# Archeometric detection of mercury: A paleopharmacological case study of skeletal remains of a child with vitamin deficiencies (Rouen, France, late 18–19th centuries)

Alexandra Zinn, Aminte Thomann, Yannick Lefrais, Olivier Dutour, Antony Colombo

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## To cite this version:

Alexandra Zinn, Aminte Thomann, Yannick Lefrais, Olivier Dutour, Antony Colombo. Archeometric detection of mercury: A paleopharmacological case study of skeletal remains of a child with vitamin deficiencies (Rouen, France, late 18–19th centuries). International Journal of Paleopathology, 2025, 49, pp.29-36. 10.1016/j.ijpp.2025.02.006. hal-05038553

HAL Id: hal-05038553

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Submitted on 19 May 2025

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**Archeometric detection of mercury: a paleopharmacological case study of skeletal remains of a child with vitamin deficiencies (Rouen, France, late 18th-19th centuries).**

**Authors:**

Alexandra Zinn¹*, Aminte Thomann², Yannick Lefrais¹, Olivier Dutour¹,³, Antony Colombo¹,³*

**Authors information:**

¹UMR 6034 Archéosciences, Université Bordeaux Montaigne, F- 33600 Pessac, France

²Inrap, F-76120 Le Grand-Quevilly, France

³École Pratique des Hautes Études - PSL Université, F-75014 Paris, France

UMR 6034 Archéosciences, Université Bordeaux Montaigne, F- 33600 Pessac, France

alexandra.zinn@u-bordeaux-montaigne.fr, antony.colombo@ephe.psl.eu

**ORCID:**

Alexandra Zinn, 0009-0003-1819-4165

Aminte Thomann, 0000-0003-3130-4966

Yannick Lefrais, none

Olivier Dutour, 0000-0001-8134-788X

Antony Colombo, 0000-0002-8855-7502

**Keywords:** Health; Vitamin deficiencies, Industrialization, Micro-CT, Energy dispersive X-ray fluorescence, Cold vapor atomic absorption spectroscopy

**Abstract:**

**Objective:** The French medico-historical literature reports the common use of mercury-based treatments until the mid-19th century. An exploratory paleopharmacological approach is presented for detecting mercury in a child's skeletal remains suffering from vitamin deficiencies. This aims to corroborate written sources and provide a way to better understand diseases therapeutic management.

**Materials:** This study focuses on a 3 to 4-year-old child showing signs of rickets and possible scurvy, from “rue Thubeuf” cemetery (Rouen, late 18th-19th centuries). Analysis was carried out on a thoracic vertebral body and the right second deciduous mandibular molar.

<footnote>*Corresponding authors:</footnote>
**Methods:** Energy dispersive X-ray fluorescence (ED-XRF) and cold vapor atomic absorption spectroscopy (CV-AAS) provided mercury detection and quantification. Micro-CT analysis was implemented to detect the interglobular dentine potentially related to vitamin D deficiency.

**Results:** The ED-XRF spectrum showed a mercury peak for the vertebra, none for the molar. The vertebra CV-AAS analysis revealed a high mercury rate of 9.373 mg/kg.

**Conclusions:** The individual was likely exposed to high mercury levels originating from therapeutic treatment, potentially for vitamin deficiencies, in the last months of life.

**Significance:** Paleopharmacological analysis is an important tool in the analysis of medical treatment in the past.

**Limitations:** Soil analysis could contribute to improved knowledge of contamination sources.

**Further research:** This approach should be expanded to more individuals to better assess the treatment frequency of vitamin deficiency diseases during industrialization.

1

# 1. Introduction

Industrialization was a complex process which led to multiple economic, social, technological, scientific, and epidemiological changes and transitions mainly during the 18th-19th centuries (Crane-Kramer and Buckberry, 2023). It started in the UK during the 18th century and swiftly expanded worldwide (Crane-Kramer and Buckberry, 2023). French industrialization came about later and was a slower and more continuous process that took place in two phases between 1830 and 1914 (Colombo et al., 2021; Perrin et al., 2023).

