Elsevier

Toxicology

Volume 186, Issues 1–2, 15 April 2003, Pages 151-157
Toxicology

Accumulation of silver from drinking water into cerebellum and musculus soleus in mice

https://doi.org/10.1016/S0300-483X(02)00743-6Get rights and content

Abstract

In spite of the general toxicity, ecotoxicity and sparsely known metabolism of silver, WHO allows silver ions (Ag) up to 0.1 mg/l in drinking water disinfection. In order to determine the accumulation and distribution of silver in a mammalian body, mice were given for 1 and 2 weeks drinking water containing a 3-fold lower concentration, namely 0.03 mg/l silver ions as silver nitrate labelled with 110mAg. The silver concentrations in different tissues were analysed by gamma radioactivity. The saturation of tissues with silver seems to occur quickly, as there were no statistical differences between silver contents of mice tissues in spite of the study design that mice were administered silver for 1 or 2 weeks. The highest concentrations were found in musculus soleus (m. soleus), cerebellum, spleen, duodenum, and myocardial muscle in the rank order. Concentrations of silver in musculus gastrocnemius (m. gastrocnemius) were found to correlate negatively with cerebrum and positively with blood and kidneys. The accumulation of silver into organs and tissues important in motor functions may be of relevance especially in emergency and catastrophe situations in which accurate motor functions may be critical. A re-evaluation of the present recommendations on the use of silver salts for disinfection of drinking water might be necessary.

Introduction

Silver salts are allowed as disinfectants of drinking water in ships, military actions etc. (EEC, 1980), so that the use of silver can last days or weeks and a possible accumulation could happen. Elementary silver or silver ions are used as active compounds in many different household water filters advertised for instance by Internet for catastrophe areas. Silver is considered toxic for humans and the recommendations of the World Health Organisation (WHO) permit maximal concentrations of 0.1 mg/l of silver ions in drinking water disinfection (WHO, 1996) but EPA (1980) recommends maximally 0.05 mg/l.

Silver is known to accumulate from water in many organisms such as brown algae (Sjöblom and Ojala, 1981), shellfish (Smith et al., 1986, George et al., 1986, Topcuoğlu et al., 1987) and fish (Garnier and Baudin, 1990, Grosell and Wood, 2001, Webb and Wood, 2002). Silver nitrate is absorbed through the lung and mucous membranes (WHO, 1996). Silver ion is transported in blood and bound into globulins (EPA, 1980). Most accumulation has been reported to occur in mammalian liver, skin and fur (Furchner et al., 1968, Beresford, 1989, Saeki et al., 2001). The systemic toxicity of silver is not well documented when silver compounds are used in wound repair treatments (Lansdown, 2002). A major part of original animal tests used for the toxicity evaluation for WHO Guidelines for drinking water disinfection by silver has been made between 1940s and 1970s (WHO, 1996). Because analysis technique and toxicology have developed and got new tools since those days, there is a need to re-evaluate those animal tests.

Silver ions are able to pass the blood–brain barrier and cerebrospinal fluid–brain barrier (Rungby, 1990). For example, in rats silver is found, e.g. in the hypothalamic neurons (Stoltenberg et al., 1994) disturbing hippocampus development (Rungby, 1990).

Silver has been reported to affect lipid peroxidation in rat liver, but not in kidney and brain (Rungby, 1990). Cardiac necroses and decrease of blood glutathione peroxidase has been reported in silver treated swine (Van Vleet and Ferrans, 1992). Toop et al. (1982) have reported an accumulation of silver in active myofibrils of cats.

Due to its microbicidal effects in water peroral silver also affects intestinal microbes (Kalachniuk et al., 1994) and potentially provokes gastrointestinal disorders. Silver compounds are known to decrease the creatine clearance, which may be due to its potential nephrotoxicity (Rosenman et al., 1987).

This study was made in order to measure the possible accumulation of silver from drinking water into tissues in male mice, because drinking waters not treated with silver contain only very little or ‘non-detectable’ amounts of silver (EPA, 1980), so that possible accumulation of silver from permanent drinking water is not reported.

Section snippets

Methods

Male outbreed NIH/S mice (10–12 weeks old, weight 23–26 g, National Institute of Health, Kuopio, Finland) were used. Before the start of the experiment the mice were adapted for 1 week to live alone in metabolic cages (Scanbur A/S, Denmark) in regulated environment with a temperature of 21±1 °C, relative air humidity of 50±20%, with 15–20 air changes per h, and a 12-h light:12-h dark cycle. The metabolic cages were cleaned once a week. Five mice received 110mAg labelled (specific radioactivity

Results

All animals survived the 1 or 2 weeks period of drinking silver nitrate treated water without any observable external signs of disturbed health equally to the controls. The concentrations of silver in the mice tissues have been given in Table 1. Pooled data for the 1 and 2 weeks’ experiment are also given, since there were no differences between silver concentrations of the tissues after 1 and 2 weeks. The statistical evaluation of differences between tissue concentrations is based on the

Discussion

Silver accumulated in mice especially into cerebellum and m. soleus. The accumulation to m. soleus has not been reported earlier. The silver contents of human corpses have been found to follow the descending order: skin, liver, adrenals, brain, thyroid, caecum, ovary and trachea (Humphreys and Routledge, 1998). Silver concentrations in different human tissues including brain tissues showed, anyhow, a great (more than 100-fold) variation and the silver concentrations of female tissues were

Acknowledgements

We thank Dr Kai Tuovinen for help with animal tests and for discussions and Jaana Leskinen for radioactivity measurings.

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