Registration Dossier

Administrative data

Description of key information

Inorganic lead compounds do not exhit toxicity in acute toxicity tests with experimental animals.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50

Additional information

Read-across approach for lead containing glass, oxide, chemicals:

The test item is covered under the definition "glass". In this context, “glass" is defined as an amorphous, inorganic, transparent, translucent or opaque substance formed by variouspowdery substances (mostly oxides) which are not present as such in the final glass: they are fully integrated into the glass matrix through the melting process and they lose their original characteristics. Thus, the available analytical information is only of quantitative nature without any indication as to elemental composition or structural purposes. Based on the definition under Regulation (EC) No 1907/2006, the test item fulfils the criteria for UVCB substances.

Substance-specific information for the test item glass, oxide, chemicals (water solubility < 100 mg/L) are not available. For this reason, read-across is anticipated to lead monoxide as a moderately soluble lead substance.

This read-across is considered justified and also conservative since lead monoxide (water solubility approx. 700 mg/L at 20°C) is one of the major starting materials (content ranging from approx. 30-80%) for the test item manufacture, and also represents the component of major toxicological concern.

For the substantiation of read-across, solubility tests (T/D and bioaccessibility) were performed with the test item in order to determine the release of lead from the “glass” matrix for a comparison to the solubility of the selected read-across substance.

The following lead concentrations were measured in two T/D tests with the test item with variable lead monoxide concentrations (starting material concentration):

Test material with a PbO content of 38.4%:

After 7 days, the dissolution of Pb ranged from 17.0 ± 1.99 µg/L (pH 8) to 18.7 ± 2.08 µg/L (pH 6).

After 28 days, the dissolution of Pb ranged from 37.8 ± 3.64 µg/L (pH 8) to 60.1 ± 17.2 µg/L (pH 6).

Based on the nominal test item amount, the maximum dissolution of Pb at pH 6 from the test item corresponded to 6.01% (w/w); based on contained lead 5.95% (w/w).

At pH 8, the maximum dissolution of Pb after 24 h based on contained Pb was 3.68 µg/L (1.03% (w/w)).

Test material with a PbO content of 78.0%:

After 7 days, the dissolution of Pb ranged from 53.8 ± 8.53 µg/L (pH 8) to 562 ± 86.1 µg/L (pH 6).

After 28 days, the dissolution of Pb ranged from 110 ± 8.28 µg/L (pH 8) to 684 ± 22.8 µg/L (pH 6).

At pH 6, the maximum dissolution of Pb from the test item was 68.4% (w/w) based on nominal test item loading. Based on contained Pb, the dissolution corresponded to 94.3 % (w/w).

At pH 8, the maximum dissolution of Pb after 24 h based on contained Pb was 29.4 µg/L (4.06 % (w/w)).

In comparison, a water solubility of lead monoxide (saturation solubility, OECD 105; Heintze 2005) of is given with 70.2 mg/L in the REACH registration dossier and in the "Voluntary Risk Assessment for Lead and Lead Compounds"; a T/D screening test at pH = 8 with a 100 mg/L loading revealed an average (+- SD) dissolved Pb concentration after 24 hours of 101 (+-0.003) µg/L.

Based on the above data, the release of Pb fromthe test item glass, oxide, chemicals is substantial, but eithersimilar or lower compared to pure PbO. Thus, read-across to lead monoxide can be considered scientifically justified and sufficiently conservative.

Discussion:

Although lead can exert toxic effects upon multiple organ systems and body functions, this toxicity manifests under conditions of sub-chronic to chronic exposure that can range from months to years in duration. Acute toxicity is not observed in animals after oral, inhalation or dermal lead oxide exposures up to the limit values of acute toxicity testing. For oral and dermal exposures, data demonstrating lack of lead oxide toxicity are available for doses of 2000 mg/kg/bw or higher. No adverse effects of inhalation are observed up to 5 mg/L lead oxide in air. The validity of these findings is reinforced by lack of acute oral and dermal toxicity for several other inorganic lead compounds similar in chemistry and solubility. Finally, toxicity in humans after true acute exposures is limited and, when documented, is generally under conditions that yield sub-chronic or chronic exposures. This finding is not unexpected given the pharmacokinetics of lead uptake into the body. Lead uptake is generally quite low and heavily reliant upon easily saturable active transport mechanisms. Once saturation of these uptake mechanisms has occurred, uptake proceeds by inefficient passive diffusion. The uptake of lead is thus highly non-linear as a function of dose with uptake efficiency declining with the amount of lead administered to a test animal or an exposed human. Although toxic under chronic exposure situations, the acute toxicity of lead oxide is low.

Justification for classification or non-classification

The current classification of lead compounds not otherwise described in Annex I is:

Xn; R20/22 (harmful by inhalation and if swallowed)

and under CLP:

Acute Tox. 4 *                       (H332)

Acute Tox. 4 *                       (H302)

Existing classifications for acute toxicity are not supported by the existing data or read across. Acute toxicity is not observed in animals after oral, inhalation or dermal exposures, up to the limit values of acute toxicity testing, for lead oxide. Acute toxicity is not observed in animals after oral exposures up to the limit values of acute toxicity testing for six different similar inorganic lead compounds.  Two similar compounds are also lacking in dermal toxicity and in irritancy properties for the skin or eyes. Although toxic under chronic exposure situations, the acute toxicity of lead oxide is predicted to be quite low and does not require classification.