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Carcinogenicity

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Description of key information

2 acceptable studies are available. The studies were conducted using rats and mice as the test species, specifically, male and female Fischer 344 rats and male and female B6C3F1 mice. The test substance was administered orally, either by gavage or in the feed. There was no indication that the study was conducted according to GLP or any relevant guidelines.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

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Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 60 male and female rats were administered the test substance at concentrations of 0, 300, 600 and 1200mg/kg bw/day in feed daily over a 2 year period. Mortality, body weights, feed consumption and clinical pathology were recorded.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl Acetate
- Molecular formula (if other than submission substance): C9H10O2
- Molecular weight (if other than submission substance): 150.17
- Smiles notation (if other than submission substance): Not documented

- Physical state: Colourless liquid with a pear-like odour.
- Analytical purity: At least 98%
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: 8743-84 and 845585
- Expiration date of the lot/batch: Not documented

- Stability under test conditions: Stable as a bulk chemical for 2 weeks at temperatures as high as 60°C.
- Storage condition of test material: Not documented
- Other: Boiling point: 215.5°C
Melting point: -51.3°C
Density: 1.0550 at 20°C
Vapour pressure: 1mmHg at 45°C
Insoluble in water but is miscible with alcohol or ether.
Species:
rat
Strain:
other: F344/N
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, Inc., (Gilroy, CA).
- Age at study initiation: Approximately 41 days old
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Rats were housed 5 per cage in Polycarbonate cages changed twice weekly, with hardwood chips as bedding.
- Diet (e.g. ad libitum): NIH-07 open formula meal rat and mouse diet available ad libitum
- Water (e.g. ad libitum): Water available ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 ± 0.4°C
- Humidity (%): 45.4 - 54%
- Air changes (per hr): Minimum of 10 air changes per hour.
- Photoperiod (hrs dark / hrs light): Fluorescent light 12 hours per day.

IN-LIFE DATES: From: To: Not documented
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Dose formulations were prepared weekly by mixing benzyl acetate with feed. The dose formulations were stored at -20°C in sealed double plastic bags for no longer than 13 days.

Dose formulations were analyzed every 6 to 8 weeks.

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Periodic analyses of the dose formulations of benzyl acetate were conducted using gas chromatography. Dose formulations were analyzed every 6 to 8 weeks.
Duration of treatment / exposure:
103 weeks
Frequency of treatment:
Daily in feed
Post exposure period:
No information provided
Dose / conc.:
300 mg/kg bw/day (nominal)
Dose / conc.:
600 mg/kg bw/day (nominal)
Dose / conc.:
1 200 mg/kg bw/day (nominal)
No. of animals per sex per dose:
60 male and 60 female per dose
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: Dose selection for rats was based on the lower final mean body weights and survival and increased incidences of chemical related lesions of 5000mg/kg bw/day in rats in a previously conducted 13 week study.
- Rationale for animal assignment (if not random): Animals were grouped by weight and assigend to cages and the cages assigned to exposure groups using tables of random numbers.

