2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether

Specific investigations: other studies

Administrative data

Endpoint:

mechanistic studies

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

review article or handbook

Title:

Effect of Piperonyl Butoxide on Cell Replication and Xenobiotic Metabolism in the Livers of CD-1 Mice and F344 Rats

Author:

Phillips, J.C., Price, R.J., Morag, E. Cunninghame, M.E., Osimitz, T.G., Cockburn, A., Gabriel, K.L., Preiss, F.J., Butler W.H., Lake, B.G.

Year:

1997

Bibliographic source:

Fund. Appl. Toxicol. 38, 64 - 74.

Materials and methods

GLP compliance:

no

Type of method:

in vivo

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether

EC Number:

200-076-7

EC Name:

2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether

Cas Number:

51-03-6

Molecular formula:

C19H30O5

IUPAC Name:

2-(2-butoxyethoxy)ethyl 6-propylpiperonyl ether

Test animals

Species:

other: mice and rats

Strain:

other: CD1 strain mice and F344 rats

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: NaPB

Duration of treatment / exposure:

42 days

Details on study design:

Type: other: enzyme induction hepatotoxicity

Results and discussion

Details on results:

The present data demonstrate that PBO can produce liver enlargement in both the mouse and rat which is associated with hyperplasia, hypertrophy, and induction of xenobiotic metabolising enzymes. At the dose levels employed in this study the hepatic effects of PBO in the mouse were similar to but less marked that those of NaPB. In the rat study, high doses of PBO were toxic. Thus, while the formation of eosinophilic nodules in mouse liver may occur by a mechanism similar to that of NaPB and other nongenotoxic inducers of hepatic xenobiotic metabolism, tumor formation in rats at greater than MTD doses is most likely associated with marked liver enzyme induction in conjiunction with a regenerative hyperplasia resulting from PBO- induced hepatoxicity.

Any other information on results incl. tables

RS-Freetext:
In summary, this data demonstrates that PBO can produce liver enlargement in the 

mouse and the rat which is associated with induction of xenobiotic metabolism, 

hypertrophy, and hyperplasia. The hepatic effects of  Piperonyl Butoxide in the 

mouse were similar to but less marked than  those produced by sodium phenobarbital

. In the rat high doses of  Piperonyl Butoxide were hepatotoxic and resulted in 

a marked reduction in  body weight. Thus while the reported formation of 

eosinophilic nodules in  mouse liver by Piperonyl Butoxide may occur by a 

mechanism(s) similar to  that of NaPB and other nongenotoxic enzyme inducers, 

the reported tumor  formation in rats at greater than the maximum tolerated dose

 is most  likely associated with marked enzyme induction in conjunction with a 

regenerative hyperplasia resulting from Piperonyl Butoxide-induced hepatotoxicity

Applicant's summary and conclusion

Conclusions:

The present data demonstrate that PBO can produce liver enlargement in both the mouse and rat which is associated with hyperplasia, hypertrophy, and induction of xenobiotic metabolising enzymes. At the dose levels employed in this study the hepatic effects of PBO in the mouse were similar to but less marked that those of NaPB. In the rat study, high doses of PBO were toxic. Thus, while the formation of eosinophilic nodules in mouse liver may occur by a mechanism similar to that of NaPB and other nongenotoxic inducers of hepatic xenobiotic metabolism, tumor formation in rats at greater than MTD doses is most likely associated with marked liver enzyme induction in conjiunction with a regenerative hyperplasia resulting from PBO- induced hepatoxicity.