Leuco polysulfided 4-[(2,4-dinitrophenyl)amino]phenol

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Remarks:

Expert Statement

Type of information:

other: Expert Statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Expert Statement, no study available

Objective of study:

absorption

distribution

excretion

metabolism

Details on test animals or test system and environmental conditions:

not applicable

Positive control reference chemical:

not applicable

Details on study design:

not applicable

Details on dosing and sampling:

not applicable

Statistics:

not applicable

Details on absorption:

Bioavailability via oral route is strongly linked to physico-chemical properties of the substance. Generally, oral absorption is favoured for molecular weights below 500 g/mol. Furthermore, a high water solubility of more than 100 mg/L and a moderate log Pow of -1 to 4 enables the substance to readily dissolve in the gastrointestinal (GI) fluids, allowing direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across membranes with the bulk passage of water. The test item is an UVCB substance and does not have a defined molecular structure but consists of large molecules well above 500 g/mol (no fraction of the substance had a MW of below 3460 Da). The water solubility of 4.86 mg/L does not favour absorption. Taken together, the physiochemical properties indicate that the bioavailability of the substance is very restriced following the oral route. This assumption is confirmed by the result of the acute toxicity study (OECD 423) and of a repeated dose toxicity study (OECD 422) with the read-across substance Leuco Sulphur Yellow (CAS: 90268 -98 -7). No substance related effects or mortality were observed.
The volatility indicates whether a substance may be available for inhalation as a vapour. Volatility decreases with increased molecular weight. In particular due to the high molecular weight in combination with a very low vapour pressure (due to the melting point abvoe 300°C), absorption of the test item via inhalation route is not expected to occur.
Dermal uptake is favoured for substances with a molecular weight <100 g/mol. The molecular weight of the substances is thus too large. In addition, the substances must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Absorption is anticipated to be low to moderate if water solubility is between 1 and 100 mg/L. The test item has a water solubility of 4.86 mg/L and a log Pow of < -1, therefore not supporting dermal absorption. Furthermore, the test substance does not contain skin sensitizing properties, which would indicate systemic availability. In addition, the test item does not impair the barrier function of the skin (no skin irritating properties), which could lead to systemic availability.

Details on distribution in tissues:

In general, the smaller the molecule, the wider the distribution. Based on its molecular weight distribution (no fractions below 3460 Da) and the hydrophilic nature of the test substance (log Pow < -1) it is assumed, that if absorbed, the test substance is not widely distributed and that distribution is only within the aqueous compartment of the organism. Furthermore, an accumulation within adipose tissue is unlikely.

Details on excretion:

Due to the high molecular weight, low water solubility and negative low Pow the substance will be ecreted in the faeces.

Details on metabolites:

The test substance is not expected to be bioavailable following oral, inhalative or dermal exposure. In case minor amounts become systemically bioavailable, a prediction of the metabolism is not possible as the test item is a UVCB substance with unknown structure. The available data indicate that the test substance is not susceptible to hydrolysis. Therefore an unaltered passage of the parent substance through the stomach can be presumed.

Conclusions:

Due to the high molecular weight and low water solubility of the test substance no absorption is expected by the oral, inhalative or dermal route. The substance is excreted in faeces.

Executive summary:

Based on physicochemical characteristics (very high molecular weight, low water solubility) no absorption by the oral, inhalative or dermal route is expected. This assumption is further supported by the results of the acute oral toxicity study, revealing no substance related effects. In case minor amounts would become systemically bioavailable, distribution in the aqueous compartment, but no wide distribution is expected. Predictions on metabolic reactions cannot be made since the chemical structure of the substance is unknown. Based on the physical-chemical data (i.a. poor water solubility) and due to the size of the molecule metabolism is assumed to be unlikely and excretion in feces is the only relvant route of elemination route.

Description of key information

Based on physicochemical characteristics (very high molecular weight, low water solubility) the absorption by the oral, inhalative or dermal route of the test substance is assumed to be very restricted. This assumption is supported by the results of the acute oral toxicity study, revealing no substance related effects and no coloration of urine and internal organs up to the highest tested concentrations. In case minor amounts would become systemically bioavailable, distribution within the aqueous compartment, but no wide distribution is assumed.

Based on the physical-chemical data (i.a. poor water solubility) and due to the size of the molecule metabolism is assumed to be unlikely and excretion in feces is the only relvant route of elemination route.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Absorption

Bioavailability via oral route is strongly linked to physico-chemical properties of the substance. Generally, oral absorption is favoured for molecular weights below 500 g/mol. Furthermore, a high water solubility of more than 100 mg/L and a moderate log Pow of -1 to 4 enables the substance to readily dissolve in the gastrointestinal (GI) fluids, allowing direct uptake into the systemic circulation through aqueous pores or via carriage of the molecules across membranes with the bulk passage of water. The test item is an UVCB substance and does not have a defined molecular structure but consists of large molecules well above 500 g/mol (no fraction of the substance had a MW of below 3460 Da). The water solubility of 4.86 mg/L does not favour absorption. Taken together, the physiochemical properties indicate that the bioavailability of the substance is very restriced following the oral route. This assumption is confirmed by the result of the acute toxicity study (OECD 423) and of a repeated dose toxicity study (OECD 422) with the read-across substance Leuco Sulphur Yellow (CAS: 90268 -98 -7). No substance related effects or mortality were observed.

The volatility indicates whether a substance may be available for inhalation as a vapour. Volatility decreases with increased molecular weight. In particular due to the high molecular weight in combination with a very low vapour pressure (due to the melting point abvoe 300°C), absorption of the test item via inhalation route is not expected to occur.

Dermal uptake is favoured for substances with a molecular weight <100 g/mol. The molecular weight of the substances is thus too large. In addition, the substances must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Absorption is anticipated to be low to moderate if water solubility is between 1 and 100 mg/L. The test item has a water solubility of 4.86 mg/L and a log Pow of < -1, therefore not supporting dermal absorption. Furthermore, the test substance does not contain skin sensitizing properties, which would indicate systemic availability. In addition, the test item does not impair the barrier function of the skin (no skin irritating properties), which could lead to systemic availability.

Distribution:

In general, the smaller the molecule, the wider the distribution. Based on its molecular weight distribution (no fractions below 3460 Da), the low solubility (4.86 mg/L) and the negative log Pow it is assumed, that if absorbed, the test substance is not widely distributed and that distribution is only within the aqueous compartment of the organism. Furthermore, an accumulation within adipose tissue is unlikely.

Metabolism:

The test substance is not expected to be bioavailable following oral, inhalative or dermal exposure. In case minor amounts become systemically bioavailable, a prediction of the metabolism is not possible as the test item is a UVCB substance with unknown structure. The available data indicate that the test substance is not susceptible to hydrolysis. Therefore an unaltered passage of the parent substance through the stomach can be presumed.

Due to the size of the molecule and the poor water solubility it is assumed that the substance is not metabolized.

Excretion:

According to the physicochemical properties of the test substance, molecular weight, hydrophilic characteristics and water solubility, the main route of excretion is expected to be via faeces.