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:
April 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

Details on test material:
- State of aggregation: solid, yellow powder
- Batch number: RY-95-001
- Expiry date: 01-07-2022
- Storage: at room temperature, in the dark

Results and discussion

Any other information on results incl. tables

Oral absorption

Acute oral toxicity studies, a repeated dose oral toxicity study and a reproduction/developmental toxicity screening test in rats are available. In the acute studies, mortality was observed at dosages >5000 mg/kg, while toxic symptoms were observed at dosages of >2000 mg/kg.

In the repeated dose study, no adverse toxicological effects were observed up to 200 mg/kg bw/d. However, yellow coloration of the gastro-intestinal tract was noted. At 1000 mg/kg bw/d, increased liver weight and enhanced epithelial desquamation of the gastro-intestinal mucosa were observed. In the reproduction/developmental screening study, no treatment-related adverse effects were noted up to 400 mg/kg bw/d in parental animals nor in the offspring.

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 yellow coloration of the gastro-intestinal tract in the repeated dose toxicity study. 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 (-3.49) 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.


Dermal absorption

Skin irritation studies in rabbits show only very slight effects which are fully reversible. An acute dermal toxicity study in rats reveals an LD50 of >2000 mg/kg bw.

In view of the relatively high molecular weight (>500 g/mol) and the low log Pow (-3.49), 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 in one of the skin sensitisation tests.


The repeated dose toxicity study showed that the substance is distributed after oral absorption, presumably via the serum. Yellow coloration of the gastro-intestinal was observed. Other organs have not been mentioned in the robust study summary. 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.

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


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.



Given the high water solubility, it is expected that the substance will be predominantly excreted via urine.

Applicant's summary and conclusion

Reactive Yellow 095 (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.