Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

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.