C.I. Acid Yellow 246

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Type of information:

other: Basic toxicokinetic assessment of Acid Yellow 246 basis of the available physicochemical properties of the substance and results from toxicological studies

Adequacy of study:

supporting study

Study period:

22 July 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

Basic toxicokinetic assessment of Acid Yellow 246 basis of the available physicochemical properties of the substance and results from toxicological studies

GLP compliance:

no

Details on absorption:

Oral/gastrointestinal absorption:
Based on the molecular weight of 517.59 g/mol for Acid Yellow 246, it can be assumed to have low oral absorption. However, with high water solubility of >100 g/L, Acid Yellow 246 may readily dissolve into the gastrointestinal fluids and may get absorbed via passive diffusion, which may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. Furthermore, in an acute oral toxicity study at the dose level of 5000 mg/kg bw, no mortality was found but dyspnea, exophthalmos, ruffled fur, and curved body position with slight diarrhea were seen. The no observed adverse effect level (NOAEL) in 28-days repeated dose toxicity study was 1000 mg/kg bw/day while in reproduction and developmental screening test was 1000 mg/kg bw/day.
So, based on the high water solubility and the findings of the oral toxicity studies suggests that Acid Yellow 246 may get absorbed to a small extent when administered via oral route at high doses.

Dermal absorption:
The molecular weight (517.59 g/mol) for Acid Yellow 246, indicates it being too large for dermal absorption. With high solubility in water (>100 g/L) and low partition coefficient (-0.77), dermal uptake is expected to be low as Acid Yellow 246 considered to be too hydrophilic to cross the lipid rich environment of the stratum corneum. The substance is not irritating to skin, and therefore an enhancement of dermal absorption can be ruled out. In support of this low dermal absorption hypothesis, the systemic toxicity of the test substance via the skin is low (acute dermal toxicity, LD50 value of > 2000 mg/kg bw for rats). Hence, Acid Yellow 246 can be expected to have low absorption via dermal route at sufficiently high doses.

Respiratory absorption:
No experimental data is available concerning the respiratory absorption of Acid Yellow 246. It was found to have melting point >287 °C, hence low volatility may be expected, which implies that the substance may not be available for inhalation as dust/aerosol. Also, the high water solubility (>100 g/L), indicates if dust is produced will get trapped in the mucus. Thus, Acid Yellow 246 can be expected to be cleared from the respiratory system if it gets inhaled. The median particle size for Acid Yellow 246 was determined to be 22 µm, hence this will limit the entry of Acid Yellow 246 to lower respiratory tract, thereby further limiting the absorption. However, as seen with oral route, absorption via respiratory exposure may take place to a limited extent at sufficiently high doses.

Details on distribution in tissues:

The systemic distribution due to 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 Acid Yellow 246 to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers.

Details on excretion:

The route of excretion for Acid Yellow 246 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. Orange feces noted for all animals treated at 400 mg/kg in the reproduction and developmental screening test. This finding supports the conclusion that the unabsorbed portion may get excreted through the feces at high doses.

Details on metabolites:

Currently no investigation regarding metabolism of Acid Yellow 246 is available. Moreover, in the genetic toxicity studies with Acid Yellow 246, there was no evidence to indicate Acid Yellow 246 or metabolite influenced hepatic metabolism. However, the high-water solubility of Acid Yellow 246 suggests that metabolism would be limited and mostly not required to facilitate renal excretion.

Conclusions:

Based on the above discussion, it can be concluded that Acid Yellow 246 would have limited degree of absorption from gastrointestinal tract when administered via oral route at sufficiently high doses, while low absorption is expected on dermal and inhalation exposure. The systemic distribution would most likely occur via the serum, while metabolism is expected to occur but would be limited and not required to facilitate renal excretion.

Executive summary:

Since no toxicokinetic studies are available for Acid Yellow 246, a basic assessment of its toxicokinetic behavior is carried out on the basis of the available physicochemical properties of the substance and results from toxicological studies. Based on the above discussion, it can be concluded that Acid Yellow 246 would have limited degree of absorption from gastrointestinal tract when administered via oral route at sufficiently high doses, while low absorption is expected on dermal and inhalation exposure. The systemic distribution would most likely occur via the serum, while metabolism is expected to occur but would be limited and not required to facilitate renal excretion.

Description of key information

Based on the above discussion, it can be concluded that Acid Yellow 246 would have limited degree of absorption from gastrointestinal tract when administered via oral route at sufficiently high doses, while low absorption is expected on dermal and inhalation exposure. The systemic distribution would most likely occur via the serum, while metabolism is expected to occur but would be limited and not required to facilitate renal excretion.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

50

Additional information

Since no toxicokinetic studies are available for Acid Yellow 246, a basic assessment of its toxicokinetic behavior is carried out on the basis of the available physicochemical properties of the substance and results from toxicological studies. Based on the above discussion, it can be concluded that Acid Yellow 246 would have limited degree of absorption from gastrointestinal tract when administered via oral route at sufficiently high doses, while low absorption is expected on dermal and inhalation exposure. The systemic distribution would most likely occur via the serum, while metabolism is expected to occur but would be limited and not required to facilitate renal excretion.