The rapid growth of science and technology driven by industrialization led to the development of advanced medical systems and public health policies, chemistry, medicine, biology and pharmacy (Durand et al., 2000; Chauveau, 2014; Crane-Kramer and Buckberry, 2023), significantly improving the quality of life (i.e., higher birth rate, reduced infants' mortality, longer life expectancy, and reduced mortality from infectious diseases) for certain privileged populations (Durand et al., 2000; Crane-Kramer and Buckberry, 2020).

Alternatively, industrialization also led to environmental and societal changes which significantly impacted people's health, such as the increase of air pollution, overpopulation in urban areas and child labor in coal mines and textile factories. These changes, which occurred differently across countries may have amplified demographic growth, reduced access to nutritional resources and limited exposure to sunlight, ultimately increasing the prevalence of
deficiency diseases such as rickets and scurvy, particularly among low to middle socio-
economical groups of population (Colombo et al., 2021).

In light of these major socio-politico-historical and environmental changes, relevant studies on the paleoepidemiology of vitamin deficiency diseases has been published in the recent years (Mays, 2014; Mays et al., 2009; Schattmann et al., 2016; Mays, 2018; Mays and Brickley, 2018; Colombo et al., 2021; Perrin et al., 2023; Crane-Kramer and Buckberry, 2023), providing a different picture of these diseases' prevalence in France and, more generally, in Europe during the Industrial Era. However, one aspect of these diseases during the industrial transition has not been yet studied: their therapeutic management and evolution.

The current study will focus on rickets and scurvy because of the co-occurrence between these two diseases (Schattmann et al., 2016). Rickets is a childhood disease resulting from severe vitamin D deficiency which impairs the mineralization of newly formed bone and can lead to skeletal deformities detectable in human skeletal remains (Estrade et al., 2017). Vitamin D is produced inside the skin from sunlight exposure and can also be supplemented by diet in smaller amounts (Holick, 2003). Insufficient mineralization during endochondral growth results in porous bone beneath the epiphyseal growth plates, particularly at the ends of long bones, while inadequate mineralization in bone formed through appositional growth leads to porosity on the subperiosteal cortical surface. Additionally, poor maintenance of existing bone tissue can cause skeletal structures to deform under mechanical forces (Ortner and Mays, 1998; Mays et al., 2006; Mays et al., 2009).

Scurvy is a disease caused by vitamin C deficiency leading to a production of poor-quality collagen, which weakens connective tissues like blood vessel walls, is characterized by hemorrhagic phenomena, and disrupts osteoid production and calcification. If left untreated, scurvy can lead to death (Mays, 2014; Stark, 2014; Schattmann et al., 2016). Furthermore, these two diseases can co-occur; resulting in the presence and interaction between the diseases (Schattmann et al., 2016).

French historical literature from the late 17th to the early 20th centuries reports several prophylactic treatments for these deficiency diseases such as plant mixtures or treatments including metals, in particular mercury (Cadet, 1742; Praslin, 1768; Portal, 1797, 1808, 1814; Virey, 1819; Chonnaux-Dubisson, 1868). Mercury, a heavy metal that is liquid at room
temperature, is now recognized as a global pollutant and highly toxic without known biological function, though it was used for centuries as a common ingredient in medicines (WHO, 2007; Bensefa-Colas, 2011; Berlin, 2015). The integration of mercury in medical practices has been reported since antiquity in Chinese, Egyptian, Greek, and Arabic medicine (Norn et al., 2008). It was used specifically to treat skin diseases, either inflammatory or infectious, such as syphilis (Claiborne, 1911), but also as a purgative and antiparasitic medication (Norn et al., 2008; Beers and Mousavi 2013).

During the 18th-19th centuries, mercury became a common treatment for rickets and scurvy, to a lesser extent (Portal, 1797, 1808, 1814; Henry and Guibourt, 1834). It was part of the so-called Bellet or Cuisinier syrups (i.e., mercurial syrups), which were special ointments and plasters containing mercury nitrate salt combined with extracts of hemlock and opium and then applied to the body to alleviate friction (Portal, 1797). Antoine Portal, a French biologist, anatomist and physician, was among the pioneers who suggested prescribing mercurial syrup for treatment (Portal, 1797). Another form of oral administration was the ingestion of grains of mercury chloride (corrosive sublimate) (Henry and Guibourt, 1834; Portal, 1814). It has also been administrated through fumigation in a heated chamber using cinnabar (crude mercury sulfide) (Abraham, 1948).

