Registration Dossier
Registration Dossier
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 278-388-8 | CAS number: 76199-85-4
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
The substance is considered poorly soluble for systemic uptake. Signs of systemic toxicity after oral exposure were only seen at the highest tested dose of 1000 mg/kg bw/day (OECD 421 and OECD 414).
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The toxicokinetic assessment is based on experimental data on physico-chemical properties and toxicological properties of the test substance CAS 76199-85-4 and its structural analogue CAS 36888-99-0. CAS 36888-99-0 contains two barbituric acid moieties whereas CAS 76199-85-4 contains only one. The other moiety is the open, not fused “semi-condensate” form. An overview on the properties is given in the read-across justification attached in chapter 13.
As can be expected from the chemical structures, both pigments have a similar molecular weight (337 and 368 g/mol), and a similar relative density. They decompose at temperatures > 380°C prior to melting.
Both are of very low solubility in both water and octanol. From these solubilities, a Log POW of 1.4 was calculated for CAS 76199-85-4.
As the substances are so insoluble, no experimental data on abiotic hydrolysis is available.
Both molecules consist of highly conjugated systems that give the molecule a rigid form.
The poor solubility, the unflexible form and the high molecular weight impair transport across biological membranes and gastrointestinal and dermal absorption is expected to be limited.
Notably, oral absorption cannot be fully ruled out because signs of systemic toxicity were observed in the OECD test guidelines 421 and 414 conducted with rats. This effect can be attributed to the partially soluble impurity of the particle, designated as "Halbkondensat CO-HK" (see "Specific investigations, IUCLID chapter 7.9.4.). This impurity was not observed in the structural analogue pigment CAS 36888-99-0.
No test-item induced coloration of internal tissues or organs was observed upon necropsy after acute and subacute oral gavage dosing at the limit dose level, indicating a low absorption and subsequent distribution of the test substance. Only a yellowish colored content of the stomach and intestine as well as discolored feces were observed, which mirrored the presence of the test substance in the gastrointestinal tract and indicated that the test item was excreted at least partially unchanged.
The test item is a powder, and inhalation of particles is possible. It is considered to be insoluble (with a soluble impurity) yet reactive in fluids that are relevant for inhalation (see “Specific investigations”). Static and dynamic assays examining the biosolubility and biopersistence, respectively, showed that the material is insoluble in biosimulants and biopersistent in phagolysosomal fluids. Thus, the test item neither dissolved nor degraded. The abiotic surface reactivity test (FRAS assay) however showed that the test item was able to induce oxidative biological damage significantly above the blank control and is therefore considered as active in the FRAS assay. A cellular based surface activity assay using macrophages showed that the test item was not able to activate alveolar macrophages.
Absorption via the skin is unlikely because the substance must be sufficiently soluble in water to partition from the stratum corneum into the epidermis. Because of the low water solubility of the test substance, dermal uptake is likely to be very low.
Overall, systemic effects after uptake via ingestion, inhalation or skin contact is expected to be minor for this test substance.
Accordingly, metabolism and distribution cannot be considered and elimination is restricted to gastrointestinal passage. Possible inertness is also indicated from the very low toxicity upon intraperitoneal injection of a high dose (2000 mg/kg bw). During the one-weak observation period, no animal died.
Also, in case of absorption, bioaccumulation is not possible since the substance is not soluble in fat.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
