Concentrates of lead and zinc compounds with sulfur resulting from hydrometallurgy (hot acid leaching, super-hot acid leaching and flotation)

Endpoint summary

Description of key information

According to transformation/dissolution study (OECD guidance 29) conducted for the substance, the most critical constituents leachable to water from this UVCB substance are lead and zinc compounds. Therefore, the toxicokinetic assessment focuses on the properties of constituents and the key values for CSA are selected based on the read-across data on the most bioavailable compounds of Pb and Zn.
Pb compounds
Lead is most easily taken up into the body through inhalation or ingestion Dermal absorption of lead through unabraded human skin is considered to be minimal (<0.1%) and thus absorption of inorganic lead compounds through the skin is considered to be of less significance than absorption through the respiratory and gastrointestinal routes. 
Lead will distribute to a variety of tissue compartments such as blood, bone and soft tissues.
Lead in blood has a half life of 30 – 45 days. Lead is retained far longer in bones - up to 30 years. Lead excretion is primary via urinary and biliary excretion routes.
Zn compounds
For the soluble zinc compounds, the available information suggests an oral absorption value of 20%. For slightly soluble and insoluble zinc compounds it is assumed that the oral absorption is ≤ 12%. The inhalation absorption for the soluble zinc compounds is a maximum of 40% and for the slightly soluble and insoluble zinc compounds inhalation absorption is at a maximum of 20%. The dermal absorption of zinc compounds through intact skin is expected to be less than 2%.
Zinc appears to be distributed to all tissues and tissue fluids.
The excretion of zinc is primarily via faeces, but also via urine, saliva, hair loss, sweat and mothers-milk.

Additional information

The health hazard assessment was conducted based on the most critical constituents of the substance. This substance is an UVCB substance and can be described as a moist solid powder which is insoluble to water. Therefore, the transformation/dissolution study (OECD guidance 29) was conducted for the substance and the results of this study were used for the chemical safety assessment.

According to the chemical composition analysis, the product consists primarily of sulphur (ca. 35 %), lead (ca. 25 %) and zinc (ca. 17 %) together with minor trace elements such as silver, silicon, aluminium, calcium and iron.

The transformation and dissolution study (OECD guidance 29) results indicated that the release at pH 6 was higher for all studied elements compared to release at pH 8. Therefore the following 7 and 28 day studies were conducted at pH 6. Based on the screening test results (loading rate 100 mg/L), the most critical components for the assessment were lead and zinc, with releases of 8282 µg/L and 75.4 µg/L, respectively. The other minor leachable metals were silver (34.7 µg/L), cadmium (0.48 µg/L) and copper (17.2 µg/L).

Results from the 7 day T/D test (loading rate 100 mg/L, pH 6) showed similar trend in release rates: 12333 µg/L (Pb), 91.4 µg/L (Zn), 15.6 µg/L (Cu), 31.4 µg/L (Ag) and 0.056 µg/L (Cd). In the 28 day test with lower loading rate (1 mg/L, pH 6), only concentrations of Pb (362.4 µg/L) and Zn (3.2 µg/L) were over the detection limits or blank sample values.

According to T/D study results, the most soluble and critical components of this substance are lead and zinc. Therefore, the studies for this endpoint have been selected as a read-across data for the critical constituents. The read-across justification is presented in CSR annex I. All read-across data for toxicokinetics are based on test data using either soluble Pb or Zn salts or measured (dissolved) Pb or Zn concentrations. The weight of evidence approach was used to make conclusions on the key value for CSA. Conclusion for this endpoint is based on read-across data from zinc and lead compounds.

Lead compounds

Animal studies serve to validate mechanistic inferences derived from observational human studies. The majority of information pertaining to lead toxicokinetics has been accurately defined in humans of different ages and degrees of susceptibility to lead toxicity. A number of toxicokinetic models have been developed to predict the effects of external lead exposure upon internal or systemic levels of lead. The Integrated Exposure Uptake Biokinetic (IEUBK) is now widely applied to assess relationships between environmental lead exposure and blood lead in children. Due to limitations in the ability of the IEUBK model to assess the deposition and subsequent remobilisation of lead from bone, use of the IEUBK model is generally restrict to predict exposures in children six years of age or younger.

Physiologically-based pharmacokinetic models (e. g. the O'Flaherty Model) have been developed to predict lead uptake in humans of all ages but is most commonly applied in the assessment of adult exposures. Both the O'Flaherty and IEUBK models are available as computer simulation models and are discusses in greater detail in IUCLID section 7.10.5.

Lead is most easily taken up into the body through inhalation or ingestion – dermal uptake makes a negligible contribution to systemic lead levels. Once taken up into the body, lead is not metabolized. However, lead will distribute to a variety of tissue compartments such as blood, bone and soft tissues. The half-life of lead in the body varies as a function of body compartment. Lead in blood has a half life of 30 – 45 days – measurement of lead in blood thus provides an integrated assessment of average lead exposure (via all routes) over the preceding month. Lead is retained far longer in bones. Depending upon bone type, the retention time of lead can vary between 8 and 30 years. Such lead can both serve as a source of endogenous lead exposure and as a cumulative index of exposure over a time frame of years. Lead excretion is primary via urinary and biliary excretion routes.

