# Metal Isotopes in Mammalian Tissues

Jeremy E. Martin, Klervia Jaouen

► To cite this version:

Jeremy E. Martin, Klervia Jaouen. Metal Isotopes in Mammalian Tissues. Annual Review of Earth and Planetary Sciences, 2025, 53, pp.119-40. 10.1146/annurev-earth-040523-024549. hal-04820153

HAL Id: hal-04820153

https://hal.science/hal-04820153v1

Submitted on 7 Oct 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_2.png" /></figure>

*Annual Review of Earth and Planetary Sciences*

# Metal Isotopes in Mammalian Tissues

Jeremy E. Martin<fnref n="1" /> and Klervia Jaouen<fnref n="2" />

Annu. Rev. Earth Planet. Sci. 2025. 53:119–40

First published as a Review in Advance on
November 26, 2024

The *Annual Review of Earth and Planetary Sciences* is
online at earth.annualreviews.org

https://doi.org/10.1146/annurev-earth-040523-024549

Copyright © 2025 by the author(s). This work is
licensed under a Creative Commons Attribution 4.0
International License, which permits unrestricted
use, distribution, and reproduction in any medium,
provided the original author and source are credited.
See credit lines of images or other third-party
material in this article for license information.

<figure><img src="image_3.png" /></figure>

ANNUAL
REVIEWS **CONNECT**

www.annualreviews.org

• Download figures

• Navigate cited references

• Keyword search

• Explore related articles

• Share via email or social media

Keywords

stable isotopes, metal, mammals, fossils, paleoecology

Abstract

Ecologists rely on a wealth of data, including field observations and light
stable isotopes, to infer dietary preferences and other ecological and phys-
iological properties in living mammals. But inferring such important traits
(e.g., trophic position, metabolism, pathologies) in extinct animals, includ-
ing humans, can be challenging because biological processes rarely mirror
morphology as preserved in the fossil record. For instance, dietary behavior
does not necessarily reflect tooth morphology. As an additional challenge,
some isotopic mammal tissues commonly used in modern ecology, such
as collagen in bone or dentine or keratin from hair, hoof, or horn, do
not generally preserve in fossil remains older than ~200 kyr. In contrast,
major constituents of bioapatite often retain their initial isotopic com-
position through fossilization processes. Recent analytical developments
in mass spectrometry now allow, using small samples, for assessment of
isotopic variability of major and trace elements such as calcium or zinc.
Here, we review the application potentials of metal (nontraditional isotopes)
for (paleo)ecological, (paleo)physiological, and (paleo)mobility inferences as
applied to mammalian research.

■ Mammals are key elements of modern ecosystems and possess a rich evolutionary history, yet inferences about their past ecologies and physiologies are challenging to retrieve using traditional geochemical toolkits.

- Metal stable isotopes provide a novel and complementary approach to unveil paleoecological and paleophysiological characteristics of extinct mammal species.

<footnote n="1">¹Laboratoire de Géologie de Lyon, Terre, Planètes, Environnement, UMR CNRS 5276, Université Claude Bernard Lyon 1, Villeurbanne, France; email: jeremy.martin@cnrs.fr</footnote>

<footnote n="2">²Géosciences Environnement Toulouse, UMR CNRS 5563, Observatoire Midi-Pyrénées, Toulouse, France</footnote>
* Within a 20-year time frame, the core of metal isotopic data in mammalian research remains small compared to traditional isotopic systems (C, O, N), which is inviting for designing cost-effective instrumentation and increasing dissemination across scientific disciplines.

# 1. INTRODUCTION

Modern mammals, including our own species, are present almost everywhere on the planet and structure both terrestrial and aquatic ecosystems. They are highly mobile organisms and cannot be observed on a continuous basis in their habitat. Their ecological role became pivotal after the Cretaceous–Paleogene mass extinction event (O’Leary et al. 2013), as evidenced by their radiation on land but also in the marine environment (e.g., Uhen 2010) and diversifying into a wealth of ecological niches, including flight (Simmons et al. 2008). Increasing fossil evidence now reveals that they played important roles during the time of the dinosaurs with body weights reaching 14 kg (Hu et al. 2005, Chimento et al. 2024) and that their Triassic ancestors experimented evolutionary novelties such as lactation and hair insulation (Oftedal 2002). All mammals share mammary glands for provisioning their young with milk, hair for insulation, and a complex set of ear bones for treating acoustic information. Understanding their current and past impact on ecosystems, including in the disciplines of paleontology, paleoanthropology, and modern ecology, involves a wealth of methodologies. Among them, stable isotope studies have already documented the diversity of diets, metabolism, and mobility of past and modern species.

This review focuses on metal isotopes as constituents of bone and teeth because such biomineralized tissues represent the principal medium when addressing archeo- and paleo-oriented questions. We also reference soft tissues with the aim of understanding the biological processes at play behind the range of values measured in bone and teeth. Mammals, as other vertebrates, mineralize their skeleton with bioapatite [Ca(PO₄)₆(OH)₂], which preserves a suite of essential and nonessential elements that record physiological and environmental information as experienced by the organism. Geochemists have long understood the importance of such recorders, focusing on elemental concentrations to reconstruct trophic positions or largely focusing on different stable light isotopic systems to derive paleoclimatic or paleoecological information (see reviews in Koch 2007, Clementz 2012, Tütken 2014). The same tissues preserve metals or alkaline earths in various concentrations whose isotopic composition can independently relate to external or endogenous body processes. These singular systems were poorly explored before key analytical developments that now allow for routine measurements of tiny fractionation amplitude. These analytical challenges were addressed thanks to the development of new geochemical proxies coming from the field of Earth sciences. Here, we describe these developments more specifically for metal isotopes, which underwent rapid developments and applications in the past 20 years. Thanks to these developments, exploration of metal isotope fractionation processes in vertebrate tissues is becoming possible using an increasing number of systems.

Metals, which make up most elements of the periodic table, are characterized as electron donors. Typically solid at atmospheric temperatures and pressures (with the exception of mercury), metals react with acids and are excellent conductors of heat and electricity. The precise measurement of their isotope ratios using multi-collector plasma ionization became possible only in the late 1990s (Blichert-Toft et al. 1997, Maréchal et al. 1999), leading to their classification as nontraditional isotopes (Johnson et al. 2004). This designation can also extend to metalloids such as silicon and nonmetals such as selenium. Unlike traditional stable isotopes, which are often analyzed in the organic matter of skeletons (e.g., carbon, nitrogen, oxygen, hydrogen, and sulfur),
nontraditional isotopes are mainly analyzed in the mineral component of the skeleton, bioapatite. Metal components, either major such as the alkaline earths (Ca, Mg) or trace metals present in minor quantities (Zn, Sr, Li), have interesting potential to be used in addition to the more traditional toolkits to help infer trophic links or reconstruct physiological processes or environmental conditions (Figure 1). Such proxies are essential in both modern and ancient settings.

The aims of this review are to provide an overview of the different proxies and their potential, realized and untapped, for studying past and recent mammals including humans; to identify key areas of research for future studies; and to highlight current limitations and challenges. We identify emerging research areas that will likely shape the field in the future.

# 2. METHODS: PAST, CURRENT, AND FUTURE CONSIDERATIONS

## 2.1. Serendipitous Approaches to Isotopic Processes

Historical accounts and the experiences of scientists reveal that implementing new proxies generally comes by chance. One exemplar was the case of carbon isotopes, now widely used as a dietary proxy in herbivore tooth enamel. The initial focus on carbon isotopes was radiocarbon (¹⁴C) and its wide application to date biological materials formed over the last 55,000 years (Hajdas et al. 2021). When it was observed that some archeological plant remains gave systematically younger ages than contemporaneous plants, this opened the way to a better understanding of photosynthetic pathways (C3, CAM, and C4 plants) (Hall 1967, Bender 1968, van der Merwe 1982). Because these photosynthetic strategies impact the carbon isotopic fractionation of plants, this fortuitous discovery led to the reconstruction of the contribution of different types of plants into human and animal diets, past and present (DeNiro & Epstein 1978, Vogel 1978, van der Merwe 1982). Subsequent studies focusing on hard tissues (bone, teeth), where dietary carbon contributes to the carbonate fraction of bioapatite, yielded major paleo-implications for reconstructing past environments or ancient diets. For example, the expansion of C4 grasslands took place during the late Miocene (Cerling et al. 1997), and herbivores experienced changes in their trophic preferences during the Plio-Pleistocene (MacFadden et al. 1999), including the contribution to the diet of extinct hominins (Van der Merwe et al. 2003, Cerling et al. 2013, Schoeninger 2014).

Unsuspected discoveries allow us to focus our attention and dedicate resources to clarify outliers. Regarding metal isotopes, Earth science studies provide a general panorama of the isotopic variability for different rock materials that led to the identification that biological materials surpassed the range of values of crustal rocks or of waters. This was initially identified in a number of systems including Ca (Skulan et al. 1997) and Zn (Cloquet et al. 2008). Earth sciences were at the center of such discoveries because they are the first to have seen the development of such tools to monitor small fractionation processes in comparison to light isotopes. Initially, the interest in exploring sex differences using iron and copper systematically included the purification and measurement of zinc (Maréchal et al. 1999, Albarède et al. 2011, Jaouen et al. 2012), often out of curiosity. It was only later that it was discovered that zinc isotopes are strongly influenced by trophic levels, highlighting their usefulness in assessing predator-prey interactions (Costas-Rodríguez et al. 2014, Jaouen et al. 2016a).

