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Basic toxicokinetics

There are no studies available in which the toxicokinetic behaviour of aminoiminomethanesulphinic acid (CAS No. 1758-73-2) has been investigated.

Therefore, in accordance with Annex VIII, Column 1, Item 8.8.1 of Regulation (EC) 1907/2006 and with Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012), assessment of the toxicokinetic behaviour of the substance aminoiminomethanesulphinic acid (CAS No. 1758-73-2) is conducted to the extent that can be derived from the relevant available information. This comprises a qualitative assessment of the available substance specific data on physico-chemical and toxicological properties according to Guidance on information requirements and chemical safety assessment Chapter R.7c: Endpoint specific guidance (ECHA, 2012)

The substance aminoiminomethanesulphinic acid is a white powder which is soluble in water (max. 27 g/L). It decomposes upon heating > 50 °C and spontaneously beyond 100 °C (exotherm) with formation of SO2. The partition coefficient octanol/water (log POW) is estimated to be -3,373 (Müller, 2012). Aminoiminomethanesulphinic acid has a molecular weight of 108.11 g/mol and a water solubility of 27 g/L at 20 °C (OECD SIDS, 2002).

 

Absorption:

Absorption is a function of the potential for a substance to diffuse across biological membranes. The most useful parameters providing information on this potential are the molecular weight, the octanol/water partition coefficient (log POW) value and the water solubility. The log POW value provides information on the relative solubility of the substance in water and lipids (ECHA, 2012).

 

Oral:

The smaller the molecule, the more easily it will be taken up. In general, molecular weights below 500 g/mol are favourable for oral absorption (ECHA, 2012). As the molecular weight of aminoiminomethanesulphinic acid is 108.11 g/mol, absorption of the molecule in the gastrointestinal tract is in general anticipated. Absorption after oral administration is also expected when the “Lipinski Rule of Five” (Lipinski et al. (2001), refined by Ghose et al. (1999)) is applied to the substance aminoiminomethanesulphinic acid.

Overall, a systemic bioavailability of aminoiminomethanesulphinic acid in humans is considered likely after oral uptake of the substance.

 

Dermal:

It is commonly accepted that smaller molecules are taken up through the skin more easily than bigger ones; the smaller the molecule, the more easily it may be taken up. In general a molecular weight below 100 g/mol favours dermal absorption, above 500 g/mol the molecule may be too large (ECHA, 2012).

In general, a molecular weight below 100 g/mol favours dermal absorption, above 500 g/mol the molecule may be too large (ECHA, 2012). As the molecular weight of aminoiminomethanesulphinic acid is 108.11 g/mol, a dermal absorption of the molecule cannot be excluded.

 

If a substance is a skin irritant or corrosive, damage to the skin surface may enhance penetration (ECHA, 2012). Furthermore, if a substance has been identifies as skin sensitizer, then some uptake must have occurred previously, although it may only have been a small fraction of the applied dose (ECHA, 2012).

As aminoiminomethanesulphinic acid is considered as skin irritants in humans, an enhanced penetration of the substances due to local skin damage cannot be excluded. However, for aminoiminomethanesulphinic acid no skin sensitisation potential has been identified.

 

Based on QSAR calculations aminoiminomethanesulphinic acid has only a low dermal absorption potential of not more than 10% is estimated based on chemical characteristics like the molecular weight, logKow and water solubility. Specifically, a permeability constant of 3.49708 cm/h was estimated resulting in a flux of 0.00005 µg/cm²/h as calculated with DERMWIN (v.2.01, 2011, modified considering the Fick´s first law). Thus, dermal absorption of aminoiminomethanesulphinic acid can be considered as nearly negligible.

Moreover, the dermal uptake of substances with a high water solubility of > 10 g/L (and log Pow < 0) will be low, as those substances may be too hydrophilic to cross the stratum corneum.

Log Pow values between 1 and 4 favour dermal absorption (values between 2 and 3 are optimal), in particular if water solubility is high. In contrast, log Pow values < –1 suggest that a substance is not likely to be sufficiently lipophilic to cross the stratum corneum, therefore dermal absorption is likely to be low (ECHA, 2012). As aminoiminomethanesulphinic acid has a log POW < 0 and water solubility of 27 g/L, dermal uptake is likely to be low.

Overall, the calculated low dermal absorption potential, the high water solubility, the high molecular weight (>100) and the fact that the substance is not sensitising to human skin implies that dermal uptake of aminoiminomethanesulphinic acid in humans is considered as low.

 

Inhalation:

Aminoiminomethanesulphinic acid, has a low vapour pressure (< 0.001 Pa) at 25 °C thus being of low volatility. Therefore, under normal use and handling conditions, inhalation exposure and thus availability for respiratory absorption of the substance in the form of vapours, gases, or mists is not expected to be significant.

The inhalation route is not relevant for substances with an MMAD of >100 µm which also have a vapour pressure smaller than 0.01 Pa and which are not used in a manner that generates respirable aerosols.

 

Accumulation:

Substances with log POW values of 3 or less would be unlikely to accumulate with the repeated intermittent exposure patterns normally encountered in the workplace but may accumulate if exposures are continuous (ECHA, 2012).

As the log POW of aminoiminomethanesulphinic acid is < 0, indicating a high solubility in water. Consequently, there is no potential for the test substance to accumulate in adipose tissue.

Overall, the available information indicates that no significant bioaccumulation of the test substance in adipose tissue is expected.

 

Distribution:

Distribution within the body through the circulatory system depends on the molecular weight, the lipophilic character and water solubility of a substance. In general, the smaller the molecule, the wider is the distribution. If the molecule is lipophilic, it is likely to distribute into cells and the intracellular concentration may be higher than extracellular concentration particularly in fatty tissues (ECHA, 2012).

The test substance, a small, polar water-soluble substance (log POW < 0), will be distributed in aqueous fluids by diffusion through aqueous channels and pores.

 

Overall, the available information indicates that the test substance will be distributed in the organism.

 

Metabolism/Excretion

The potential metabolites following enzymatic metabolism of aminoiminomethanesulphinic acid were predicted using the OECD QSAR ToolBox 2.3.0 (OECD, 2011). QSAR calculations of the substance aminoiminomethanesulphinic acid predicted potential metabolites using liver, skin and microbial simulators. 2 liver, 6 skin, and 4 microbial metabolites were predicted.

 

On the basis of the physic-chemical properties of aminoiminomethanesulphinic acid the main route of excretion is expected to be by urinary excretion. 

 

 

References

ECHA (2012). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Ghose et al. (1999). A Knowledge-Based Approach in Designing Combinatorial or Medicinal

Lipinski et al. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 46: 3-26.

OECD SIDS (2002). OECD SIDS Methanesulfinic acid, Aminoimino / CAS 1758-73-2 /