Bis[O,O-bis(2-ethylhexyl) dithiophosphorato-S,S']dioxodi-μ-thioxodimolybdenum

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

expert statement

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

other: expert statement based on available study results

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Materials and methods

Objective of study:

other: TK assessment based on available data

Test material

Test material information

Constituent 1

Reference substance name:

Bis[O,O-bis(2-ethylhexyl) dithiophosphorato-S,S']dioxodi-μ-thioxodimolybdenum

EC Number:

273-381-6

EC Name:

Bis[O,O-bis(2-ethylhexyl) dithiophosphorato-S,S']dioxodi-μ-thioxodimolybdenum

Cas Number:

68958-92-9

Molecular formula:

C32H68Mo2O6P2S6

IUPAC Name:

Bis[O,O-bis(2-ethylhexyl) dithiophosphorato-S,S']dioxodi-μ-thioxodimolybdenum

Test material form:

liquid

Applicant's summary and conclusion

Executive summary:

No specific study was performed on the absorption, distribution, metabolism, excretion (ADME) of this substance (S-930), but data currently available on physical-chemical properties and from in vivo and in vitro toxicology studies were evaluated.

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastrointestinal tract. As the water solubility of S-930 is very limited with≤0.25μg/L at 20°C, only traces of the substance (if any) will dissolve into the gastrointestinal fluids. In addition potential uptake via passive diffusion will be hampered by its large molecular weight (995). S-930 is lipophilic, as reflected in its partition coefficient (log Pow > 8.7). This implies that the substance may be taken up by micellar solubilisation. The substance has no ionisable groups, which could potentially hamper uptake.

For risk assessment purposes oral absorption of S-930 is set at 50%, based on its limited water solubility and its high molecular weight and taking into account its lipophilicity, which is expected to result in micellar solubilisation, after which some uptake is expected. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

Once absorbed, distribution of the substance throughout the body is expected to be limited based on its limited water solubility and high molecular weight. Absorbed S-930 is expected to be excreted via urine and via bile. Based on its high partition coefficient (log Pow > 8.7), it is likely that S-930 will accumulate in adipose tissue.

S-930 has a very low vapour pressure (below 4.0*10-3 Pa at 25°C), which indicates that exposure via air will be very limited. However, since S-930 is a liquid, exposure can be expected after formation of aerosols. If aerosols reach the tracheobronchial region, S-930 is not expected to dissolve in the mucus lining the respiratory tract as the water solubility is very low. The substance can be coughed or sneezed out of the body. As lipophilic substances have the potential to be absorbed directly across the respiratory tract epithelium, some uptake can be expected, although this is expected limited related to its high molecular weight. Taking all data together, it is concluded that for risk assessment purposes as worst case the inhalation absorption of S-930 should be set at 10%.

As S-930 is a liquid, uptake through the skin can take place. As the water solubility of S-930 is limited, partition from the stratum corneum into the epidermis is expected to be low. On the other hand, its ability to dissolve in lipids will favour crossing of epidermal barriers. Any movement through a skin barrier will be hampered by its molecular size. According to the criteria given in the REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of S-930 do meet the criteria for limited dermal absorption (MW 995; log Pow > 8.7), for risk assessment purposes dermal absorption is set at 10%.