Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Overview of the toxicology of MK92K

 

Approach to meeting the data requirements

 

MK92K is a complex mixture (classed as a UVCB substance) consisting largely of chemically related alkylphenyl quaternary pyridinium compounds. Based on pH measurements (pH 1.2 in aqueous solution), the substance is considered to be corrosive. Testing for a number of toxicological endpoints is therefore waived in accordance with Column 2 of Annexes VII and VIII of the REACH Regulation, for scientific reasons and on animal welfare grounds in accordance with Directive 86/609/EEC.

 

Toxicokinetics

 

The physicochemical properties of the substance including its ionic nature and molecular weight indicate that systemic absorption is likely to be limited in extent. This is supported by data available for related quaternary ammonium compounds, which report oral absorption of <2.5% and dermal penetration of 0.5%. No data are available for the extent absorption following inhalation exposure, however this is again considered unlikely to be significant. The default assumption in REACH guidance that inhalation absorption is twice that of oral absorption also suggests limited systemic exposure by this route. The physical nature of the substance (a highly viscous, non-volatile liquid) and its use pattern also means that inhalation is not a relevant route of exposure for workers.  A published Canadian review of the toxicity of the quaternary ammonium compounddidecyldimethylammonium chloride (DDAC) reports some oxidative metabolism of the decyl sidechain, but no molecular cleavage by N-dealkylation.

 

Acute toxicity

Testing for acute toxicity is waived in accordance with Column 2 of Annexes VII and VIII of the REACH Regulation for scientific reasons and on animal welfare grounds, due to the corrosive nature of the substances.

 

Irritation and corrosion

 

The substance is considered to be corrosive as a consequence of its pH; no further testing is required. Classification under the CLP Regulation with Skin Corr. 1B (H314); causes severe skin burns and eye damage.

 

Sensitisation

Testing for skin sensitisation is waived in accordance with Column 2 of Annexes VII and VIII of the REACH Regulation, for scientific reasons and on animal welfare grounds, due to the corrosive nature of the substance.

 

Repeated dose toxicity

 

No repeated dose toxicity data are available for MK92K and no studies are proposed. Published reviews by the US EPA and Canadian Regulatory authorities of the available data for the related quaternary ammonium compoundsalkyldimethyl benzyl ammonium chloride (ADBAC)anddidecyldimethylammonium chloride (DDAC) are available.Read-across between different quaternary ammonium compounds is considered to be appropriate as the available metabolism data do not identify any molecular cleavage, which would liberate different chemical species and potentially result in significantly different toxic effects.

 

Data show that the effects of oral administration of thesequaternary ammonium compounds are almost entirely local (due to corrosive/irritant effects on the gastrointestinal tract) or are non-specific systemic effects (reduced food consumption and weight gain, poor condition and nutrition) secondary to local toxicity. The results confirm the findings of older, published studies. At higher dose levels, the local effects of the test material were severe enough to cause mortality as a consequence of effects on the gastrointestinal tract, reduced food consumption and weight loss. Based on the likely low systemic availability and the corrosive nature of the substance, the scientific value of performing repeated dose oral toxicity studies with MK92K is considered to be very limited. The effects of the substance are very likely to be limited to the site of contact and non-specific secondary effects. Testing for repeated dose toxicity cannot therefore be supported on scientific grounds an additionally for reasons of animal welfare. The dose levels used in any studies of repeated dose toxicity would be limited by the corrosivity of the substance in order to avoid significant local effects on the gastrointestinal tract. The results of any studies would not therefore add any value to the database or be of any relevance to the risk assessment for workers or for the general population.

 

Repeated dose dermal toxicity data are also available for ADBAC and DDAC and are published in reviews by the US EPA and Canadian Regulatory authorities. The results of these studies show that dose levels are limited by local effects and that no systemic toxicity is observed. The corrosive nature of MK92K and its likely low dermal absorption similarly means that only local effects would be observed in any repeated dose dermal toxicity study. No testing is therefore proposed. This route of exposure is potentially relevant for workers; the dermal exposure of workers to the substance must therefore be eliminated or minimised through the use of engineering controls (process containment) and/or through the use of appropriate personal protective equipment (chemical resistant gloves, faceshield etc.).

 

No data are available for repeated dose inhalation toxicity, however MK92K is a very viscous, non-volatile liquid and is not used in a way which is likely to generate inhalable particles. Inhalation exposure under the normal conditions of use of MK92K is therefore not predicted and studies using inhalation exposure would be of limited relevance for the worker risk assessment.

