2-benzylideneheptanal

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: 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:

data from handbook or collection of data

Justification for type of information:

Peer reviewed journal research article

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Short-term toxicity of Amyl Cinnamic Aldehyde in Rats

Author:

F. M. B. CARPANINI, I. F. GAUNT, M. G. WRIGHT, P. GRASSO, S.D. GANGOLLI.

Year:

1973

Bibliographic source:

Food and cosmetic toxicology, Vol.11, 725-734, 1973.

Reference 2

Reference Type:

publication

Title:

Screening level hazard characterization of high production volume chemicals

Author:

High Production Volume Chemicals Branch, Risk Assessment Division Office of Pollution Prevention and Toxics, Environmental Protection Agency

Year:

2008

Bibliographic source:

Report by US Environmental Protection Agency, 1-22, March 2008. P

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Short term toxicity potential of Amyl Cinnamic Aldehyde was studied in CFE strain rats.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-benzylideneheptanal

EC Number:

204-541-5

EC Name:

2-benzylideneheptanal

Cas Number:

122-40-7

Molecular formula:

C14H18O

IUPAC Name:

2-benzylideneheptanal

Details on test material:

- Name of test material (as cited in study report): alpha-Amyl cinnamaldehyde
- Molecular formula : C14H18O
- Molecular weight : 202.2952g/mol
- Smiles notation (if other than submission substance): c1(\C=C(\CCCCC)C=O)ccccc1
- InChl (if other than submission substance): 1S/C14H18O/c1-2-3-5-10-14(12-15)11-13-8-6-4-7-9-13/h4,6-9,11-12H,2-3,5,10H2,1H3/b14-11-
- substance type: organic
- physical state: liquid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Amyl cinnamic aldehyde
- Molecular formula (if other than submission substance): C14H18O
- Molecular weight (if other than submission substance): 202.2952 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): 3%

Test animals

Species:

rat

Strain:

other: CFE

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF breeding colony
- Age at study initiation: No data
- Weight at study initiation: Male: 100-125 g, Female: 90-120 g
- Fasting period before study: No data
- Housing: Animals housed in cages in animal room maintained at 21±1 °C with relative humidity 50-60%.
- Diet (e.g. ad libitum): Spillers Laboratory small animal diet, ad. libitum.
- Water (e.g. ad libitum): Water, ad. libitum.
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21±1 °C
- Humidity (%):50-60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light):
No data
IN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: feed

Details on route of administration:

No data

Vehicle:

other: Spillers Laboratory small animal diet

Details on oral exposure:

Details on oral exposure
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): 4-5 days
- Mixing appropriate amounts with (Type of food): Spillers Laboratory Small Animal Diet
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: 0,6.1,29.9 and 287.3 mg/kg/day for males
0,6.7, 34.9 and 320.3 mg/kg/day for females
- 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:

14 weeks

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

0,6.1,29.9 and 287.3 mg/kg/day for males (0, 80, 400, 4000 ppm )

Doses / concentrations 2

Remarks:

0,6.7, 34.9 and 320.3 mg/kg/day for females ((0, 80, 400, 4000 ppm )

No. of animals per sex per dose:

15 male and 15 female/dose
Test control: 15 male and 15 female
Satellite Control: 5 male and 5 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data
- Cage side observations checked in table [No.?] were included. respiratory distress and weight loss were observed

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations:
Animals were weigh initially and then weekly up to 14 weeks.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes , The food consumption were measured over the 24-hr period
preceding each weighing.

- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes

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

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: ml/rat/day at 0, 5, 9, 14 week

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

HAEMATOLOGY: Yes
- Time schedule for collection of blood: 2, 6, 14 week
- Anesthetic used for blood collection: Yes (Barbiturates anesthesia)
- Animals fasted: No data
Parameters checked in table [No.?] were examined: Yes, The hematological investigations consisted of measurement of hemoglobin ,content, packed cell volume, and counts of erythrocytes, total leucocytes and
individual types of leucocytes. Reticulocytes were counted in the samples from control rats
and those fed the highest level of amyl Cinnamic aldehyde .

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 2, 6, 14 week
- Animals fasted: No data
- Parameters checked in table [No.?] were examined: Yes, Serum was analyzed for the content of urea, glucose, total protein and albumin and for the activities of glutamio oxalacetic and glutamic-pyruvic transaminases and of lactic dehydrogenase.