Mercury was recommended to treat nurses and their sick patients, including infants, children and pregnant women until the emergence of negative side effects, such as excessive salivation (Praslin, 1768; Portal, 1808, 1814). Regardless of the method of administration, mercury treatment led to detrimental consequences: behavior alterations, oral irritation, dental decay, gastrointestinal inflammation, weight loss (Dracobly, 2004; Powell and Cook, 2005), possible neurological, renal, respiratory, dermatological, reproductive, and developmental complications, and ultimately, death (Risher and Amler, 2005).

Mercury was also used to treat rickets and scurvy, as rickets may have been considered a consequence of other diseases including venereal infections, scrofula, scurvy, or other dermatological, degenerative, hereditary diseases (Chonnaux-Dubisson, 1868; Portal, 1797, 1814). It is only in the second half of the 19th century that Bouvier (1856) and Saint-Germain (1883) considered rickets as a unique disease in France.
During the 19th century, cod liver oil (the only effective treatment for rickets, before the discovery of vitamin D) was offered as a treatment. In 1827, it was first introduced in France by Pierre-Fidèle Bretonneau and Armand Trousseau (Schlienger and Monnier, 2019) but mercury was predominantly recommended as a treatment for rickets until the mid-19th century (Weatherill, 1833).

The variability of mercury compounds, combined with differences in dosage and exposure duration, poses significant challenges for paleopharmacological research. Mercury toxicity and absorption pathways in the human body depend on the specific chemical form and route of exposure (Clarkson, 2007; Berlin et al., 2015). In nature, mercury exists in various chemical states, including inorganic forms, which includes elemental mercury (Hg⁰) and its two oxidation states: mercurous (Hg–Hg²⁺) and mercuric (Hg²⁺) cations (mercuric salts), as well as organic compounds such as methyl- and ethyl-mercury (Clarkson, 2007; Bensefa-Colas, 2011; Alvarez-Fernandez, 2020).

While liquid elemental mercury is poorly absorbed (reduced health risks), it is highly volatile. Inhaled "mercury vapors" are readily absorbed into the lungs; the central nervous system being the most vulnerable target. Vapor exposure, often seen in occupational settings, has been responsible for numerous cases of mercury poisoning (Clarkson, 2007; Alvarez-Fernandez, 2020). Hg²⁺ can enter the body through ingestion or dermal contact; the kidneys and gastrointestinal tract being the primary targets. However, due to the relative stability and low solubility of mercury salts, their bioavailability and absorption are limited (Berlin et al., 2015; Clarkson, 2007; Alvarez-Fernandez, 2020). Methyl-mercury, on the contrary, is highly lipid-soluble and absorbable, and easily crosses the cellular membranes (Berlin et al., 2015; Clarkson, 2007; Alvarez-Fernandez, 2020).

The mechanism of mercury accumulation in the organs, skin, and hair is well documented but remains unclear regarding bone and dental tissue. However, it has been hypothesized that mercury can bond with carbonates in bones or replace calcium ions in hydroxyapatite (Garcia et al., 2001; Saber-Tehrani et al., 2007; Brigato et al., 2009). Based on this premise, studies have been carried out to detect and quantify mercury in human skeletal remains (Rasmussen et al., 2008; Emslie, 2019; Lopez-Costas, 2016; Lombardo et al., 2022). Nevertheless, identification of mercury as a treatment in archeological human remains is uncommon (Lombardo et al., 2022; Fiorin et al., 2018, Gismondi et al., 2018, Hardy et al., 2012)
Historically, two mercury forms were widely used in pharmacology until the 20th century: calomel, a mercurous chloride, and elemental mercury vapor (Clarkson, 2007; Bensefa-Colas, 2011). Paleopharmacology is a recent field of research, aiming to identify medicinal substances and plants used in ancient cultures through the analysis of organic remains in archaeological contexts (Hardy et al., 2009; Cox, 2014). This paper presents an exploratory archeometric work to detect mercury in human osteoarcheological remains that might have been used as a treatment in a nineteenth-century French child suffering from vitamin deficiencies (rickets and scurvy).

