Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

The substance MK92K is classified as corrosive based on the basis of pH measurements. The likely poor systemic absorption of the substance (predicted from its physicochemical properties and by read-across from other quaternary ammonium compounds) indicates that the effects of MK92K will be predominantly or entirely local (i.e. at the site of contact) and therefore that reproductive toxicity is unlikely.

 

The available reproductive toxicity data for the related quaternary ammonium compoundsalkyldimethyl benzyl ammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) have been reviewed by the US EPA (2006). The data are summarised below.

 

In a two-generation rat toxicity study performed with ADBAC at dietary dose levels of up to 2000 ppm (161 mg/kg bw/d), findings were limited to reduced weight gain in parental animals and offspring at the highest dose level. Reproductive parameters were unaffected by treatment. Similarly, in a two-generation rat toxicity study performed with DDAC at dietary dose levels of up to 1500 ppm (113 mg/kg bw/d), findings were limited to reduced weight gain in parental animals and offspring at the highest dose level. Reproductive parameters were unaffected by treatment.

 

The low systemic absorption of the substance MK92K and its corrosive nature indicate that effects relevant to fertility or reproduction are unlikely. The value of any investigation of reproductive 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 results of the multi-generation reproductive toxicity studies performed using the ADBAC and DDAC further indicate the absence of reproductive toxicity for quaternary ammonium compounds.

 

Testing for reproductive toxicity testing is therefore considered to be scientifically unjustified and cannot be supported on animal welfare grounds.


Short description of key information:
No data are avaialble and not testing is proposed: a waiver is proposed for this endpoint. The substance MK92K is classified as corrosive based on the basis of pH measurements. The likely poor systemic absorption of the substance (predicted from its physicochemical properties and by read-across from other quaternary ammonium compounds) indicates that the effects of MK92K will be predominantly or entirely local (i.e. at the site of contact) and therefore that reproductive toxicity is unlikely.

Effects on developmental toxicity

Description of key information
No data are avaialble and not testing is proposed: a waiver is proposed for this endpoint. The substance MK92K is classified as corrosive based on the basis of pH measurements. The likely poor systemic absorption of the substance (predicted from its physicochemical properties and by read-across from other quaternary ammonium compounds) indicates that the effects of MK92K will be predominantly or entirely local (i.e. at the site of contact) and therefore that direct developmental toxicity is unlikely. 
Additional information

The substance MK92K is classified as corrosive based on the basis of pH measurements. The likely poor systemic absorption of the substance (predicted from its physicochemical properties and by read-across from other quaternary ammonium compounds) indicates that the effects of MK92K will be predominantly or entirely local (i.e. at the site of contact) and therefore that developmental toxicity is unlikely.

 

The available developmental toxicity data for the related quaternary ammonium compoundsalkyldimethyl benzyl ammonium chloride (ADBAC) and didecyldimethylammonium chloride (DDAC) have been reviewed by the US EPA (2006). The data are summarised below.

 

No evidence of developmental toxicity was seen in a rabbit study performed with ADBAC at dose levels of up to 60 mg/kg bw/d. Marked toxicity was seen at 60 mg/kg bw/d, with signs of toxicity also observed at 10 and 30 mg/kg bw/d. The maternal NOAEL in this study was 3 mg/kg bw/d, based on clinical signs, reduced weight gain and food consumption at dose levels of 10 mg/kg bw/d and higher. No evidence of development al toxicity was seen in a rat study performedwith ADBACat dose levels of up to 9 mg/kg bw/d. A maternal NOAEL of 3 mg/kg bw/d was determined, based on clinical signs at the top dose level of 9 mg/kg bw/d.

In a study in rabbits performed with DDAC at dose levels of up to 10 mg/kg bw/d, reduced foetal survival and reduced foetal weight was seen at the top dose level but was associated with marked maternal toxicity, including mortality. Maternal toxicity was also observed at 3 mg/kg bw/d, resulting in a maternal NOAEL of 1 mg/kg bw/d for this study. In a rat study performed with DDAC at dose levels of up to 20 mg/kg bw/d. Signs of toxicity were observed at 10 and 20 mg/kg bw/d, with reduced weight gain at the top dose level of 20 mg/kg bw/d and reduced food efficiency at 10 and 20 mg/kg bw/d. A maternal NOAEL of 1 mg/kg bw/d was therefore determined for this study. Developmental toxicity (increased skeletal variations) was noted only at the top dose level of 20 mg/kg bw/d and is clearly associated with maternal toxicity.

  

The low systemic absorption of the substance MK92K and its corrosive nature indicate that direct developmental toxicity is 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. The results of the developmental toxicity studies performed using the ADBAC and DDAC further indicate the absence of specific developmental toxicity for quaternary ammonium compounds.

 

Testing for developmental toxicity is therefore considered to be scientifically unjustified and cannot be supported on animal welfare grounds.

Justification for classification or non-classification

No data are availabel, however reproductive and developmental toxicity are not predicted for MK92K, therefore no classification is propose according to the CLP Regulation 1272/2008.