Positive control:
No information provided.
Observations and examinations performed and frequency:
All animals were observed twice daily. Body weights and clinical findings were recorded weekly for the first 13 weeks, every 4 weeks thereafter and at teh end of the study. Blood was collected from the retroorbital sinus of rats at the 15 month interim evaluations to determine haematology and clinical chemistry parameters, including haematocrit, haemoglobin, erythrocytes, mean erythrocyte volume, mean erythrocyte haemoglobin, platelets, reticulocytes and leucocyte count and differential and cholesterol, triglyceride, alkaline phosphatase, creatine kinase, and sorbitol dehydrogenase. The brain, right kidney and liver were weighed at the 15 month interim analysis. The pancreas of the male rats was assayed for pancreatic enzyme levels at the 15 month interim evaluation.
A complete necropsy was performed on all animals. At necropsy all organs and tissues were examined for gross lesions and all major tissues were microscopically examined.
Complete histopathological examinations were performed on all animals. Tissue examinations included adrenal gland, brain, oesophagus, femur, heart, kidney, large intestine, liver, lung, mammary gland, nose, ovary and pancreas, among others.
Sacrifice and pathology:
Animals were sacrificed and necropsy was performed on all animals.
Other examinations:
No additional information provided.
Statistics:
Survival Analyses: The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958). Dose-related effects on survival used Cox's method for testing 2 groups for equality and Tarone's life table test to identify dose-related trends.
Calculation of Incidence: For calculation of statistical significance the incidences of most neoplasms and all nonneoplastic lesions are given as the ratio of the number of affected animals to the number of animals with the site examined microscopically.
Analysis of Neoplasm Incidences: Logistic regression analysis in addition to the life table test, the Fisher exact test and the Cochran-Armitage trend test. Continuity-corrected tests were used in the analysis of neoplasm incidence and reported P values were one-sided.
Analysis of Continuous Variables: Organ and body weight data were analyzed using non-parametric multiple comparison procedures of Dunnett and Williams. Clinical chemistry and haematology data were analyzed using the non-parametric multiple comparison methods of Dunn and Shirley. Jonckheere's test was used to assess the significance of the dose related trends and to determine whether a trend-sensitive test (Williams' or Shirly test) was more appropriate for pairwise comparisons than a test that does not assume a monotonic dose-related trend(Dunnett's or Dunn's test). Average severity values were analyzed for significance using the Mann-Whitney test.
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):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
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:
CLINICAL SIGNS AND MORTALITY
The survival rates among exposed rats were similar to those of the controls. In males, at least 54% of the animals survived to study termination in the 0 ppm dose group, 68% in the 300mg/kg bw/day group, 60% in the 600mg/kg bw/day group and 66% in the 1200mg/kg bw/day group. In females, 60 % of the animals survived to study termination in the 0 mg/kg bw/day dose group, 60% in the 300mg/kg bw/day group, 74% in the 600mg/kg bw/day group and 56% in the 1200mg/kg bw/day group

BODY WEIGHT AND WEIGHT GAIN
The mean body weights of male rat groups receiving 300 and 600mg/kg bw/day were similar to those of the control group. The mean body weights of the 1200mg/kg bw/day males and exposed females were approximately 5% lower than those of the control groups throughout the study.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The average feed consumption by all exposure groups was similar to that of the control groups, with only the 1200mg/kg bw/day males consuming slightly less feed throughout the study. No clinical findings were associated with the administration of benzyl acetate.

FOOD EFFICIENCY
Not examined

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Not examined

OPHTHALMOSCOPIC EXAMINATION
Not examined

HAEMATOLOGY
The haematology profiles of rats at the 15 month interim showed no chemical-related effects for the parameters measured.

CLINICAL CHEMISTRY
Alkaline phosphatase activity was slightly lower in 1200mg/kg bw/day males than control males but the relationship to chemical administration was inconclusive. Pancreatic enzyme activity were measured in male rats only but no statistically significant differences occurred between any exposure group and the control group for any of the enzymes.

URINALYSIS
Not examined

NEUROBEHAVIOUR
Not examined

ORGAN WEIGHTS
No information provided

GROSS PATHOLOGY
No biologically noteworthy changes in the incidences of neoplasms or nonneoplastic lesions occurred in any organ in male or female rats, except for a significant decrease in the incidence of uterine stromal polyps in the 600mg/kg bw/day females. However, this was not considered to be chemical related. The incidence of various lesions in all rat groups were within the normal range for the species in studies of this type.

HISTOPATHOLOGY: NON-NEOPLASTIC
In males, there was no biologically noteworthy change in the incidence of nonneoplastic lesions observed in any organ.
In females, a significant decrease in the incidence of uterine stromal polyps was observed in the 600mg/kg bw/day treatment group. However, this was not considered to be treatment/chemical related.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
In males, there was no biologically noteworthy change in the incidence of neoplastic lesions observed in any organ.

HISTORICAL CONTROL DATA (if applicable)
No information provided

OTHER FINDINGS
No additional information
Relevance of carcinogenic effects / potential:
Not relevant as test substance not considered to have carcinogenic effects at the doses used in this study.
Dose descriptor:
NOAEL
Effect level:
1 200 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects at highest dose level
Critical effects observed:
no

The results indicate that the rats could have tolerated higher doses due to the similarity in survival and minimal body weight differences between control and exposed groups and the absence of chemical-related lesions.