## 2. Material and methods

### 2.1. Archeological context and excavated skeletal human remains

The skeletal remains under investigation were excavated from the archeological site of “rue Thubeuf” located in Rouen, France (Figure 1), a city with poor sunlight exposure and a high risk of vitamin D deficiency (Chapuy et al., 1997). The archaeological excavation was located near an ancient necropolis, the Saint-Gervais priory and its church, containing early medieval burials, and within the limits of the Saint-Gervais parish cemetery, which was used from 1780 to 1883 (Jimenez, 2019). During the excavation, 53 burials were uncovered. Among them, 18 were studied.

<figure><img src="image_3.png" /><figcaption>Figure 1. From left to right: The location of Rouen in France, the archeological site of “rue Thubeuf”, and the location of Individual SP5 in situ (red arrow).</figcaption></figure>
## 2.2 Individual SP5

Individual SP5 originates from the cemetery area dated to the late 18th - 19th centuries and was recovered from a primary burial, positioned supine with the upper and lower limbs extended, which are joined at the knees and ankles. The archeothanatological and taphonomical study suggests that Individual SP5 was interred in a coffin (Jimenez, 2019). Age at death estimation was carried out using Moorrees et al. (1963), based on dental mineralisation stages. Pathological indications of scurvy and rickets were based on lesions described by Brickley et al. (2018); Snoddy et al. (2018), Brickley and Morgan, (2023), and included porosity and/or subperiosteal new bone formation (SPNB) of the maxillary bone, mandible, costo-chondral rib flaring, biomechanical bending of upper limb long bones, long bone metaphyseal flaring/cupping of ends, metaphyseal long bone cortical porosity, and mineralization defects of dentine.

The second lower deciduous molar, developing from birth to 3 years old according to Moorrees et al. (1963), was selected for evaluation of interglobular dentin (IGD) to identify potential deficiency events during life (d'Ortenzio et al., 2018). In addition, a thoracic vertebral body, a highly vascularized bone, was chosen to access cortical and trabecular bone in order to provide information about the last months of life.

## 2.3 Analytical methods

### 2.3.1 Micro-computed tomography (µCT) analysis

Useful to detect IGD (Colombo et al., 2019), the µCT scans were acquired using a General Electric v|tome|x S microscanner at the UAR 3626 PLACAMAT, University of Bordeaux, at a resolution of 12 µm. Acquisition parameters were: rotation of 360°, 1400 images, frame averaging of 3, exposure time of 500 ms, voltage of 110kV, and current of 200 µA. The reconstructed images were analyzed with Avizo 8.1 software.

### 2.3.2 X-ray Fluorescence for mercury detection on both bone and tooth samples

Energy Dispersive X-ray Fluorescence (ED-XRF) was conducted using a SEA6000VX ID_6501 ED-XRF spectrometer at the UMR 6034 Archéosciences Bordeaux, Bordeaux Montaigne University. The device has an X-ray tube using a rhodium target (50kV/1ma) with a Vortex silicon drift detector. Data was processed using X-Ray software. To detect mercury (Hg), two analysis conditions were set up at 15 kV and 50 kV; each parameter was adapted to
light and heavy elements respectively and assessed with a collimator of 1.2 mm in diameter and with a peak acquisition time of 300 s.

### 2.3.3 Cold Vapor Atomic Absorption Spectroscopy (CV-AAS) on bone and tooth samples

The atomic absorption process allows for mercury quantification, unlike ED-XRF which only confirms its presence. It was used in the final stage of the methodology to minimize destruction of the osteoarchaeological samples. Standard mercury solutions of known concentrations were used to calibrate the measurements. The thoracic vertebra and second deciduous mandibular molar were cut in half with a diamond wire saw and were pulverized in an agate mortar. The resulting powder was analyzed with a DMA-80 Tricon at the UMR 5805 EPOC, University of Bordeaux. The cortical and trabecular parts of the bone could not be isolated because of the weight required for the analysis. The device accuracy was tested with a certified sample of estuarine sediment, 277R, with a verified mercury concentration of 128 µg/kg (see Supplementary Information Table 1). Subsequently, 100 mg of powder from each sample were deposited in crucibles and examined for 6 minutes each after calibration.

