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. Furthermore, based on the composition analysis most critical constituent is sulphur and zinc sulphate. Therefore, the chemical safety assessment focuses on the properties of these constituents. The key values for CSA are selected based on the read-across data on bioavailable Pb and Zn compounds and sulphur. As there is no available skin irritation studies for sulphur endpoint conclusion is based on the harmonised classification entry of this constituent.  
Skin irritation: Irritant based on the harmonised classification (Skin Irrit. 2) of the most critical constituent (sulphur) in the target substance with respect to skin irritation.
Eye irritation: Severe irritant based on animal study on the read-across substance, zinc sulphate.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Used in risk assessment report for ZnSO4, acceptable for assessment.Read-across justificaton:Read-across from the most critical and bioavailable constituents (zinc and its compounds):The target substance is a solid inorganic UVCB substance and insoluble in water. Therefore, the transformation/dissolution study (OECD guidance 29) was conducted for the target substance to focus on the most critical bioavailable constituents of the substance. 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. The read-across on zinc and its compounds are used in the chemical safety assessment for those endpoints where the adverse effects of the target substance can be affected by zinc content of the substance. The read-across data was justified in order to avoid unnecessary animal testing.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No information

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Approximately 98.1 mg of the test material

Duration of treatment / exposure:

Single instillation, no eye wash

Observation period (in vivo):

At 1, 24, 48 and 72 hours, 7, 14 and 21 days after exposure.

Number of animals or in vitro replicates:

Three male animals

Details on study design:

No further details

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24 h

Score:

ca. 2

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 48 h

Score:

2.7

Max. score:

3

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 72 h

Score:

ca. 2.7

Max. score:

3

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 h

Score:

ca. 2

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 48 h

Score:

ca. 2.7

Max. score:

4

Reversibility:

not specified

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 72 h

Score:

ca. 3.7

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

Corneal injury was seen as slight dulling of the normal lustre (opacity grade 0) and/or epithelial damage (10% of the corneal area) in two animals. This injury had resolved within 24 hours in one animal and within 72 hours in the other animal. Irritation of the conjuctivae was seen as redness (mean scores over 24-72 hours 2, 2.7 and 2.7), chemosis (mean scores 2, 2.7 and 3.7) and discharge.Yellow/white spots were observed in the tissue of the lower eyelid, nictitating membrane and/or sclera in all animals from day 7 until termination. These spots were described as signs of necrosis and consisted of encapsulated material of unknown origin which caused protrusions at termination of the study.

Other effects:

Reduced elasticity of the eyelids was noted in one animal, 72 hours and 7 days after instillation.

None       

Interpretation of results:

highly irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

Based on the degree and persistence of the corneal injury, zinc sulphate is considered to cause severe ocular irritation

Executive summary:

In a well-performed eye irritation/corrosion study, conducted according to Directive 92/69/EEC B.5 and OECD guideline 405, three male New Zealand White rabbits were treated by instillation of approximately 98.1 mg of zinc sulphate (ZnSO_4.7H₂O) into the conjuctival sac of one eye. The other eye remained untreated and served as control. The eyes (unrinsed) were examined at 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation.

No symptoms of systemic toxicity were observed and no mortality occurred.

Corneal injury was seen as slight dulling of the normal lustre (opacity grade 0) and/or epithelial damage (10% of the corneal area) in two animals. This injury had resolved within 24 hours in one animal and within 72 hours in the other animal.

Irritation of the conjuctivae was seen as redness (mean scores over 24-72 hours 2, 2.7 and 2.7), chemosis (mean scores 2, 2.7 and 3.7) and discharge.

Yellow/white spots were observed in the tissue of the lower eyelid, nictitating membrane and/or sclera in all animals from day 7 until termination. These spots were described as signs of necrosis and consisted of encapsulated material of unknown origin which caused protrusions at termination of the study. Reduced elasticity of the eyelids was noted in one animal, 72 hours and 7 days after instillation.

Based on the degree and persistence of the corneal injury, zinc sulphate is considered to cause severe ocular irritation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

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 to focus on the most critical and bioavailable constituents of the target substance. The read-across data on these critical constituents were then used for the chemical safety assessment in order to avoid unnecessary animal testing.

