Trisodium 5-[[4-chloro-6-(ethylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Type of information:

other: Toxicokinetic assessment based on the physicochemical properties and toxicological data as recommended by the REACH Guidance R7.c

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Toxicokinetic assessment based on the physicochemical properties and toxicological data as recommended by the REACH Guidance R7.c

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium 5-[[4-chloro-6-(ethylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

EC Number:

276-911-4

EC Name:

Trisodium 5-[[4-chloro-6-(ethylphenylamino)-1,3,5-triazin-2-yl]amino]-4-hydroxy-3-[(2-sulphonatophenyl)azo]naphthalene-2,7-disulphonate

Cas Number:

72829-25-5

Molecular formula:

C27H22ClN7O10S3.3Na

IUPAC Name:

trisodium 5-({4-chloro-6-[ethyl(phenyl)amino]-1,3,5-triazin-2-yl}amino)-4-hydroxy-3-[(2-sulfonatophenyl)diazenyl]naphthalene-2,7-disulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Results and discussion

Any other information on results incl. tables

Absorption

Oral/gastrointestinal absorption:

Based on the molecular weight of 802.01g/mol for Reactive Red 024:1, it can be assumed to have moderate oral absorption. However, with the high water solubility of 434 g/L, Reactive Red 024:1 may readily dissolve into the gastrointestinal fluids and be absorbed via passive diffusion. In an acute oral toxicity study with Reactive Red 024:1 (1972), higher doses (>1000 mg/kg bw) caused ataxia, muscular hypotonia, hypoventilation, dyspnoea, inhibition of the response to pain (pinching) and convulsions. 5 males and 3 females at the dose of 10000 mg/kg bw were found dead after 1-2 days. In the 28-days repeated dose toxicity study with the structurally similar substance Reactive Red 286,red stained feces were noted in males and females at all dose levels (100, 300 and 1000 mg/kg bw/day). Red discoloration was also detected macroscopically in multiple organs, like kidneys, mesenteric lymphnodes and stomach. In the micronucleus assay withstructurally similar substance Reactive Red 286, the animals showed discoloured urine after treatment with 2000 mg/kg b.w. indicating the bioavailability of the substance. 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, Reactive Red 024:1 is expected to be absorbed by the gastrointestinal tract when administered orally.

Dermal absorption:

Based on the molecular weight of 802.01g/mol for Reactive Red 024:1, poor dermal absorption is expected. With high solubility in water (434 g/L) and low partition coefficient (-3.52), dermal uptake is expected to be low as Reactive Red 024:1 can be considered to be too hydrophilic to cross the lipid rich environment of the stratum corneum. The surface tension of 62.9 mN/m for Reactive Red 024:1 also suggests a low dermal uptake from skin surfaces. Reactive Red 024:1 is neither corrosive nor irritating to the skin as well as eyes. Hence, the experimental data also suggests a low dermal uptake. However, the findings from the acute oral toxicity with Reactive Red 024:1 as well as repeated dose oral toxicity study and micronucleus assay with Reactive Red 286, 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:

Reactive Red 024:1 is expected to have low volatility based on high melting point of >350 °C, and hence may not be available for inhalation as a vapour. Further, the high water solubility (434 g/L), indicates if vapours are produced will be trapped in the mucus. However, the effects observed in the acute oral toxicity study with Reactive Red 024:1 as well as repeated dose oral toxicity study and micronucleus assay with the structurally similar substance Reactive Red 286, 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 Reactive Red 024:1to 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.

Metabolism

In the genetic toxicity studies including bacterial reverse mutation assays with Reactive Red 024:1, mammalian cell gene mutation assay with Reactive Red 286 and available toxicity studies, there was no evidence to indicate Reactive Red 024:1 or metabolite influenced hepatic metabolism. However, in a chromosomal aberration test with Chinese hamster lung fibroblasts (V79), the structurally similar substance Reactive Red 286, was found to be clastogenic in the absence of metabolic activation, while it was not clastogenic in the presence of metabolic activation. This indicates hepatic metabolism may lead to reduced toxicity, however, it should be taken into consideration that rat S9 fraction is not equivalent to the human metabolism. Further, the high water solubility of Reactive Red 024:1 suggests that metabolism would be limited and not required to facilitate renal excretion.

Excretion

Route of excretion for Reactive Red 024:1 has not been investigated. However, owing to the hydrophilic nature of the substance, it will be expected to be predominantly excreted via urine, while any unabsorbed remaining fraction being excreted in the feces.

Applicant's summary and conclusion

Conclusions:

Reactive Red 024:1 would be absorbed primarily in gastrointestinal tract, while limited absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and not required to facilitate renal excretion.

Executive summary:

Reactive Red 024:1 would be absorbed primarily in gastrointestinal tract, while limited absorption via dermal and inhalation exposure can be expected. Systemic distribution would most likely occur via the serum, while metabolism would be limited and not required to facilitate renal excretion.