Potassium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 064 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 320 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

303 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

910 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Additional information - workers

INTRODUCTORY NOTE

Potassium chloride is a white crystaline powder with a melting point of 773°C and soluble in water, alcohol and glycerol (BIBRA, 1989). Potassium chloride is readily absorbed via the gastro-intestinal tract as shown by the available data. But, there are no data on potassium chloride available using the dermal and the inhalation route. Due to the low vapor pressure and the low octanol water partition coefficient of the substance, the potential for dermal or inhalation absorption is low (UNEP 2003). Consequently deriving DNELs for dermal and inhalation route are of minor importance.

Furthermore, there is information available that potassium chloride causes irritations to the mucous membranes. Overall, based on the availble data from an in-vitro experiment, limited animal dataand limited data with volunteers, potassium chloride (KCl) is considered to be non-irritating to the skin or the eye

WORKER

DNEL SYSTEMIC

In general, for worker the oral DNELs are not relevant. Only the dermal and inhalation route are regarded to be relevant for the situation of workers.

DNEL (systemic, longterm, dermal route)

Starting point for the dermal DNEL derivation is the result of a long term feeding study in rats in which a NOAEL for systemic effects of 1820 mg/kg bw/d highest test dose, was determined, indicating that the systemic toxicity is rather low

NOAEL 1820 mg/kg bw/day

Interspecies differences rat versus human: 4.

For remaining interspecies differences: 1*

For interspecies differences in workers: 3**

For reliability of the dose response: 1

For quality of the whole database: 1

Conversion oral to dermal: 0.5***

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* In an evaluation by ECETOC 2003 and in draft report of ECETOC 2010 it is considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor. This view is supported by data generated by the ERASM project (Batke et al, 2010)

** based on the considerations in draft ECETOC report, 2010, the default factor was changed

*** Due to the considerations above and according to the TGD R8 of ECHA (2008, p 25) limited dermal absorption has to be assumed leading to a factor of 0.5

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Overall Factor 6

DNEL (systemic, longterm, dermal route): 303 mg/kg bw/day

DNEL (systemic, longterm, inhalation route)

There is no valid subchronic or chronic repeated dose toxicity study available using inhalation exposure route. Thus, for setting DNEL (long term, inhalation route) the data from oral exposure route have to be taken into account: Based on the considerations above. that due to the low vapor pressure of the substance, and the potential for inhalation exposure is assumed low (UNEP 2003), it can be calculated:

NOAEL 1820 mg/kg bw/day

Interspecies differences rat versus human: 4.

For remaining interspecies differences: 1*

For interspecies differences in workers: 3**

For reliability of the dose response: 1

For quality of the whole database: 1

Conversion oral to inhalation: 1***

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* In an evaluation by ECETOC 2003 and in draft report of ECETOC 2010 it is considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor. This view is supported by data generated by the ERASM project (Batke et al, 2010)

** based on the considerations in draft ECETOC report, 2010, the default factor was changed

*** based on water solubility absorption via inhalation can be assumed

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Overall Factor 12

Based on a body weight for worker of 70 kg and a respiratory volume of (light activity) for workers 8 h exposure of 10 m³ / person: DNEL (systemic, long term, inhalation route): 1064 mg/m³/day

DNEL (reproduction toxicity; fertility and development)

The available long term and development studies do not indicate reproductive toxicity, consequently, no DNEL for reproductive toxicity is derived.

DNEL systemic, short term

A DNEL (systemic short term) should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposure. At room temperature potassium chloride is a crystalline powder and therefore there is some evidence that high peak exposure can occur. However, in the case of potassium chloride acute dermal or inhalation toxicity studies are not available. Therefore acute toxicity studies using the oral route have to be taken into account. As acute toxicity studies aim the derivation of LD50 values, these studies in general, ignore the sublethal or even well tolerated dose levels and are therefore considered to involve too large uncertainities, especially, when additionally route to route extrapolation has to be considered.

For these cases the ECHA guidance document R8, 2008 proposes to modify the long-term DNELs by multiplying with a factor of 5 Consequently:

DNEL (systemic, short term, dermal route): 910 mg/kg bw/day

DNEL (systemic, short term, inhalation route): 5320 mg/m³/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

273 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 365 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

182 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

910 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

91 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

455 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Additional information - General Population

INTRODUCTORY NOTE

Potassium chloride is a white crystaline powder with a melting point of 773°C and soluble in water, alcohol and glycerol (BIBRA, 1989). Potassium chloride is readily absorbed via the gastro-intestinal tract as shown by the available data. But, there are no data on potassium chloride available using the dermal and the inhalation route. Due to the low vapor pressure and the low octanol water partition coefficient of the substance, the potential for dermal or inhalation absorption is low (UNEP 2003).

