Registration Dossier

Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Experimental data from various test chemicals
Justification for type of information:
Data for the target chemical is summarized based on data from various test chemicals
Cross-referenceopen allclose all
Reason / purpose:
read-across source
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
Subchronic repeated dose oral toxicity was performed to evaluate the toxic nature of the test chemical in rats
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
not specified
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals and environmental conditions:
No data
Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Feed
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
Duration of treatment: 8 weeks
Duration of exposure: 7 weeks
Frequency of treatment:
Daily
Remarks:
0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg)
No. of animals per sex per dose:
Total: 40 males and 40 females
0 mg/Kg: 5 males and 5 females
215 mg/Kg: 5 males and 5 females
316 mg/Kg: 5 males and 5 females
460 mg/Kg: 5 males and 5 females
680 mg/Kg: 5 males and 5 females
1000 mg/Kg: 5 males and 5 females
1470 mg/Kg: 5 males and 5 females
2160 mg/Kg: 5 males and 5 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice weekly

BODY WEIGHT: Yes
- Time schedule for examinations:No data available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, twice weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations:No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: NO data
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, all surviving rats were sacrificed by necropsy

HISTOPATHOLOGY: No data
Other examinations:
No data
Statistics:
No data
Clinical signs:
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The mean body weight gain for males of the 4600 ppm dose group was 4% less than that of the control group. Female rats in the same dose group had a 4% increase in body weight gain when compared with the controls. At a dietary concentration of 6800 ppm, the mean body weight gain for males was 9% less than the controls; it was 1 % less for females of the 6800 ppm group when compared to the controls.
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
316 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effects were noted at the mentioned dose level
Critical effects observed:
not specified
Conclusions:
The No observed Adverse Effect level (NOAEL) for the test chemical is considered to be 316 mg/Kg bw.
Executive summary:

Subchronic repeated dose oral toxicity study was performed to determine toxic nature of the test chemical. The study was performed using 5 male and 5 female rats at dose level of 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg). The rats were given treated feed for 7 weeks and untreated feed for 1 week; controls were fed control diet for 8 weeks. Body weights and feed consumption for all rats were measured twice weekly, At the end of the study, all surviving rats were sacrificed for necropsy. The mean body weight gain for males of the 4600 ppm dose group was 4% less than that of the control group. Female rats in the same dose group had a 4% increase in body weight gain when compared with the controls. At a dietary concentration of 6800 ppm, the mean body weight gain for males was 9% less than the controls; it was 1 % less for females of the 6800 ppm group when compared to the controls. No deaths occurred in any dosed group. One female control rat died on study. Based on the observations made, the No observed Adverse Effect level (NOAEL) for the test chemical is considered to be 316 mg/Kg bw.

Reason / purpose:
read-across source
Reference
Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from peer reviewed journal
Qualifier:
according to
Guideline:
other: Principle mentioned below
Principles of method if other than guideline:
A chronic toxicity study was conducted in Osborn-Mendel rats to evaluate the toxic effects of cinnamaldehyde.
GLP compliance:
not specified
Limit test:
yes
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: Weanling rats
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were housed individually in wire cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available
Route of administration:
oral: feed
Vehicle:
other: Feed
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: No data available

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified.
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 1000, 2500 or 10000 ppm (0, 5, 125 or 500 mg/Kg bw)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
16 weeks
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
0, 10000, 2500 or 1000 ppm (0, 500, 125 or 5 mg/Kg bw)
Basis:
no data
No. of animals per sex per dose:
Total: 80 animals
0 ppm: 10 males, 10 females
1000 ppm: 10 males, 10 females
2500 ppm: 10 males, 10 females
10000 ppm: 10 males, 10 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): No data available
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, weekly
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 3, 6, 12 and 22 months
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: On all animals included in the study.
- Parameters examined: White cell counts, red cell counts, haemoglobins and haematocrits.

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters examined: No data available

URINALYSIS: No data available - Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters examined No data available

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
Tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

HISTOPATHOLOGY: Yes
Liver, kidneys, spleen, heart, testes, abdominal and thoracic viscera, and one hind leg, for bone, bone marrow and muscle were preserved, embedded, sectioned and stained with haematoxylin-eosin prior to microscopic examination.
Statistics:
No data available
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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:
effects observed, treatment-related
Description (incidence and severity):
Slight hepatic cell swelling was noted and slight hyperkeratosis of squamous portion of the stomach at a dose of 500 mg/Kg bw
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Test material given through feed. No effects observed
Critical effects observed:
not specified
Conclusions:
The no observad adverse effect level (NOAEL) was considered to be 125 mg/kg when Osborne-Mendel rats were exposed to test chemicals for 16 weeks.
Executive summary:

In a chronic toxicity oral study, test substance was evaluated in male and female Osborne-Mendel rats where the test chemical was administered by diet at concentration of 0, 1000, 2500 or 10000 ppm (0, 5, 125 or 500 mg/kg body weight). No effects were noted when the rats were exposed to 2500 ppm (125 mg/kg body weight) while treatment with 10000 ppm (500 mg/kg body weight) resulted in slight hepatic cell swelling and slight hyperkeratosis of squamous portion of the stomach. Therefore, the no observed adverse effect level (NOAEL) was considered to be 125 mg/kg body weight when test chemical were administered by diet to male and female Osborne-Mendel rats for 16 weeks.