Analytical difficulties in measuring relative abundances of a given isotopic system represent a major limitation to understanding and investigating the relevance of the new proxy of interest. For example, difficulties can be related to the detection limit of the instrument and the minimum quantity of the required sample, procedures for sample digestion using acids for the purpose of breaking down any chemical bond (e.g., presence of organic matter in bone, dentine—the worse material to treat being milk) prior to purification using ion-exchange resins in the clean
<figure><img src="image_4.png" /><figcaption>Figure 1</figcaption></figure>

A synthetic summary of the different scales behind metal isotopic fractionation in mammals. (a) At the scale of the living population, elements are transferred from one trophic level to another and can be interpreted in terms of dietary preferences thanks to shared physiological processes among mammals. Importantly, the isotopic composition of any consumer's tissue will be determined by the mass-weighted isotopic average of all the dietary sources. In the extreme, incorporating a little bone into a diet will offset Ca isotopic values because bone is a Ca-rich source with a light Ca isotopic pool. Animal silhouettes are from PhyloPic.org. (b) Shown here is one example of how life history accounts for major shifts in isotopic compositions through maternal provisioning (milk), adult dietary diversification, and other physiological processes (diseases, pathologies). Analyzing teeth requires a framework such as a tooth eruption calendar, which differs from one species to another or even between individuals. This is a *Panthera leo* eruption calendar adapted from Smuts et al. (1978). (c) At a wider scale, mammals do move across different environments, which are characterized by their substrate, running waters, and vegetation, all determining a local or regional baseline for metal isotopes. Some isotopic systems may not be sensitive to substrate effects (e.g., stable Ca and Sr), but other systems are (e.g., stable Mg, radiogenic Sr) and can be used to reconstruct mobility among mammals.

In the laboratory, the time required to develop an efficient purification protocol of the element of interest, subsequent interferences during isotopic measurements (see Tacail et al. 2020) (see Section 2.3) and elemental contamination within the laboratory (García et al. 2017, Jaouen et al. 2020). All of these delay the development of the use of the proxy of interest.
## 2.2. Tissue Types

Bone and teeth are the tissues of choice because they concentrate metal isotopes (and allow for smaller sampling than soft tissues), can be relatively easier to store and process in the laboratory (they usually do not stink or decay), and are the only remains available in archeological or paleontological contexts.

Sampling is usually destructive, and the amount of sample needed depends on the sensitivity of the mass spectrometer (the concentration needed in one sample to achieve a measurement) and its concentration in the sampled material. For example, major constituents of bioapatite (Ca, Mg) are present at the percent level or thousands of parts per million. Trace metals, as their name implies, are much less concentrated to about several hundreds of parts per billion or parts per million depending on the element and thus require more material. Heterogeneity in concentration also exists between individuals or within a single bone or tooth and should be considered if possible. Some approaches will necessitate whole tooth crowns [e.g., Nd present at the parts per billion level in enamel (Plomp et al. 2019)], whereas others may only require smaller sampling spots [e.g., for Ca present at around 35% in enamel (Tacail et al. 2017, 2019)]. Measurements obtained in each case may not be interpreted the same way with respect to environmental or physiological seasonality. In other words, adjusting for sampling size will impact temporal resolution of elements incorporated in hard tissue at the daily, weekly, or monthly scale and even beyond. One also needs to address mineralization processes that may affect the tempo of information gathered into a single tissue. For example, enamel mineralizes under two steps: secretion and maturation (Suda & Gustafson 1962, Passey & Cerling 2002, Trayler & Kohn 2017), and models may be implemented to untangle time-related information (Passey & Cerling 2002, Passey et al. 2005, Green et al. 2018). It is worth noting that such models are being applied to dentine (Yang et al. 2023) and could next be developed for the more challenging enamel-tissue types that show a more complex mineralization. The preservation of precious fossil materials is a major concern for curators, paleontologists, anthropologists, and isotope geochemists, in particular for tooth enamel. To address this issue, researchers are developing less destructive methods such as laser ablation analyses (Tacail et al. 2016) or protocols allowing the purification of different elements of interest from a single sample (e.g., McCormack et al. 2022, Guiserix et al. 2024).

Studying incremental tissues in modern species is important as it allows us to characterize variations linked to physiology or the environment (e.g., Kennedy et al. 2002, Newsome et al. 2009). As such, climate, waters, plants, and soils on the one hand or sex, ontogenetic status, health, and parental care on the other hand impact the isotopic variability recorded in mineralized tissues. The challenge is therefore to capture these changes along a histologically defined timeline using microsampling at the scale of the individual. This can be achieved using microdrills that will later be purified in the clean lab (Tacail et al. 2017, 2019; Hassler et al. 2021b, Pederzani et al. 2024) or through laser ablation if isobaric interferences for a given isotopic system are resolved.

## 2.3. Analytical Challenges of Metal Isotopes Measured in Bioapatite

Once a sample has been taken, the first step is acid digestion. This ensures complete breakdown of chemical bonds between the sample constituents prior to further chemical treatment. This step is important to ensure the effectiveness of ion-exchange resins and break down potential remaining organic matter that may interfere with the sample during measurement on the spectrometer. Several approaches can be undertaken to break down organic matter from bone or soft tissues, and those include the alternative use of a mixture of hydrogen peroxide and nitric or chlorohydric acids. When these methods are insufficient (e.g., high organic content in hard tissues or various soft tissues), samples can be incinerated in a ventilated furnace (Hoffmann et al. 2021) or
be dissolved in nitric acid and be subjected to elevated temperature and pressure conditions in a
dedicated microwave (e.g., milk sample in Tacail et al. 2017 or Martin et al. 2023). In brief, the
dissolved sample is then purified through ion-exchange chromatography using dilute acids, and
the final aliquot containing only the element of interest (Ca, Mg, Zn, or any other element) is
collected into a Teflon beaker, evaporated, and redissolved at the aimed concentration prior to its
isotopic ratio measurement. An overview of the procedures in the clean lab for treating tooth and
bone samples is provided by Martin et al. (2017).

Metal isotopes do not combine with carbon or oxygen to create gas and therefore cannot be an-
alyzed by the traditional gas source known as isotope ratio mass spectrometry (IRMS). Measuring
their relative abundances requires ionization, either in a plasma using multi-collector-inductively
coupled plasma-mass spectrometry (MC-ICP-MS) or in the void using thermal ionization mass
spectrometry (TIMS). Initially, this was achieved using TIMS and was eventually developed using
MC-ICP-MS. Both methods require multi-collector mass spectrometers to resolve the individual
measurements of masses simultaneously. Multi-collector mass spectrometers have been designed
(magnet, acceleration tube geometry, and adjustable collectors) to measure nontraditional isotope
ratios with a high precision (see examples of MC-ICP-MS analytical developments in Blichtert-
Toft et al. 1997, Maréchal et al. 1999, Albarède 2004, and Moynier et al. 2021). While the TIMS
approach allows for a more stable signal during acquisition, samples experience a long and pro-
gressively increasing thermal monitoring process during measurement. On the other hand, the
MC-ICP-MS approach is less stable because of the plasma medium but allows for a higher
throughput (see the pros and cons of both types of instruments in Walczyk 2004). Each element
has its own technical challenges, and given the high price of mass spectrometers and time dedi-
cated to instrument tuning and measurements, each laboratory promotes its own approach based
on its research focus. During measurement of isotope ratios on the instrument, the recurring is-
sue relates to solving isobaric interferences, i.e., measuring equal masses in the isotope of interest
versus that of an unwanted isotope or compound. For instance, doubly charged strontium (⁸⁸Sr²⁺)
and ⁴⁴Ca⁺ cannot be solved from each other on MC-ICP-MS due to their nearly identical mass-
to-charge ratios (Tacail et al. 2014). Interferences are therefore avoided (or mitigated) with prior
purification of samples in the clean lab to keep only the element that will be measured. Again, this
approach depends on the respective composition of a given sample and whether one needs to tar-
get a more concentrated element. For example, if the aim is to target Ca only, it is unlikely that the
powder sample will be large enough to comprise other associated trace metals. On the other hand,
targeting trace metals (Zn, Sr) implies a larger quantity of matter, and therefore the threshold for
measuring more abundant elements (Ca, Mg) will be exceeded. This amount can also be species
dependent: Primate and marine mammal teeth are richer in Zn compared to those of other mam-
mal species, and therefore they require less than 5 mg of sampled material, whereas a cervid tooth
requires more than 10 mg. Strontium concentrations are also richer among marine species and
terrestrial herbivores compared to those of terrestrial carnivores (Balter 2004, Peek & Clementz
2012).

MC-ICP-MS can be connected to laser ablation systems, but two problems must be consid-
ered. Laser ablation implies the direct ionization of all elements constituting the sample, hence
creating interferences that would have been removed via purification procedure. This should be
investigated system by system (e.g., Copeland et al. 2008, Tacail et al. 2016). Laser ablation of-
ten requires flat sample surfaces to maintain proper focus of the laser beam, or else significant
measurement errors can occur (e.g., Balter et al. 2012). This is done by cutting and polishing the
sample. So, while laser ablation seems spatially resolved and minimally destructive (an ablation
spot can be 50 µm in diameter or less), one must take into account the fact that samples are being
cut and the approach may be more destructive than it seems.
TIMS and MC-ICP-MS are often versatile in their use within a laboratory due to different research interests of lab members or external users. Instruments are regularly tuned/detuned to allow dedicated measurement sessions of a given isotopic system. These instruments require costly maintenance and can frequently break down. This reality can lead to significant delays in research, particularly in laboratories with limited financial resources. Therefore, mutualization is often implemented within or between laboratories/institutions in order to manage costs related to instrument acquisition, maintenance, and consumables. One downside is that tuning is a constant and time-consuming step when changing measurement parameters from one isotopic system to another. Element-dedicated, cost-effective mass spectrometers could be one avenue of research to help develop the measurement of given systems. Yet, once analytical barriers can be resolved, a full array of applications and explorations becomes possible.

## 2.4. Controlled Feeding Experiments

Understanding fractionation processes in hard tissues requires isotopic and concentration measurements of other tissues (e.g., muscle, blood, urine) beyond bone to understand the balance of isotopic compositions between different body reservoirs under varying parameters (e.g., temperature, food, physiological status). This can be achieved using animal models but is not without major organizational and ethical challenges. Controlling for different parameters such as food quality or quantity, temperature, or other external proxies will allow one to address how the different reservoirs behave and what range of values is expected. Again, there is an effort of pooling animal tissues coming from those experiments in order to minimize the killing of animals and take advantage of a controlled settings. Data on Zn, Fe, Cu, Ca, Sr, and Li isotopes have been coming from a single experiment on sheep (Balter et al. 2010, 2013; Balter & Vigier 2014; Tacail et al. 2014) and on pigs (Lewis et al. 2017, Hassler et al. 2021b), and on K, Zn, and $\delta^{15}$N on rats (Leichliter et al. 2021, Tacail et al. 2023, Bourgon et al. 2024) and minipigs (Mahan et al. 2018, 2020, 2022; Tacail et al. 2023). Still, the amount of data on mammals is limited.

