Aluminium potassium bis(sulphate)

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.05 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

87.5

Modified dose descriptor starting point:

NOAEC

Value:

1 142 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAEL-oral mouse repeated dose chronic: 8160 mg/kg bw/day. Oral absorption rate: 1%, Inhalative absorption rate: 50%, Body weight worker: 70 kg. Inhalative volume worker 8h: 10m³. Derivation NOAEC: 8160/100x2x70/10= 1142 mg/m³ aluminium potassium bis sulphate. Derivation DNEL long-term systemic inhalative workers: Interspecies: mouse/human:7. Remaining differences: 2.5. Intraspecies: workers: 5. Exposure duration: chronic/chronic= 1. Dose-response: 1. Quality of whole database: 1. Remaining uncertainties:1. Derivation DNEL workers oral long-term systemic: 1142/7/2.5/5/1/1= 13.05 mg Aluminium potassium bis sulphate/kg bw/day.

AF for dose response relationship:

1

Justification:

Reliability of dose-response: 1

AF for differences in duration of exposure:

1

Justification:

derivation from repeated dose chronic oral study: 1

AF for interspecies differences (allometric scaling):

7

Justification:

correction for differences mouse/human: 7

AF for other interspecies differences:

2.5

Justification:

Remaining differences: 2.5

AF for intraspecies differences:

5

Justification:

worker: 1

AF for the quality of the whole database:

1

Justification:

Completeness and consistency of available data: 1

AF for remaining uncertainties:

1

Justification:

Low remaining uncertainties: 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:

no hazard identified

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

Toxicokinetics, metabolism and distribution:

Based on the results of the key studies and supporting studies of the read across substances as inorganic aluminium salts and potassium sulfate and the expert statement about absorption and excretion of aluminium, potassium and sulfate as dissociation products of aluminium potassium bis sulphate, the oral absorption rate is max. 1%, dermal absorption rate max. 0.5% and inhalative absorption rate is assumed to be 50% based on IPCS-, ATSDR-, GR- and CEPA-reports from 1998, 2008, 2010 although Yokel and McNamara estimated a fractional absorption of aluminium of 1.5 - 2% (balance of urinary excretion and airborne soluble aluminium of workers 2001).

Acute Toxicity:

Based on the long-term key study from Oneda et al. the calculated LD50-mouse oral should be > 2000 mg/kg bw.

This result was used for classification of the substance.

Based on the oral NOAEL of the key study the inhalative NOAEL of the substance was calculated.

Calculated NOAEL-inhalative: 13.05 mg/m³.

The corresponding LC50 -inhalative should be LC50 inhalative > 5 mg/L air (Limit CLP).

Based on the key study ( ATSDR report and publication of Lansdown) the calculated LD50-dermal

of aluminium potassium bis sulphate from read across substance aluminium sulfate resulted in an

calculated LD50-dermal of 100000 mg/kg bw aluminium potassium bis sulphate.

Based on all acute toxicity results aluminium potassium bis sulphate is not classified as acute oral, inhalative and dermal toxic

according EU regulation 1272/2008 and EU regulation 286/2011 (2. ATP).

Irritation/corrosion:

Based on the results of the key studies of skin and eye irritation with aluminium sulfate and aluminium ammonium sulfate as

read across substances of aluminium potassium bis sulphate, the substance aluminium potassium bis sulphate is not

classified as skin irritating and eye irritating/eye corrosive according to EU regulation 1272/2008 and EU regulation 286/2011 (2. ATP).

Sensitisation:

Because the read across study results on aluminium sulfate and aluminium chlorohydrate show no skin

sensitisation and skin sensitisation effects of potassium sulfate are unknown, therefore aluminium potassium bis sulphate

is not classified as "skin sensitising" according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Repeated dose toxicity:

Repeated dose toxicity: oral

Based on the Key study from Oneda et al. and the other supporting studies the NOAEL-20 month chronic oral systemic mouse

is NOAEL-20 month mouse = 8160 mg/kg bw/day Aluminium potassium bis sulphate.