Data source

Reference
Reference Type:
publication
Title:
WoE of repeated dose oral toxicity study for CAS no 2654-57-1
Author:
Sustainability Support Services (Europe) AB
Year:
2019
Bibliographic source:
WoE report, Sustainability Support Services (Europe) AB, 2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Refer below principle
Principles of method if other than guideline:
WoE for the target CAS is summarized based on data from various test chemicals
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of the test chemical: 4-methyl-1-phenyl-3-pyrazolidone
- Molecular formula: C10H12N2O
- Molecular weight: 176.218 g/mol
- Substance type: Organic

Test animals

Species:
rat
Strain:
other: 2. not specified; 3. Osborne Mendel rats
Details on species / strain selection:
No data
Sex:
male/female
Details on test animals and environmental conditions:
2. No data
3. TEST ANIMALS
- Source: No data available
- Age at study initiation: Weanling rats
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were housed individually in wire cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimatization period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: feed
Details on route of administration:
No data
Vehicle:
other: Feed
Details on oral exposure:
2. PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg)

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data

3. PREPARATION OF DOSING SOLUTIONS: No data available
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified.
- Storage temperature of food: No data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): Feed
- Concentration in vehicle: 0, 1000, 2500 or 10000 ppm (0, 5, 125 or 500 mg/Kg bw)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
2. Duration of treatment: 8 weeks
Duration of exposure: 7 weeks

3. 16 weeks
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg) / 2
Remarks:
0, 10000, 2500 or 1000 ppm (0, 500, 125 or 5 mg/Kg bw) / 3
No. of animals per sex per dose:
2. Total: 40 males and 40 females
0 mg/Kg: 5 males and 5 females
215 mg/Kg: 5 males and 5 females
316 mg/Kg: 5 males and 5 females
460 mg/Kg: 5 males and 5 females
680 mg/Kg: 5 males and 5 females
1000 mg/Kg: 5 males and 5 females
1470 mg/Kg: 5 males and 5 females
2160 mg/Kg: 5 males and 5 females

3. Total: 80 animals
0 ppm: 10 males, 10 females
1000 ppm: 10 males, 10 females
2500 ppm: 10 males, 10 females
10000 ppm: 10 males, 10 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data
Positive control:
No data

Examinations

Observations and examinations performed and frequency:
2. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. Mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice weekly

BODY WEIGHT: Yes
- Time schedule for examinations:No data available

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, twice weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations:No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: NO data
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available

3. CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as gfood/kg body weight/day: Yes, weekly
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At 3, 6, 12 and 22 months
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: On all animals included in the study.
- Parameters examined: White cell counts, red cell counts, haemoglobins and haematocrits.

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters examined: No data available

URINALYSIS: No data available - Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters examined No data available

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER: No data available
Sacrifice and pathology:
2. GROSS PATHOLOGY: Yes, all surviving rats were sacrificed by necropsy

HISTOPATHOLOGY: No data

3. GROSS PATHOLOGY: Yes, Tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

HISTOPATHOLOGY: Yes, Liver, kidneys, spleen, heart, testes, abdominal and thoracic viscera, and one hind leg, for bone, bone marrow and muscle were preserved, embedded, sectioned and stained with haematoxylin eosin prior to microscopic examination.
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The mean body weight gain for males of the 4600 ppm dose group was 4% less than that of the control group. Female rats in the same dose group had a 4% increase in body weight gain when compared with the controls. At a dietary concentration of 6800 ppm, the mean body weight gain for males was 9% less than the controls; it was 1 % less for females of the 6800 ppm group when compared to the controls.
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
3. Slight hepatic cell swelling was noted and slight hyperkeratosis of squamous portion of the stomach at a dose of 500 mg/Kg bw
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
2
Effect level:
316 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effects were noted at the mentioned dose level
Dose descriptor:
NOAEL
Remarks:
3
Effect level:
125 other: mg/Kg bw
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No significant effects were noted at the mentioned dose level

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The No observed Adverse Effect level (NOAEL) for the test chemical is considered to be 316 mg/Kg bw.
Executive summary:

Data available for the various test chemicals was reviewed to determine the toxic nature of the test chemical. The studies are as mentioned below:

Subchronic repeated dose oral toxicity study was performed to determine toxic nature of the test chemical. The study was performed using 5 male and 5 female rats at dose level of 0, 2150, 3160, 4600, 6800, 10,000, 14,700 or 21,600 ppm (0, 215, 316, 460, 680, 1000, 1470 or 2160 mg/Kg). The rats were given treated feed for 7 weeks and untreated feed for 1 week; controls were fed control diet for 8 weeks. Body weights and feed consumption for all rats were measured twice weekly, At the end of the study, all surviving rats were sacrificed for necropsy. The mean body weight gain for males of the 4600 ppm dose group was 4% less than that of the control group. Female rats in the same dose group had a 4% increase in body weight gain when compared with the controls. At a dietary concentration of 6800 ppm, the mean body weight gain for males was 9% less than the controls; it was 1 % less for females of the 6800 ppm group when compared to the controls. No deaths occurred in any dosed group. One female control rat died on study. Based on the observations made, the No observed Adverse Effect level (NOAEL) for the test chemical is considered to be 316 mg/Kg bw.

In another study, Chronic toxicity oral study for the test compound cinnamic aldehyde was studied in male and female Osborne-Mendel rats. The test compound was fed through the diet at a concentration of 0, 100, 2500 or 10000 ppm (0, 5, 125 or 500 mg/Kg bw). No effects were noted on microscopic examination at 125 mg/KG bw. Slight hepatic cell swelling was noted and slight hyperkeratosis of squamous portion of the stomach at a dose level of 500 mg/Kg bw. The No observed Adverse Effect Level (NOAEL) for the test compound cinnamaic aldehyde in Osborne-

Mendel rats is found to be 125 mg/Kg bw.

Based on the observations made, the No observed Adverse Effect level (NOAEL) for the test chemical is considered to be 316 mg/Kg bw.