## 3. Results

Individual SP5 died at the estimated age of 3 to 4 years old and displayed multiple signs of deficiencies probably linked to rickets and scurvy (Table 1, Figure 2).

<table><caption>Table 1: Paleopathological lesions related to vitamin deficiencies observed on the skeletal remains of Individual SP5 *</caption><thead><tr><td>Paleopathological signs on SP5 indicative of:</td><td>Rickets</td><td>Scurvy</td></tr></thead><tbody><tr><td>Porosity and/or SPNB** of the maxillary bone</td><td></td><td>✓</td></tr><tr><td>Porosity and/or SPNB of the mandible (coronoid process, medial face)</td><td></td><td>✓</td></tr><tr><td>Porosity and/or SPNB of the maxillary and/or mandibular alveolar bone</td><td></td><td>✓</td></tr><tr><td>Costo-chondral rib flaring (a combination of impaired/defective mineralization and biomechanical deformity)</td><td>✓</td><td>✓</td></tr><tr><td>Biomechanical bending of upper limb long bones</td><td>✓</td><td></td></tr><tr><td>Long bone metaphyseal flaring/cupping of ends</td><td>✓</td><td>✓</td></tr><tr><td>Metaphyseal long bone cortical porosity</td><td>✓A**</td><td>✓</td></tr><tr><td>Mineralization defects of dentine</td><td>✓A/H**</td><td></td></tr></tbody></table>

Brickley et al. (2018); Snoddy et al. (2018), Brickley and Morgan, (2023)

<footnote>*Information derived from Jimenez, (2019), following the paleopathological diagnostic tools:</footnote>

<footnote>** SPNB: subperiosteal new bone formation, A: Active, H: Healed</footnote>
<figure><img src="image_4.png" /><figcaption>Figure 2. (a) *in situ* burial of Individual SP5, complete skeleton; (b) pathological signs associated with possible scurvy, including periosteal reaction and microporosity of the maxilla, medial aspect of the mandibular ramus and right temporal bone; (c) pathological signs associated with possible scurvy and rickets: deformations of the rib sternal extremities; (d) pathological signs associated with rickets: accentuated anteroposterior curvatures of the ulna and metaphyseal modifications of distal femur and proximal tibia.</figcaption></figure>

The µCT images of the second lower deciduous molar allowed the detection of a small amount of IGD at the base of dentine horns. The amount of IGD might correspond to a low deficiency event that occurred between birth and six months old (Figure 3). ED-XRF analysis enabled us to produce spectra for the vertebral body and tooth samples from Individual SP5. A peak, corresponding to mercury, was detected in the trabecular bone (Figure 4a) but not in the cortical bone (Figure 4b) or in the tooth (Figure 4c). The CV-AAS analysis of the SP5 samples revealed contrasting mercury concentrations; the dental sample showed a non-significant level of 0.084 mg/kg (± 10% uncertainty), whereas the vertebral body exhibited a
significantly higher concentration of 9.373 mg/kg (± 10% uncertainty), over a hundred times greater than that found in the dental sample.

<figure><img src="image_5.png" /><figcaption>Figure 3. µCT scan of the right mandibular second deciduous molar (sagittal section, resolution of 12 µm) of Individual SP5. The white circle identifies the interglobular dentine (IGD).</figcaption></figure>
<figure><img src="image_6.png" /></figure>

<figure><img src="image_7.png" /></figure>

<figure><img src="image_8.png" /><figcaption>Figure 4. ED-XRF spectra of the samples from the individual SP5: (a) trabecular bone</figcaption></figure>
of the thoracic vertebral body; (b) cortical bone of the thoracic body; (c) right mandibular deciduous second molar.

