1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Data source

Reference

Reference Type:

publication

Title:

DISPOSITION OF 2-(2-QUINOLYL)-1,3-INDANDIONE (D. C. YELLOW #11) IN RATS DOSED ORALLY OR INTRAVENOUSLY.

Author:

Salah M. El Dareer, Jack R. Kalin, Kathleen F. Tillery, Donald L. Hill

Year:

1988

Bibliographic source:

Journal of Toxicology and Environmental Health: Current Issues Vol 23(3), 1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Data is from Journal with permission

Principles of method if other than guideline:

In-vivo toxicokinetic study for a series of D&C Yellow No. 11 was conducted. Toxicokinetic parameters such as uptake and elimination rate constants, and bioconcentration factors were determined based on concentrations of test chemicals in male Fischer 344 rats.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

EC Number:

232-318-2

EC Name:

1,3-isobenzofurandione, reaction products with methylquinoline and quinoline

Cas Number:

8003-22-3

Molecular formula:

C18H11NO2

IUPAC Name:

2-(quinolin-2-yl)-2,3-dihydro-1H-indene-1,3-dione

Details on test material:

- Name of test material (as cited in study report): 2‐(2‐quinolyl)‐1,3‐indandione (d. c.yellow 11)
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): Radio chemical purity was 99.5%

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

intravenous

Vehicle:

other: Ethanol-Emulphor-water (3:3:4, v/v)

Doses / concentrations

Remarks:

Doses / Concentrations:
0.932mg/kg, 0.116 mCi/kg, 1 ml/kg).

Control animals:

not specified

Results and discussion

Preliminary studies:

Excretion:
Half-Life Values Derived for Elimination of Radioactivity
from Plasma and Various Tissues of Rats Dosed Intravenously with [14C]DCY (0.932 mg/kg)

Sample Absorbtion Alpha Beta
Cut tissue 32 79 1368
Liver 9* 17 1205
Lungs _b 14 2533
Kidneys 16* 41 2374
Fat 14 141 3260
Skin 6 52 3811
Muscle — 23 1910
Plasma — 49 1604
Whole blood — 19 2900
a-Since there was no significant difference between the tissueconcentrations of radioactivity at 5,15, and 30 min after dosing, the existence of this phase is questionable.
b- No absorption phase noted.

Main ADME results

Type:

excretion

Results:

Fecal excretion accounted for 81.1% of the administered radioactivity at 24 h, 87.5% at 48 h, and 89.1% at 72 h. Urinary excretion represented 16.0% of the dose at 24 h, 16.7% at 48 h, and 16.9% at 72 h.

Metabolite characterisation studies

Metabolites identified:

no

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Liver – Liver contained the lightest concentration of radioactivity at time points less than 1 h.

Kidney- whereas at latter time points Kidney had the highest concentrations.
No bio-accumulation potential based on study results

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): low bioaccumulation potential based on study results
According to the study [14C] DCY was rapidly distributed, metabolized, and excreted by rats. In 24 h after intravenous dosing, rats excreted 81.1% of the dose in the feces and 16.0% of the dose in the urine. For rats fitted with biliary cannulas, 54.5% of the dose, all of which was metabolites of [14C]DCY, was recovered in the bile 4 h. Associated with the rapid and extensive biliary excretion of metabolites of intravenously administered I14C]DCY was the appearance of large amounts of radioactivity in the feces and also, at intermediate time points, in the liver, gut contents, and gut tissue. In conclusion, rats rapidly distribute, metabolize, and excrete [14C]DCY. Since no toxic effects were evident, this study has provided no basis for assuming that exposure to small amounts of DCY would be hazardous to the health of humans.

Executive summary:

According to the study [¹⁴C] DCY was rapidly distributed, metabolized, and excreted by rats. In 24 h after intravenous dosing, rats excreted 81.1% of the dose in the feces and 16.0% of the dose in the urine. For rats fitted with biliary cannulas, 54.5% of the dose, all of which was metabolites of [¹⁴C]DCY, was recovered in the bile 4 h. Associated with the rapid and extensive biliary excretion of metabolites of intravenously administered I¹⁴C]DCY was the appearance of large amounts of radioactivity in the feces and also, at intermediate time points, in the liver, gut contents, and gut tissue. In conclusion, rats rapidly distribute, metabolize, and excrete [¹⁴C]DCY. Since no toxic effects were evident, this study has provided no basis for assuming that exposure to small amounts of DCY would be hazardous to the health of humans.