Piperonal

Carcinogenicity

Description of key information

No evidence of carcinogenicity was reported in a study in which rats were administered piperonal in the diet at concentrations of 0.1 or 0.5% (approximately 50 or 250 mg/kg body weight/day, respectively) for a period of 2 years (Bar and Griepentrog, 1967).
No inhalation or dermal carcinogenicity studies have been conducted.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1967

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

Deviations:

yes

Remarks:

(Quantitative data not provided. Limited details in study design provided.)

GLP compliance:

no

Remarks:

(Study pre-dates GLP requirements)

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Information not reported.

Route of administration:

oral: feed

Vehicle:

not specified

Details on exposure:

The diet was prepared and stored refrigerated for no more than 3 days.
Drinking water: ad libitum
In addition to the above, each rat received 10 g pork liver and 1 drop of cod-liver oil per week, as well as some green fodder in the form of grass and sprouted oats.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Information not reported.

Duration of treatment / exposure:

2 years

Frequency of treatment:

Daily

Post exposure period:

Information not reported.

Remarks:

Doses / Concentrations:
0.5% or 5,000 ppm
Basis:
nominal in diet

Remarks:

Doses / Concentrations:
0.1% or 1,000 ppm
Basis:
nominal in diet

No. of animals per sex per dose:

10/sex in low-dose group and 30/sex in high-dose group.

Control animals:

yes, plain diet

Details on study design:

Male and female rats received a diet containing 0, 0.1, or 0.5% (equivalent to 0, 1,000, or 5,000 ppm, respectively, or approximately 50 or 250 mg/kg body weight/day, respectively) of piperonal for a period of 2 years.

Positive control:

Information not reported.

Observations and examinations performed and frequency:

The appearance, behavior, and weight increase was kept under observation.

Sacrifice and pathology:

All animals which died before the termination of the test as well as those killed at the end of the testing period were dissected and subjected to postmortem and histological examination. Histopathological evaluation was conducted on liver, kidneys, suprarenal glands, heart, spleen, pancreas, cerebellum, and any identified tumours.

Other examinations:

Information not reported.

Statistics:

Information not reported.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

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

Details on results:

No findings were reported when male and female rats were administered 0.1 or 0.5% piperonal in the diet for a period of 2 years. Survival at the 2-year timepoint was 6/20 at the low-dose level and 25/60 at the high-dose level (data were not presented by sex). No effects on growth were observed over the course of the study and no histopathological changes or carcinogenicity were reported.

Relevance of carcinogenic effects / potential:

No findings were reported when male and female rats were administered 0.1 or 0.5% piperonal in the diet for a period of 2 years. No effects on growth were observed over the course of the study and no histopathological changes or carcinogenicity were reported.

Dose descriptor:

dose level: 0.1% (1,000 ppm)

Basis for effect level:

other: No findings were reported.

Dose descriptor:

dose level: 0.5% (5,000 ppm)

Basis for effect level:

other: No findings were reported.

Conclusions:

No findings were reported when male and female rats were administered 0.1 or 0.5% piperonal in the diet for a period of 1.5 to 2 years.

Executive summary:

Heliotropin (piperonal) was well tolerated when adminsitered in the diet at concentrations of 0.1 or 0.5% for 2 years. Survival at the 2-year timepoint was 6/20 at the low-dose level and 25/60 at the high-dose level (data were not presented by sex). No effects on growth were observed over the course of the study and no histopathological changes or carcinogenicity were reported. Based on the findings from this study, the NOAEL can be considered to be high dose level of 0.5% (5,000 ppm) in the diet (equivalent to approximately 250 mg/kg body weight/day).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

250 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The whole database is of sufficient quality.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No evidence of carcinogenicity was reported in a study in which rats were administered piperonal in the diet at concentrations of 0.1 or 0.5% (approximately 50 or 250 mg/kg body weight/day, respectively) for a period of 2 years. As a result, the substance does not meet the criteria for classification according to Regulation (EC) No 1272/2008, Annex I section 3.6.

Additional information

The carcinogenicity of heliotropin (piperonal) was evaluated in a study conducted by Bar and Griepentrog (1967). In this study, male and female rats (10/sex in the low-dose group and 30/sex in the high-dose group; strain not specified) were administered heliotropin (piperonal) at dietary concentrations of 0.1 or 0.5% (approximately 50 or 250 mg/kg body weight/day, respectively) for a period of 2 years. Observations included appearance, behaviour, body weight, and histopathology. All animals (early decedents and those surviving to the 2-year timepoint) were subjected to a gross necropsy and a histopathological evaluation was conducted on liver, kidneys, suprarenal glands, heart, spleen, pancreas, cerebellum, and any identified tumours. Survival at the 2-year timepoint was 6/20 at the low-dose level and 25/60 at the high-dose level (data were not presented by sex). No effects on growth were observed over the course of the study and no histopathological changes or carcinogenicity were reported. Based on the findings from this study, the NOAEL can be considered to be 250 mg/kg body weight/day.