**4. Discussion**

The µCT-scan showed a small area of IGD revealing a potential low vitamin D deficiency episode occurring between birth and the age of 6 months. This level of vitamin D deficiency is **unlikely** responsible for the bone modifications observed macroscopically, suggesting that Individual SP5 might have suffered from at least two episodes of vitamin D deficiency throughout their lifetime (d'Ortenzio et al., 2018; Jimenez, 2019). **Indicated by macroscopic changes, the second, more severe episode might have occurred after the selected tooth completed its development (c. 3 years old), as no IGD has been identified in the dentine. Also, this second vitamin D deficiency event might have been associated with vitamin C deficiency (as some bone signs are consistent with possible scurvy). Vitamin deficiencies closer to the death of Individual SP5 might have been treated with mercury-based medicines.**

The ED-XRF revealed the presence of mercury in the trabecular part of the bone sample, which was quantified in the whole bone sample using CV-AAS, revealing concentrations over a hundred times greater than in the tooth. This trabecular bone concentration might be considered abnormal. First, in comparison to other paleopharmacological studies (Table 2), our results fall within the higher range of other cases of mercury detection. Our value is similar to the Alghero child (Sardinia, late 16th century) who was probably treated with mercury, the bone values ranged from 8.482 to 10.008 mg/kg (Lombardo et al., 2022). Second, mercury in vivo reference values in human blood is considered normal between 0.005 and 0.01 mg/L (WHO, 2008). Even if bone and blood are very different tissues, given that mercury accumulation in bones typically occurs through the bloodstream, the significant difference between the concentration in our bone sample (9.373 mg/kg) and expected blood levels is noteworthy, although not directly comparable. This discrepancy suggests that the mercury concentration in the Individual SP5's bone sample is unlikely to represent a normal value.

Table 2: Summary of ante-mortem mercury contamination studies in human osteoarchaeological remains from past populations in Europe (adapted from Alvarez-Fernandez et al., 2020; Lombardo, 2022).
<table><thead><tr><td>Reference</td><td>Period (AD)</td><td>Location</td><td>Context of mercury use</td><td>Tissue sampled</td><td>Hg concentration (mg/kg)</td></tr></thead><tbody><tr><td>Present study</td><td>19<sup>th</sup></td><td>France</td><td>Medical treatment?</td><td>Bone</td><td>9.373 ± 10%</td></tr><tr><td>Present study</td><td>19<sup>th</sup></td><td>France</td><td>Medical treatment?</td><td>Teeth</td><td>0.084 ± 10%</td></tr><tr><td>Rasmussen et al., 2008</td><td>12<sup>th</sup> - 19<sup>th</sup></td><td>Denmark</td><td>Medical treatment</td><td>Bone</td><td>0.180 ± 0.048</td></tr><tr><td>Rasmussen et al., 2008</td><td>12<sup>th</sup> - 19<sup>th</sup></td><td>Denmark</td><td>Medical treatment</td><td>Bone</td><td>0.05 ± 0.11</td></tr><tr><td>Rasmussen et al., 2008</td><td>12<sup>th</sup> - 19<sup>th</sup></td><td>Denmark</td><td>Use and production of mercury-based products (red ink or medical treatment)</td><td>Bone</td><td>0.068 ± 0.232</td></tr><tr><td>Rasmussen et al., 2017</td><td>13<sup>th</sup> - 19<sup>th</sup></td><td>Denmark</td><td>Medical treatment</td><td>Bone</td><td>0.014 ± 0.019</td></tr><tr><td>Walser et al., 2019</td><td>11<sup>th</sup> - 12<sup>th</sup></td><td>Iceland</td><td>Medical treatment</td><td>Bone</td><td>0.223 ± 0.333</td></tr><tr><td>Alexandrovskaya and Alexandrovskiy, 2005</td><td>14<sup>th</sup> - 17<sup>th</sup></td><td>Russia</td><td>Gilding vapours and industry</td><td>Bone</td><td>0.3 ± 0</td></tr><tr><td>Alexandrovskaya and Alexandrovskiy, 2005</td><td>15<sup>th</sup> - 17<sup>th</sup></td><td>Russia</td><td>Medical treatment, gilding vapours, barometer, cosmetics and dyes</td><td>Bone</td><td>0.9 ± 4.3</td></tr><tr><td>Panova et al., 2018</td><td>16<sup>th</sup> - 17<sup>th</sup></td><td>Russia</td><td>Medical treatment and poisoning</td><td>Bone</td><td>5.720 ± 26.740</td></tr><tr><td>Kępa et al., 2012</td><td>15<sup>th</sup></td><td>Poland</td><td>Medical treatment</td><td>Bone</td><td>2-2.8</td></tr><tr><td>Rasmussen et al., 2013</td><td>16<sup>th</sup> - 17<sup>th</sup></td><td>Czech Republic</td><td>Medical treatment</td><td>Bone</td><td>0.064 ± 0.014</td></tr><tr><td>Gómez-González et al., 2020</td><td>12<sup>th</sup> - 13<sup>th</sup></td><td>Spain</td><td>Medical treatment</td><td>Bone</td><td>0.066</td></tr><tr><td>Rasmussen et al., 2012</td><td>16<sup>th</sup> - 17<sup>th</sup></td><td>Italy</td><td>Medical treatment</td><td>Bone</td><td>8.8 ± 5.5</td></tr><tr><td>Lombardo et al., 2022</td><td>Renaissance</td><td>Sardinia</td><td>Medical treatment</td><td>Bone</td><td>9.759 ± 0.221<br>8.968 ± 0.401</td></tr><tr><td>Lombardo et al., 2022</td><td>Renaissance</td><td>Sardinia</td><td>Medical treatment</td><td>Teeth</td><td>3.748 ± 0.317</td></tr></tbody></table>

