Reaction mass of 4-tert-butylphenyl diphenyl phosphate and bis(4-tert-butylphenyl) phenyl phosphate and triphenyl phosphate

Endpoint summary

Additional information

No studies on toxicokinetics are available for tBuTPP. The available toxicity studies provide no or little information. Therefore the assessment is primarily based on physicochemical properties, supported by some toxicological indications.

 

Physical/chemical properties

The physical/chemical properties that are of importance to assess the toxicokinetics behaviour of tBuTPP are:

• Water solubility – 3.2 mg/L
• Molecular weight – 382 g/mol
• Log Kow – 4.68
• Vapour pressure - 0.00108 Pa (20°C)

 

Absorption

Based on log Kow, t-BuTPP is relatively highly lipophilic and therefore oral/GI-absorption by passive diffusion is expected to be limited. Reasonably micellular solubilisation will be the major mechanism for absorption, also because it has a low water solubility and a moderate low molecular weight. Oral acute toxicity studies indicate some visible adversal effects in GI-tract, adrenals, testes and lungs. This indicate that absorption has occurred, although it gives no indication of the amount of absorbed substance.

Due to the low vapour pressure of tBuTPP, respiratory exposure is unlikely to occur on a large scale. However, when respiratory exposure has occurred, absorption will be similar to oral absorption.

Because of its highly lipophilic character the dermal penetration of t-BuTPP into the stratum corneum will be high. Because of its low water solubility the rate of penetration from the stratum corneum into the epidermis is likely to be low. This would be supported by the outcome of the skin sensitization study (LLNA), in which the SI was >3 in all concentrations tested, however, no dose-response was observed. One theoretical explanation might be that the majority of the dermal applied substance stays in the local stratum corneum and only a small fraction has been absorbed into the epidermis.

 

Distribution, metabolism and excretion

Based on the physical chemical properties the substance will be distributed into cells and to a lower extent into the extracellular spaces. Since it’s highly lipophilic character it is anticipated that it tends to be accumulated in adipose tissues and in lipophilic layers like the stratum corneum. In one study (SE Hastings, Sauerhoff, 1981) a significantly higher concentration of phosphates was found in the urine of exposed animals. This was theoretically clarified by excretion of metabolites. There is no indication of metabolism rate and excretion rates.

 

Conclusion:

T-BUTPP can be absorbed after oral and respiratory exposure, but the amount of absorption cannot be predicted. Dermal absorption is considered to be very low, but accumulation in the stratum corneum is expected. No information is available about the distribution, metabolism and excretion.

For risk assessment purposes, absorption via the oral and inhalation route are assumed to be similar, based on the absence of effects in 90-day studies via both routes. For dermal absorption, it was assumed as a worst-case that absorption was similar to oral absorption.