According to the chemical composition analysis, the main phases of the substance are lead sulphate and zinc sulphide. 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.. 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 and composition analysis, the most soluble and critical components of this substance are lead, zinc and sulphur. The read-across justification is presented in CSR annex I. All read-across data for toxicology are based on test data using either soluble Pb or Zn salts or measured (dissolved) Pb or Zn concentrations. No data on sulphur is used for the chemical safety assessment. However, since sulphur is classified as skin irritant with harmonised classification entry of Skin Irrit. 2 H315, the self-classification of the target substance was derived based on the sulphur concentration by using the CLP mixture rules (the C&L procedure is presented in IUCLID section 13). Conclusions on the skin and eye irritation was done based on the weight of evidence of Pb and zinc read-across data and the known skin irritation properties of sulphur.

Pb compounds

Reliable animal data were found indicating that the following read-across substances; lead oxide and lead phosphite lack irritating properties for the skin or the eyes. The experimental data are reinforced by a lack of reports of skin or eye irritation in the many occupational exposure environments which provide opportunities for exposure of lead and sparingly soluble lead compounds to the skin and eyes. Specific studies of lung irritation were not found, but the lack of inhalation toxicity from lead oxide in both acute toxicity testing and inhalation cancer bioassays combine with an absence of reports of lung irritation in occupational settings to suggest classification is not needed.

No studies were found documenting corrosive properties of lead and sparingly soluble lead compounds in either experimental animals or humans. Given the negative findings of acute toxicity and irritation studies and the absence of reports from occupationally exposed workers, corrosive properties are not to be expected of lead or its sparingly soluble compounds.

Zn compounds

Zinc sulphate showed no skin irritation in several animal studies, but displayed severe eye irritation in rabbits (Van Huygevoort, 1999). This eye irritation study was conducted according to OECD guideline 405. Three male New Zealand White rabbits were treated by instillation of approximately 98.1 mg of zinc sulphate (ZnSO4.7H2O) into the conjunctival sac of one eye. The other eye remained untreated and served as control. The eyes (unrinsed) were examined at 1, 24, 48 and 72 hours and 7, 14 and 21 days after instillation.

No symptoms of systemic toxicity were observed and no mortality occurred. Corneal injury was seen as slight dulling of the normal lustre (opacity grade 0) and/or epithelial damage (10% of the corneal area) in two animals. This injury had resolved within 24 hours in one animal and within 72 hours in the other animal. Irritation of the conjunctivae was seen as redness (mean scores over 24-72 hours 2, 2.7 and 2.7), chemosis (mean scores 2, 2.7 and 3.7) and discharge. Yellow/white spots were observed in the tissue of the lower eyelid, nictitating membrane and/or sclera in all animals from day 7 until termination. These spots were described as signs of necrosis and consisted of encapsulated material of unknown origin which caused protrusions at termination of the study. Reduced elasticity of the eyelids was noted in one animal, 72 hours and 7 days after instillation.

Based on the degree and persistence of the corneal injury, zinc sulphate is considered to cause severe ocular irritation.

Conclusions

Based on the mineralogical composition, in addition to lead two major constituents of this target substance 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.

The assessment of irritation properties of the substance is based on the overall weight of evidence from the composition of the target substance, the bioavailability and the toxicity of the most relevant components (zinc compounds, lead compounds and sulphur). The most critical components related to the irritation were identified to be sulphur and zinc sulphate.

No irritation studies were available for sulphur. However, sulphur has harmonised classification entry of Skin Irrit. 2 H315. Zinc sulphate is considered to cause severe ocular irritation based on the available animal study. Zinc sulphate has also harmonised classification entry of Eye Dam. 1 H318.

Thus, based on the composition of the target substance and CLP mixture rules the substance will be classified for Skin Irrit. 2 H315 and Eye Dam. 1 H318.

Justification for selection of skin irritation / corrosion endpoint:
No study conducted for the target UVCB substance. Also no studies are available for the most critical constituent in the substance (sulphur) with respect to skin irritation. However, the self-classification by using the CLP mixture rules triggers this hazard class for the target substance based on the the concentration and harmonized classification of sulphur.

Justification for selection of eye irritation endpoint:
No study conducted for the target UVCB substance. The key value was selected based on the read-across data from the most hazardous component (zinc sulphate) with respect to eye irritation in the substance.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based upon the overall observations,concentrations of the critical constituents in the substance, read across from lead and zinc compounds and known skin irritation classification of sulphur, permits the conclusion to be drawn that the substance is irritating to skin and eyes.

The substance will be classified for Skin Irrit. 2 H315 and for Eye Damage 1 H318 according to CLP Regulation 1272/2008 and Xi; R38/41 according to the Directive 67/548/EEC.