The most documented isotope fractionation for a metal through controlled feeding experiments is probably that of zinc. To date, six controlled feeding experiments have been described in the literature on five animal species [mouse, sheep, rat, minipig, and gilt-head seabream (Balter et al. 2010, 2013; Moynier et al. 2013, Bourgon et al. 2024; Mahan et al. 2018; McCormack et al. 2024)]. Within the same organism, the isotopic ratios of Zn are highly fractionated. Bones show much higher $\delta^{66}$Zn values compared to muscles and livers, regardless of species.

One issue encountered during studies is the short length of the experiment, which does not allow the bone to fully remodel (Bourgon et al. 2024) and could therefore explain contradicting diet-bone offsets documented in these studies. These offsets are not linked to the redox state of Zn, which is predominantly present in the form of $Zn^{2+}$ in nature, but to its speciation with various amino acids or minerals (Moynier et al. 2013).

The documentation of the Zn isotope composition of organs and food helped understanding of the trophic level spacing frequently identified for mammals and fish (Jaouen et al. 2016a,b, 2022; Bourgon et al. 2020, 2021; McCormack et al. 2021, 2022; Guiserix et al. 2024; Pederzani et al. 2024). For mammals, the fact that muscles are highly depleted in heavy Zn isotopes explains why carnivores show lower Zn isotope ratios in their tissues compared to herbivores, except for those consuming bones (Bourgon et al. 2021, Jaouen et al. 2022, Guiserix et al. 2024). The scenario is less clear for piscivores, which should not show lower Zn isotope ratios compared to their prey if they consume them entirely. However, McCormack et al. (2024) demonstrated that all tissues of gilt-head seabream are depleted in heavy Zn isotopes compared to their food, potentially explaining this pattern. Controlled feeding experiments also refuted the hypothesis that the presence of phytate in food would promote the absorption of heavy Zn isotopes through
preferential precipitation of light Zn isotopes in the stomach (Jaouen et al. 2013, 2019a; Bourgon et al. 2024).

Isotope fractionation of calcium has been documented through three independent feeding ex-
periments (the mouse, Göttingen minipigs, and sows by Hirata et al. 2008, Heuser et al. 2016, and
Hassler et al. 2021a, respectively). There is a fractionation during bone mineralization of about
-0.3‰ between bone and diet (Δ$^{44/42}$Ca) as demonstrated by Heuser et al. (2016) and Hassler
et al. (2021b), challenging previous observations of a nearly twice larger offset reported in mamm-
mals (see review in Tacail et al. 2020). Expanding controlled feeding experiments in other animals,
including exploring food type variability (plants, meat, bone, insects), will be key to refining our
understanding of processes controlling Ca isotope fractionation.

Feeding experiments designed to understand other isotopic systems such as strontium and potassium have relied on pigs, minipigs, quails, and rats (Lewis et al. 2017, Tacail et al. 2023). Stable Sr results (δ$^{88}$Sr) recovered a 0.3‰ offset toward lighter values in bone compared to the diet. Stable K results (δ$^{41}$K) indicate that the body reservoir is about +0.4 to +0.5‰ higher than the diet.

3. THE USE OF METAL ISOTOPES IN MAMMAL ECOLOGY, PALEONTOLOGY, AND ARCHEOLOGY

The core of our understanding of fractionation processes for metal isotopes has been established on wild modern mammals (Figure 1). Although controlled experiments are key to understanding fractionation processes (see above), crucial questions regarding the evolution of natural ecosystems are to be investigated only through the lens of wild animal remains. The great advantage of working with modern mammals is to confront isotopic data with firsthand observation of behaviors obtained in the field or by, for example, analyzing collected feces, DNA characterization, flushing out stomach contents, seasonality, or GPS or satellite data. Indeed, other challenges are associated with the study of living organisms, with some species being difficult or impossible to follow (e.g., deep-diving marine mammals or those having nocturnal habits).

Curated mammal specimens from historical collections provide a wealth of information on their ecology in habitats, especially when not altered by anthropogenic activities. Biodiversity declines in the nineteenth century up to this day mean that a wealth of information on ecology or behavior is being lost. Yet, researchers should certainly maintain and/or develop collaborations with existing national parks and help monitor naturally deceased specimens before the interaction of modern mammals in their habitat becomes completely lost. Osteological collections are of great value, and retrospectively, values obtained thanks to such specimens may help in conservation efforts by better characterizing the ecology of studied organisms. Other sources of material may come from custom confiscated material or from stranded marine mammals. The sections below aim to synthesize knowledge gained on mammals' metabolism, dietary preferences, and mobility using metal isotopes as well as identify future directions of research.

**3.1. Trophic Level Proxies**

Several elements exhibit different isotope compositions between trophic levels and are briefly
presented below (e.g., stable systems of Ca, Mg, Zn, Sr). A number of other elements have never
been investigated or indicate that further exploration would be worthy for applications in trophic
studies (K, Tacail et al. 2023; Nd, Plomp et al. 2019; Hg, Perrot et al. 2012). All of these elements
become incorporated into bioapatite during the lifetime of the organism, holding the potential to
record ancient dietary signatures.

Calcium isotopic abundance in vertebrate bioapatite represents an important proxy to retrieve
ecological information in extant and extinct organisms. Its high concentration (>30%) in bone
<figure><img src="image_5.png" /><figcaption>**Figure 2**</figcaption></figure>

Exploring predator-prey relationships in large terrestrial mammals using one metal isotope system against carbon isotopes allows us to underline where predators are sourcing their prey. (a) The distribution in calcium versus carbon isotopes in modern-day East Africa shows that leopards preferentially prey upon mammals that live in forested environments, whereas lions and hyenas are opportunistic and include herbivores from both forested and open habitats. In addition, Ca isotopes may hold information on herbivore dietary preferences, with grazers displaying lower values than browsers on average. (b) The distribution in zinc versus carbon isotopes in a Pleistocene assemblage from Southeast Asia reveals that carnivores primarily rely on herbivore prey from a forested environment. Note that the outlier carnivore is a hyena (see Section 3.1 in the main text for explanations). Black arrows indicate predator-prey links. Data in panel a are from Martin et al. (2018) (see **Supplemental Table 1**); data in panel b are from Bourgon et al. (2020) (see **Supplemental Table 2**).

and teeth offers numerous advantages for minimal sampling allowing for high-resolution patterns, minimizing the destructive approach to sampling, and minimizing blank contamination during chemical purification. Seminal work demonstrated a trophic level effect of Ca isotopes with decreasing values and increasing trophic level (Skulan et al. 1997, Skulan & De Paolo 1999). The reliability of Ca isotopes for retrieving such information was later questioned in both marine (Clementz et al. 2003, Messa et al. 2022) and terrestrial (Melin et al. 2014) contexts. The mechanisms at play behind isotopic fractionation are poorly understood, although they seem mostly driven by the dietary bowl. For example, it will be simpler to trace back the dietary preferences of a specialist than of a generalist that incorporates a variety of Ca sources. Similarly, bone-eating mammals (such as hyenas) will display the most distinctive values because bone itself is a major source of light Ca (Heuser et al. 2011). Nevertheless, combining C and Ca isotopes will permit discrimination of dietary preferences of carnivores in open- versus closed-vegetation ecosystems and refine predator-prey relationships (Martin et al. 2018, Tacail et al. 2020) (Figure 2a). Finally, plant organs do fractionate light Ca isotopes (see review in Tacail et al. 2020), and there exists a potential to identify selective dietary habits among herbivores, pending a survey of plant Ca isotopic diversity (Figure 2a).

Magnesium stable isotopes in mammal bone and teeth show an increase in δ²⁶Mg values with increasing trophic level as explored in modern African assemblages (Martin et al. 2014, 2015). Preliminary results discussed the possibility that Mg isotopes could distinguish between plant physiologies as detected in mammal tissues (Martin et al. 2014), but this needs further

**Supplemental Material** >
investigation. Analytical challenges remain, and other ecosystems, including aquatic ones, have not been explored. Given its medium concentration in bone apatite, the diagenetic behavior of Mg must also be assessed before it is applied to the study of ancient faunas.

During a pilot study, the isotopic variability of Fe, Cu, and Zn in the bones of modern African mammals did not recover a clear difference between the Zn isotopic ratios of carnivores and herbivores, even though the latter tended to have higher δ⁶⁶Zn on average (Jaouen et al. 2013). However, it was shown that vegetarians tended to have blood enriched in heavy Zn isotopes (Van Heghe et al. 2012, Costas-Rodríguez et al. 2014) compared to omnivores. Given the lack of precise geographical origin for the bones studied in South Africa (Jaouen et al. 2013), and the fact that the natural parks from which they originated spanned hundreds of kilometers, Jaouen et al. (2016a) designed a study that focused on a smaller geographical area to see if a trophic distinction could be observed. Using material coming from a region with a diameter of about 15 km at Koobi Fora, Kenya, a clear difference between herbivores and carnivores was observed in bones and teeth. Hyenas, however, tended to have higher isotopic ratios than other carnivores, which was later confirmed for three other Pleistocene sites in Asia and Europe (Jaouen et al. 2016a, 2022; Bourgon et al. 2021; Guiserix et al. 2024) (Figure 2b). This peculiarity was attributed to their consumption of bones, which are enriched in heavy Zn isotopes. This hypothesis is supported by results from a controlled feeding experiment on rats (Bourgon et al. 2024). Zinc isotope ratios of omnivores logically fall between those of carnivores and herbivores (Bourgon et al. 2020, 2021). Zn isotopes seem to be more sensitive to plant consumption than nitrogen isotopes. Indeed, nitrogen isotopes analyzed in bone or tooth proteins derive primarily from the dietary protein intake, itself mainly inherited from animal products consumed, if any. Thus, animal resource consumption quickly obscures plant consumption. It could be expected that the zinc isotopic composition of dental enamel is primarily impacted by animal resources, given that most foods high in Zn belong to this category and that zinc from animal resources is more bioavailable, but omnivory seems to be easier to document with Zn compared to nitrogen isotopes (Leichliter et al. 2021, 2023).

