Silver carbonate

Endpoint summary

Description of key information

Oral exposure: three oral repeated dose animal toxicity studies (Tamimi et al. 1998; Kim et al., 2008 and 2010) were identified as key studies for poorly soluble silver substances (as silver nanomaterial) and soluble silver compounds (as silver nitrate). The studies were well conducted and reported, but the study reported by Tamimi et al (1998) has some limitations due to the route of administration. The studies by Kim et al (2008 and 2010) were conducted using silver nanomaterial as test material; in the absence of relevant and reliable data on non-nano silver, these studies were used as a worst case.
Inhalation exposure: Information is based on SCOEL (1993): The Scientific Committee on Occupational Exposure Limits (SCOEL). Recommendations from Scientific Expert Group on Occupational Exposure Limits for Metallic Silver. Document No. SEG/SUM/25B 1993.  The relevant studies are summarized in IUCLID sections 7.10.

Additional information

Oral exposure:

The studies by Kim et al (2008 and 2010) were conducted using silver nanomaterial as test material; in the absence of relevant and reliable data on non-nano silver, these studies were used as a worst case.

In the study reported by Kim et al. (2008), treatment of male and female rats with silver nanoparticles for 28 days revealed effects on red blood cell parameters at and above 300 mg/kg bw/d. Evidence of liver damage was observed by increases of alkaline phosphatase, cholesterol and total protein levels at dose levels of 300 and 1000 mg/kg bw/d. Histopathological examinations revealed bile duct hyperplasia in livers already for low dose group animals.

As in the 28 -day study, the target organ for the silver nanoparticles was found to be the liver in both male and female rats after 90-day of exposure (Kim et al. 2010). Significant dose-related changes were found in alkaline phosphatase and cholesterol levels of male and female rats at and above 125 mg/kg bw/d, indicating slight liver damage. Histopathology revealed slightly higher incidences of bile-duct hyperplasia with or without necrosis, fibrosis and/or pigmentation in treated animals together with a dose-dependent accumulation of silver in all tissues examined. Bile duct hyperplasia with or without necrosis/fibrosis was regarded as minimal and due to silver nanoparticles.

 

• Metallic silver: 13-week repeated dose oral toxicity study in rats with silver nanomaterial:
  NOAEL 30 mg/kg bw/d

 

The study reported by Tamimi et al. (1998) has its limitations resulting from the route of administration and the uncertainties about the real dose levels given. Animals were exposed by swabbing of the oral cavity with a mouth wash containing silver nitrate at different concentrations. Dose levels are stated in mg/kg without any further explanation. It can be assumed that by swabbing of the oral cavity with the mouth wash only a certain amount of the substance available in the swab is applied to the mucosal surface, and in addition, only a relatively small amount is assumed to be swallowed and available by the oral route.

The main effects observed in the study are local effects (staining of teeth and tongue and mild inflammation of the gum, tongue and oesophagus) resulting from the route of administration. However, beside an effect on platelet counts, which can be regarded as of questionable toxicological relevance, no signs of systemic effects were observed at the high dose level of 150 mg/kg, which can be regarded as a NOAEL for systemic effects. Taking the uncertainties related to the route of administration into consideration it appears appropriate to assume that only a minor amount of the dose applied was available for systemic oral toxicity. Thus as a default approach, about 1% is assumed as the available dose resulting in a NOAEL of 1.5 mg/kg bw/d. In the same study, the acute oral toxicity of the mouthwash was investigated and LD50 values of about 430 mg/kg are presented for male and female rats.

 

• Silver nitrate: 30-day repeated dose toxicity study in rats with mouth wash containing silver nitrate
  NOAELcorr: 1.5 mg/kg bw/d

 

Inhalation Exposure:

In the SCOEL (1993) document on OELs for metallic silver (attached to section 13 of the technical dossier) it is stated that, since the main chronic effects of silver and silver salts is argyria of skin, eyes, nails, mucous membranes and/or internal organs, the OELs are derived based on occupational exposure reports.

Local argyria may result from dust of metallic silver or aerosols of silver salts, and systemic argyria is observed after ingestion of silver compounds only. Local argyrosis, as deposition in the conjunctivae of the eyes, seems to be the most sensitive effect (Buckley et al, 1965; Rungby J, 1986; Green and Su, 1987). These effects are irreversible, but they are cosmetic rather than damaging to health.

 

In a study conducted by Wölbling et al. (1988), no cases of argyria were observed in workers exposed to metallic silver (0.003-0.54 mg/m³), but argyrosis was observed in workers exposed to silver compounds in the range of 0.005-0.38 mg/m³(Roseman et al, 1979 and 1987; Pifer et al, 1989). Perrone et al (1977) observed 4 argyria cases of the eye in workers exposed to 0.022 mg/m³(respirable dust) / 0.31 mg/m³(total dust) of metallic silver.

 

In conclusion, silver salts appear to cause effects at lower concentrations than metallic silver. Total dust is more indicative than respirable dust for local argyrosis in the conjunctivae of the eyes. All data together indicate a threshold effect in the range 0.2-0.5 mg/m³total silver dust.