URINALYSIS: Yes
- Time schedule for collection of urine: 6,12 and Final week of treatment.
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. Yes , the specific gravity and volume of urine produced in a 6-hr period
of water deprivation. At the same time, samples of the urine were examined for appearance,
microscopic constituents and content of cells, glucose, ketones, bile salts and blood. At wk 6
and 13, urine was also collected from the rats over a 2-hr period following a water load of
25 ml/kg and between 16 and 20 hr after the water load.

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

OTHER: organ weight; Organ stomach, small intestine and caecum were weighed.

Sacrifice and pathology:

Sacrifice and pathology
GROSS PATHOLOGY: Yes, the rats were killed by exsanguinations under barbiturate anesthesia. Samples of salivary gland, trachea, aorta, thymus, lymph nodes, urinary bladder, colon, rectum, pancreas, uterus, skeletal muscle were observed

HISTOPATHOLOGY: Yes , The tissue that appeared to be abnormal were fixed in 10 %
buffered formalin. Pa&En-wax sections of these tissues were stained with haematoxylin and
eosin for microscopic examination.

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Food efficiency:

not specified

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

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Ophthalmological findings:

not specified

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Urinalysis findings:

effects observed, non-treatment-related

Description (incidence and severity):

No statistically significant change were observed at all dose group compare to control.

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

The only statistically significant differences in the absolute organ weights of treated and control rats were seen after treatment of 6 week. These consisted of lower stomach weights in the males given 287.3 mg/kg bw amyl cinnamic aldehyde and lower small intestine weights in the females given 320.3 mg/kg bw. In the latter case, the difference was not significant when the organ weights were expressed relative to body weights.

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Patchy lungs in three male rats (two at 6.1 mg/kg bw of test substance level and one control) and pale kidneys in some male rats in all groups including controls. Small mammary adenomas were found in two treated female rats.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

One female rat shows respiratory depression, on histopathological examination of tissue revealed pneumonia and an abscess of renal pelvis. Vacuolation of some liver cells, protein casts in kidney tubules and sign of chronic lung infection. The incidence of these findings was low and was similar in both treated and control rats.

Histopathological findings: neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Mammary adenomas were reported in two female rats.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

23 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant change were observed on the clinical sign/food consumption,body weight, hematological examinations,clinical chemistry,urine analysis ,organ weight, gross pathology and histopathology

Remarks on result:

other: No significant change were observed on the clinical sign/food consumption,body weight, hematological examinations,clinical chemistry,urine analysis ,organ weight, gross pathology and histopathology

2

Key result

Dose descriptor:

NOAEL

Effect level:

36 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No significant change were observed on the clinical sign/food consumption,body weight, hematological examinations,clinical chemistry,urine analysis ,organ weight, gross pathology and histopathology

Remarks on result:

other: No significant change were observed on the clinical sign/food consumption,body weight, hematological examinations,clinical chemistry,urine analysis ,organ weight, gross pathology and histopathology

Target system / organ toxicity

Critical effects observed:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Any other information on results incl. tables

Table. Mean body weights and consumption of food and water for rats fed amyl cinnamic aldehyde at 0-200 mg/kg bw of the diet for 14 wk

Dietary level (ppm)	Body Weight (g) at week				Weight gain (g) at 14 week	Food Consumption (g/rat/day) at Week				Mean food consumption (g/rat/day)
	0	5	9	14		0	5	9	14
Males
0	113	352	435	494	381	17.1	22.1	22.7	19.9	22.1
80	118	356	449	509	391	16.9	25.9	23.7	20.5	22.3
400	114	353	440	502	388	15.0	23.4	23.5	20.7	21.8
4000	116	343	428	490	374	16.6	21.8	22.1	19.7	20.6
Female
0	104	226	267	297	193	15.4	16.5	18.4	14.7	17.8
80	106	232	274	305	199	14.9	18.6	20.4	16.1	17.6
400	104	238	280	311	207	14.7	19.4	21.6	14.0	18.6
4000	104	225	264	292	188	14.3	17.3	19.3	15.1	16.4

                                                                                                                                  

 

 

 

Dietary level (ppm)	Water Consumption (ml/rat/day) at wk				Mean water consumption (ml/rat/day)
	0	5	9	14
Males
0	20.3	28.3	27.6	30.1	26.9
80	20.2	28.7	26.5	29.8	25.8
400	18.3	27.9	28.0	30.5	25.8
4000	20.1	27.7	28.1	29.3	27.5
Female
0	20.9	23.7	23.3	23.5	23.0
80	22.6	27.0	27.2	27.5	24.9
400	21.6	27.0	27.4	24.5	24.5
4000	20.1	27.2	26.1	25.6	25.0

