Blue MGi 1037-Na (notification presscake)

Endpoint summary

Description of key information

No experimental data on absorption, distribution, metabolism and excretion are available for the substance. This toxicokinetic assessment is based on the physico-chemical properties and existing toxicological data. Based on these, limited oral and inhalation absorption and negligible dermal absorption are expected.Metabolism via hydrolysis is not expected. Bioaccumulation of the substance is not expected after repeated exposure. The substance is expected to be predominantly excreted via faeces.

 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No experimental data on absorption, distribution, metabolism and excretion are available for the source and target substance. The toxicokinetic assessment is based on their physicochemical properties and existing toxicological data.

Absorption

Generally, oral absorption is favoured for molecular weights below 500 g/mol, while molecular weights above 1000 g/mol do no longer favour absorption. Blue MGi 1037-Na shows good water solubility (37.85 g/L) which enables its dissolution in the gastrointestinal fluids. The hydrophilic properties are also demonstrated by the low log Pow value (< -4.06) . Due to the high molecular weight (777 g/mol) the substance is considered to be unable to pass through aqueous pores and the transport through the epithelial barrier by bulk passage of water can be excluded. On the other hand, small amounts may be transported into epithelial cells by endocytosis or persorption. These characteristics indicate that absorption following oral exposure will be very limited. This assumption is confirmed by the results of the acute oral toxicity study where only coloured faeces/diarrhea was observed after treatment with the substance and high dosing did not lead to any mortalities.

Decomposition of the compound at high temperatures (280 °C) and the low vapor pressure indicate that the substance will not be available for inhalation as a vapor under standard environmental conditions. The substance is a powder and inhalation of dust might occur. Generally, particles with an aerodynamic diameter below 100 µm have the potential to be inspired, particles below 50 µm may reach the thoracic region and those below 15 µm are able to pass into the alveolar region of the respiratory tract. Since 50 % (by mass) of the particles are smaller than 23.6 µm and 10 % smaller than 9.4 µm a significant amount of the substance is expected to reach the thoracic region and alveolar region upon exposure to dust. The potential for adsorption directly across the respiratory tract epithelium is negligible based on the very low Pow and high molecular weight. However, still a small amount may be taken up by endocytosis or persorption and transported to the blood via the lymphatic system.

Dermal absorption is also considered to take place to a very limited amount. The powdered substance will readily dissolve in moisture of the skin surface due to their water solubility. The high water solubility, the molecular weight and the negative Pow indicate a very low uptake of the substance into the stratum corneum. The source substance Blue MGi 1037 was not found to be irritating to the rabbit skin. Slight erythema was observed in a single animal one hour after treatment, but showing complete reversibility after 24 hours. No skin effects were observed in the Guinea pig maximization test with the source substance. However, in the acute dermal toxicity study slight focal erythema was observed after treatment with Blue MGi 1037 in some of the animals, but was found to be reversible after a few days. The LD50 was determined to be > 2000 mg/kg bw. Therefore, only minimal damage to enhance the penetration of the stratum corneum is expected upon exposure to the target substance.

Distribution

As mentioned above the physicochemical properties of the substance favour a limited systemic absorption following oral, inhalative and dermal uptake. The high molecular weight will limit the entry of the molecules via aqueous pores and only small amounts may enter the systemic circulation by endocytosis or persorption. After being absorbed into the body, the substance is likely not distributed into the interior part of the cells due to their hydrophilic properties (negative Pow) and in turn the extracellular concentration may be higher than the intracellular concentration.

The low Pow indicates no bioaccumulation potential for the target and source substance. All values are well below 3 and therefore both substances are not considered to be bioaccumulative. This has been confirmed in fish bioaccumulation study with Blue MGi 1037, where the BCF was below 1.

Metabolism

For the source substance Blue MGi 1037 the chromosomal aberration study in vitro indicates a difference in genotoxic effects with regard to the use of a metabolic activation system in the test. In the Ames test no mutagenicity was observed after treatment with Blue MGi 1037 with and without metabolic activation. However, the chromosomal aberration assay shows a clastogenic outcome only in the experimental parts applying a continuous treatment without a metabolic activation system, suggesting a direct way of interference with cellular macromolecules and a sufficient detoxification of the substance and/or repair of DNA damage in the experimental parts with pulse treatment in the absence and presence of metabolic activation. Based on the results obtained in the hydrolysis study performed with Blue MGi 1037 the source and target substance can be considered as hydrolytically stable at physiological pH (no degradation observed) and also at acidic and alkaline pH values (half life times of several days at pH 4 and 9 and 50°C). Thus, metabolism via hydrolysis is not expected.

Excretion

Substances with high water solubility are prone to excretion via urine, but the molecular weight above 300 g/mol limits this pathway. The high molecular weight favours excretion via bile and faeces. Excretion via faeces has been confirmed by the results of the acute oral toxicity study (Blue MGi 1037 Na) and repeated dose toxicity study (Blue MGi 1037) where coloured faeces/diarrhea was observed after treatment with the substance.