Several hypotheses can be put forward to understand the abnormal levels of mercury in Individual SP5. According to the literature, the presence of mercury in ancient bones can be linked to medical treatments for diseases such as leprosy and syphilis in Europe (Rasmussen et al., 2008; 2013; Lombardo et al., 2022; Alvarez-Fernandez et al., 2020). Other direct factors can also induce abnormal mercury concentrations; for example, the presence or use of dental amalgams, cosmetics, or pigments (Alexandrovskaya and Alexandrovskiy 2005,
Rasmussen et al., 2008). Consumption of contaminated food (Emslie et al., 2021; Bocca et al., 2018) can also cause elevated mercury levels. Indirect factors like air pollution (Alvarez-Fernandez et al., 2020; Lopez-Costas et al., 2020), mining, metallurgical practices (Parker et al., 2023), craft practices, such as millinery (Matthews David et al., 2023), volcanic emissions (Walser et al., 2019), or mortuary ritual (Yamada et al., 1995; Avila et al., 2014) can also lead to high concentrations.

The environmental, historical and social context surrounding the excavation site needs to be taken into account. The risk of the contamination of our samples through the soil and sediments is unlikely as the local geology in Rouen does not contain mercury-rich minerals or materials (Quesnel et al., 2007). Hence, post-depositional mercury linked to the geology/metallogeny of the soil is unlikely.

Socio-historical research on the Saint-Gervais district of Rouen during the 19th century revealed that it was known as the "cotton parish" with its "rouenneries" (i.e., painted cotton canvas), evidenced by the "greniers à étentes" (i.e., drying sheds) used for spreading and drying fabrics after dyeing (Petit and de La Conté, 2011; Jimenez, 2019; Lecherbonnier, 2023). Rouen was the second French center for "indiennage": the partial coloring methods of cotton fabrics involving metallic mordants (Chassagne, 1996; Petit and de La Conté, 2011). However, mercury was not used in this craft since it had no relevant chemical properties for dyeing or color fixation processes in textiles (Viel, 2005). Thus, the possibility of mercury contamination due to the local textile industry is unlikely. However, Rouen was also known for its earthenware, which could have potentially used mercury in the gilding and enameling processes (Germain-Donnat, 2006). Nevertheless, the workshops were not located in the Saint Gervais district, but rather on the Seine River left bank, which renders unlikely mercury contamination from this type of source (Germain-Donnat, 2006).