Based on the available data from in vitro experiments, limited animal data and limited data with volunteers potassium chloride (KCl) is considererd to ne non-irritating to the skin or the eye. Consequently no DNELs for local effects are calculated..

.

DNEL SYSTEMIC

DNEL (systemic, long term, oral route)

Starting point for the DNEL derivation is the result of a long term feeding study in rats in which a NOAEL for systemic effects of 1820 mg/kg bw/d, highest test dose, was determined, indicating that the systemic toxicity is rather low

NOAEL 1820 mg/kg bw/day

Interspecies differences rat versus human: 4.

For remaining interspecies differences: 1*

For interspecies differences in general public: 5**

For reliability of the dose response: 1

For quality of the whole database: 1

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* In an evaluation by ECETOC 2003 and in draft report of ECETOC 2010 it is considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor. This view is supported by data generated by the ERASM project (Batke et al, 2010)

** based on the considerations in draft ECETOC report, 2010, the default factor was changed

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Overall factor: 20

DNEL (systemic, long-term, oral route): 91 mg/kg bw/day

DNEL (systemic, long-term, dermal route)

Starting point for the dermal DNEL derivation is the result of a long term feeding study in rats in which a NOAEL for systemic effects of 1820 mg/kg bw/d highest test dose, was determined, indicating that the systemic toxicity is rather low

NOAEL 1820 mg/kg bw/day

Interspecies differences rat versus human: 4.

For remaining interspecies differences: 1*

For interspecies differences in general public: 5**

For reliability of the dose response: 1

For quality of the whole database: 1

Conversion oral to dermal: 0.5***

-------------------------------------------------------------------

* In an evaluation by ECETOC 2003 and in draft report of ECETOC 2010 it is considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor. This view is supported by data generated by the ERASM project (Batke et al, 2010)

** based on the considerations in draft ECETOC report, 2010, the default factor was changed

*** Due to the considerations above and according to the TGD R8 of ECHA (2008, p 25) limited dermal absorption has to be assumed leading to a factor of 0.5

-------------------------------------------------

Overall Factor 10

DNEL (systemic, longterm, dermal route): 182 mg/kg bw/day

DNEL (systemic, longterm, inhalation route)

There is no valid subchronic or chronic repeated dose toxicity study available using inhalation exposure route. Thus, for setting DNEL (long term, inhalation route) the data from oral exposure route have to be taken into account: Based on the considerations above. that due to the low vapor pressure and the low octanol water partition coefficient of the substance, the potential for inhalation absorption is assumed low (UNEP 2003), it can be calculated:

NOAEL 1820 mg/kg bw/day

Interspecies differences rat versus human: 4.

For remaining interspecies differences: 1*

For interspecies differences in general public: 5**

For reliability of the dose response: 1

For quality of the whole database: 1

Conversion oral to inhalation: 1**

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* In an evaluation by ECETOC 2003 and in draft report of ECETOC 2010 it is considered that routine application of the factor of 2.5 is scientifically unjustified as a default factor. This view is supported by data generated by the ERASM project (Batke et al, 2010)

** based on the considerations in draft ECETOC report, 2010, the default factor was changed

-------------------------------------------------

Overall Factor 20

Based on a body weight for general public of 60 kg and a respiratory volume of 20 m³ / person/ 24 h:

DNEL (systemic, long term, inhalation route): 273 mg/m³/day

DNEL (reproduction toxicity; fertility and development)

The available long term and development studies do not indicate reproductive toxicity, consequently, no DNEL for reproductive toxicity is derived.

.

DNEL systemic, short term

A DNEL (systemic short term) should be derived if an acute toxicity hazard has been identified and if there is a potential for high peak exposure. At room temperature potassium chloride is a crystalline powder and therefore there is some evidence that high peak exposure can occur.

However, in the case of potassium chloride acute dermal or inhalation toxicity studies are not available. Therefore acute toxicity studies using the oral route have to be taken into account. As acute toxicity studies aim the derivation of LD50 values, these studies in general, ignore the sublethal or even well tolerated dose levels and are considered to involve too large uncertainities, especially, when additionally route to route extrapolation has to be considered.

For these cases the ECHA guidance document R8, 2008 proposes to modify the long-term DNELs by multiplying with a factor of 5

Consequently:

DNEL (systemic, short term, oral route): 455 mg/kg bw/day

DNEL (systemic, short term, dermal route): 910 mg/kg bw/day

DNEL (systemic, short term, inhalation route): 1365 mg/m³/day