Regarding strontium, although the great majority of studies deal with radiogenic Sr (⁸⁷Sr/⁸⁶Sr) (see Section 3.4), stable Sr (δ⁸⁸/⁸⁶Sr) isotopes interestingly show a decrease from herbivores to carnivores (Knudson et al. 2010), which has been confirmed in a controlled feeding study involving pigs (Lewis et al. 2017) and more recently in modern and archeological mammal bones from South Africa and Europe (Guiserix et al. 2022, 2024).

Potassium is present in bioapatite with a concentration of several hundred of parts per million. Its isotopic composition (δ⁴¹K) has recently been investigated in biological tissues via interference resolution using collision cell MC-ICP-MS (Hobin et al. 2021, Moynier et al. 2021). In the frame of controlled feeding experiments involving pigs, rats, and quails, Tacail et al. (2023) recognized a conserved K physiology among endothermic vertebrates, and they foresee applications in future dietary studies.

Preliminary studies have been conducted on boron stable isotopes (δ¹¹B) on mammal bone (Bernard et al. 2013) and human teeth (Li et al. 2021) highlighting that dietary potential for other isotopic systems deserves further exploration.

Mercury is a contaminant of major concern in current health studies. The anthropogenic release of inorganic Hg (e.g., coal burning) into the atmosphere enters ecosystems thanks to methylation processes. The produced methyl-Hg is readily bioavailable and bioaccumulates in various tissues. Previous research has measured in soft tissues (liver) a significant difference in δ²⁰²Hg composition between predators and prey (Laffont et al. 2009, 2011; Perrot et al. 2012; Masbou et al. 2018). The isotopic compositions have not yet been explored in bone tissues, but Hg concentrations are lower than in soft tissues and demethylation during physiological processes must be further tested to understand the potential of Hg isotopes in dietary investigations.
<figure><img src="image_6.png" /><figcaption>Figure 3</figcaption></figure>

Calibrating nontraditional isotope proxies for trophic level inference requires validation against traditional toolkits. Here, Ca isotopes measured in enamel (a) and Zn isotopes measured in bone (b) are plotted against N isotopes measured in enamel in modern faunal assemblages of large terrestrial African mammals using data from independent isotopic studies and unrelated individuals of the same genus and/or species. Because N isotopes are a widely used trophic proxy in modern faunas, testing correlation with nontraditional isotopes opens perspectives to infer dietary preferences in the fossil record where collagen has already decayed. Sources for Ca isotope data are from Martin et al. (2018) and Tacail et al. (2019), sources for Zn isotopes are from Jaouen et al. (2013, 2016a), and sources for enamel-bound nitrogen isotopes are from Leichliter et al. (2023) and Lüdecke et al. (2022) (see **Supplemental Table 3**). Error bars represent 1 standard deviation of the mean. Animal silhouettes are from PhyloPic.org.

To conclude, one way to control for the dietary significance of metal isotopes is to compare them to nitrogen isotopes, a traditional isotope system widely used among the community of ecologists as a trophic level proxy. Comparing Ca isotopes with N isotopes in large modern African mammals reveals a good fit between the two proxies (Figure 3), and we advocate for extending this approach using other metal isotopes.

**Supplemental Material** >

## 3.2. Maternal Care, a Typical Mammalian Characteristic

Maternal care, involving milk secretion by the mother and consumption by neonates, is unique to mammals. Although deep-time evidence for lactation is difficult to ascertain due to its soft-tissue nature, this peculiar trait finds its evolutionary roots during the Permo–Triassic among cynodonts (Oftedal 2002). Yet, the later evolutionary success of modern mammals (Eutheria) is certainly linked with their unique reproductive strategies and may partly explain their expansive radiation following the Cretaceous–Paleogene crisis (Funston et al. 2022). Maternal care offers important clues about the ecology of ancient mammals as well as human ancestors in documenting birthing intervals, cultural practices, maternal survival, and duration of nursing. Previous approaches to explore such characteristics using nitrogen isotopes have revealed a 3–5‰ trophic level enrichment between mother and offspring (e.g., Fogel 1989, Newsome et al. 2010). Recent discoveries using calcium, zinc, and strontium isotopes all demonstrate relevant potentials (Chu et al. 2006, Tacail et al. 2017, Jaouen et al. 2020, Guiserix et al. 2022), which opens possible application in the absence of organic matter preservation.
In order to produce milk, nursing mothers catabolize their tissues, with the resulting effect that offsprings consume their mothers' tissues. This is reflected in the nursing neonate with nitrogen isotopic values one trophic level higher than the mother. Fractionation processes within mammal bodies in nontraditional isotopes have not been fully explored and, as detailed in a previous section (Section 2.4), this represents a major research theme.

Most nontraditional isotope records on breastfeeding have been established on enamel be-
cause tooth type corresponds to an eruption calendar and could therefore allow one to target the
prenatal versus post-weaning intervals. Modern dentine was also targeted as it is not remodeled
and could yield enough collagen for comparing trace metal results with nitrogen isotopes (Martin
et al. 2023). Calcium isotopes include studies on different mammals such as sheep, pigs, cervids,
odontocetes, and humans (Chu et al. 2006, Tacail et al. 2017, Hassler et al. 2021b, Li et al. 2022).
The general pattern shows the lowest values in teeth formed in utero and the highest values in
teeth formed after weaning with the underlying explanation that milk is a source of ⁴⁰Ca-depleted
values (Chu et al. 2006, Tacail et al. 2017). One mammalian exception so far has been recorded
in odontocete teeth with the nursing period corresponding to the highest values as explained
by seawater incidental intake during nursing (Martin et al. 2023). As concerns zinc isotopes, the
lowest values were measured in human teeth that mineralized after weaning, while the highest
values correspond to teeth formed during the nursing period (Jaouen et al. 2020). A similar
pattern has been measured for strontium isotopes in baboon enamel (Guiserix et al. 2022) with
the lowest values in utero. Sr and Ca behave the same way and may share the same fractionation
mechanisms due to their ionic radius (Tsutaya & Yoneda 2015).

**3.3. Metabolism Proxies**

An organism must maintain homeostatic conditions for any given element to ensure metabolic function. Failure to do so entails diseases or pathologic conditions. Therefore, metabolic processes at play control the distribution of isotopes at the cellular level. Previous studies have contributed to assessing the landscape of isotopic composition for different organs in order to understand metabolic processes (Balter et al. 2010, Jaouen et al. 2019a, Hassler et al. 2021b, Messa et al. 2022, Tacail et al. 2023).

Conversely, perturbations of the homeostatic conditions, as observed from the measurement of anomalous tissue reservoir isotopic compositions, hint at pathological conditions. As concerns nontraditional isotopes, the use of natural abundances as a diagnostic tool is booming, especially regarding copper isotopes (Albarède et al. 2017, Aranaz et al. 2022b). Such studies aim at finding new diagnostic or prognostic tools, or help determine associated mechanisms. Several pathologies are currently being explored including Alzheimer's disease using Zn isotopes (Moynier et al. 2017), ophthalmic diseases (Aranaz et al. 2022a), chronic kidney disease (Tanaka et al. 2017, Shroff et al. 2022, Dosseto et al. 2023), or bone loss (Heuser & Eisenhauer 2010, Morgan et al. 2012, Channon et al. 2015, Eisenhauer et al. 2019). In parallel, the effects of metabolic perturbations that are non-pathologic, such as post-prandial effects, menopause, or aging, can also be monitored in patients using blood tests or urine samples, which is helpful in following daily changes in bodily fluids' isotopic compositions. For a detailed review of metal isotopes as diagnostic tools for diseases in humans, see Sullivan et al. (2023). Except for sex-related metabolism (Jaouen et al. 2012), no study has investigated the recording of metabolic traits in mineralized tissues.

**3.4. Provenance Proxies**

Mammals are mobile organisms, and some species are capable of long-distance migrations as gov-
erned by the seasonal availability of resources or for completing reproductive cycles. In the marine
realms, cetaceans are highly mobile, and some whale species perform latitudinal migration to give birth in warm waters and forage in high-latitude nutrient-rich environments. At the scale of a given population, some individuals may or may not migrate, and mobility can imprint a measurable record in various tissues. Therefore, provenance proxies (δ¹³C, δ¹⁸O, δD) have been implemented to reconstruct the foraging grounds of a number of mammalian species (Cherel et al. 2007, Hobson et al. 2010, Newsome et al. 2010, Bentaleb et al. 2011).

Among metals, the most widely used proxy is the radiogenic ratio of $^{87}$Sr/$^{86}$Sr. Strontium is incorporated in phosphatic tissues such as bone or teeth during mineralization. Although strontium elemental concentration can be a useful tracer of diet through the biopurification process (Sillen 1986, Balter 2004), the strontium isotope composition (expressed as $^{87}$Sr/$^{86}$Sr) is not linked to any trophic signature. On the other hand, it directly reflects the isotopic composition of water and substrate, which have characteristic isotope signatures depending on the type of rock that is weathered out. Stated briefly, because rubidium ($^{87}$Rb) decays into strontium ($^{87}$Sr), older rocks such as gneiss will be more radiogenic (high $^{87}$Sr/$^{86}$Sr ratio) than sediments (low $^{87}$Sr/$^{86}$Sr ratio). The surrounding environment of those substrates (waters, soils, plants, etc.) will harbor the value of the substrate, providing a local strontium isotope imprint. Such isotopic ratios can therefore be used to characterize the environment where the organism was living and can be used in provenance studies in ecology (e.g., Ziegler et al. 2016), archeology (Bentley 2006), or paleoecology (e.g., Martin et al. 2016). It therefore adds value to evaluate the contribution of other isotope sources (here Sr isotopes in particular), such as the composition of ingested water and the composition of the substrate (i.e., soil and bedrock) on which the mammalian assemblage lives and feeds. Moreover, such methodology is easily implemented because chemical purification of bone or teeth necessitates the elution of Sr from Ca to remove interferences during analytical measures of the isotope ratios. Sr can therefore be collected separately from the same sample aliquot as Mg, Ca, C, or O. Importantly, a reference map (Willmes et al. 2018) of the isotopic composition of the rock substrate helps one appreciate available variability and represents a framework to test hypotheses of mobilities—for example using models—and can even be applied to ancient contexts (Wooller et al. 2021, Kowalik et al. 2023).

