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EU RISK ASSESSMENT – DIMETHYL SULPHATE

 

Toxico-kinetics, metabolism, and distribution

DMS can be absorbed via respiratory and oral routes. For oral absorption this is concluded from toxicodynamic data. No information is provided on the metabolism of DMS in animals following oral administration. The information on inhalatory or dermal exposure is limited and no quantitative conclusion can be drawn.

In an inhalatory study in rats a rapid disappearance of DMS from the exposure chamber was reported (40 minutes after exposure to 4.7-127 mg/m3). Blank chambers (DMS, no animal) were run as controls. At the higher dose levels (50.3 and 127 mg/m3) the disappearance rate was decreased, probably due to a decreased minute volume caused by DMS (Mathison, 1995). This study provides information on uptake of DMS, however does not allow quantification of the percentage of absorption.

In the urine of mice exposed by inhalation to3H-DMS (average concentration 16.3 mg/m³ and 0.32 mg/m³ for 135 and 60 min resp.) 84-94% of the radiolabel was collected from urine at 48 hours. Less than 0.5% of estimated dose was recovered in the urine as labelled methylated purines (Löfroth, 1974). Due to the limited report this study is considered not suitable for quantitative evaluation.

After an intravenous injection of 75 mg/kg bw in the rat, DMS was no longer detectable in the blood after 3 minutes (Swann, 1968B).

After inhalatory and dermal exposure DMS is reported to be slowly hydrolysed to methanol and sulphuric acid in the tissues, however no quantitative data are provided (Kühn, 1994). Other minor metabolites may be methylsulphate, formaldehyde, and formate. Methylsulphate is stated not to decompose to sulphate (Mathison, 1995), however this statement is not understandable.

When rat liver- and nasal microsomes were incubated with DMS (2 mM in water) only minor amounts of formaldehyde were found with liver microsomes and traces with rat nasal microsomes (Dahl, 1983).

 

Conclusion

The data are insufficient to quantify the kinetic behaviour of DMS after inhalatory exposure, however, apparently absorption is high. No quantitative information on absorption via the oral and dermal route of exposure is available.