Repeated dose toxicity: inhalation

Based on the peer-reviewed report (key study) from Gezondheidsraad Health Council of the Netherlands(2010)

and the supporting study from Finelli et al. the calculated NOAEC-86 weeks chronic inhalative systemic toxicity

for rat is 6.2 mg/m³ Aluminium potassium bis sulphate .

Repeated dose toxicity: dermal

Based on the peer-reviewed report from Environment Canada Health Canada (2010) and the publication from

Flarend et al (2001) the calculated NOAEL-43 days of the subchronic dermal study is

8.52 mg /kg bw/day Aluminium potassium bis sulphate.

Based on the results of the long-term Repeated Dose oral, inhalative and dermal toxicity studies

there is no classification on repeated dose toxicity of the substance aluminium potassium bis sulphate

according EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Genetic toxicity:

Based on the well documented in vitro Mammalian Aberration key study from Ishidate et al. and the additional supporting and

Weight of Evidence studies the resulting NOEL-48h for in vitro Mammalian Chromosome Aberration Test at Chinese

hamster lung fibroblasts V79 is NOEL = 3.9 mmol/L = 1006 mg/L aluminium potassium bis sulphate.

Result: negative

Based on the negative results of the Key study, supporting in vitro studies and the Key in vivo study the substance is not classified as genetic toxic according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Toxicity to reproduction:

Toxicity to reproduction

No effects on fertility were observed for concentration up to 3000 ppm (max).

Based on the key study on aluminium sulfate as Read-across substance from Hirata-Koizumi et al. (2011) and OECD SIDS report as supporting study on potassium sulfate as Read-across substance the calculated NOAEL for aluminium potassium bis(sulphate) from NOAEL aluminium sulfate (41 mg/kg bw/day) is 31 mg aluminium potassium bis(sulphate). The NOAEL of potassium sulfate is 1500 mg/kg bw/day. The LOAEL could not be determined because there were not any adverse effects ascertained. Aluminium potassium bis(sulphate) dissociates in water to the AL 3 +-, K+- and SO42- ions which are the same as the ions of the dissolved Read-across substances Aluminium sulfate and potassium sulfate.

Development toxicity/teratogenicity

Based on the well documented key study on development toxicity/ teratogenicity from Kanoh et al. (1988) and the OECD SIDS report as supporting study with potassium sulfate as read across substance of aluminium potassium bis sulphate, it is concluded that alum possesses no teratogenic effect in rats fed the diet containing ranging from 0.32 to 10% during the second trimester of gestation.

Calculated for Aluminium potassium bis sulphate anhydrous:

LD0 = 250 - 2000 mg AlK(SO4)2*12 H2O/kg bw = 136 mg/kg bw - 1088 mg /kg bw Aluminium potassium bis sulphate.

NOAEL: 0.32-10% Aluminium potassium bis sulphate*24H2O or AlK(SO4)2*12 H2O in diet - no teratogenic effects in rats.

Calculated for Aluminium potassium bis sulphate anhydrous:

NOAEL: 121 - 4031 mg/kg bw/day Aluminium potassium bis sulphate anhydrous - no teratogenic effects in rats.

Based on the OECD SIDS report as supporting study of potassium sulfate as read across substance there are the following results:

Toxicity subgroup: There were no treatment-related deaths and no signs of overt clinical toxicity. There were no effects on body weight, food consumption, or food efficiency. Functional observational battery (FOB) and motor activity tests identified no treatment-related changes in behavior, function, or motor activity. No treatment-related histopathological changes were reported.

NOAEL: 1500 mg/kg bw/day (general toxicity)

LOAEL: No adverse effects were seen on general toxicity endpoints.

Based on the results of Key study and Supporting study on toxicity to reproduction of the Read across substances aluminium sulfate and

potassium sulfate and Key study and the Supporting study on development toxicity of aluminium potassium bis(sulphate) 24 -hydrate and

the Supporting OECD study of potassium sulfate the substance aluminium potassium bis(sulphate) is not classified for toxicity to reproduction according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Based on the safety management measures during manufacture, the industrial formulation uses

of the substance there are only the long-term systemic inhalative effects to workers to be

considered.

Systemic inhalative short-term effects, systemic and local dermal long- and short-term effects to the workers do not need to be

considered.

