Reaction mass of Sodiumbis[1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-) and Sodium [1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphtholato(2-)][1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-) and Sodiumbis[1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-)

Endpoint summary

Description of key information

Based on its physicochemical properties systemic availability of the test substance is given but limited. When taken up by the oral route, the substance is likely to be absorbed through the walls of the gastrointestinal tract by absorption and/or diffusion. The physicochemical properties do not favor transdermal absorption. Considering the non-solid state and low vapor pressure of the test substance it is expected to be non-inhalable under normal use conditions. The substance is expected to be distributed but not metabolized within the body if becoming systemically available. Based on the chemical characteristics intestinal excretion is assumed to be the major route. According to the physiochemical properties and the fast excretion of the test substance, bioaccumulation is unlikely.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicokinetic analysis of reaction mass of sodium [1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphtholato(2-)][1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-) and sodium bis[1-[(2-hydroxy-4-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-) and sodium bis[1-[(2-hydroxy-5-nitrophenyl)azo]-2-naphtholato(2-)]chromate(1-)

The test substance is a solid at room temperature (fine powder) with a molecular weight (MW) of 689.5 g/mol. The water solubility is moderate. However, the solubility in water is not a constant, but increases with the mass of test item applied (31 mg/L with a loading rate of 0.1 g/L at pH 6.6; 85 mg/L with a loading rate of 0.5 g/L at pH 6.7 at 20 °C). A log P_ow of 1.3 to 1.9 was determined.

Absorption

After oral uptake, the chance of systemic absorption through the gastro-intestinal (GI) barrier depends on the physicochemical properties of the substance. For a conclusive judgment on the substance´ potential to reach systemic circulation, important physiochemical factors such as molecular weight, water solubility and the log P_ow value should be considered. The substance is moderately hydrophilic (log P_ow 1.3 to 1.9) and is moderately soluble in water (31 – 85 mg/L), thus the substance will dissolve into the GI fluids. However, the passage via aqueous pores or the carriage through the epithelial barrier by the bulk passage of water is favored for molecules with a molecular weight below 200 g/mol. Therefore, these routes are limited due to the size of the molecule (689.5 g/mol).

Repeated dose toxicity studies reported a black discoloration of the animals and their inner organs, indicating a partial absorption of the test substance (BASF SE, 2018; BASF SE, 2016). It is possible, that substance uptake occurs at the small intestines. These have a very large surface and the transit time is longest, thereby increasing the chance of substance uptake via e.g. persorption or pinocytosis. There are indices that the substance is not susceptible for hydrolysis (BASF SE, expert statement) or biodegradation (BASF SE, 2016). Thus, the chance of a pre-uptake degradation via stomach-/GI-fluids or intestinal bacteria is limited.

The substance is handled in a non-solid form. Thus, inhalation is very limited under regular working conditions. Even if the substance would be available in solid form, exposure to the test substance as vapor would be very limited if handled at room temperature, according to the very low vapor pressure (6.84E-30 Pa at 25 °C, EPISuite calculation for a structural isomer, CAS 64611-73-0, see read-across justification). Theoretically, if inhalation of particles occurred during handling, the water solubility (31 – 85 mg/L) indicates that the test substance might be dissolved in the mucus of the respiratory tract. Due to the log P_ow of 1.3 – 1.9 absorption directly across the respiratory tract epithelium by passive diffusion is also possible. However, absorption may be limited due to the molecule size (689.5 g/mol).

Considering the moderate hydrophilic character and the moderate solubility, particles of the test substance might dissolve in the surface moisture of the skin. Dermal uptake of substances <100 g/mol is favored. The MW of the test substance of 689.5 g/mol prevents dermal absorption. According to the solubility (31 - 85 mg/L) a low dermal uptake can be anticipated. However, due to the log P_ow of 1.3 - 1.9 penetration into the stratum corneum is favored and hence dermal absorption cannot be excluded. The assumption that limited dermal absorption occurs is strengthened by results of an acute dermal study in rabbits showing an LD50 >2000 mg/kg bw (BASF SE, 2016). Application of the test substance onto the skin of rabbits induced no irritations (BASF SE, 1980), which in turn could have favored direct absorption into the systemic circulation. However, the test substance has shown sensitizing properties (BASF SE, 2016). Since sensitizing processes take place beneath the stratum corneum, this is a clear sign, that a small part of the substance penetrates the skin barrier and becomes systemically available.

Distribution

In a repeated dose toxicity study, black discoloration of the skin and the inner organs of the animals has been reported (BASF SE, 2018). The discoloration vanished after the substance administration period. Furthermore, the discoloration vanished during histological preparation of different tissue samples. Based on the molecular size (689.5 g/mol), the log P_ow (1.3 – 1.9) and the water solubility (31 – 85 mg/L) as well as the observations within the repeated dose toxicity study, it is suggested, that a fraction of the test substance enters interstitial fluids and is distributed within the aqueous compartment of the organism. Consequently, deposition and accumulation especially within adipose tissue is unlikely.

Metabolism

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 colored feces 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 supposed to be via feces. This presumption is strengthened by the observation of black colored feces after substance administration (BASF SE, 2016). In contrast, the high molecular weight of over 500 g/mol limits the urinary excretion. Furthermore urine coloration was inconspicuous.

Summary

Based on its physicochemical properties systemic availability of the test substance is given but limited. When taken up by the oral route, the substance is likely to be absorbed through the walls of the gastrointestinal tract by absorption and/or diffusion. The physicochemical properties do not favor transdermal absorption. Considering the non-solid state and low vapor pressure of the test substance it is expected to be non-inhalable under normal use conditions. The substance is expected to be distributed but not metabolized within the body if becoming systemically available. Based on the chemical characteristics intestinal excretion is assumed to be the major route. According to the physiochemical properties and the fast excretion of the test substance, bioaccumulation is unlikely.

 

References

Eukesolar Black ER Liquid - dried; Determination of the Ready Biodegradability in the CO2-Evolution Test, unpubliahed report, BASF SE, 2016

Eukesolar Black ER Liquid - dried Skin Sensitisation: Local Lymph Node Assay, unpublished report, BASF SE, 2016

Eukesolar Black ER Liquid - dried. Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Wistar Rats Oral Administration (Gavage), unpublished report, BASF SE, 2018

Summary of Results [Not QAU-Checked]. Eukesolar Black ER Liquid - dried. Test Study in Male and Female Wistar Rats Oral Administration (Gavage), unpublished report, BASF SE, 2016

Gewerbetoxikologische Grundpruefung. unpublished report, BASF SE, 1980