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

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50

Additional information

All available studies indicate a very low acute oral toxicity of inorganic lead compounds. There was also no evidence of any local or systemic toxicity associated with the oral administration of any of seven different lead compounds (including lead pthalate). Whether or not the compound contained the anion of an inorganic acid or an organic acid had no effect upon toxicity, and literature searches found no indications that anions present in high production volume compounds not tested would impart properties of toxicity different from those that have been tested. Based upon these overall observations, both experimental data and read across from other lead compounds permits the conclusion to be drawn that lead styphnate will not be acutely toxic via oral exposure routes.

Acute toxicity was not observed in animals after inhalation or dermal exposures up to the limit values of acute toxicity testing for a smaller number of compounds. Inhalation studies were restricted to lead oxide, a material found to have a particle size distribution that would approximate that of other sparingly soluble lead compounds and lead metal powder. Pulmonary deposition modelling further indicated that lead oxide provided a good surrogate for other lead compounds in that similar pulmonary deposition patterns, and corresponding local and systemic exposures, would be similar to those of other compounds. Read across from lead oxide inhalation data to other compounds was thus scientifically justified and in the interests of animal welfare. Similarly, a group of three compounds (lead oxide, lead pthalate and dibasic lead phosphite) were tested for dermal toxicity and irritation endpoints. The three compounds selected spanned the range of chemistries (organic and inorganic anions) and solubilities found for a number of other lead compounds. Data demonstrating lack of toxicity and irritant properties were generated for and provide a basis for read across for other lead compounds that is similarly scientifically justified and in the interests of animal welfare. The uniformly negative acute toxicity profile is mirrored by observations in humans where toxicity in humans after true acute exposures is very limited. When human toxicity is observed it 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 inorganic lead metal compounds appears to be quite low via all exposure routes.

Justification for classification or non-classification

The current classification of lead styphnate 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 of lead styphnate are not supported by the existing data. Acute toxicity from lead pthalate is not observed in animals after oral or dermal exposures up to the limit values of acute toxicity testing. Test data further show a lack of irritant properties for the skin and eyes for lead pthalate. Analogous substances show similar toxicological profiles, further confirming a lack of acute toxic properties.

Although toxic under chronic exposure situations, the acute toxicity of lead styphnate appears to be quite low and does not require classification.