Following the same principles, one can explore other metal proxies if spatial variability (e.g., a substrate map) has been established a priori. Implementation using such a spatial approach can be applied to the recent past where physical landscapes have barely changed compared to extant contexts, but it is less obvious in an ancient setting where paleogeography has changed. The primary importance in exploring additional mobility proxies is to better constrain provenances when a single proxy can yield ambiguous results due to its chemical behavior. Other provenance proxies consist of lead (Mehl et al. 2019, Evans et al. 2022) or neodymium (Plomp et al. 2019), but their low concentration in bone apatite makes them challenging to analyze. Nevertheless, they offer promising perspectives when Sr of substratum origin is mixed with sea breeze (coastal environments) or mixed with fertilizers as concerns modern-day ecosystems (Vitória et al. 2004) or when old igneous substrates cannot be differentiated isotopically from rubidium-rich substrates in radiogenic strontium composition (Evans et al. 2022). Pb also suffers from human-induced pollution but conversely may also allow one to pinpoint specific anthropogenic sources of pollution (Delile et al. 2016, López-Costas et al. 2020). Anthropogenic pollution influences the quality of the modern mammal record but also represents an opportunity to source the origin of the pollution of concern. In addition, such isotopic systems may represent opportunities to investigate the antiquity of anthropogenic pollution in the archeological record.

The above examples mainly deal with terrestrial ecosystems, but mobility among mammals can be important in marine contexts where organisms cover large horizontal distances and even vertical foraging into the abysses. Again, $^{87}$Sr/$^{86}$Sr has proved its utility in numerous ecological
studies involving fishes (Kennedy et al. 2002), and the homogeneous oceanic value reflects a char-
acterization of marine versus freshwater habitats. Major limitations in this isotopic system are that
estuarine waters rapidly mix with homogeneous values of seawater, and the fine-tuning becomes
useful along the different river drainages that reflect substrates. In human populations, those sys-
tems are mostly useful to track seafood preferences. Li isotopes show a large variability in values
and also permit the dichotomy between marine, estuarine, and freshwater habitats (Thibon et al.
2022), as also recently reported for sulphur isotopes (Goedert et al. 2020) as measured in verte-
brate bioapatite in both cases. Ca isotopes show a similar behavior as radiogenic Sr (Holmden
et al. 2012). Although not yet characterized for this application in vertebrate tissues, Ca isotopes
may prove interesting in their application to ancient vertebrates when Sr is diagenetically reset
and where teeth are absent (turtles, mysticetes).

Comparing mercury isotope values of freshwater fish tissues to human hair of an Amazonian community consuming them reveals very interesting patterns, according to Laffont et al. (2009, 2011). The observed isotope fractionation differs when odd or even stable isotopes are considered. Specifically, δ²⁰²Hg is enriched by +2‰ between prey and consumers (Laffont et al. 2009), whereas Δ²⁰¹Hg remains unaffected. A similar pattern has been observed between marine fish tissues and European human hair (Laffont et al. 2011), but with a significantly different Δ²⁰¹Hg ratio. In their study, Laffont et al. (2011) demonstrated that the residence time of monomethylmercury on the water surface controls Δ²⁰¹Hg, which varies greatly between riverine, coastal, and oceanic environments. Therefore, the combination of different Hg isotope ratios can reveal both trophic and provenance information.

# 4. LIMITS AND PERSPECTIVES

A major limitation to our understanding of inferring and/or modeling the ecology and biology
of mammals is inherent to the difficulty of collecting data (stomach content, feeding behavior,
direct observations) in the wild, and this becomes especially true from remote areas (e.g., ma-
rine environments, closed canopy forests). It is needless to stress that such ecological inference
for extinct species is even more difficult to assess. Ecologists have long recognized the utility of
isotopes in providing a spatial and temporal framework because diet, trophic position, or prove-
nance can be directly derived from various biological tissues. As a generality, mineralized accreted
tissues (e.g., teeth, bone, otoliths) provide time resolution of various biological and environmen-
tal variables allowing several biological and ecological questions to be addressed. In this review,
we have underlined the complementary toolkit provided by metal isotopes, with the potential to
serve applications in archeology and paleontology. Yet, it is important to acknowledge that a sin-
gle system alone cannot account for all the information, and the need to further comprehend new
isotopic systems requires cross-checking the variability of natural objects through a multi-proxy
approach. The first prospect is therefore to encourage research that will be based on a multi-proxy
approach. As such, continuing efforts in measuring on the same samples of different isotopic sys-
tems are key to understanding one system. For example, if calcium and zinc have the potential to
be applied in ancient ecosystems to infer trophic positions, one needs to design research in the
modern world to compare calcium and zinc isotope results with known trophic level proxies such
as N isotopes (e.g., Jaouen et al. 2019b, Martin et al. 2023) (Figure 3), C isotopes (e.g., Martin
et al. 2018, Bourgon et al. 2020, Jaouen et al. 2022) (Figure 2), or compound-specific amino acid
isotope compositions (Leichliter et al. 2023, Moubtahij et al. 2024) or even different metal iso-
topes (Guiserix et al. 2024). Conversely, past and ongoing research has highlighted the utility of
N isotopes as trophic level indicators (e.g., Leichliter et al. 2021, 2023; Lüdecke et al. 2022), yet
it is known that spatial heterogeneity of N renders it difficult to compare one ecosystem with
another one because this blurs information for moving species. In such cases, baseline effects
should be investigated for other systems, which in return will help one better understand the
framework in interpreting data for trophic reconstructions using metal isotopes (e.g., McCormack
et al. 2021).

Another avenue of research involves building models in order to predict spatial variability (Bataille et al. 2021), metabolic cycling in the animal's body using box modeling (Jaouen et al. 2019a, Hassler et al. 2021a), or temporal incorporation of isotopic data (Yang et al. 2023). Such models rely on the compilation of isotopic data to create maps or define source reservoirs, which will be used to infer the mobility of organisms or the relative contribution of food types into their diet.

Finally, investigations in deep time require a monitoring of diagenetic processes (Heuser et al. 2011). Post-mortem modifications of the original chemical composition blur or obliterate the potential interpretations based on the studied isotopic systems in fossil remains. It should be stressed that diagenesis is complex and will not alter bioapatite in a homogeneous way. Some elements are more mobile than others, and this depends on temperature, pH conditions of circulating fluids, and/or redox conditions. Experimentally controlled conditions can help in monitoring the effects of diagenesis across different tissue types that are available to fossilization such as compact versus porous bone or enamel (Reynard & Balter 2014, Weber et al. 2021). Mixing models can be useful to predict diagenetic effects knowing the range of expected isotopic values for all isotopic systems of interest (e.g., Martin et al. 2017).

SUMMARY POINTS

1. Metal isotopes, sometime referred to as nontraditional isotopes, were first investigated by geoscientists who developed an array of mass spectrometers designed to ionize elements and measure their isotopic ratios. Biological materials had not been investigated for their metal isotopic composition prior to the late 1990s.

2. Application of metal isotope research to biological materials, including mammal ecology, biology, and physiology, is a relatively new field and was actively supported in the areas of biomedicine, archeology, and paleontology with the intent to diagnose disease and implement new proxies for paleodietary inferences.

3. The field of metal isotope research is by essence multidisciplinary and has started to gather experimentally controlled studies to better assess the significance of the different isotopic records. Predictive models represent key areas of research for guiding sampling strategies of natural objects (biomaterial, water, soils, rocks).

FUTURE ISSUES

1. The main limitation to the dissemination of metal isotope research to a wider community is mostly related to running costs. The initial investment in clean-lab suites, instrument acquisition, and running, excluding dedicated technical staff, largely surpasses $1 million. It is definitely not achievable at small universities and even less so in low- and middle-income countries. Promoting student and researcher access to such new methodologies must be supported via international exchange programs, trainings, and workshops.
2. Multi-collector mass spectrometers have been designed to measure a wide array of isotope systems, including improvements to fine motor cup configuration, electrostatic analyzers, and magnet geometry. One paradox is that investment in such instruments requires different partners, who will each request measurements of one or two different isotopic systems. This creates lengthy tuning between sessions and various technical tuning problems. Designing simpler, element-dedicated instruments will both diminish costs and increase result outputs, boosting statistical significance in our understanding of those isotopic systems.

3. Decompartmentalizing research areas boosts multidisciplinary research. It is worth investing in the training of young generations in the use of these new metal isotope systems. Exploration of the periodic table is far from done, and we need students eager to learn skills in chemistry and physics while choosing a career path in ecology, medicine, forensics, archeology, paleontology, or other disciplines. Metal isotope research is a fantastic medium for creative projects, and the focus on mammals as presented in this review is just one door to this world.

## DISCLOSURE STATEMENT

The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.

## ACKNOWLEDGMENTS

J.E.M. thanks colleagues at Laboratoire de Géologie de Lyon, Terre, Planètes, Environnement, and more specifically at École Normale Supérieure de Lyon during the period 2014–2023, for the rich scientific exchanges and for providing an engaging environment for the development of his research activities on nontraditional isotopes. The authors thank K. Uno and the Editorial Committee for the invitation to publish in the *Annual Review of Earth and Planetary Sciences* as well as an anonymous reviewer for providing constructive comments on an earlier version of this work. J.E.M. was supported by CNRS-INSU and by ANR-19-CE31-0006-01. K.J. was supported by ERC grant 803676.