Conclusions:
Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female F344/N rats following oral administration of the test substance at 300mg/kg bw/day, 600mg/kg bw/day or 1200mg/kg bw/day over 2 years. As a result of this, the test substance dose not require classification according to Regulation EC No. 1272/2008.
Executive summary:

In the study conducted by Abdo et al (1993), the test substance, Benzyl Acetate, was investigated for its carcinogenic potential in groups of 60 male and female F344/N rats. The rats were fed the test substance in feed containing 0, 300, 600 or 1200mg/kg bw/day benzyl acetate daily over a two year period.

Survival of exposed rats was comparable to that of the controls. The mean body weights of the 1200mg/kg bw/day males and exposed females were approximately 5% lower than those of the controls throughout most of the study. The feed consumption by 1200mg/kg bw/day fed males was slightly lower than that of the controls. No biologically significant changes in haematology or clinical chemistry parameters were found that could be attributed to benzyl acetate administration. No compound related increased incidences of neoplasms or nonneoplastic lesions occurred in male or female F344/N rats receiving benzyl acetate for two years.

Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female F344/N rats following oral administration of the test substance at 300mg/kg bw/day, 600 mg/kg bw/day or 1200 mg/kg bw/day over 2 years.

As a result of this, the test substance does not require classification according to Regulation EC No. 1272/2008.

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 60 male and female mice were administered the test substance at concentrations of 0, 33, 100 and 300mg/kg bw/day in feed daily over a 2 year period. Mortality, body weights, feed consumption and clinical pathology were recorded.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): Benzyl Acetate
- Molecular formula (if other than submission substance): C9H10O2
- Molecular weight (if other than submission substance): 150.17

- Physical state: Colourless liquid with a pear-like odour.
- Analytical purity: At least 98%
- Impurities (identity and concentrations): Not documented
- Composition of test material, percentage of components: Not documented
- Isomers composition: Not documented
- Purity test date: Not documented
- Lot/batch No.: 8743-84 and 845585
- Expiration date of the lot/batch: Not documented

- Expiration date of radiochemical substance (if radiolabelling): Not documented
- Stability under test conditions: Stable as a bulk chemical for 2 weeks at temperatures as high as 60°C.
- Storage condition of test material: Not documented
- Other: Boiling point: 215.5°C
Melting point: -51.3°C
Density: 1.0550 at 20°C
Vapour pressure: 1mmHg at 45°C
Insoluble in water but is miscible with alcohol or ether.
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Laboratories, Inc. (Gilroy, CA).
- Age at study initiation: 40 days old
- Weight at study initiation: Not documented
- Fasting period before study: Not documented
- Housing: Housed individually in polycarbonate cages on hardwood bedding which was changed weekly.
- Diet (e.g. ad libitum): NIH-07 open formula meal rat and mouse diet ad libitum
- Water (e.g. ad libitum): Automatic watering system ad libitum.
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.6 ± 0.6°C
- Humidity (%): 45 - 52.6%
- Air changes (per hr): a minimum of 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light per day.

IN-LIFE DATES: From: To: Not documented
Route of administration:
oral: feed
Vehicle:
not specified
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Dose formulations were prepared weekly by mixing benzyl acetate with feed. The dose formulations were stored at -20°C in sealed double plastic bags for no longer than 13 days.

Dose formulations were analyzed every 6 to 8 weeks.