 

 

 

 

 

 

 

 

 

Table: Hematological values of rats fed 0-200 mg/kg bw amyl cinnamic aldehyde in the diet for 2, 6 or 14 wk

Sex and Dietary level (ppm)						Leucocytes
	No. of rats	Hb (g/100 ml)	PCV (%)	RBC (10^6/mm^3)	Retics (% of RBS)	Total (10^3/mm^3)	Differential (%)
							N	E	L	M
Week 2
Male
0	5	13	43	6.20	1.80	6.67	9	1	89	1
400	5	13.3	42	6.20	-	5.16	7	0	91	2
4000	5	13.5	43	6.41	1.72	6.09	7	1	90	2
Female
0	5	12.4	41	5.99	0.90	3.95	10	0	88	1
400	5	12.8	43	6.16	-	3.89	9	1	88	2
4000	5	12.8	43	6.45	1.69	3.47	7	2	89	2
Week 6
Male
0	5	14.1	44	6.81	0.64	7.52	13	1	84	2
400	5	14.3	45	7.13	-	6.66	14	0	85	1
4000	5	13.9	45	6.94	0.93	6.19	12	1	86	1
Female
0	5	13.4	43	6.16	1.06	4.33	18	2	79	1
400	5	13.3	42	6.14	-	4.33	16	2	80	2
4000	5	13.6	43	6.18	1.46	2.93	13	2	83	2
Week 14
Male
0	15	15.3	44	7.15	0.80	6.20	21	2	76	1
80	15	14.9	44	7.10	-	6.46	15	2	82	1
400	15	15.1	44	7.00	-	6.21	17	2	80	1
4000	15	15.1	44	7.32	0.49	6.55	14	1	84	1
Female
0	15	14.4	43	6.58	0.69	3.55	16	2	81	1
80	15	14.6	44	6.70	-	3.91	18	3	78	1
400	15	14.5	43	6.65	-	3.34	12	2	85	1
4000	15	14.1	43	6.63	0.71	3.21	16	2	81	1

Hb = Haemoglobin PCV = Packed cell volume RBC = Red blood cells Reties = Reticulocytes N = Neutrophils E = Eosinophils L = Lymphocytes M= Monocytes

 

Table. Values of serum analyses for rats treated with 0-200 mg/kg bw amyl cinnamic aldehyde in the diet for 2, 6 or 14 Week

Sex and Dietary level (ppm)	No. of rats	GOT (IU)	GPT (IU)	LDH (IU)	Glucose (mg/100 ml)	Urea (mg/100 ml)	Protein (g/100 ml)	Albumin (g/100 ml)
Week 2
Male
0	5	46	6	897	-	15	5.9	5.5
400	4	43	6	945	-	13	5.8	5.4
4000	5	41	6	875	-	16	5.8	5.5
Female
0	5	51	7	1169	105	17	-	4.2
400	4	59	6	1280	115	17	-	4.0
4000	5	52	7	971	113	16	-	4.1
Week 6
Male
0	5	56	8	974	81	18	7.1	3.5
400	5	52	7	1071	81	15	7.1	4.0
4000	5	57	12	988	70	18	7.4	3.6
Female
0	5	46	9	941	75	19	7.3	3.8
400	5	45	6	907	88	19	7.1	4.1
4000	4	46	7	897	50	20	7.3	4.2
Week 14
Male
0	15	46	10	769	141	15	7.4	3.7
80	15	43	9	783	124	16	7.4	4.0
400	15	43	10	794	112	18	7.4	4.0
4000	15	46	9	811	121	19	7.4	4.1
Female
0	15	45	7	803	115	18	7.5	4.4
80	15	45	8	790	111	19	7.8	4.6
400	15	43	9	845	126	15	7.6	4.2
4000	15	44	7	860	120	15	7.6	4.2

 

 

 

 

 

 

 

 

 

 

Table. Mean value of renal concentration/ dilution tests and urinary cell excretion in rats fed amyl cinnamic aldehyde at 0-200 mg/kg bw amyl cinnamic aldehyde in the diet for 2, 6 or 14 week.