During the industrialization period, major cities had mirror or hat factories, where craftsmen frequently used mercury for mirrors' reflective layer and hats' felt production (Matthews David et al., 2023; Guillerme, 2007). Archival research has identified several mirror and hat factories within the perimeter of the archeological site during the 19th century (Petit and de La Conté, 2011). Even though mercury contamination of working adults in this area remains possible, it is unlikely that very young children were exposed to the same extent.
Given the young age at death of Individual SP5 and their pathological status, an exposure due to labor conditions appears unlikely and the hypothesis of poisoning through medication or food, favored. The potential for food contamination, in particular methylmercury in fish, is also unlikely since contamination arose with industrialization and large-scale mercury emissions in the later 20th century (Danel, 2019).

The medico-historical literature has highlighted the use of mercury in numerous medical treatments, and specifically for diseases such as rickets and scurvy during the 18th-19th (Portal, 1797, 1808, 1814; Henry and Guibourt, 1834, Danel 2019). Though it is impossible to determine with certainty the origin of high concentration of mercury in Individual SP5's bone sample, the medication hypothesis is reasonable.

The variation in mercury presence and concentration between bone and tooth samples warrants discussion. Bone remodeling, vascularization, and bone porosity, especially for trabecular bone, may allow a more thorough and rapid absorption of mercury compared to the dental matrix (Rasmussen et al., 2017; Rasmussen et al., 2013). It is therefore possible that a short exposure to mercury could explain the difference in levels found in the two samples. In addition, the development of the mandibular deciduous second molar was likely complete at the time of mercury exposure, so that mercury could no longer be easily absorbed in dental mineral tissues but might still be in bones having undergone remodeling (Clarkson et al., 2007; Vincent et al., 2010; Valentin and Streffer, 2002). These data support an exposure to mercury at the end of the individual's life.

The hypothesis of a brief exposure to mercury is in line with Hutchinson and Moon's studies, which show that the impact of mercurial treatment can lead to tooth growth disturbance during enamel development (Hutchinson 1878, 1887; Moon 1884). Hutchinson observed differences between the teeth of individuals with congenital syphilis and teeth with anomalies attributed to mercury exposure (Hutchinson, 1878). However, several factors can influence the manifestation of mercurial teeth, including the dose of mercury administered to the individual, the rate of mercury absorption and the total duration of treatment (Berlin, 2015). These considerations indicate that the effects of mercury treatment on teeth can vary considerably. As Individual SP5's molar showed no enamel growth anomalies, and the other teeth do not show any abnormal development, the hypothesis of a prolonged mercury
treatment can be ruled out. Thus, a brief exposure in the last months of its life, resulting in severe poisoning, is plausible.

**5. Conclusion**

Individual SP5, a young child buried in Rouen, France during the 19th century, likely suffered from a couple of vitamin deficiency diseases; rickets and possible scurvy. A high concentration of mercury was detected in the bone sample of this individual and reveals a potential case of ante-mortem mercury poisoning.

Mercury was commonly used as a medical treatment against rickets, and to a lesser extent scurvy in the 18th-19th centuries. Research into the potential origins and sources of mercury contamination in Rouen included soil metallogeny, environmental factors, and the use of mercury in the professional/industrial sector. These unlikely sources of contamination in Individual SP5 renders the hypothesis that medical treatment was the source high concentrations of mercury reasonable. If this is the case, Individual SP5 might reflect the first paleopathologically documented case of mercury treatment associated with vitamin deficiencies. This case study highlights the importance of adopting a paleopharmacological approach, combined with medico-historical research, to better understand therapeutic practices in the past.

**Acknowledgments**

This study received financial support from the French government as part of the "Investissements d'avenir" IdEx program at the University of Bordeaux / GPR "Human Past." The authors would like to express their gratitude to the research labs UMR 5199 PACEA, UMR 6034 Archéosciences Bordeaux, and UMR 5805 EPOC for providing free access to the necessary instrumentation for the archeometric analyses, and especially to Nicolas Vanderesse, Éric Pubert, Alexandra Coynel, Cécile Bossy and Thomas Colard for their support. Finally, the

authors are thankful to the anonymous reviewers and editors of the journal, especially Anne L. Grauer, for their pertinent comments and Theodore L. West for his precise and appreciated editing of the English language, all of them having contributed greatly to improving the manuscript.
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