It is likely that these would be covered by the generic fluoride search terms in the key expert group reviews.

Toxicity search terms

72.             The EFSA list appears to be the most comprehensive, with both general searches and targeted searches for the three key endpoints under consideration. However, the NTP search contains a more extensive set of neurotoxicity search terms.

Species search terms

73.             EFSA and NTP use specific search terms to capture both human and experimental animal data (ANSES covers both sets of data without using specific search terms), while HRB and CADTH focus only on human data. NTP noted that updated searches for experimental data did not strengthen the confidence assessment based on the human evidence available and removed the animal evidence stream from later drafts of the publication.

74.             The various EFSA searches incorporate slightly different terms to cover/exclude experimental animal data. The set of terms to be used in subsequent searches will need careful consideration.

Preliminary overview

75.           Table 1  below provides an overview of the search details for the key reviews, focusing on PubMed/Medline.

76.          The EFSA review would appear to be a good starting point for development of a search strategy, as it is recent and relatively comprehensive in terms of the endpoints covered and the chemical, toxicity and species search terms included.

Table 1: Overview of search strategies from existing reviews

Updated searches

77.             Preliminary searches were conducted in February 2026 in PubMed, using the EFSA search strings (conducted in October 2023 and January 2024) as a basis (key searches 1A, 2A, 3A, 4A and 5A), but with various modifications to account for potential areas of improvement in the search strategy: key searches 1B, 2B and 3B incorporated the more extensive set of neurotoxicity search terms utilised by the NTP; searches 1C, 2C and 3C incorporated the unique chemical search terms included by the NTP; searches 1D, 2D and 3D incorporated the unique chemical search terms included from TRACE (these were found not to impact the number of hits, hence retrospective searching was deemed unnecessary in PubMed/Medline); searches 1E, 2E and 3E are retrospective searches to cover the intervening period between the NTP and EFSA search dates, incorporating the more extensive set of neurotoxicity search terms utilised by the NTP; searches 1F, 2F and 3F are retrospective searches to cover the intervening period between the NTP and EFSA search dates, incorporating the unique chemical search terms utilised by the NTP. Table 2 - Table 5 below provide an overview of the number of hits for each of the updated key searches.

Table 2: Preliminary PubMed/Medline search results – key search 1 (human)

Table 3: Preliminary search results – key search 2 (animal)

Table 4: Preliminary search results – key search 3 (targeted neurotoxicity)

Table 5: Preliminary search results – key searches 4 (targeted bone) and 5 (targeted thyroid)