Reaction mass ofDisodium [1-{[2-(hydroxy-kO)-3,5-dinitrophenyl]diazenyl-kN1}naphthalen-2-olato(2-)-kO][3-(hydroxy-kO)-4-{[2-(hydroxy-kO)naphthalen-1-yl]diazenyl-kN1}-7-nitronaphthalene-1-sulfonato(3-)]chromate(2-) andDisodium [1-{[2-(hydroxy-kO)-3,5-dinitrophenyl]diazenyl-kN2}naphthalen-2-olato(2-)-kO][3-(hydroxy-kO)-4-{[2-(hydroxy-kO)naphthalen-1-yl]diazenyl-kN1}-7-nitronaphthalene-1-sulfonato(3-)]chromate(2-)

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based on physicochemical properties and toxicological data available as recommended by ECHA REACH guidance

Adequacy of study:

key study

Study period:

2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Objective of study:

absorption

distribution

excretion

metabolism

toxicokinetics

Principles of method if other than guideline:

Assessment based on physicochemical proeprties and toxicological data available as recommended by ECHA REACH guidance.

GLP compliance:

no

Absorption

Oral/gastrointestinal absorption:

Based on the molecular weight of 884.6 g/mol for Acid Black 107, it can be assumed to have moderate oral absorption. With the high water solubility of 55 g/L, Acid Black 107 may readily dissolve into the gastrointestinal fluids and be absorbed via passive diffusion.

In the acute oral toxicity studies with Acid Black 107, higher doses (>1000 mg/kg bw) caused dyspnoea, ataxia, ventricumbency, muscular hypotonia, inhibition of the response to pain (pinching), diarrhea, hyperreflexia, hypoventilation and reduction in spontaneous motility. 2 out 5 females died at 8000 mg/kg bw.

In the combined repeated dose toxicity study with reproductive and developmental screening with the structurally similar substance Acid blue 317, oral administration of the test substance lead tochanges that included blue staining of various parts of the body, blue bedding, blue/dark faeces. The macroscopic examination performed on animals which received Acid Blue 317 at 300 and 1000 mg/kg bw/day, revealed abnormal (blue) colouration of skeletal muscle, sciatic nerves, mammary tissue, axillary lymph nodes, brain, eyes, and the majority of the tissues in the abdominal and thoracic cavities, with abnormal colouration of the contents of the gastro‑intestinal (GI) tract. Blue colouration in animals receiving 100 mg/kg bw/day, was generally limited to the mesenteric lymph nodes, contents of the GI tract and staining of the tails in occasional males. At the high dose level, external blue staining of the offspring was apparent in-life and confirmed at necropsy. 

These findings were indicative of absorption taking place from the gastrointestinal tract. Hence, on the basis of hydrophilic nature and the findings of the toxicological studies as discussed above, Acid Black 107 is expected to be absorbed by the gastrointestinal tract when administered orally.

Dermal absorption:

Based on the molecular weight of 884.6g/mol for Acid Black 107, poor dermal absorption is expected. With high solubility in water (55 g/L) and low partition coefficient (0.357), dermal uptake is expected to be low as Acid Black 107 can be considered to be hydrophilic in nature to cross the lipid rich environment of the stratum corneum.The surface tension of 50.6 mN/m for Acid Black 107 also suggests a low dermal uptake from skin surfaces.

Acid Black 107 is neither corrosive nor irritating to the skin or eyes. It was not sensitising to the skin of guinea pigs. Hence, the experimental data also suggests a low dermal uptake. However, the findings from the acute oral toxicity studies with Acid Black 107 as well as combined repeated dose oral toxicity study with reproductive and developmental screening with Acid Blue 317, indicates the potential for absorption following ingestion and it is therefore possible that the substance will also be absorbed if it is exposed dermally. Nonetheless, absorption will be limited and only substantial at higher dosage and the test substance will be quickly excreted owing to the high water solubility.

Respiratory absorption:

Acid Black 107 exists as a solid powder and expected to have low volatility based on high melting point of >350°C, and hence may not be available in inhalable forms. Further, the high water solubility (55 g/L), indicates that the dust will be trapped in the mucus if it happens to enter the respiratory tract. However, the findings from the acute oral toxicity studies with Acid Black 107 as well as combined repeated dose oral toxicity study with reproductive and developmental screening with Acid Blue 317, indicate the potential for absorption following ingestion and it is therefore possible that the substance will also be absorbed if it is inhaled. Nonetheless, absorption will be limited and only substantial at higher dosage and the test substance will be quickly excreted owing to the high water solubility.

Distribution

Systemic distribution due to the high water solubility would most likely occur via the serum. Owing to the high molecular size and hydrophilic nature of the substance (low n-octanol/water partition coefficient and high water solubility), access of Acid Black 107 to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers, whileaccumulation in body fat is unlikely to occur. However,in thecombined repeated dose oral toxicity study with reproductive and developmental screening with Acid Blue 317, at 1000 mg/kg bw/day, external blue staining of the offspring was apparent in-life and confirmed at necropsy. Hence, it is evident that ACID BLUE 317 was able to cross the placental barrier. Based on this, Acid Black 107 can also be expected to cross placental barrier.

Metabolism

In the genetic toxicity studies including a bacterial reverse mutation assay, a mammalian cell gene mutation assay and a micronucleus assay with Acid Black 107, and available toxicity studies, there was no evidence to indicate Acid Black 107 or metabolite influenced hepatic metabolism. Further the high water solubility of Acid Black 107 suggests that metabolism would be limited and not required to facilitate renal excretion.

Excretion

Route of excretion for Acid Black 107 has not been investigated. However, in the combined repeated dose oral toxicity study with reproductive and developmental screening with Acid Blue 317, test substance administration at high doses lead to blue/dark faeces. Hence, excretion through faeces may also a play a role in the excretion of the substance. However, owing to the hydrophilic nature of the substance, it will be expected to be predominantly excreted via urine.

Conclusions:

Acid Black 107 would be absorbed primarily in gastrointestinal tract, while some absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and excretion expected to occur via the urine and feces.

Executive summary:

Acid Black107 would be absorbed primarily in gastrointestinal tract, while some absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and excretion expected to occur via the urine and feces.

Description of key information

Acid Black 107 would be absorbed primarily in gastrointestinal tract, while some absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and excretion expected to occur via the urine and feces.