Sex and dietary level (ppm)	No. of rats	Cell excretion (10^3/hr)	Concentration test				Dilution Test (2 hr)
			Specific gravity		Volume (ml)		Specific Gravity	Volume (ml)
			0-6 hr	16-20 hr	0-6 hr	16-20 hr
Week 2
Male
0	5	5.4	1.062	-	1.5	-	-	-
400	5	4.8	1.061	-	2.2	-	-	-
4000	5	3.1	1.066	-	1.2	-	-	-
Female
0	5	3.7	1.057	-	2.2	-	-	-
400	5	2.5	1.062	-	2.1	-	-	-
4000	5	4.3	1.060	-	1.6	-	-	-
Week 6
Male
0	5	3.7	1.049	1.068	2.3	0.7	1.010	7.2
400	5	4.0	1.054	1.076	2.9	0.9	1.012	5.5
4000	5	3.9	1.056	1.065	2.5	1.4	1.009	6.4
Female
0	5	2.6	1.049	1.072	1.4	0.8	1.010	3.2
400	5	2.8	1.037	1.075	1.6	0.6	1.007	3.6
4000	5	3.8	1.045	1.073	1.0	0.7	1.013	2.7
Week 14
Male
0	12	3.2	1.060	1.072	1.9	1.0	1.011	6.7
80	12	3.6	1.056	1.067	1.7	1.5	1.012	6.0
400	12	3.2	1.062	1.067	1.4	1.4	1.014	5.5
4000	12	3.6	1.060	1.065	1.6	1.4	1.012	6.7
Female
0	12	2.2	1.062	1.079	0.5	0.3	1.010	5.3
80	12	2.9	1.051	1.068	0.9	0.6	1.011	4.4
400	12	3.8	1.049	1.068	0.7	0.3	1.012	4.9
4000	12	4.1	1.051	1.063	1.2	1.1	1.008	5.3

 

 

 

 

Table: Relative organ weights of rats fed amyl cinnamic aldehyde at 0-200 mg/kg bw of the diet for 2, 6 or 14 weeks.

Sex and Dietary level (ppm)	No. of rats	Relative organ weights (g/100 g body weight)												Terminal Body Weight (g)
		Brain	Heart	Liver	Spleen	Kidney	Stomach	Small Intestine	Caecum	Adrenals+	Gonads ++	Pituitary +	Thyroid +
Week 2
Male
0	5	0.76	0.41	3.33	0.33	0.86	0.60	3.42	0.36	24.2	1.16	3.84	6.99	226
400	5	0.70	0.41	3.32	0.28	0.82	0.52	3.18	0.35	24.5	1.18	3.89	6.97	240
4000	5	0.75	0.40	3.73	0.30	0.87	0.55	3.21	0.34	25.1	1.21	4.02	8.02	229
Female
0	5	0.94	0.43	3.40	0.34	0.84	0.58	3.45	0.36	38.1	51.9	5.82	9.35	169
400	5	1.00	0.44	3.47	0.34	0.87	0.58	3.37	0.37	37.7	55.1	6.33	8.76	163
4000	5	0.97	0.43	3.51	0.35	0.86	0.57	3.38	0.37	36.6	46.0	5.84	9.52	167
Week 6
Male
0	5	0.51	0.34	2.77	0.25	0.69	0.44	1.80	0.24	18.6	1.00	3.40	4.68	372
400	5	0.51	0.35	2.80	0.24	0.71	0.39	1.91	0.23	16.9	0.94	3.56	5.43	369
4000	5	0.54	0.35	3.06	0.24	0.77	0.46	1.92	0.27	19.4	1.06	3.40	5.65	338
Female
0	5	0.76	0.35	2.75	0.28	0.67	0.51	2.64	0.38	35.2	59.3	4.51	7.77	223
400	5	0.76	0.33	2.56	0.24	0.65	0.62	2.47	0.32	34.7	41.4	4.41	8.40	213
4000	5	0.76	0.34	2.87	0.28	0.70	0.54	2.31	0.39	36.7	47.7	4.66	8.80	217
Week 14
Male
0	15	0.40	0.28	2.42	0.17	0.60	0.39	1.62	0.24	13.7	0.77	2.34	4.20	476
80	15	0.38	0.28	2.51	0.18	0.58	0.41	1.62	0.24	12.2	0.72	2.40	4.23	492
400	15	0.39	0.28	2.45	0.18	0.60	0.38	1.63	0.23	13.1	0.79	2.35	4.27	485
4000	15	0.40	0.27	2.66	0.17	0.64	0.38	1.67	0.25	13.5	0.79	2.44	4.48	467
Female
0	15	0.64	0.32	2.20	0.22	0.58	0.49	2.20	0.33	24.7	45.0	4.73	7.07	280
80	15	0.61	0.31	2.20	0.23	0.58	0.49	2.25	0.32	25.3	39.3	4.31	7.26	289
400	15	0.61	0.33	2.25	0.22	0.60	0.48	2.17	0.32	26.0	44.7	4.77	6.60	291
4000	15	0.63	0.32	2.35	0.24	0.61	0.51	2.15	0.36	25.7	47.4	4.70	6.90	276

 

+ Weights of this organ are expressed in mg/100 g body weight.