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Periodic analyses of the dose formulations of benzyl acetate were conducted using gas chromatography. The stability of 33mg/kg bw/day dose formulations stored in the dark at -20°C was established for at least three weeks. Dose formulations were analyzed every 6 to 8 weeks.
Duration of treatment / exposure:
103 weeks
Frequency of treatment:
Daily in feed
Post exposure period:
No information provided
Dose / conc.:
33 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
Dose / conc.:
300 mg/kg bw/day (nominal)
No. of animals per sex per dose:
60 male and 60 female per dose
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: Dose selection was based on decreased final mean body weights of all exposed groups in a previously conducted 13 week study.
- Rationale for animal assignment (if not random): Animals were grouped by weight and assigend to cages and the cages assigned to exposure groups using tables of random numbers.
Positive control:
No information provided.
Observations and examinations performed and frequency:
All animals were observed twice daily. Body weights and clinical findings were recorded weekly for the first 13 weeks, every 4 weeks thereafter and at the end of the study. Blood was collected from the retroorbital sinus of mice at the 15 month interim evaluations to determine haematology and clinical chemistry parameters, including haematocrit, haemoglobin, erythrocytes, mean erythrocyte volume, mean erythrocyte haemoglobin, platelets, reticulocytes and leucocyte count and differential and cholesterol, triglyceride, alkaline phosphatase, creatine kinase, and sorbitol dehydrogenase. The brain, right kidney and liver were weighed at the 15 month interim analysis.
A complete necropsy was performed on all animals. At necropsy all organs and tissues were examined for gross lesions and all major tissues were microscopically examined.
Complete histopathological examinations were performed on all animals. Tissue examinations included adrenal gland, brain, oesophagus, femur, heart, kidney, large intestine, liver, lung, mammary gland, nose, ovary and pancreas, among others.
Sacrifice and pathology:
Animals were sacrificed and necropsy was performed on all animals.
Other examinations:
No additional information provided
Statistics:
Survival Analyses: The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958). Dose-related effects on survival used Cox's method for testing 2 groups for equality and Tarone's life table test to identify dose-related trends.
Calculation of Incidence: For calculation of statistical significance the incidences of most neoplasms and all nonneoplastic lesions are given as the ratio of the number of affected animals to the number of animals with the site examined microscopically.
Analysis of Neoplasm Incidences: Logistic regression analysis in addition to the life table test, the Fisher exact test and the Cochran-Armitage trend test. Continuity-corrected tests were used in the analysis of neoplasm incidence and reported P values were one-sided.
Analysis of Continuous Variables: Organ and body weight data were analyzed using non-parametric multiple comparison procedures of Dunnett and Williams. Clinical chemistry and haematology data were analyzed using the non-parametric multiple comparison methods of Dunn and Shirley. Jonckheere's test was used to assess the significance of the dose related trends and to determine whether a trend-sensitive test (Williams' or Shirly test) was more appropriate for pairwise comparisons than a test that does not assume a monotonic dose-related trend(Dunnett's or Dunn's test). Average severity values were analyzed for significance using the Mann-Whitney test.
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):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
CLINICAL SIGNS AND MORTALITY
Survival of exposed males was similar to that of the control groups. Survival of exposed females increased with exposure levels with survival of 300mg/kg bw/day females significantly higher that that of the control group. Almost all deaths occurred during the last 9 months of the study with only 5 animals dying during the first 15 months.

BODY WEIGHT AND WEIGHT GAIN
Mean body weigts of exposed mice were consistently lower than that of the controls, with the exception of the 33mg/kg bw/day dose group. The mean body weight of males in the 100mg/kg bw/day treatment group was up to 10% lower and those in the 300mg/kg bw/day were up to 13% than that of the control group. The body weight of females in the 100mg/kg bw/day group was up to 12% lower and that of the 300mg/kg bw/day females was up to 16% lower than that of the control group. The lower mean body weights of the 100 and 300mg/kg bw/day males and females began after approximately 4-8 weeks after exposure and continued throughout the study. A decrease in mean body weight of all control and exposed males and females occurred between weeks 49 and 53 (males) and weeks 50 and 54 (females). Recovery of the mean body weights was apparent by week 57 (males) and week 58 (females).

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
The average feed consumption by all exposed mice was similar to that of the control groups. Feed consumption in the 100 and 300mg/kg bw/day males was lower than that by the control group at week 4. No clinical findings were attributed to benzyl acetate administration.

FOOD EFFICIENCY
Not examined

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Not examined

OPHTHALMOSCOPIC EXAMINATION
Not examined

HAEMATOLOGY
The haematology profiles at the 15 month interim evaluation showed no chemical-related effects.

