Molybdenum, bis(N,N-dibutylcarbamodithioato-κS,κS')dioxodi-μ-thioxodi-, stereoisomer

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:

other: expert statement

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:

Molybdenum, bis(N,N-dibutylcarbamodithioato-κS,κS')dioxodi-μ-thioxodi-, stereoisomer

EC Number:

825-571-0

Cas Number:

60428-79-7

Molecular formula:

C18H36Mo2N2O2S6

IUPAC Name:

Molybdenum, bis(N,N-dibutylcarbamodithioato-κS,κS')dioxodi-μ-thioxodi-, stereoisomer

Test material form:

solid: particulate/powder

Applicant's summary and conclusion

Executive summary:

No specific study was performed on the absorption, distribution, metabolism, excretion (ADME) of this substance (S-600), 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. Since the water solubility of Molybdenum, bis(N,Ndibutyl­carbamodithioato-κS,κS’)dioxodi-μ-thioxodi-, stereoisomer (S-600) is very low (< 0.1 µg/L at 20°C), only traces of the substance will dissolve into the gastrointestinal fluids and become available for uptake. Furthermore, its high molecular weight (approx. 697) and high partition coefficient (log Pow > 7.2) will prevent uptake via passive diffusion (passage of small watersoluble molecules through aqueous pores or carriage across membranes with the bulk passage of water). However, the high partition coefficient indicates the substance may be taken up by micellar solubilisation.

 

For risk assessment purposes oral absorption of S-600 is set at 10%, based on its very low water solubility, its high molecular weight and its high log Pow. 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 low water solubility, high log Pow and high molecular weight. Orally absorbed S-600 may be metabolized in the gastro-intestinal tract and the liver. Absorbed S-600 and its metabolites are expected to be excreted via urine. Based on its high partition coefficient (log Pow > 7.2), it is likely that S-600 will accumulate in adipose tissue.

 

S-600 has a very low vapour pressure (< 1.3 * 10-8Pa at 20°C), which indicates that exposure via air will be limited. S-600 is a solid (at room temperature) with inhalable particles that can reach the tracheobronchial region. Here S-600 will only dissolve in the mucus lining of the respiratory tract to a very small extent, based on its low water solubility and high log Pow. Therefore, the substance is considered to enter the body to a limited extent and the largest part will leave the lungs e.g. through coughing. Taken all data together, it is concluded that for risk assessment purposes the inhalation absorption of S-600 should be set at 10%.

 

As S-600 is a solid, uptake through the skin is unlikely to occur unless it is dissolved in a body fluid (sweat). The log Pow is high (>7.2) and indicates a slow uptake in the stratum corneum. The water solubility of S-600 is limited, therefore partition from the stratum corneum into the epidermis will be hampered. 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.

 

Since the physical/chemical properties of S-600 meet the criteria for limited dermal absorption (MW approx. 697; log Pow > 7.2), for risk assessment purposes dermal absorption should be set at 10%. The substance does not have skin irritating properties, thus the substance is not expected to interfere with dermal epithelia which could potentially increase uptake.

 

Based on the above data, for risk assessment purposes the dermal absorption of S-600 is set at 10%.