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Toxicological information

Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented and scientifically acceptable

Data source

Reference
Title:
No information
Author:
Jochheim CM et al. (2002). Glutathione-dependent metabolism|of the antitumor agent Sulofenur. Evidence for the formation|of p-chlorophenylisocyanate as a reactive intermediate.|Chem. Res. Toxicol. 15, 240-248

Materials and methods

Type of study / information:
Metabolism of the antitumor agent sulofenur. Evidence for the formation of p-chlorophenyl isocyanate as a reactive intermediate
Principles of method if other than guideline:
glutathione and N-acetylcysteine conjugates of p-chlorophenyl isocyanate excreted into bile and urine after an ip dose of sulofenur to rats were examined by mass spectrometry and combined liquid chromatography-tandem mass spectrometry
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlorophenyl isocyanate
EC Number:
203-176-9
EC Name:
4-chlorophenyl isocyanate
Cas Number:
104-12-1
Molecular formula:
C7H4ClNO
IUPAC Name:
1-chloro-4-isocyanatobenzene
Details on test material:
solufenur (>99% pure) was synthesized at Eli Lilly & Co.

Results and discussion

Any other information on results incl. tables

RM-Freetext:
Sulofenur is suggested to undergo bioactivation in vivo to the reactive p-chlorophenyl isocyanate which, in turn, is
trapped in the form of GSH adduct and processed further to the corresponding N-acetyl-L-cysteine conjugate.

Applicant's summary and conclusion

Executive summary:

Sulofenur is suggested to undergo bioactivation in vivo to the reactive p-chlorophenyl isocyanate which, in turn, is
trapped in the form of GSH adduct and processed further to the corresponding N-acetyl-L-cysteine conjugate.