 

Genetic toxicity

 

Reproductive and developmental toxicity

 

No data are available for MK92K and no studies are proposed. Published reviews by the US EPA and Canadian Regulatory authorities of the available data for the related quaternary ammonium compoundsalkyldimethyl benzyl ammonium chloride (ADBAC)anddidecyldimethylammonium chloride (DDAC) are available.The results of these studies indicate the absence of specific developmental toxicity for quaternary ammonium compounds.

 

The low systemic absorption of the substance MK92K and its corrosive nature indicate that specific reproductive toxicity and direct developmental toxicity are unlikely. The value of any investigation of developmental toxicity in animal studies would be severely limited by the corrosivity of the substance, which would limit the dose levels used in any study. The corrosivity and likely anti-bacterial action of MK92K would be likely to cause gastrointestinal disturbance, malabsorption and secondary bodyweight effects which may result in indirect toxicity to the foetus only at maternally toxic dose levels. Testing for reproductive and developmental toxicity is therefore considered to be scientifically unjustified and cannot be supported on animal welfare grounds.

DNEL derivation

 

Local DNEL values

 

MK92K is a corrosive substance. No dose-response data are available and consequently a quantitative dose descriptor is not available. REACH guidance states that corrosivity is a non-threshold effect for which a DNEL cannot usually be derived. Local DNEL values are therefore not derived for MK92K.

 

Dermal systemic DNEL values

 

MK92K is a corrosive substance for which dermal absorption is considered likely to be very low. The effects of dermal exposure will be dominated by those at the site of contact (i.e. local effects) and systemic toxicity is considered to be unlikely. No testing has been performed on scientific grounds and for reasons of animal welfare. No dose-response data are available and consequently a quantitative dose descriptor is not available. Systemic dermal DNEL values are therefore not derived for MK92K.

 

Inhalation systemic DNEL values

 

MK92K is a corrosive substance. No studies using inhalation exposure are available; however inhalation is not considered to be a relevant route of exposure for this substance due to its physicochemical properties and patterns of use. The extent of systemic absorption is unknown but is not considered likely to be significant as for other routes of exposure. The effects of inhalation exposure would therefore be dominated by those at the site of contact (i.e. local effects) and systemic toxicity is considered to be unlikely. No testing has been performed on scientific grounds and for reasons of animal welfare. No dose-response data are available and consequently a quantitative dose descriptor is not available. Systemic inhalation DNEL values are therefore not derived for MK92K.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

DNEL values

There is no direct exposure of the general population to MK92K through the uses described in this CSR. Indirect exposure of the general population via the environment may theoretically occur, but is considered likely to be negligible due to the limited environmental release of the substance.

Local DNEL values

 

MK92K is a corrosive substance. No dose-response data are available and consequently a quantitative dose descriptor is not available. REACH guidance states that corrosivity is a non-threshold effect for which a DNEL cannot usually be derived. Local DNEL values are therefore not derived for MK92K.

 

Dermal systemic DNEL values

 

MK92K is a corrosive substance for which dermal absorption is considered likely to be very low. The effects of dermal exposure will be dominated by those at the site of contact (i.e. local effects) and systemic toxicity is considered to be unlikely. No testing has been performed on scientific grounds and for reasons of animal welfare. No dose-response data are available and consequently a quantitative dose descriptor is not available. Systemic dermal DNEL values are therefore not derived for MK92K.

 

Inhalation systemic DNEL values

 

MK92K is a corrosive substance. No studies using inhalation exposure are available; however inhalation is not considered to be a relevant route of exposure for this substance due to its physicochemical properties and patterns of use. The extent of systemic absorption is unknown but is not considered likely to be significant as for other routes of exposure. The effects of inhalation exposure would therefore be dominated by those at the site of contact (i.e. local effects) and systemic toxicity is considered to be unlikely. No testing has been performed on scientific grounds and for reasons of animal welfare. No dose-response data are available and consequently a quantitative dose descriptor is not available. Systemic inhalation DNEL values are therefore not derived for MK92K.

 

Oral systemic DNEL values

 

No repeated dose oral toxicity data are available and no studies are proposed. Due to the corrosive nature of the substance and its likely limited oral absorption, it can be predicted that the effects of oral exposure would be local (or secondary to local effects) with little potential for systemic toxicity. Due to the patterns of use of the substance, oral exposure of the general population is not predicted. No dose-response data are available and consequently a quantitative dose descriptor is not available. Systemic oral DNEL values are therefore not derived for MK92K.