CLINICAL CHEMISTRY
Some differences in mean values were observed for exposed groups compared to control groups. Triglycerides and cholesterol levels were slightly lower in exposed male and female mice and the alkaline phosphatase activity was lower in the 100 and 300mg/kg bw/day females than in the control group.

URINALYSIS
Not examined

NEUROBEHAVIOUR
Not examined

ORGAN WEIGHTS
No information provided

GROSS PATHOLOGY
No information provided.

HISTOPATHOLOGY: NON-NEOPLASTIC
Nose: Dose-related increased incidences and severities of nonneoplastic lesions occurred in the nose of male and female mice all exposure groups. The nasal lesions consisted of atrophy and degeneration primarily of the olfactory epithelium, cystic hyperplasia of the nasal submucosal glands and exudate and pigmentation of the nasal mucosal epithelium. Atrophy consisted of depletion of bipolar neurons from the sensory cell layer of the olfactory epithelium while degeneration was characterised by disorganisation of the remaining sensory and sustentacular cells with enlarged or occasionally pyknotic nuclei. The most commonly affected areas of the nose were the dorsal nasal septum, the dorsal arch of the dorsal septum and ethmoid turbinates and the dorso-medial aspect of the ethmoid turbinates. In some instances, the atrophied and degenerated epithelium contained gland-like structures several microns in diameter similar to hyperplastic Bowman's glands. The submucosal Bowman's glands in the affected regions were often hyperplastic and cystic and contained exudate in many mice. The epithelial cells of the hyperplastic glands were enlarged and occasionally extended upward to connect directly with the nasal meatus. Exudate was also present in the nasal meatus of some animals. A significant amount of finely granular, brown pigment was usually present in the affected olfactory epithelial cells and was similar to that in the olfactory epithelium of the control mice, however, the amount of pigment was increased.
The nasal mucosal changes of atrophy, degeneration and cystic hyperplasia of the glandular ducts occurred in the majority of male and female control mice and the exposed animals. However, the severity of these lesions was greater and the incidence of the additional lesion of pigmentation was increased in exposed animals in a dose-related manner. The atrophic and degenerative changes were usually minimal in severity in the 33mg/kg bw/day group but progressed to moderate severity in the 300mg/kg bw/day males and females. No neoplasms or preneoplastic treatment related lesions occurred in the nose.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No increased incidences of neoplasms in male and female mice could be attributed to exposure of benzyl acetate.
Liver: The incidence of hepatocellular adenoma and hepatocellular adenoma and carcinoma (combined) occurred with a dose-related negative trend in male mice with the combined incidence in the 300mg/kg bw/day group significantly lower than that in the control group. This effect was only observed in males.
Uterus: A significant decrease in the incidence of uterine stromal polyps occurred in the 33 and 100mg/kg bw/day females.

HISTORICAL CONTROL DATA (if applicable)
No information

OTHER FINDINGS
No additional findings.
Relevance of carcinogenic effects / potential:
Not relevant as there was no evidence of carcinogenic effects at the doses used in this study.
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
histopathology: neoplastic

No additional information

Conclusions:
Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female B6C3F1 mice following oral administration of the test substance at 33, 100 and 300mg/kg bw/day over 2 years. As a result of this, the test substance does not require classification according to Regulation EC No. 1272/2008.
Executive summary:

In the study conducted by Abdo et al (1993), the test substance, Benzyl Acetate, was investigated for its carcinogenic potential in groups of 60 male and female B6C3F1 mice. The mice were fed the test substance in feed containing 0, 33, 100 or 300mg/kg bw/day benzyl acetate daily over a two year period.

Survival of all exposed mice, except the 300mg/kg bw/day females was similar to that of the control groups. Survival of 300mg/kg bw/day females was significantly higher than that of the control group. Throughout the 2 -year study, the mean body weights of 100 and 300mg/kg bw/day males and females were 2 to 14% lower than those of the control groups. No biologically significant changes in haematology or clinical chemistry parameters were observed inmice receiving 33, 100 or 300mg/kg bw/day benzyl acetate.

Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female B6C3F1 mice following oral administration of the test substance at 33, 100 and 300mg/kg bw/day over 2 years. As a result of this, the test substance does not require classification according to Regulation EC No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
chronic
Species:
mouse
Quality of whole database:
Acceptable studies conducted by the NTP

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a study conducted by Abdo (1986), groups of 50 rats of each sex were administered 0,250, or 500 mg/ kg benzyl acetate in corn oil by gavage, 5 days per week for 103 weeks. Additional groups of 50 rats of each sex were included at the start of the two-year studies to serve as untreated controls. These controls were sacrificed early in the study (weeks 42-44 for rats) as a result of a program wide decision that vehicle controls are more appropriate than untreated controls for interpreting the results of gavage studies.Under the conditions of these studies, benzyl acetate increased the incidence of acinar-cell adenomas of the exocrine pancreas in male F344/ N rats; the gavage vehicle may have been a contributing factor. No evidence of carcinogenicity was found for female F344/N rats. The carcinogenic potential of Benzyl Acetate is inconclusive based on the results of this study.

In a study conducted by Abdo (1986), groups of 50 mice of each sex received 0,500, or 1,000 mg/ kg benzyl acetate in corn oil by gavage, 5 days per week for 103 weeks. Additional groups of 50 mice of each sex were included at the start of the two-year studies to serve as untreated controls. These controls were sacrificed early in the study (weeks 53-55 for mice) as a result of a program wide decision that vehicle controls are more appropriate than untreated controls for interpreting the results of gavage studies.Under the conditions of these studies, for male and female B6C3F1 mice there was some evidence of carcinogenicity in that benzyl acetate caused increased incidences of hepatocellular adenomas and squamous cell neoplasms of the forestomach.The carcinogenic potential of Benzyl Acetate is inconclusive based on the results of this study.

In the study conducted by Abdo et al (1993), the test substance, Benzyl Acetate, was investigated for its carcinogenic potential in groups of 60 male and female F344/N rats. The rats were fed the test substance in feed containing 0, 300, 600 or 1200mg/kg bw/day benzyl acetate daily over a two year period.

Survival of exposed rats was comparable to that of the controls. The mean body weights of the 1200mg/kg bw/day males and exposed females were approximately 5% lower than those of the controls throughout most of the study. The feed consumption by 1200mg/kg bw/day fed males was slightly lower than that of the controls. No biologically significant changes in haematology or clinical chemistry parameters were found that could be attributed to benzyl acetate administration. No compound related increased incidences of neoplasms or nonneoplastic lesions occurred in male or female F344/N rats teceiving benzyl acetate for two years.

Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female F344/N rats following oral administration of the test substance at 300mg/kg bw/day, 600mg/kg bw/day or 1200mg/kg bw/day over 2 years. As a result of this, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

In the study conducted by Abdo et al (1993), the test substance, Benzyl Acetate, was investigated for its carcinogenic potential in groups of 60 male and female B6C3F1 mice. The mice were fed the test substance in feed containing 0, 33, 100 or 300mg/kg bw/day benzyl acetate daily over a two year period.

Survival of all exposed mice, except the 300mg/kg bw/day females was similar to that of the control groups. Survival of 300mg/kg bw/day females was significantly higher than that of the control group. Throughout the 2 -year study, the mean body weights of 100 and 300mg/kg bw/day males and females were 2 to 14% lower than those of the control groups. No biologically significant changes in haematology or clinical chemistry parameters were observed in mice receiving 33, 100 or 300mg/kg bw/day benzyl acetate.

Under the conditions of this study, there was no evidence of carcinogenic activity of benzyl acetate in male or female B6C3F1 mice following oral administration of the test substance at 33, 100 and 300mg/kg bw/day over 2 years. As a result of this, the test substance does not require classification according to Regulation EC No. 1272/2008 or Directive 67/548/EEC.

The key study was determined to be the study conducted by Abdo in 1993 conducted in mice and rats as it primarily focuses on carcinogenesis following dietary adminstration of the test substance. While the other Abdo study from 1986 covers carcinogenicity, it is not as specific and therefore, cannot be considered to be the key study.


Justification for classification or non-classification

Based on the results of the key study, the test substance does not require classification according to Directive 67/548/EEC or Regulation EC No. 1272/2008.