++ Weights of female gonads are expressed in mg/100 g body weight.

Applicant's summary and conclusion

Conclusions:

The repeated dose oral toxicity study of Amyl cinnamic aldehyde was studied in CFE strain rats by administering doses of test substance in diet for male 0,6.1,29.9 and 287.3 mg/kg/day and for female 0,6.7, 34.9 and 320.3 mg/kg/day .Therefore NOAEL were 23 mg/kg bw/day in males and 36 mg/kg bw/day in females as insited by study.

Executive summary:

Repeated oral dose toxicity study ofAmyl cinnamic aldehyde was studied in CFE strain rats. Doses of test substance administered orally in diet were6.1, 29.9 and 287.3 mg/kg/day for males and 6.7, 34.9 and 320.3 mg/kg/day for females. Test substance was fed to groups of 15 male rats (body weight loo-125 g) and15 females (body weight 90-120 g) for 14 wk.Additional groups of five rats were fed with 6.1, 29.9 and 287.3 mg/kg/day for males and 6.7, 34.9 and 320.3 mg/kg/day for females. Animals were fed on Spillers laboratory small animal diet. Water is provided to animals throughout study. Hematological screening, serum analysis and urine analysis were done. After appropriate period of feeding the rats were killed by exsanguination under barbiturates anesthesia. Gross pathology and histopathology investigation were done.Apart from three rats, no abnormalities were seen in behavior or appearance of animal. No mortality was reported in the study.Animals were weigh initially and then weekly thereafter. Increase in body weight at each dose level was reported. There were no statistically significant differences between treated and control groups in rate of body-weight gain. There were no statistically significant differences between treated and control groups in food consumption. The mean intakes of amyl cinnamic aldehyde over the 14wk period were 6.1, 29.9 and 287.3 mg/kg/day by the males of the groups given 4, 20 and 200 mg/kg bw of test substance in the diet and 6.7, 34.9 and 320.3 mg/kg/day by the females. There were no statistically significant differences between treated and control groups in water consumption. The mean water consummation over 14wk period were 25.8, 25.8 and 27.5 ml/rat/day by the males and female, mean water consummation values were 24.9, 24.5 and 25 respectively.There were no significant differences between treated and control groups in the results of the hematological examinations. Hematological examinations were done on blood samples collected at 2, 6 and 14 week of study. Hemoglobin, Packed cell volume, RBC, Reticulocytes and Leucocytes were examined.A measurement of urinary concentrating ability was made during the final week of treatment by measuring the specific gravity and volume of urine produced in a 6-hr period of water deprivation. At the same time, samples of the urine were examined for appearance, microscopic constituents and content of cells, glucose, ketones, bile salts and blood. At wk 6 and 13, urine was also collected from the rats over a 2-hr period following a water load of 25 ml/kg and between 16 and 20 hr after the water load. The only statistically significant differences in the absolute organ weights of treated and control rats were seen after treatment of 6 week. These consisted of lower stomach weights in the males given 287.3 mg/kg bw amyl cinnamic aldehyde and lower small intestine weights in the females given 320.3 mg/kg bw. In the latter case, the difference was not significant when the organ weights were expressed relative to body weights. Patchy lungs in three male rats (two at 6.1 mg/kg bw of test substance level and one control) and pale kidneys in some male rats in all groups including controls. Small mammary adenomas were found in two treated female rats.   One female rat shows respiratory depression, on histopathological examination of tissue revealed pneumonia and an abscess of renal pelvis. Mammary adenomas were reported in two female rats. Vacuolation of some liver cells, protein casts in kidney tubules and sign of chronic lung infection. The incidence of these findings was low and was similar in both treated and control rats.One female rat shows respiratory depression, on histopathological examination of tissue revealed pneumonia and an abscess of renal pelvis. Mammary adenomas were reported in two female rats. Vacuolation of some liver cells, protein casts in kidney tubules and sign of chronic lung infection. The incidence of these findings was low and was similar in both treated and control rats. Therefore NOAEL were approximately 23 mg/kg bw in males and 36 mg/kg bw in females as per study.