Discussion on absorption rate:

Human data are available and superced the animals studies that have been conducted - one of which is described here. Detailed studies on dermal uptake in humans are described in IUCLID section 7.10.5. Dermal absorption of lead through unabraded human skin is considered to be minimal and thus absorption of inorganic lead compounds through the skin has previously been considered to be of less significance than absorption through the respiratory and gastrointestinal routes. The most recent guideline-conformed in-vitro dermal absorption study (Toner and Roper, 2005) has established absorption of lead to be less than 0.1%. Other quantitative estimates of dermal absorption are limited in reliability with the most rigorous study (Moore et. al. 1980) suggesting uptake on the order of 0.01 – 0.18%. However, the data from many published studies on this aspect largely lack compliance with current guideline requirements, and their reliability and relevance for human health risk assessment is questionable.

Zinc coumpounds

Zinc compounds release, depending on their solubility, zinc cations which determine the biological activity of the respective zinc compounds. Based on the mineralogical composition, two major constituents of this target substance in addition to lead are zinc and sulphur. Zinc appears in sulphide form in the target substance. According to the 7-day and 28-day transformation/dissolution study at 100, 10 and 1 mg loadings (OECD guidance 29) zinc and sulphur are also soluble from the target substance. Since sulphur can appear either in sulphide or sulphate form in water, the read-across data focuses on the properties of zinc sulphate and other bioavailable forms of zinc (see read-across justification in Annex I of the CSR).

Zinc is an essential trace element which is regulated and maintained in the various tissues mainly by the gastrointestinal absorption and secretion during high and low dietary zinc intake and because of the limited exchange of zinc between tissues, a constant supply of zinc is required to sustain the physiological requirements. The zinc absorption process in the intestines includes both passive diffusion and a carrier-mediated process. The absorption can be influenced by several factors such as ligands in the diet and the zinc status. Persons with adequate nutritional levels absorb 20-30% and animals absorb 40-50%. Persons that are zinc deficient absorb more, while persons with excessive zinc intake absorb less.

For the soluble zinc compounds, the available information suggests an oral absorption value of 20%. This value can be considered as the lower bound range at adequate nutritional levels. The oral absorption of the slightly soluble zinc oxide has been shown to be 60% of that of the soluble zinc compounds. This corresponds to approximately 12-18%. No oral absorption information is available for the remaining slightly soluble and insoluble zinc compounds (i. e., ZnO, Zn(OH)2, Zn3(PO4)2, ZnCO3, Zn, ZnS). However, considering that these substances have lower water solubility than ZnO, it can be conservatively assumed that the oral absorption of these compounds is ≤ 12%.

Animal data suggests that there is pulmonary absorption following inhalation exposure. Half-life values of 14 and 6.3 hours were reported for dissolution of zinc oxide. The absorption of inhaled zinc depends on the particle size and the deposition of these particles therefore data was provided on the particle size distribution of zinc aerosol from three different industry sectors. The particle size distribution data was evaluated by using a multiple path particle deposition (MPPDep) model. This model revealed that for zinc aerosols the largest part of the deposition is in the head region and much less in the tracheobronchial and pulmonary region. Although most of the material deposited in the head and tracheobronchial region is rapidly translocated to the gastrointestinal tract, a part will also be absorbed locally.

Based on data for local absorption of radionuclides in the different airway regions, it can be assumed that the local absorption of the soluble zinc compounds will be approximately 20% of the material deposited in the head region, 50% of the material deposited in the tracheobronchial region and 100% of the material deposited in the pulmonary region. For the slightly soluble and insoluble zinc compounds a negligible absorption can be assumed for materials deposited in the head and the tracheobronchial region. 100% of the deposited slightly or insoluble zinc compounds are assumed to be absorbed in the pulmonary tract. The deposited material will be cleared via the lung clearance mechanisms into the gastrointestinal tract where it will follow oral absorption kinetics. Therefore the inhalation absorption for the soluble zinc compounds is a maximum of 40% and for the slightly soluble and insoluble zinc compounds inhalation absorption is at a maximum of 20%. These values can be assumed as a reasonable worst case, because they are considered to cover existing differences between the different zinc industry sectors with respect to the type of exercise activities (and thus breathing rate) and particle size distribution.

The available information from in vivo as well as the in vitro studies suggests the dermal absorption of zinc compounds through intact skin to be less than 2%. In vitro studies that estimated dermal absorption values only on the basis of the zinc levels in the receptor medium without taking into account the zinc present in the stratum corneum appear to underestimate absorption values derived from in vivo studies. Such zinc trapped in the skin layers may become systemically available at a later stage. Quantitative data to evaluate the relevance of this skin depot are however lacking. Given the efficient homeostatic mechanisms of mammals to maintain the total body zinc and the physiologically required levels of zinc in the various tissues to be constant, the anticipated slow release of zinc from the skin is not expected to disturb the homeostatic zinc balance of the body. Considering the available information on dermal absorption, the default for dermal absorption of all zinc compounds (solutions or suspensions) is 2%. Based on the physical appearance, for dust exposure to zinc and zinc compounds a 10-fold lower default value of 0.2% is a reasonable assumption.

Zinc appears to be distributed to all tissues and tissue fluids and it is a cofactor in over 200 enzyme systems. The excretion of zinc is primarily via faeces, but also via urine, saliva, hair loss, sweat and mothers-milk.