## LITERATURE CITED

* Albarède F. 2004. The stable isotope geochemistry of copper and zinc. *Rev. Mineral. Geochem.* 55(1):409–27

* Albarède F, Télouk P, Balter V. 2017. Medical applications of isotope metallomics. *Rev. Mineral. Geochem.* 82:851–85

* Albarède F, Télouk P, Lamboux A, Jaouen K, Balter V. 2011. Isotopic evidence of unaccounted for Fe and Cu erythropoietic pathways. *Metallomics* 3:926–33

* Aranaz M, Costas-Rodríguez M, Lobo L, García M, González-Iglesias H, et al. 2022a. Homeostatic alterations related to total antioxidant capacity, elemental concentrations and isotopic compositions in aqueous humor of glaucoma patients. *Anal. Bioanal. Chem.* 414:515–24

* Aranaz M, Valencia-Agudo E, Lobo L, Pereiro R. 2022b. Microsampling of biological fluids for elemental and isotopic analysis by ICP-MS: strategies and applications for disease diagnosis. *J. Anal. Atom. Spectrom.* 37:50–68

* Balter V. 2004. Allometric constraints on Sr/Ca and Ba/Ca partitioning in terrestrial mammalian trophic chains. *Oecologia* 139:83–88

* Balter V, Braga J, Télouk P, Thackeray JF. 2012. Evidence for dietary change but not landscape use in South African early hominins. *Nature* 489:558–60
Balter V, Lamboux A, Zazzo A, Télouk P, Leverrier Y, et al. 2013. Contrasting Cu, Fe, and Zn isotopic patterns in organs and body fluids of mice and sheep, with emphasis on cellular fractionation. *Metallomics* 5:1470–82

Balter V, Vigier N. 2014. Natural variations of lithium isotopes in a mammalian model. *Metallomics* 6:582–86

Balter V, Zazzo A, Moloney AP, Moynier F, Schmidt O, et al. 2010. Bodily variability of zinc natural isotope abundances in sheep. *Rapid Commun. Mass Spectrom.* 24:605–12

Bataille CP, Jaouen K, Milano S, Trost M, Steinbrenner S, et al. 2021. Triple sulfur-oxygen-strontium isotopes probabilistic geographic assignment of archaeological remains using a novel sulfur isoscape of western Europe. *PLOS ONE* 16:e0250383

Bender MM. 1968. Mass spectrometric studies of carbon 13 variations in corn and other grasses. *Radiocarbon* 10:468–72

Bentaleb I, Martin C, Vrac M, Mate B, Mayzaud P, et al. 2011. Foraging ecology of Mediterranean fin whales in a changing environment elucidated by satellite tracking and baleen plate stable isotopes. *Mar. Ecol. Prog. Ser.* 438:285–302

Bentley RA. 2006. Strontium isotopes from the earth to the archaeological skeleton: a review. *J. Archaeol. Method Theory* 13:135–87

Bernard A, Tütken T, Gerdes A. 2013. *Boron isotopes in bones and teeth: a new proxy for dietary reconstructions and its resistance to diagenetic alteration.* 7th International Bone Diagenesis Meeting, Lyon, Fr., Oct. 22–25

Blichtert-Toft J, Chauvel C, Albarède F. 1997. Separation of Hf and Lu for high-precision isotope analysis of rock samples by magnetic sector-multiple collector ICP-MS. *Contrib. Mineral. Petrol.* 127:248–60

Bourgon N, Jaouen K, Bacon AM, Dufour E, McCormack J, et al. 2021. Trophic ecology of a Late Pleistocene early modern human from tropical Southeast Asia inferred from zinc isotopes. *J. Hum. Evol.* 161:103075

Bourgon N, Jaouen K, Bacon AM, Jochum KP, Dufour E, et al. 2020. Zinc isotopes in Late Pleistocene fossil teeth from a Southeast Asian cave setting preserve paleodietary information. *PNAS* 117:4675–81

Bourgon N, Tacail T, Jaouen K, Leichliter JN, McCormack J, et al. 2024. Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach. *Metallomics* 16:mfae026

Cerling TE, Harris JM, MacFadden BJ, Leakey MG, Quade J, et al. 1997. Global vegetation change through the Miocene/Pliocene boundary. *Nature* 389:153–58

Cerling TE, Manthi FK, Mbua EN, Leakey LN, Leakey MG, et al. 2013. Stable isotope-based diet reconstructions of Turkana Basin hominins. *PNAS* 110:10501–6

Channon MB, Gordon GW, Morgan JL, Skulan JL, Smith SM, Anbar AD. 2015. Using natural, stable calcium isotopes of human blood to detect and monitor changes in bone mineral balance. *Bone* 77:69–74

Cherel Y, Hobson KA, Guinet C, Vanpe C. 2007. Stable isotopes document seasonal changes in trophic niches and winter foraging individual specialization in diving predators from the Southern Ocean. *J. Anim. Ecol.* 76:826–36

Chimento NR, Agnolín FL, García-Marsà J, Manabe M, Tsuihiji T, Novas FE. 2024. A large therian mammal from the Late Cretaceous of South America. *Sci. Rep.* 14:2854

Chu NC, Henderson GM, Belshaw NS, Hedges RE. 2006. Establishing the potential of Ca isotopes as proxy for consumption of dairy products. *Appl. Geochem.* 21:1656–67

Clementz MT. 2012. New insight from old bones: stable isotope analysis of fossil mammals. *J. Mammal.* 93:368–80

Clementz MT, Holden P, Koch PL. 2003. Are calcium isotopes a reliable monitor of trophic level in marine settings? *Int. J. Osteoarchaeol.* 13:29–36

Cloquet C, Carignan J, Lehmann MF, Vanhaecke F. 2008. Variation in the isotopic composition of zinc in the natural environment and the use of zinc isotopes in biogeosciences: a review. *Anal. Bioanal. Chem.* 390:451–63

Copeland SR, Sponheimer M, le Roux PJ, Grimes V, Lee-Thorp JA, et al. 2008. Strontium isotope ratios (⁸⁷Sr/⁸⁶Sr) of tooth enamel: a comparison of solution and laser ablation multicollector inductively coupled plasma mass spectrometry methods. *Rapid Commun. Mass Spectrom.* 22:3187–94

Costas-Rodríguez M, Van Heghe L, Vanhaecke F. 2014. Evidence for a possible dietary effect on the isotopic composition of Zn in blood via isotopic analysis of food products by multi-collector ICP-mass spectrometry. *Metallomics* 6:139–46
Delile H, Keenan-Jones D, Blichtert-Toft J, Goiran JP, Arnaud-Godet F, et al. 2016. A lead isotope perspective on urban development in ancient Naples. *PNAS* 113:6148–53

DeNiro MJ, Epstein S. 1978. Influence of diet on the distribution of carbon isotopes in animals. *Geochim. Cosmochim. Acta* 42:495–506

Dosseto A, Lambert K, Cheikh Hassan HI, Fuller A, Borst A, et al. 2023. Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease. *Metallomics* 15:mfad009

Eisenhauer A, Müller M, Heuser A, Kolevica A, Glüer CC, et al. 2019. Calcium isotope ratios in blood and urine: a new biomarker for the diagnosis of osteoporosis. *Bone Rep.* 10:10020

Evans JA, Pashley V, Mee K, Wagner D, Parker Pearson M, et al. 2022. Applying lead (Pb) isotopes to explore mobility in humans and animals. *PLOS ONE* 17:e0274831

Fogel ML. 1989. Nitrogen isotope tracers of human lactation in modern and archaeological populations. *Annual Report of the Director of the Geophysical Laboratory*, Vol. 88, pp. 111–17. Washington, DC: Carnegie Inst.

Funston GF, dePolo PE, Sliwinski JT, Dumont M, Shelley SL, et al. 2022. The origin of placental mammal life histories. *Nature* 610:107–11

Garçon M, Sauzéat L, Carlson RW, Shirey SB, Simon M, et al. 2017. Nitrile, latex, neoprene and vinyl gloves: a primary source of contamination for trace element and Zn isotopic analyses in geological and biological samples. *Geostand. Geoanal. Res.* 41:367–80

Goedert J, Amiot R, Berthet D, Fourel F, Simon L, Lécuyer C. 2020. Combined oxygen and sulphur isotope analysis—a new tool to unravel vertebrate (paleo)-ecology. *Sci. Nat.* 107:10

Green DR, Smith TM, Green GM, Bidlack FB, Tafforeau P, Colman AS. 2018. Quantitative reconstruction of seasonality from stable isotopes in teeth. *Geochim. Cosmochim. Acta* 235:483–504

Guiserix D, Albalat E, Ueckermann H, Davechand P, Iaccheri LM, et al. 2022. Simultaneous analysis of stable and radiogenic strontium isotopes in reference materials, plants and modern tooth enamel. *Chem. Geol.* 606:121000

Guiserix D, Dodat PJ, Jaouen K, Albalat E, Cardoso JM, et al. 2024. Stable isotope composition and concentration systematics of Ca and trace elements (Zn, Sr) in single aliquots of fossil bone and enamel. *Geochim. Cosmochim. Acta* 367:123–32

Hajdas I, Ascough P, Garnett MH, Fallon SJ, Pearson CL, et al. 2021. Radiocarbon dating. *Nat. Rev. Methods* *Primers* 1:62

Hall RL. 1967. Those late corn dates: isotopic fractionation as a source of error in carbon-14 dates. *Mich. Archaeol.* 13:171–80

Hassler A, Martin JE, Merceron G, Garel M, Balter V. 2021a. Calcium isotopic variability of cervid bioapatite and implications for mammalian physiology and diet. *Palaeogeogr. Palaeoclimatol. Palaeoecol.* 573:110418

Hassler A, Martin JE, Ferchaud S, Grivault D, Le Goff S, et al. 2021b. Lactation and gestation controls on calcium isotopic compositions in a mammalian model. *Metallomics* 13:mfab019

Heuser A, Eisenhauer A. 2010. A pilot study on the use of natural calcium isotope (¹⁴Ca/¹⁰Ca) fractionation in urine as a proxy for the human body calcium balance. *Bone* 46:889–96

Heuser A, Eisenhauer A, Scholz-Ahrens KE, Schrezenmeir J. 2016. Biological fractionation of stable Ca isotopes in Göttingen minipigs as a physiological model for Ca homeostasis in humans. *Isotopes Environ. Health Stud.* 52:633–48

Heuser A, Tütken T, Gussone N, Galer SJ. 2011. Calcium isotopes in fossil bones and teeth—diagenetic versus biogenic origin. *Geochim. Cosmochim. Acta* 75:3419–33

Hirata T, Tanoshima M, Suga A, Tanaka YK, Nagata Y, et al. 2008. Isotopic analysis of calcium in blood plasma and bone from mouse samples by multiple collector-ICP-mass spectrometry. *Anal. Sci.* 24:1501–7

Hobin K, Costas Rodríguez M, Vanhaecke F. 2021. Robust potassium isotopic analysis of geological and biological samples via multicollector ICP-mass spectrometry using the “extra-high resolution mode.” *Anal. Chem.* 93:8881–88

