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Key value for chemical safety assessment

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No specific data on the toxicokinetics of MK92K are available. The likely toxicokinetic properties of the substance are addressed using theoretical considerations and by read-across from structurally similar substances: 1-(phenylmethyl)-alkyl pyridinium chloride derivatives.

 

No toxicokinetic data are available for these substances, however the data on related quaternary ammonium compounds are summarised by the WHO (1998), EPA (2006) and in a Canadian review (Henderson, 1992).

 

Absorption

 

Significant absorption of quaternary ammonium compounds is unlikely due to their highly ionic nature. WHO (1998) report the oral absorption of quaternary ammonium compounds in general to be poor. A published Canadian review of the toxicity of the quaternary ammonium compounddidecyldimethylammonium chloride (DDAC) notes experiments in rats in which up to 99% of orally administered radioactivity was recovered in the faeces and less than 2.5% in the urine (Henderson, 1992). The published US EPA summary of the toxicity of alkyldimethyl benzyl ammonium chloride (ADBAC) also reports that the majority (up to 98%) of administered radioactivity is eliminated in the faeces, with limited (5-8%) urinary excretion (EPA, 2006).

 

The dermal absorption of quaternary ammonium compounds is likely to be low based on the chemical structure, ionic nature, molecular weight and lack of lipophilicity of the substance. Absorption of this group of substances through skin is also indicated to be very low based on an absence of reports of systemic effects following dermal exposure (WHO, 1998). However it is noted that the substance is corrosive, therefore it is possible that systemic absorption may occur following significant accidental dermal exposures resulting in skin burns, where the normal barrier integrity of the skin is compromised. Buistet al(2007) report very low dermal penetration (0.5%) for the quaternary ammonium compound didecyldimethylammonium chloride (DDAC) in human skinin vitroover a 48-hour period.

 

No data are available for absorption following inhalation exposure, however it is considered unlikely that absorption by his route of exposure would be significant. Although not relevant to the human risk assessment, the WHO document notes that the systemic absorption of quaternary ammonium compounds following parenteral administration is ‘possible’.

 

Distribution

 

No data on distribution are available. However given the water solubility of the substance, it is likely to be widely distributed via the circulation if absorbed.

 

Metabolism

 

No data are available for the substance; however significant metabolism is not predicted given the likely poor systemic absorption. 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 (Henderson, (1992).

 

Excretion

 

Data indicate that quaternary ammonium compounds are largely excreted in the faeces (WHO, 1998; Henderson, 1992). The poor absorption and chemical nature of the substance (specifically the lack of lipophilicity) indicate that substance MK92K has no potential for bioaccumulation potential.

 

WHO (1998). QUATERNARY AMMONIUM COMPOUNDS. International Programme on Chemical Safety (IPCS Poisons Information Monograph G022 (Group PIM).

Buist HE, de Heer C, van Burgsteden JA & Van der Sandt JJ (2007). Dermatokinetics of didecyldimethylammonium chloride and the influence of some commercial biocidal formulations on its dermal absorption in vitro.

 

EPA (2006). Toxicology Disciplinary Chapter for the Re-Registration Eligibility Decision (RED) Risk Assessment of alkyldimethyl benzyl ammonium chloride (ADBAC).

 

Henderson ND (1992). A review of the environmental impact and toxic effects of DDAC. Environmental Protection Division, BC Environment.