Dicopper hydroxide phosphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.022 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEC

Value:

3.32 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

1.67 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEC for CuHP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point)

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.4 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Dose descriptor starting point:

NOAEL

Value:

31.44 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

220.08 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

1.25

Justification:

Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.

AF for intraspecies differences:

5

Justification:

The default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

General

DNEL derivation for the test substanceDicopper hydroxide phosphate (CuHP)is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEC for CuHP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.

 

Step 2: Modification of the starting point:

NOAEC (Cu2O): 2 mg/m^3

 

As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:

M (Cu2O): 143.1 g/mol

M (Cu): 63.5 g/mol

M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.

 

Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %

NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3

 

The NOAEC for CuHP is calculated:

The molecular weight for CuHP is239.1g/mol.

The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is necessary for CuHP as 2 Cu molecules are present.

 

NOAEC (CuHP): 1.76 mg/m^3 * (239.1 g/mol/2*63.5 g/mol))

= 3.32 mg/m^3(starting point for DNEL derivation)

 

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 3.32 mg/m^3

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m^3

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m^3

Frequency of exposure in study: 5 days/week, 6 hours/day

Frequency of worker exposure: 5 days/week, 8 hours/day

 

Corrected inhalatory NOAEC for workers

= 3.32 mg/m^3 * (6.7 m^3/10 m^3) * (5/5) * (6/8)

= 1.67 mg/m^3

 

Step 3: Use of assessment factors: 75

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5 

Exposure duration AF: 6

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, worker = 0.022 mg/m^3

 

 

Short term systemic inhalation DNEL, worker

The test material is not classified and labelled for acute systemic toxicity (inhalation), according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

Short and long term local inhalation DNEL, worker

No data on long term local toxicity after inhalation is available. Data on acute local toxicity after inhalation is available and showed no specific local effects. The substance is not classified for acute inhalation, therefore no adverse effects on the respiratory system are expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL local, long term and acute (inhalation) is required. In addition DNEL for local effects does also not need to be derived as no eye irritation (leading to classification) and in conclusion no indication of local mucosal membrane damages has been identified (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8).

 

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of CuHP is derived from NOAEL of Cu, calculated in an oral repeated dose toxicity study with CuSO4 on rats (Hebert, 1993), assuming that toxicity is triggered by the concentration of Cu. The oral NOAEL is 16.7 mg/kg bw/day for Copper. To adjust the NOAEL for CuHP as follows:

The molecular weight for CuHP is 239.1 g/mol.

The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is necessary for CuHP as 2 Cu molecules are present.

NOAEL (CuHP): 16.7 mg/kg bw/day * (239.1 g/mol/2*63.5 g/mol)

= 31.44 mg/kg bw/day(starting point for DNEL derivation)

 

Step 2: Modification of the starting point:

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.

 

Factor for dermal NOAEL= 50 % oral / 10 % dermal= 5

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

oral NOAEL 31.44 mg/kg bw/day * 5 * (7/5) =220.08 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 50

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 1.25 (Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.)

Intraspecies AF (worker): 5

Exposure duration AF: 2

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 4.40 mg/kg bw/day

 

Short term systemic dermal DNEL, worker

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Short term and long term local dermal DNEL, worker

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

Worker – Hazard for the eyes

The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Thus, no qualitative risk assessment is required. 

 

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.

- EFSA Scientific Report (2008) 187, 1-101 Conclusion on the peer review of copper compounds.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.004 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Dose descriptor starting point:

NOAEC

Value:

3.32 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

0.59 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEC for CuHP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

No allometric scalling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.57 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

NOAEL

Value:

31.44 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

157.2 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

1.25

Justification:

Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.

AF for intraspecies differences:

10

Justification:

The default value for the relatively homogenous group "general population" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.28 mg/kg bw/day

DNEL related information

DNEL derivation method:

other: The long term oral DNEL for the general population is derived based on the acceptable daily intake (ADI) published by the WHO (EFSA Scientific Report (2008).

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.84 mg/kg bw/day

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

0.33

DNEL extrapolated from long term DNEL

Explanation for the modification of the dose descriptor starting point:

The test material is classified for acute oral toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (oral) is extrapolated from the long term DNEL with multiplication by factor of 3 (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (oral) is derived from the acceptable daily intake (ADI) for copper.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General

DNEL derivation for the test substanceDicopper hydroxide phosphate (CuHP)is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

 

General population – Hazard via inhalation route

Long term systemic inhalation DNEL, General population

The NOAEC for CuHP is derived from the NOAEC of Cu2O, determined in a 4-week inhalation study carried out according to OECD Test Guideline 412 in rats (Kirkpatrick, 2010), assuming that toxicity is triggered by the concentration of Cu. Within this study animals were exposed to a dust aerosol atmosphere of the test substance for 6 hours per day for 5 days per week.

 

Step 2: Modification of the starting point:

NOAEC (Cu2O): 2 mg/m^3

 

As toxicity is triggered by the concentration of Cu, the NOAEC based on Cu is calculated:

M (Cu2O): 143.1 g/mol

M (Cu): 63.5 g/mol

M (Cu) is multiplied with a factor of 2 due to 2 Cu atoms in Cu2O.

 

Percentage of Cu in Cu2O: 127/143.1 = 0.88 * 100 % = 88 %

NOAEC (Cu): 2 mg/m^3 * 88 % /100 = 1.76 mg/m^3

 

The NOAEC for CuHP is calculated:

The molecular weight for CuHP is239.1g/mol.

