Aluminum zirconium chloride hydroxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

22.7 mg/m³

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

409 mg/m³

Explanation for the modification of the dose descriptor starting point:

The route to route extapolation was conducted in accordance with ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version: 2.1, November 2012.

AF for dose response relationship:

1

Justification:

Default when starting point is a NOAEL.

AF for differences in duration of exposure:

6

Justification:

Default for sub-acute to chronic.

AF for interspecies differences (allometric scaling):

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for other interspecies differences:

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for intraspecies differences:

3

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.

AF for the quality of the whole database:

1

Justification:

A reliable, guideline conform study conducted under GLP principles is the basis. Thus, AF=1.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties know, thus AF=1.

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:

108 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEL

Value:

650 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default when starting point is a NOAEL.

AF for differences in duration of exposure:

1

Justification:

Exposure during organogenesis, thus AF=1.

AF for interspecies differences (allometric scaling):

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for other interspecies differences:

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for intraspecies differences:

3

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.

AF for the quality of the whole database:

2

Justification:

Applied as an additional safety factor, since the underlying study was conducted before internationally agree guidelines were available, and not conducted/reported under GLP principles.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified, thus AF=1.

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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.7 mg/m³

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEC

Value:

202 mg/m³

Explanation for the modification of the dose descriptor starting point:

The route to route extapolation was conducted in accordance with ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health, Version: 2.1, November 2012.

AF for dose response relationship:

1

Justification:

Default when starting point is a NOAEL

AF for differences in duration of exposure:

6

Justification:

Default for sub-acute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for other interspecies differences:

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for intraspecies differences:

5

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003).

AF for the quality of the whole database:

1

Justification:

A reliable, guideline conform study conducted under GLP principles is the basis. Thus, AF=1.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified, thus AF=1.

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:

65 mg/kg bw/day

Most sensitive endpoint:

developmental toxicity / teratogenicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEL

Value:

650 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default when starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

Exposure during organogenesis, thus AF=1.

AF for interspecies differences (allometric scaling):

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for other interspecies differences:

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for intraspecies differences:

5

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003).

AF for the quality of the whole database:

2

Justification:

Applied as an additional safety factor, since the underlying study was conducted before internationally agree guidelines were available, and not conducted/reported under GLP principles.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified, thus AF=1.

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:

15.5 mg/kg bw/day

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEL

Value:

464 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default when starting point is a NOAEL

AF for differences in duration of exposure:

6

Justification:

Default for sub-acute to chronic.

AF for interspecies differences (allometric scaling):

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for other interspecies differences:

1

Justification:

Inter-species variability with respect to toxicokinetics following oral or dermal administration of inorganic aluminium or zirconium substances is not to be expected: absorption of both metals from the gastrointestinal tract has been shown to be low to negligible, thus indicating poor systemic availability. Moreover, any metabolism of Al or Zr as inorganic ions can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between experimental animals and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 and for remaining differences of 1 instead of using the respective default factors of 4 and 2.5, respectively.

AF for intraspecies differences:

5

Justification:

This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003).

AF for the quality of the whole database:

1

Justification:

A reliable, guideline conform study conducted under GLP principles is the basis. Thus, AF=1.

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified, thus AF=1.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified