Developmental toxicity of cadmium in infants and children: a review

Summary

Chandravanshi, Shiv, and Kumar (Indian forensic-science institutions: Faridabad-Haryana, Greater Noida, and Ghaziabad) conducted a systematic review published in Environmental Analysis Health and Toxicology (Vol. 36, No. 1, 2021, 18 pages, open access CC BY-NC) synthesizing the human and animal literature on developmental toxicity of cadmium during in utero and early-life exposure. The review covers four organ-system endpoint domains: kidney dysfunction, neurobehavioral and cognitive dysfunction, pregnancy outcomes, and carcinogenesis. It characterizes the exposure biomarker matrices used across the reviewed literature: maternal blood, cord blood, breast milk, urine, placenta, and hair cadmium. The authors compiled Table 1, which aggregates 13 primary studies across 10 jurisdictions, with cadmium exposure levels from maternal blood, urinary cadmium, umbilical cord blood, and breast milk, alongside the developmental outcomes observed in each. The review supports the conclusion that in utero and early-life cadmium exposure is associated with impaired kidney function, reduced cognitive performance, adverse pregnancy outcomes, and elevated cancer risk in infants and children, but does not itself generate primary occurrence data or primary exposure measurements.

Key numbers

The 13 studies compiled in Table 1 (page 6 of the review) cover the following exposure ranges and outcomes by jurisdiction:

For renal biomarkers discussed in the Renal Dysfunctions section (pages 5 and 7): increased urinary excretion of beta-2-microglobulin and retinol-binding protein (URBP) indicate kidney tubular damage; elevated albumin, Cystatin C, and decreased glomerular filtration rate indicate glomerular damage. The developing kidney is at higher risk than the adult kidney until age 2 to 3 years, as glomerular and tubular functions continue to develop until that age (page 5, citing Trzcinka-Ochocka et al. 2004 and Bernard 2004).

The review notes that urine cadmium concentration is a well-accepted biomarker of long-term cadmium exposure in humans. High concentrations in infant urine relative to adult urine reflect lower kidney accumulation of cadmium due to higher rates of urinary excretion in infants compared to adults (pages 5 and 7, citing Kippler et al. 2010 and Jean et al. 2018).

Evidence Fitness

This source is rated Context only. It is a narrative review synthesizing primary evidence from other studies and does not generate primary occurrence measurements or exposure data applicable to a specific food matrix. It provides context for the pediatric developmental toxicology of cadmium that supports characterization of vulnerable populations and sensitive life stages, and is appropriately cited on the cadmium metal page under toxicology and vulnerable populations sections. It does not support contamination profile values for any ingredient or product page, and it does not constitute occurrence evidence suitable for pool admission in any certification threshold-setting workflow.

Methods (brief)

The authors conducted a literature search using Google Scholar with terms including “cadmium,” “developmental,” “neurotoxicity,” “cognition,” and “kidney dysfunctions” (Abstract). The search covered human and animal studies across multiple epidemiological designs (cohort, case-control, cross-sectional) and experimental animal models. The review focuses on English-language articles and reports, with emphasis on recent and more robust studies. No formal PRISMA protocol or inclusion/exclusion criteria table is published; this is a narrative review rather than a registered systematic review.

The paper contains no primary analytical chemistry: no instrument type, no LOD/LOQ, no CRM recovery, and no speciation data are reported by the review itself, as these pertain to the primary studies it synthesizes.

LOD/LOQ: Not reported by this review (review paper only).

CRM recovery: Not reported by this review (review paper only).

Instrument: Not reported by this review (review paper only).

Regulatory context

The review does not tabulate regulatory limits on cadmium in food. It references the IARC Group 1 carcinogen classification for cadmium (page 8, citing IARC 1993 and IARC 2012). The U.S. NHANES biomonitoring data referenced in the review (Ciesielski et al. 2012) used urinary cadmium as the exposure metric for the U.S. child population.

Limitations

The review is a narrative synthesis without a registered protocol, explicit PRISMA flow, or defined eligibility criteria. The search strategy is limited to Google Scholar with terms listed only in the abstract. Table 1 aggregates studies across diverse jurisdictions, exposure biomarker matrices, and outcome endpoints without quantitative pooling or heterogeneity assessment, so the table is appropriately read as an illustrative compilation rather than a meta-analysis. The review does not address confounding factors systematically across the reviewed studies. Several primary studies cited had modest sample sizes (75 to 119 subjects). The review is published by Indian forensic-science authors in a Korean environmental health journal; the institutional and editorial context differs from EFSA, JECFA, or ATSDR synthesis documents that constitute the principal cadmium toxicology reference corpus.

Implications

This review provides the most recent (2021) secondary-synthesis reference consolidating the pediatric cadmium developmental toxicology literature across kidney, neurological, and pregnancy-outcome endpoints. Its principal role in this corpus is as a citing reference on the cadmium metal page under toxicology, vulnerable populations, and kidney and neurobehavioral sections. It corroborates the direction and magnitude of effects described in primary regulatory and scientific synthesis documents (EFSA 2009, ATSDR 2012, JECFA 2022) without superseding those documents as a basis for threshold setting, because it does not generate primary occurrence data or formally pool primary evidence.

For certification purposes, this review supports the case that the infant and child population is a vulnerable subgroup requiring cadmium exposure limits below those calibrated for general adult chronic exposure, consistent with the government-limit default methodology. It does not alter any occurrence-based pooling calculation or add new numeric government-floor data.

For educational purposes, Table 1 provides a compact multi-jurisdiction summary of cadmium developmental toxicology studies and their exposure biomarker levels that is well-suited to course material illustrating the range of cadmium exposure levels observed in pediatric populations across different geographic and economic settings.

The review’s discussion of urinary biomarkers for renal toxicity (beta-2-microglobulin, retinol-binding protein, Cystatin C, albumin, N-acetyl-beta-D-glucosaminidase, KIM-1) is useful context for the cadmium metal page’s testing section, as these are the standard clinical markers for cadmium-induced kidney damage in the pediatric population (pages 5 to 7).

Provenance notes

Open access under CC BY-NC license. Source retrieved from PMC OA S3 (PMC8207007, PMID 33730790). SHA-256 of the PDF: 74f3f299c40d2954e63aa4a4ed8402d5967815c5ab78c0e3820c16cbdbe2ebf3. The authors declare no conflict of interest. No concerns about retrieval or document versioning.

Update history

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