Further, local effects to the eyes of workers are not to be considered according to safety management measures.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

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:

15.54 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):

525

Modified dose descriptor starting point:

NOAEL

Value:

8 160 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEL oral long-term chronic mouse: 8160 mg/kg bw/day. Oral absorption rate: 1%. Derivation NOAEL oral: 8160/100= 81.60 mg/kg bw/day aluminium potassium bis sulphate. Route-to-route extrapolation oral/oral:1. Interspecies mouse/human 7. Remaining uncertainties: 3. Intraspecies General population: 10. Exposure duration: chronic-chronic 1. Dose-response:1. Remaining uncertainties: 3. Quality of whole database: 1. Uncertainties low: 1. Oral absorption rate: 1%. Derivation DNEL oral systemic long-term General population: 8160/100/x100/1/7/2.5/10/1/1/3= 15.54 mg aluminium potassium bis sulphate/kg bw/day.

AF for dose response relationship:

1

Justification:

Reliability of dose-response:1

AF for differences in duration of exposure:

1

Justification:

Chronic-chronic study:1

AF for interspecies differences (allometric scaling):

7

Justification:

Interspecies mouse-human: 7

AF for other interspecies differences:

2.5

Justification:

Remaining differences: 2.5

AF for intraspecies differences:

10

Justification:

Intraspecies General population: 10

AF for the quality of the whole database:

1

Justification:

Completeness and consistency: 1

AF for remaining uncertainties:

3

Justification:

Remaining uncertainties low: 3

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

Additional information - General Population

Toxicokinetics, metabolism and distribution:

Based on the results of the key studies and supporting studies of the read across substances as inorganic aluminium salts and potassium sulfate and the expert statement about absorption and excretion of aluminium, potassium and sulfate as dissociation products of aluminium potassium bis sulphate, the oral absorption rate is max. 1%, dermal absorption rate max. 0.5% and inhalative absorption rate is assumed to be 50% based on IPCS-, ATSDR-, GR- and CEPA-reports from 1998, 2008, 2010 and from CEPA also 2010 although Yokel and McNamara estimated a fractional absorption of aluminium of 1.5 - 2% (balance of urinary excretion and airborne soluble aluminium of workers 2001).

Acute Toxicity:

Based on the long-term key study from Oneda et al. the calculated LD50-mouse oral should be > 2000 mg/kg bw.

This result was used for classification of the substance.

Based on the oral NOAEL of the key study the inhalative NOAEL of the substance was calculated.

Calculated NOAEL-inhalative: 13.05 mg/m³.

The corresponding LC50 -inhalative should be LC50 inhalative > 5 mg/L air (Limit CLP).

Based on the key study ( ATSDR report and publication of Lansdown) the calculated LD50-dermal

of aluminium potassium bis sulphate from read across substance aluminium sulfate resulted in an

calculated LD50-dermal of 100000 mg/kg bw aluminium potassium bis sulphate.

Based on all acute toxicity results aluminium potassium bis sulphate is not classified as acute oral, inhalative and dermal toxic

according EU regulation 1272/2008 and EU regulation 286/2011 (2. ATP).

Irritation/corrosion:

Based on the results of the key studies of skin and eye irritation with aluminium sulfate and aluminium ammonium sulfate as

read across substances of aluminium potassium bis sulphate, the substance aluminium potassium bis sulphate is not

classified as skin irritating and eye irritating/eye corrosive according to EU regulation 1272/2008 and EU regulation 286/2011 (2. ATP).

Sensitisation:

Because the read across study results on aluminium sulfate and aluminium chlorohydrate show no skin

sensitisation and skin sensitisation effects of potassium sulfate are unknown, therefore aluminium potassium bis sulphate

is not classified as "skin sensitising" according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Repeated dose toxicity:

Repeated dose toxicity: oral

Based on the Key study from Oneda et al. and the other supporting studies the NOAEL-20 month chronic oral systemic mouse

is NOAEL-20 month mouse = 8160 mg/kg bw/day Aluminium potassium bis sulphate.

Repeated dose toxicity: inhalation

Based on the peer-reviewed report (key study) from Gezondheidsraad Health Council of the Netherlands(2010) and the supporting study

from Finelli et al. the calculated NOAEC-86 weeks chronic inhalative systemic toxicity for rat is 6.2 mg/m³ Aluminium potassium bis sulphate.