Hobson KA, Barnett-Johnson R, Cerling T. 2010. Using isoscapes to track animal migration. In *Isoscapes: Understanding Movement, Pattern, and Processes on Earth Through Isotope Mapping*, ed. J West, G Bowen, T Dawson, K Tu, pp. 273–98. Dordrecht, Neth.: Springer
Hoffmann R, Riechelmann S, Liebetrau V, Eisenhauer A, Immenhauser A. 2021. Calcium isotope values of modern and fossil cephalopod shells—trophic level or proxy for seawater geochemistry? *Chem. Geol.* 583:120466

Holmden C, Papanastassiou DA, Blanchon P, Evans S. 2012. $\delta^{44}/^{40}$Ca variability in shallow water carbonates and the impact of submarine groundwater discharge on Ca-cycling in marine environments. *Geochim. Cosmochim. Acta* 83:179–94

Hu Y, Meng J, Wang Y, Li C. 2005. Large Mesozoic mammals fed on young dinosaurs. *Nature* 433:149–52

Jaouen K, Balter V, Herrscher E, Lamboux A, Télouk P, Albarède F. 2012. Fe and Cu stable isotopes in archeological human bones and their relationship to sex. *Am. J. Phys. Anthropol.* 148:334–40

Jaouen K, Beasley M, Schoeninger M, Hublin JJ, Richards MP. 2016a. Zinc isotope ratios of bones and teeth as new dietary indicators: results from a modern food web (Koobi Fora, Kenya). *Sci. Rep.* 6:26281

Jaouen K, Pons ML, Balter V. 2013. Iron, copper and zinc isotopic fractionation up mammal trophic chains. *Earth Planet. Sci. Lett.* 374:164–72

Jaouen K, Pouilloux L, Balter V, Pons ML, Hublin JJ, Albarède F. 2019a. Dynamic homeostasis modeling of Zn isotope ratios in the human body. *Metallomics* 11:1049–59

Jaouen K, Richards MP, Le Cabec A, Welker F, Rendu W, et al. 2019b. Exceptionally high $\delta^{15}$N values in collagen single amino acids confirm Neandertals as high-trophic level carnivores. *PNAS* 116:4928–33

Jaouen K, Szpak P, Richards M. 2016b. Zinc isotope ratios as indicators of diet and trophic level in arctic marine mammals. *PLOS ONE* 11(3):e0152299

Jaouen K, Trost M, Bourgon N, Colleter R, Le Cabec A, et al. 2020. Zinc isotope variations in archeological human teeth (Lapa do Santo, Brazil) reveal dietary transitions in childhood and no contamination from gloves. *PLOS ONE* 15:e0232379

Jaouen K, Villalba-Mouco V, Smith GM, Trost M, Leichliter J, et al. 2022. A Neandertal dietary conundrum: insights provided by tooth enamel Zn isotopes from Gabasa, Spain. *PNAS* 119:e2109315119

Johnson CM, Beard BL, Albarède F. 2004. Overview and general concepts. *Rev. Mineral. Geochem.* 55:1–24

Kennedy BP, Klaue A, Blum JD, Folt CL, Nislow KH. 2002. Reconstructing the lives of fish using Sr isotopes in otoliths. *Can. J. Fish. Aquat. Sci.* 59:925–29

Knudson KJ, Williams HM, Buikstra JE, Tomczak PD, Gordon GW, Anbar AD. 2010. Introducing $\delta^{88}/^{86}$Sr analysis in archaeology: a demonstration of the utility of strontium isotope fractionation in paleodietary studies. *J. Archaeol. Sci.* 37:2352–64

Koch PL. 2007. Isotopic study of the biology of modern and fossil vertebrates. In *Stable Isotopes in Ecology and Environmental Science*, ed. R Michener, K Lajtha, pp. 99–154. Malden, MA: Blackwell

Kowalik N, Anczkiewicz R, Müller W, Spötl C, Bondioli L, et al. 2023. Revealing seasonal woolly mammoth migration with spatially-resolved trace element, Sr and O isotopic records of molar enamel. *Q. Sci. Rev.* 306:108036

Laffont L, Sonke JE, Maurice L, Hintelmann H, Puilly M, et al. 2009. Anomalous mercury isotopic compositions of fish and human hair in the Bolivian Amazon. *Environ. Sci. Technol.* 43:8985–90

Laffont L, Sonke JE, Maurice L, Monrroy SL, Chincheros J, et al. 2011. Hg speciation and stable isotope signatures in human hair as a tracer for dietary and occupational exposure to mercury. *Environ. Sci. Technol.* 45:9910–16

Leichliter JN, Lüdecke T, Foreman AD, Bourgon N, Duprey NN, et al. 2023. Tooth enamel nitrogen isotope composition records trophic position: a tool for reconstructing food webs. *Commun. Biol.* 6:373

Leichliter JN, Lüdecke T, Foreman AD, Duprey NN, Winkler DE, et al. 2021. Nitrogen isotopes in tooth enamel record diet and trophic level enrichment: results from a controlled feeding experiment. *Chem. Geol.* 563:120047

Lewis J, Pike AW, Coath CD, Evershed RP. 2017. Strontium concentration, radiogenic ($^{87}$Sr/$^{86}$Sr) and stable ($\delta^{88}$Sr) strontium isotope systematics in a controlled feeding study. *STAR Sci. Technol. Archaeol. Res.* 3:45–57

Li Q, Nava A, Reynard LM, Thirlwall M, Bondioli L, Müller W. 2022. Spatially-resolved Ca isotopic and trace element variations in human deciduous teeth record diet and physiological change. *Environ. Archaeol.* 27:474–83

Li Z, Miao HW, Li BK, Lu H. 2021. Comparative study of B content and $\delta^{11}$B in the enamel of isolated teeth from brothers in the same family. *Rapid Commun. Mass Spectrom.* 35:e9171
López-Costas O, Kylander M, Mattielli N, Álvarez-Fernández N, Pérez-Rodríguez M, et al. 2020. Human bones tell the story of atmospheric mercury and lead exposure at the edge of Roman World. *Sci. Total Environ.* 710:136319

Lüdecke T, Leichliter JN, Aldeias V, Bamford MK, Biro D, et al. 2022. Carbon, nitrogen, and oxygen stable isotopes in modern tooth enamel: a case study from Gorongosa National Park, central Mozambique. *Front. Ecol. Evol.* 10:958032

MacFadden BJ, Solounias N, Cerling TE. 1999. Ancient diets, ecology, and extinction of 5-million-year-old horses from Florida. *Science* 283:824–27

Mahan B, Antonelli MA, Burckel P, Turner S, Chung R, et al. 2020. Longitudinal biometal accumulation and Ca isotope composition of the Göttingen minipig brain. *Metallomics* 12:1585–98

Mahan B, Moynier F, Jørgensen AL, Habekost M, Siebert J. 2018. Examining the homeostatic distribution of metals and Zn isotopes in Göttingen minipigs. *Metallomics* 10:1264–81

Mahan B, Tacail T, Lewis J, Elliott T, Habekost M, et al. 2022. Exploring the K isotope composition of Göttingen minipig brain regions, and implications for Alzheimer's disease. *Metallomics* 14:mfac090

Maréchal CN, Télouk P, Albarède F. 1999. Precise analysis of copper and zinc isotopic compositions by plasma-source mass spectrometry. *Chem. Geol.* 156:251–73

Martin JE, Deesri U, Liard R, Wattanapituksakul A, Suteethorn S, et al. 2016. Strontium isotopes and the long-term residency of thalattosuchians in the freshwater environment. *Paleobiology* 42:143–56

Martin JE, Tacail T, Balter V. 2017. Non-traditional isotope perspectives in vertebrate palaeobiology. *Palaeontology* 60:485–502

Martin JE, Tacail T, Cerling TE, Balter V. 2018. Calcium isotopes in enamel of modern and Plio-Pleistocene East African mammals. *Earth Planet. Sci. Lett.* 503:227–35

Martin JE, Tacail T, Simon L, Hassler A, Télouk P, Balter V. 2023. Inferring odontocete life history traits in dentine using a multiproxy approach (δ¹⁵N, δ⁴⁴/⁴²Ca and trace elements). *Rapid Commun. Mass Spectrom.* 37:e9612

Martin JE, Vance D, Balter V. 2014. Natural variation of magnesium isotopes in mammal bones and teeth from two South African trophic chains. *Geochim. Cosmochim. Acta* 130:12–20

Martin JE, Vance D, Balter V. 2015. Magnesium stable isotope ecology using mammal tooth enamel. *PNAS* 112:430–35

Masbou J, Sonke JE, Amouroux D, Guillou G, Becker PR, Point D. 2018. Hg-stable isotope variations in marine top predators of the Western Arctic Ocean. *ACS Earth Space Chem.* 2:479–90

McCormack J, Bourgon N, Sinet-Mathiot V, Rezek Z, Smith GM, et al. 2022. Combining collagen extraction with mineral Zn isotope analyses from a single sample for robust palaeoecological investigations. *Archaeol. Anthropol. Sci.* 14:137

McCormack J, Jaouen K, Bourgon N, Sisma-Ventura G, Tacail TJ, et al. 2024. Zinc isotope composition of enameloid, bone and muscle of gilt-head seabreams (*Sparus aurata*) raised in pisciculture and their relation to diet. *Mar. Biol.* 171:65

McCormack J, Szpak P, Bourgon N, Richards M, Hyland C, et al. 2021. Zinc isotopes from archaeological bones provide reliable trophic level information for marine mammals. *Commun. Biol.* 4:683

Mehl ACSB, Ishida LY, de Faria RA. 2019. Analysis of carbon, oxygen, strontium and lead isotopes in human teeth: inferences for forensic investigation. In *XXVI Brazilian Congress on Biomedical Engineering. IFMBE Proceedings*, Vol. 70/71, ed. R Costa-Felix, J Machado, A Alvarenga, pp. 71–77. Singapore: Springer

Melin AD, Crowley BE, Brown ST, Wheatley PV, Moritz GL, et al. 2014. Calcium and carbon stable isotope ratios as paleodietary indicators. *Am. J. Phys. Anthropol.* 154:633–43

Messa CM, Sims KW, Scott SR, Clementz MT. 2022. Stable Ca isotope fractionation in Cenozoic marine mammals: beyond biomineralization and trophic positioning. In *Isotopic Constraints on Earth System Processes*, ed. KW Sims, K Maher, DP Schrag, pp. 301–28. Hoboken, NJ: Am. Geophys. Union

