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

Carcinogenicity

Administrative data

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 451 (Carcinogenicity Studies)

Deviations:

yes

Remarks:

NTP study protocol

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Piperonyl butoxide

IUPAC Name:

Piperonyl butoxide

Details on test material:

PBO technical grade, 88.4%
Lor No 5
Niagara Chemical Company FMC, Middleport, new York, USA

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: feed

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

107 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 5000 ppm, 10000 ppm
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 250, 500 mg/kg bw/day
Basis:
other: calculated

No. of animals per sex per dose:

50

Control animals:

yes, plain diet

Examinations

Statistics:

Taone test for mortality
Cochran-Armitage test for positive dose-related trend in the incidence of lymphomas and Fisher exact test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

reduced body weights at both treatment levels

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Relevance of carcinogenic effects / potential:

In the female rats, lymphomas occurred at incidences that were dose related (P = 0.007); in a direct comparison, the incidence
of the tumor in the high-dose group was higher (P = 0.020) than that in the control group (controls 1/20, low-dose 7/50, high-dose 15/50). However, the incidence of lymphomas, leukemias, and reticuloses in historical-control female Fischer 344 rats at the same laboratory was 19/191 (10%). These historical-control groups include one with an incidence of animals with lymphoma or leukemia of 7/20 (35%) and another with an incidence of 6/20 (30%). Thus, the incidence of lymphomas in the control female rats of the present bioassay may have been abnormally low, and the occurrence of the higher incidence in the dosed groups cannot be clearly related to administration of piperonyl butoxide.

Effect levels

1

Dose descriptor:

LOAEL

Effect level:

5 000 mg/kg diet

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: Effect type: toxicity (migrated information)

2

Dose descriptor:

NOAEL

Effect level:

10 000 mg/kg diet

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: No carcinogenic effect observd

Remarks on result:

other: Effect type: carcinogenicity (migrated information)

Any other information on results incl. tables

Taone test for mortality

Cochran-Armitage test for positive dose-related trend in the incidence of lymphomas and Fisher exact test

Applicant's summary and conclusion

Conclusions:

It is concluded that under the conditions of this bioassay, piperonyl butoxide was not carcinogenic for Fischer 344 rats

Executive summary:

Groups of 50 rats of each sex were administered piperonyl butoxide in the diet at one of two doses, either 5,000 or 10,000 ppm, for 107 weeks. Matched controls consisted of 20 untreated rats of each sex. All surviving rats were killed at the end of the period of administration of the test chemical.

Mean body weights of dosed groups of rats and mice of each sex were lower than those of corresponding control group, and the

depressions in body weights were dose related. Survival of the rats was unaffected by the piperonyl butoxide and was

80% or greater in all groups at week 90 of the bioassay; thus, sufficient numbers of dosed and control rats and mice of each sex

were at risk for the development of late-appearing tumors.

In the female rats, lymphomas occurred at incidences that were dose related (P = 0.007); in a direct comparison, the incidence

of the tumor in the high-dose group was higher (P = 0.020) than that in the control group (controls 1/20, low-dose 7/50, high-dose 15/50). However, the incidence of lymphomas, leukemias, and reticuloses in historical-control female Fischer 344 rats at the same laboratory was 19/191 (10%). These historical-control groups include one with an incidence of animals with lymphoma or leukemia of 7/20 (35%) and another with an incidence of 6/20 (30%). Thus, the incidence of lymphomas in the control female rats of the present bioassay may have been abnormally low, and the occurrence of the higher incidence in the dosed groups cannot be clearly related to administration of piperonyl butoxide.