Registration Dossier

Administrative data

basic toxicokinetics, other
Type of information:
other: Theoretical toxicokinetic assessment based on ECHA guidance
Adequacy of study:
key study
Study period:
February 2018
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
other company data
Report date:

Materials and methods

Objective of study:
other: toxicokinetic assessment based on physico-chemical properties and available toxicological data
Test guideline
no guideline followed
Principles of method if other than guideline:
Toxicokinetic assessment according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c, section R.7.12.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Trisodium 1-amino-4-[[3-[[4-chloro-6-[(3-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate
EC Number:
EC Name:
Trisodium 1-amino-4-[[3-[[4-chloro-6-[(3-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate
Cas Number:
Molecular formula:
trisodium 1-amino-4-[[3-[[4-chloro-6-[(3-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-2,4,6-trimethyl-5-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate
Test material form:
solid: particulate/powder

Results and discussion

Any other information on results incl. tables

Oral absorption

Acute oral toxicity studies and a combined repeated dose oral toxicity study with the reproduction/developmental toxicity screening test (including a dose range finding study) in rats are available. In the acute studies, mortality was observed at dosages >3000 mg/kg, while toxic symptoms were observed at dosages of >1000 mg/kg.

In the combined repeated dose study, no adverse toxicological effects were observed up to 1000 mg/kg bw/d. However, blue coloration of several body parts and organs were noted.


In view of the relatively high molecular weight, the available ionisable groups and the hydrophilic character, the substance will not be absorbed to a high extent from the gastrointestinal tract. However, some absorption occurs, given the blue coloration of organs in the repeated dose toxicity study and the mortality observed in the acute oral studies. Therefore an oral absorption factor of 10% is assumed.


Inhalatory absorption

No acute inhalation toxicity studies are available. The substance may be marketed in different forms, from dusty solids to granules to sticky press cakes. Therefore, the particle size distribution may differ significantly. Particles below 100 µm can be inhaled. In view of the low log Pow (-3.88) and the hydrophilic character, the substance will not be absorbed significantly across the respiratory epithelium. Once inhaled, the substance would readily diffuse/dissolve into the mucus lining the respiratory tract. Due to the high water solubility, the substance will be retained in the mucus and transported out of the respiratory tract. An inhalation absorption factor of 10% is therefore assumed. Though not tested, respiratory sensitization effects can still occur, as only small amounts of substance are needed to induce such effects.


Dermal absorption

Skin irritation studies in rabbits show only slight effects which are fully reversible, even under occlusive conditions and on abraded skin. In the guinea pig maximisation test, nearly all animals showed skin irritation effects after induction and challenge with the test substance, while no skin reactions were observed in non-induced animals and in vehicle-challenged animals. Acute dermal toxicity studies are not available.


In view of the relatively high molecular weight (>500 g/mol) and the low log Pow (-3.88), the substance will not significantly be dermally absorbed and therefore a dermal absorption factor of 10% is assumed. This is strengthened by the high water solubility (332 g/L), making the substance too hydrophilic to cross the lipid rich environment of the stratum corneum. Some uptake can occur though, as the substance was found to be a skin sensitizer. However, for a substance to be a skin sensitizer, only a small fraction may be needed to induce such effects.


The repeated dose toxicity study showed that the substance is widely distributed after oral absorption, presumably via the serum. Blue coloration of the rectum, ileum, caecum, colon, stomach, kidneys, lymph nodes, skin, jejunum, testes, epididymides, uterus, vagina, duodenum and thymus was observed. The liver, lungs and brains have not been discussed. Due to the high molecular weight and hydrophilic character, the substance will probably not enter the central nervous system as it will not pass the blood-brain barrier. In the offspring of the highest dose group, blue coloration of the GI tract was observed, due to exposurein uteroor via the milk.

Given the low log Pow, the substance will not accumulate in fat tissues.

The substance showed a skin sensitization potential. Water-soluble reactive dyes with amongst others an anthraquinone derivative group connected to a reactive group, are known to induce allergic contact dermatitis.


No information on metabolism can be derived from the available studies. Given the high water solubility, metabolism may be limited as it is not required to facilitate renal excretion.



The substance is at least partly excreted via the faeces, given the blue colored faeces in the repeated dose toxicity study. Given the high water solubility, it is expected that the substance will be predominantly excreted via urine.

Applicant's summary and conclusion

Reactive Blue 049 (meta) will be absorbed to a limited extent via the oral, inhalatory and dermal routes of exposure. Systemic distribution most likely occurs via the serum, while it is anticipated that metabolism will be limited. Excretion will primarily occur via the urine, and to some extent via the faeces.