Morgan JL, Skulan JL, Gordon GW, Romaniello SJ, Smith SM, Anbar AD. 2012. Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes. *PNAS* 109:9989–94

Moubtahij Z, McCormack J, Bourgon N, Trost M, Sinet-Mathiot V, et al. 2024. Isotopic evidence of high reliance on plant food among Later Stone Age hunter-gatherers at Taforalt, Morocco. *Nat. Ecol. Evol.* 8:1035–45
Moynier F, Foriel J, Shaw AS, Le Borgne M. 2017. Distribution of Zn isotopes during Alzheimer's disease. *Geochem. Perspect. Lett.* 3:142–50

Moynier F, Fujii T, Shaw AS, Le Borgne M. 2013. Heterogeneous distribution of natural zinc isotopes in mice. *Metallomics* 5:693–99

Moynier F, Hu Y, Wang K, Zhao Y, Gérard Y, et al. 2021. Potassium isotopic composition of various samples using a dual-path collision cell-capable multiple-collector inductively coupled plasma mass spectrometer, Nu instruments Sapphire. *Chem. Geol.* 571:120144

Newsome SD, Clementz MT, Koch PL. 2010. Using stable isotope biogeochemistry to study marine mammal ecology. *Mar. Mammal Sci.* 26:509–72

Newsome SD, Etnier MA, Monson DH, Fogel ML. 2009. Retrospective characterization of ontogenetic shifts in killer whale diets via δ¹³C and δ¹⁵N analysis of teeth. *Mar. Ecol. Progr. Ser.* 374:229–42

Oftedal OT. 2002. The mammary gland and its origin during synapsid evolution. *J. Mammary Gland Biol. Neoplasia* 7:225–52

O'Leary MA, Bloch JI, Flynn JJ, Gaudin TJ, Giallombardo A, et al. 2013. The placental mammal ancestor and the post-K-Pg radiation of placental. *Science* 339:662–67

Passey BH, Cerling TE. 2002. Tooth enamel mineralization in ungulates: implications for recovering a primary isotopic time-series. *Geochim. Cosmochim. Acta* 66:3225–34

Passey BH, Cerling TE, Schuster GT, Robinson TF, Roeder BL, Krueger SK. 2005. Inverse methods for estimating primary input signals from time-averaged isotope profiles. *Geochim. Cosmochim. Acta* 69:4101–16

Pederzani S, Britton K, Trost M, Fewlass H, Bourgon N, et al. 2024. Stable isotopes show *Homo sapiens* dispersed into cold steppes ~45,000 years ago at Ilsenhöhle in Ranis, Germany. *Nat. Ecol. Evol.* 8:578–88

Peek S, Clementz MT. 2012. Sr/Ca and Ba/Ca variations in environmental and biological sources: a survey of marine and terrestrial systems. *Geochim. Cosmochim. Acta* 95:36–52

Perrot V, Pastukhov MV, Epov VN, Husted S, Donard OF, Amouroux D. 2012. Higher mass-independent isotope fractionation of methylmercury in the pelagic food web of Lake Baikal (Russia). *Environ. Sci. Technol.* 46:5902–11

Plomp E, von Holstein IC, Koornneef JM, Smeets RJ, Baart JA, et al. 2019. Evaluation of neodymium isotope analysis of human dental enamel as a provenance indicator using 10¹³ Ω amplifiers (TIMS). *Sci. Just.* 59:322–31

Reynard B, Balter V. 2014. Trace elements and their isotopes in bones and teeth: diet, environments, diagenesis, and dating of archeological and paleontological samples. *Palaeogeogr. Palaeoclimatol. Palaeoecol.* 416:4–16

Schoeninger MJ. 2014. Stable isotope analyses and the evolution of human diets. *Annu. Rev. Anthropol.* 43:413–30

Shroff R, Lalayiannis AD, Fewtrell M, Schmitt CP, Bayazit A, et al. 2022. Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease. *Kidney Int.* 102:613–23

Sillen A. 1986. Biogenic and diagenetic Sr/Ca in Plio-Pleistocene fossils of the Omo Shungura Formation. *Paleobiology* 12:311–23

Simmons NB, Seymour KL, Habersetzer J, Gunnell GF. 2008. Primitive Early Eocene bat from Wyoming and the evolution of flight and echolocation. *Nature* 451:818–21

Skulan J, DePaolo DJ. 1999. Calcium isotope fractionation between soft and mineralized tissues as a monitor of calcium use in vertebrates. *PNAS* 96:13709–13

Skulan J, DePaolo DJ, Owens TL. 1997. Biological control of calcium isotopic abundances in the global calcium cycle. *Geochim. Cosmochim. Acta* 61:2505–10

Smuts GL, Anderson JL, Austin JC. 1978. Age determination of the African lion (*Panthera leo*). *J. Zool.* 185:115–46

Suga S, Gustafson G. 1962. Studies on the development of rat enamel by means of histochemistry, microradiography and polarized light microscopy. *Arch. Oral Biol.* 7:223–244

Sullivan KV, Moore RE, Vanhaecke F. 2023. The influence of physiological and lifestyle factors on essential mineral element isotopic compositions in the human body: implications for the design of isotope metallomics research. *Metallomics* 15:mfad012
Tacail T, Albalat E, Télouk P, Balter V. 2014. A simplified protocol for measurement of Ca isotopes in biological samples. *J. Anal. Atom. Spectrom.* 29:529–35

Tacail T, Le Houedec S, Skulan JL. 2020. New frontiers in calcium stable isotope geochemistry: perspectives in present and past vertebrate biology. *Chem. Geol.* 537:119471

Tacail T, Lewis J, Clauss M, Coath CD, Evershed R, et al. 2023. Diet, cellular, and systemic homeostasis control the cycling of potassium stable isotopes in endothermic vertebrates. *Metallomics* 15:mfad065

Tacail T, Martin JE, Arnaud-Godet F, Thackeray JF, Cerling TE, et al. 2019. Calcium isotopic patterns in enamel reflect different nursing behaviors among South African early hominins. *Sci. Adv.* 5:eaaax3250

Tacail T, Télouk P, Balter V. 2016. Precise analysis of calcium stable isotope variations in biological apatites using laser ablation MC-ICPMS. *J. Anal. Atom. Spectrom.* 31:152–62

Tacail T, Thivichon-Prince B, Martin JE, Charles C, Viriot L, Balter V. 2017. Assessing human weaning practices with calcium isotopes in tooth enamel. *PNAS* 114:6268–73

Tanaka YK, Yajima N, Higuchi Y, Yamato H, Hirata T. 2017. Calcium isotope signature: new proxy for net change in bone volume for chronic kidney disease and diabetic rats. *Metallomics* 9:1745–55

Thibon F, Goedert J, Séon N, Weppe L, Martin JE, et al. 2022. The ecology of modern and fossil vertebrates revisited by lithium isotopes. *Earth Planet. Sci. Lett.* 599:117840

Trayler RB, Kohn MJ. 2017. Tooth enamel maturation reequilibrates oxygen isotope compositions and supports simple sampling methods. *Geochim. Cosmochim. Acta* 198:32–47

Tsutaya T, Yoneda M. 2015. Reconstruction of breastfeeding and weaning practices using stable isotope and trace element analyses: a review. *Am. J. Phys. Anthropol.* 156:2–21

Tütken T. 2014. Isotope compositions (C, O, Sr, Nd) of vertebrate fossils from the Middle Eocene oil shale of Messel, Germany: implications for their taphonomy and palaeoenvironment. *Palaeogeogr. Palaeoclimatol. Palaeoecol.* 416:92–109

Uhen MD. 2010. The origin (s) of whales. *Annu. Rev. Earth Planet. Sci.* 38:189–219

Van der Merwe NJ. 1982. Carbon isotopes, photosynthesis, and archaeology: Different pathways of photosynthesis cause characteristic changes in carbon isotope ratios that make possible the study of prehistoric human diets. *Am. Sci.* 70:596–606

Van der Merwe NJ, Thackeray JF, Lee-Thorp JA, Luyt J. 2003. The carbon isotope ecology and diet of *Australopithecus africanus* at Sterkfontein, South Africa. *J. Hum. Evol.* 44:581–97

Van Heghe L, Engström E, Rodushkin I, Cloquet C, Vanhaecke F. 2012. Isotopic analysis of the metabolically relevant transition metals Cu, Fe and Zn in human blood from vegetarians and omnivores using multicollector ICP-mass spectrometry. *J. Anal. Atom. Spectrom.* 27:1327–34

Vitória L, Otero N, Soler A, Canals A. 2004. Fertilizer characterization: isotopic data (N, S, O, C, and Sr). *Environ. Sci. Technol.* 38:3254–62

Vogel JC. 1978. Isotopic assessment of the dietary habits of ungulates. *S. Afr. J. Sci.* 74:298

Walczyk T. 2004. TIMS versus multicollector-ICP-MS: coexistence or struggle for survival? *Anal. Bioanal. Chem.* 378:229–31

Weber K, Weber M, Menneken M, Kral AG, Mertz-Kraus R, et al. 2021. Diagenetic stability of non-traditional stable isotope systems (Ca, Sr, Mg, Zn) in teeth—an in-vitro alteration experiment of biogenic apatite in isotopically enriched tracer solution. *Chem. Geol.* 572:120196

Willmes M, Bataille CP, James HF, Moffat I, McMorrow L, et al. 2018. Mapping of bioavailable strontium isotope ratios in France for archaeological provenance studies. *Appl. Geochem.* 90:75–86

Wooller MJ, Bataille C, Druckenmiller P, Erickson GM, Groves P, et al. 2021. Lifetime mobility of an Arctic woolly mammoth. *Science* 373:806–8

Yang D, Bowen GJ, Uno KT, Podkovyroff K, Carpenter NA, et al. 2023. BITS: a Bayesian Isotope Turnover and Sampling model for strontium isotopes in proboscideans and its potential utility in movement ecology. *Methods Ecol. Evol.* 14:2800–13

Ziegler S, Merker S, Streit B, Boner M, Jacob DE. 2016. Towards understanding isotope variability in elephant ivory to establish isotopic profiling and source-area determination. *Biol. Conserv.* 197:154–63