Tetrasodium 5-[4-chloro-6-(N-ethyl-anilino)-1,3,5-triazin-2-ylamino]-4-hydroxy-3-(1,5-disulfonatonaphthalen-2-ylazo)-naphthalene-2,7-disulfonate

Basic toxicokinetics

Some information in this page has been claimed confidential.

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Assessment based on physicochemical properties and toxicological studies

Adequacy of study:

weight of evidence

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The toxicokinetic properties of Reactive Red 245 were assessed based on the physicochemical properties and toxicological studies available as described in ECHAs guidance R7.C.

GLP compliance:

no

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Monoazo Red SR 6947
- Identification: FAT 40'406/A
- Batch No: SR 6947/14

Radiolabelling:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

FAT 40406 is a dark red-brown powder with a molecular weight of 954.21 g/mol. The calculated log Pow value is ca -10.6 and the solubility in water is 339 g/L.

Gastrointestinal absorption: Water-soluble substances may readily dissolve into the gastrointestinal fluids. However, absorption of very hydrophilic substances by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. The high molecular weight of the substance does also not favor absorption. However, the 28-days repeated dose study shows toxic effects in the kidneys of rats receiving 1000 mg/kg/day. The kidneys were macroscopically discolored dark red. This was considered an effect of the dark red color of the test article itself. Renal tubular vacuolation was seen histologically. The vacuoles appeared to contain pigment which is thought to be the test article. The degree of vacuolation or amount of pigment did not reduce after 15 days without treatment. There was an increase in renal tubular basophilia, mainly in male recovery animals, which suggests that the presence of the pigment for a prolonged period may cause some degeneration. On the other hand no evidence is provided for systemic availability of the substance by the oral route. Therefore, most likely, the substance is only substantially absorbed at high concentrations by the gastrointestinal tract, but is rapidly excreted in the urine, preventing the systemic availability of the substance, but resulting in toxic effects in the kidneys.

Dermal absorption: The high water solubility (>10000 mg/L) and the log Pow lower than -1 suggests that the substance may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Furthermore, in the available acute dermal study, no effects were observed. Therefore, dermal uptake will be very unlikely and a ratio of 0.1 for oral to dermal absorption is assumed and therefore used for DNEL derivation.

Respiratory absorption: No experimental data is available concerning the respiratory hazard of the substance. Water soluble dust would readily diffuse/dissolve into the mucus lining of the respiratory tract. However, very hydrophilic substances can be transported out of the respiratory tract, when molecular weights are larger than 200. Furthermore, the low log Pow does not favor absorption. However, signs of toxic effects in the kidney, present in the oral toxicity study, indicates 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 substance will be quickly excreted.

Applicant's summary and conclusion

Conclusions:

FAT 40406 is only substantially absorbed at high concentrations by the gastrointestinal tract, but is rapidly excreted in the urine, preventing the systemic availability of the substance, but resulting in toxic effects in the kidneys.

Executive summary:

Since no toxicokinetic studies are available for the FAT 40406, however the assessment is carried out based on the available physicochemical properties and results from other toxicological studies. Basis of the availble information, FAT 40406 is only substantially absorbed at high concentrations by the gastrointestinal tract, but is rapidly excreted in the urine, preventing the systemic availability of the substance, but resulting in toxic effects in the kidneys. In addition, dermal uptake will be very unlikely and a ratio of 0.1 for oral to dermal absorption is assumed; however absorption will be limited and only substantial at higher dosage through inhalation and the substance will be quickly excreted.