Repeated dose toxicity: dermal

Based on the peer-reviewed report from Environment Canada Health Canada (2010) and the publication from

Flarend et al (2001) the calculated NOAEL-43 days of the subchronic dermal study is

8.52 mg /kg bw/day Aluminium potassium bis sulphate.

Based on the results of the long-term Repeated Dose oral, inhalative and dermal toxicity studies

there is no classification on repeated dose toxicity of the substance aluminium potassium bis(sulphate)

according EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Genetic toxicity:

Based on the well documented in vitro Mammalian Aberration key study from Ishidate et al. and the additional supporting and

Weight of Evidence studies the resulting NOEL-48h for in vitro Mammalian Chromosome Aberration Test at Chinese

hamster lung fibroblasts V79 is NOEL = 3.9 mmol/L = 1006 mg/L aluminium potassium sulfate.

Result: negative

Based on the negative results of the Key study, supporting in vitro studies and the Key in vivo study the substance is not classified as genetic toxic according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

Toxicity to reproduction:

Toxicity to reproduction

No effects on fertility were observed for concentration up to 3000 ppm (max).

Based on the key study on aluminium sulfate as Read-across substance from Hirata-Koizumi et al. (2011) and OECD SIDS report as supporting study on potassium sulfate as Read-across substance the calculated NOAEL for aluminium potassium bis(sulphate) from NOAEL aluminium sulfate (41 mg/kg bw/day) is 31 mg aluminium potassium bis(sulphate). The NOAEL of potassium sulfate is 1500 mg/kg bw/day. The LOAEL could not be determined because there were not any adverse effects ascertained. Aluminium potassium bis(sulphate) dissociates in water to ions the AL 3+, K+ and SO42- which are the same as the ions of the dissolved Read-across substances Aluminium sulfate and potassium sulfate.

Development toxicity/teratogenicity

Based on the well documented key study on development toxicity/ teratogenicity from Kanoh et al. (1988) and the OECD SIDS report as supporting study with potassium sulfate as read across substance of aluminium potassium bis sulphate, it is concluded that alum possesses no teratogenic effect in rats fed the diet containing ranging from 0.32 to 10% during the second trimester of gestation.

Calculated for Aluminium potassium bis sulphate anhydrous:

LD0 = 250 - 2000 mg AlK(SO4)2*12 H2O/kg bw = 136 mg/kg bw - 1088 mg /kg bw Aluminium potassium bis sulphate.

NOAEL: 0.32-10% Aluminium potassium bis sulphate*24H2O or AlK(SO4)2*12 H2O in diet - no teratogenic effects in rats.

Calculated for Aluminium potassium bis sulphate anhydrous:

NOAEL: 121 - 4031 mg/kg bw/day Aluminium potassium bis sulphate anhydrous - no teratogenic effects in rats.

Based on the OECD SIDS report as supporting study of potassium sulfate as read across substance there are the following results:

Toxicity subgroup: There were no treatment-related deaths and no signs of overt clinical toxicity. There were no effects on body weight, food consumption, or food efficiency. Functional observational battery (FOB) and motor activity tests identified no treatment-related changes in behavior, function, or motor activity. No treatment-related histopathological changes were reported.

NOAEL: 1500 mg/kg bw/day (general toxicity)

LOAEL: No adverse effects were seen on general toxicity endpoints.

Based on the results of Key study and Supporting study on toxicity to reproduction of the Read across substances aluminium sulfate and

potassium sulfate and Key study and the Supporting study on development toxicity of aluminium potassium bis(sulphate) 24 -hydrate and

the Supporting OECD study of potassium sulfate the substance aluminium potassium bis(sulphate) is not classified for toxicity to reproduction according to EU regulation EU 1272/2008 and EU regulation 286/2011 (2. ATP).

According to the safety management measures during manufacture and formulation of products

and because of low concentration of the substance as additive there are only to be considered the

systemic oral long-term effects to general population.

The other systemic and local long- and short-term inhalative and dermal effects to the general population

and the local effects to the eyes of general population are not relevant.