Phenol, 2,4-dinitro-, sulfurized, thiosulfonated

Endpoint summary

Description of key information

Based on its physicochemical properties (water solubility = 617 g/L, log Pow = -1.37, mean MW > 600000 Da) the systemic availability of the test substance via oral, dermal or inhalation route is very limited. Upon absorption, it is expected that the substance is distributed in the aqeous compartment of the organism. An assessment of metabolic pathways is not possible, since the chemical structure of the test substance is unknown. Based on the high MW intestinal excretion is assumed to be the major route. Bioaccumulation can be excluded.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic analysis of Solubilised Sulphur Black 1

The test substance is a solid at room temperature (powder) with a median particle size D50 = 294 µm (D10 = 74 µm; D90 = 694 µm). It is manufactured and handled as liquid /aqueous preparation. The test substance is an UVCB substance with an unknown chemical structure and a mean molecular weight of above 600000 Da. Its water solubility is 617 g/L at room temperature and it is basically insoluble in organic solvents, including n-octanol. The log Pow is negative (-1.37).

Absorption

After oral uptake, the amount of systemic absorption through the gastro-intestinal (GI) barrier depends on the physicochemical properties of the substance. For a conclusive judgement on the substance´s potential to reach systemic circulation, important physicochemical factors such as molecular weight, water solubility and the log Pow value should be considered. The substance has an excellent water solubility (617 g/L) and will dissolve readily into the GI fluids. Due to its highly hydrophilic character (log Pow = -1.37), the mean MW > 600000 Da and no fraction with a MW < 9500 Da, absorption is severely restricted.

The assumption that the test item is poorly absorbed is strengthened by results of the oral toxicity studies in rats (acute oral and repeated dose oral toxicity), which reported black coloured faeces/diarrhea after test item administration [1 and 6] and no adverse effets. There are indications that the substance is not susceptible for hydrolysis (SCC GmbH, expert statement) or biodegradation [2]. Thus, the chance of a pre-uptake degradation via stomach-/GI-fluids or intestinal bacteria is limited.

The test substance is solely handled and used as liquid formulation. Thus, inhalation exposure to the test substance is very limited under regular working conditions. Theoretically, if inhalation would occur it is expected that the test substance readily dissolves in the mucus of the respiratory tract. A direct transfer across the respiratory tract epithelium by passive diffusion might also be possible. But absorption may be very limited due to the molecule weight (≥ 600000 Da).

Considering the very hydrophilic character and high MW, dermal absorption is expected to be negligible. For substances with log P values <0, poor lipophilicity will limit penetration into the stratum corneum and hence dermal absorption. 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. In vitro assays did not determine skin/eye irritating properties of the test substance [3,4]. Furthermore, the test substance did neither show skin sensitizing properties in a mouse LLNA [5] nor did the test substance show signs of skin damaging/penetrating potential.

Distribution

Based on its mean MW (> 600000 Da), and the hydrophilicity (log Pow = -1.37) it is assumed, that if absorbed, the test substance is distributed within the aqueous compartment of the organism. An accumulation within adipose tissue can be excluded. Moreover, there are no indications that the test item passes the placenta or umbilical cord in the absence of any signs of toxicity in offspring animals [6].

Metabolism

The test substance is a UVCB substance with an unknown chemical structure. Consequently, a prediction of metabolic pathways is not possible. 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. Furthermore, the test substance is considered to be not readily biodegradable. This could indicate that the substance is not a suitable substrate for the intestinal flora. The observation of black coloured faeces/diarrhea is another indication that the test substance passes the gastrointestinal tract without chemical modification/bacterial metabolisation.

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. This is strengthened by the observation of black coloured faeces after oral substance [1 and 6] and the absence of discoloured urine.

References

[1] Acute oral Toxicity Study (Acute Class Method) of Test Item Solubilised Sulphur Black 1 in Rats, unpublished report, Toxi-Coop, 2017

[2] Ready Biodegradability of Solubilised Sulphur Black 1 in a Closed Bottle Test, unpublished report, Toxi-Coop, 2017

[3] In Vitro Skin Irritation Test with Solubilised Sulphur Black 1 in the EPISKIN Model,unpublished report, Toxi-Coop, 2017

[4] In vitro Eye Irritation Test with Solubilised Sulphur Black 1 in the EpiOcularTM Model, unpublished report, Toxi-Coop, 2017

[5] Skin Sensitization Study: Local Lymph Node Assay of Solubilised Sulphur Black 1 in Mice (Pooled Treatment Group Approach),unpublished report, Toxi-Coop, 2018

[6] Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test with Solubilised Sulphur Black 1 in Rats, Toxi-Coop, 2019