The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is necessary for CuHP as 2 Cu molecules are present.

 

NOAEC (CuHP): 1.76 mg/m^3 * (239.1 g/mol/2*63.5 g/mol))

= 3.32 mg/m^3(starting point for DNEL derivation)

 

No modification for absorption is used as the same exposure route is considered. Following corrections were performed:

 

Relevant dose descriptor (NOAEC): 3.32 mg/m^3

Frequency of exposure in study: 5 days/week, 6 hours/day

Frequency of general population exposure: 7 days/week, 24 hours/day

 

Corrected inhalatory NOAEC for general population

= 3.32 mg/m^3 * (5/7) * (6/24)

= 0.59 mg/m^3

 

Step 3: Use of assessment factors: 150

Interspecies AF, allometric scaling (rat to human): 1

Interspecies AF, remaining differences: 2.5

Intraspecies AF (general population): 10

Exposure duration AF: 6

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, general population = 0.004 mg/m^3

 

 

Short term systemic inhalation DNEL, worker

The test material is not classified and labelled for acute systemic toxicity (inhalation), according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

Short and long term local inhalation DNEL, general population

No data on long term local toxicity after inhalation is available. Data on acute local toxicity after inhalation is available and showed no specific local effects. The substance is not classified for acute inhalation, therefore no adverse effects on the respiratory system are expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL local, long term and acute (inhalation) is required. In addition DNEL for local effects does also not need to be derived as no eye irritation (leading to classification) and in conclusion no indication of local mucosal membrane damages has been identified (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8).

 

 

General population – Hazard via dermal route

Long term systemic dermal DNEL, General population

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of CuHP is derived from NOAEL of Cu, calculated in an oral repeated dose toxicity study with CuSO4 on rats (Hebert, 1993), assuming that toxicity is triggered by the concentration of Cu. The oral NOAEL is 16.7 mg/kg bw/day for Copper. To adjust the NOAEL for CuHP as follows:

The molecular weight for CuHP is 239.1 g/mol.

The atomic weight for Cu is ca. 63.5 g/mol, and should be multiplied where > 1 Cu molecule is present, which is necessary for CuHP as 2 Cu molecules are present.

NOAEL (CuHP): 16.7 mg/kg bw/day * (239.1 g/mol/2*63.5 g/mol)

= 31.44 mg/kg bw/day(starting point for DNEL derivation)

 

Step 2: Modification of the starting point:

In order to derive the general population DNEL (long-term dermal exposure), the NOAEL assessed in the 90-day repeated dose oral toxicity study (Hebert, 1993) is identified as the relevant dose descriptor. Assuming that dermal absorption is 10 % of the applied test substance (EFSA Scientific Report (2008)) and the oral absorption in rats is 50 % (EFSA Scientific Report (2008)) as a worst case, and considering the appropriate modification and assessment factors, the worker DNEL (long-term dermal exposure) is calculated.

 

Factor for dermal NOAEL= 50 % oral / 10 % dermal= 5

Frequency of exposure in study: 7 days/week

Frequency of general population exposure: 7 days/week

 

oral NOAEL 31.44 mg/kg bw/day * 5 * (7/7) =157.2 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 100

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 1.25 (Reduced from the default value of 2.5 based on similarities observed between rat and human toxicokinetic mechanisms for the uptake of copper following oral administration.)

Intraspecies AF (general population): 10

Exposure duration AF: 2

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, general population = 1.57 mg/kg bw/day

 

 

Short term systemic dermal DNEL, General population

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Short term and long term local dermal DNEL, General population

The test material is not classified and labelled for skin sensitization or skin irritation, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

 

General population – Hazard via oral route

Long term systemic oral DNEL, General population

In order to derive the general population DNEL the acceptable daily intake (ADI) for copper was used (EFSA Scientific Report (2008)). This value ensures an appropriate level of protection also with regard to children.

The ADI value = 0.15 mg Cu/kg bw/day

DNEL (CuHP) = 0.15 mg/kg bw/day x (239.1 g/mol/2*63.5 g/mol)

= 0.28 mg/kg bw/day

 

In conclusion, long term systemic oral DNEL, general population = 0.28 mg/kg bw/day

 

 

Short term systemic oral DNEL, General population

The test material is classified for acute oral toxicity cat. 4, according to Regulation (EC) No 1272/2008 (CLP). The acute systemic DNEL (oral) is extrapolated from the long term DNEL with multiplication by factor of 3 (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). The long term systemic DNEL (oral) is derived from the acceptable daily intake (ADI) for copper.

For Steps 1-3 please refer to “Long term systemic oral DNEL, General population”

 

Step 4: extrapolation from the long term DNEL

A factor of 3 is used: long term DNEL*3= short term DNEL

0.28*3=0.84 mg/kg bw/day                                             

In conclusion, short term systemic oral DNEL, general population = 0.84 mg/kg bw/day

 

General population – Hazard for the eyes

The test item is not classified for eye irritation or severe eye damage according to Regulation (EC) No 1272/2008 (CLP). Thus, no qualitative risk assessment is required. 

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. November 2014.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.

- EFSA Scientific Report (2008) 187, 1-101 Conclusion on the peer review of copper compounds.