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Description of key information

Acute oral and dermal toxicity studies are available for amyl cinnamic aldehyde. An acute inhalaton toxicity study is available for the read-across substance hexyl cinnamic aldehyde.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The investigations were completed prior to adoption of formal test guidelines but in principle the requirements of the test guidelines were initially derived from existing study designs and this series of investigations is considered to be consistent with the aims and objectives of the guidelines published subsequently.
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of rats, guinea pigs or mice were administered test material by oral intubation. Rats and guinea pigs were fasted prior to dosing. After administration the animals were observed for a period of two weeks and signs of toxicity or morbidity recorded together with any mortalities that occurred.
A median lethal dose was calculated using the method of Litchfield and Wilcoxon.
The purpose of the study was to determine oral toxicity of the materials in relation to food additive uses and so no effort to obtain chemically pure test materials was made but commercially available samples were used.
GLP compliance:
no
Remarks:
conducted prior to adoption of GLP principles
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals or test system and environmental conditions:
No study specific details provided. Groups of 10 young adult Osborne-Mendel rats were fasted for 18 hours prior to dosing (food was returned and available ad libitum from immediately after dosing). The rats were group housed and dosed by intubation.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No details provided for dose levels administered or how many groups were dosed in the study.
Doses:
No information
No. of animals per sex per dose:
Five
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: No information
- Other examinations performed: clinical signs, body weight gains and mortality
Statistics:
Litchfield and Wilcoxon method used to calculate median lethal dose and response slope with 95% confidence intervals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 730 mg/kg bw
Based on:
test mat.
95% CL:
1.2
Remarks on result:
other: 95% CL values of 1.2-1.6 quoted for slope of the dose response curve, Slope = 1.4
Mortality:
No information provided for group mortality except time of death was between 4 hours and day 5 after dosing .
Clinical signs:
other: Depression and porphyrin-like deposit around the eyes
Gross pathology:
No information
Other findings:
No information
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of amyl cinnamic aldehyde was calculated to be 3730 mg/kg bw which exceeds the limit dose level of 2000 mg/kg bw and so no classification is required for acute oral toxicity.
Executive summary:

Amyl cinnamic aldehyde was orally administered by intubation to groups of ten rats (five per sex) and mortality data analysed to calculate a median lethal oral dose. According to Litchfield and Wilcoxon method the LD50 was 3730 mg/kg bw. This result indicates amyl cinnamic aldehyde (2 -benzylideneheptanal) does not require classification for acute oral toxicity according to CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 730 mg/kg bw
Quality of whole database:
Klimisch reliability score = 2 for sole study available

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 to 16 April 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test is non GLP and no test material analysis is present (including assessment of aerosol characteristics), therefore it cannot be Klimisch 1. However, concentration was checked and pathological examination was conducted. Moreover, guidelines are similar to the subsequent OECD 403, therefore a Klimisch 2 reliability score can be assigned.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
no data on acclimation period, on oxygen concentration, assessment of aerosol characteristics
Principles of method if other than guideline:
standard method in general compliance with the procedures subsequently incorporated into OECD TG 403
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories Ltd.; Wilmington Mass.
- Age at study initiation: 8 weeks old
- Weight at study initiation: 175-225 g
- Fasting period before study: no fasting period
- Housing: individually housed in stainless steel, wire meshed-bottom cages
- Diet (e.g. ad libitum): certified laboratory rat diet ad libitum except during the four hours of inhalation exposure
- Water (e.g. ad libitum): tap water ad libitum except during the four hours of inhalation exposure
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.5 ºC
- Humidity (%): 47.5%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel whole body exposure chamber
- Exposure chamber volume: 400 L chamber compartmentalised with each compartment being 7''x3''x4''
- Method of holding animals in test chamber: no data
- Source and rate of air: airflow rate through the chamber was set at 45 L/min
- Method of conditioning air: no data
- System of generating particulates/aerosols:aerosol was generated using a Thermo Systems Inc. six jet atomizer. The atomizer was used at a pressure of 13 psig with two jets in operation.
- Method of particle size determination: hourly air samples from the inhalation chamber were passed through a Casella Cascade Impactor. The distribution and size of particles which deposited on each of the 4 stages of the impactor were determined by light microscopy.
- Treatment of exhaust air: decontamination of chamber air was done by passing the air through a HEPA filter, an activated charcoal filter and a liquid scrubber.
- Temperature, humidity, pressure in air chamber: 23.5 ºC; 47.5% RH; the negative pressure within the chamber with respect to the room atmosphere was set at less than 0.5 inches of water

VEHICLE
- Composition of vehicle (if applicable): Not Applicable
- Concentration of test material in vehicle (if applicable): Not Applicable
- Justification of choice of vehicle: Not Applicable
- Lot/batch no. (if required): Not Applicable
- Purity: Not Applicable


Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
The animals were exposed only to one concentration. They were exposed to a nominal concentration of hexyl cinnamic aldehyde (HCA) of 5.00 mg/L resulting in a measured chamber concentration of 2.12 mg/L
No. of animals per sex per dose:
A total of 10 animals were exposed, 5 male and 5 female
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed on the day of exposure and on days 2, 3, 4, 7 and 14 after the day of the exposure
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology, clinical signs, body weight, histopathology
Statistics:
No information
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.12 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air (nominal)
Exp. duration:
4 h
Mortality:
There were no mortalities
Clinical signs:
other: There were no clinical changes of possible toxicological importance
Body weight:
Body weight losses occurred on the days following exposure; the losses were generally made good by day 7 of the study. Body weight gains during the second week of the observation period were considered to be satisfactory
Gross pathology:
The only changes considered to be of possible toxicological importance were enlarged bronchial lymph nodes sometimes accompanied by pulmonary congestion, or multiple grey-green pinpoint foci in the lungs
Other findings:
- Histopathology:

MALES:
animal 1. Chronic respiratory disease, mild
animal 2. Degeneration, tubular, diffuse, unilateral in left testis and pulmonary congestion and edema, diffuse, severe
animal 3. Chronic respiratory desease, severe
animal 4. Chronic respiratory disease, mild
animal 5. Chronic respiratory desease, severe


FEMALES:
animal 1. Chronic respiratory disease, mild
animal 2. No pathological alteration in kidneys and Chronic respiratory disease, severe with one section showing pulmonary congestion and edema
animal 3. Chronic respiratory disease, moderate
animal 4. Hydrometra in uterus and Chronic respiratory disease
animal 5. Dermatitis, ulcerative chronic focal in cervical region and chronic respiratory disease.

Administration of hexyl cinnamic aldehyde (HCA) by the inhalation route did not produce any systemic toxicity in the albino rat.

Focal greyish-green areas observed grossly on lungs were characterised histologically by aggregates of mononuclear leucocytes mainly about blood vessels and air passages and occasionally extending to alveolar walls, some interstitial fibrosis and infiltration by foamy macrophages. These lessions were considered to be spontaneous and caused as a result of a mild infection with murine respiratory mycoplasmosis. Pulmonary oedema and mild congestion revealed in some rats could be attributed to euthanasia. Testicular tubular degeneration and hydrometra in some rats were also considered incidental.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal concentration LC50 for rats following inhalation of 2-benzylidene octanal, (HCA), for combined sexes data was greater than 2.12 mg/L (analytical concentration) or 5.00 mg/L (nominal concentration).
Executive summary:

In a limit acute inhalation toxicity study performed similarly to the OECD test guideline No. 403, groups of young adult Sprague-Dawley rats (5/sex) were exposed by inhalation route to liquid aerosols of hexyl cinnamic aldehyde (HCA) for 4 hours to whole body at concentration of  5.00 mg/L (nominal, corresponding to 2.12 mg/L analytical). Animals then were observed for14days.

 

LC50 Combined > 2.12 mg/L (analytical concentration) / 5.00 mg/L (nominal concentration)

 

There were no mortalities under the test conditions. The only changes that were considered possibly to be attributable to treatment were a minimal loss of body weight on the days immediately following treatment and enlarged bronchial lymph nodes at the terminal kill, multiple grey-green foci on the lungs and occasional pulmonary congestion. As the actual concentration reached was only 2.12 mg/L, it is difficult to conclude on the classification of HCA. However it is mentioned in the OECD Guideline No. 403 (2009) that "when testing aerosol the primary goal should to be achieve a respirable particle size and this is possible with most test article at a concentration of 2.00 mg/L". Moreover, there was no mortality and observed lessions were considered by the study authors to be spontaneous and caused as a result of a mild infection with murine respiratory mycoplasmosis. Pulmonary edema and mild congestion revealed in some rats could be attributed to euthanasia. Testicular tubular degeneration and hydrometra in some rats were also considered incidental by the study authors.

Based on the above discussion, under the test conditions, HCA is not classified according to the Directive 67/548/EEC and the Regulation (EC) No. 1272/2008. This study is considered as acceptable and satisfies the guideline requirement for an acute inhalation toxicity study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 120 mg/m³ air
Quality of whole database:
Klimisch reliability score = 2 for sole study available (read-across study)

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Summary report dated 2 January 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Not a complete report, only results presented.
Qualifier:
no guideline followed
Principles of method if other than guideline:
The dermal LD50 value was derived for amyl cinnamic aldehyde using four treated rabbits. Clinical symptoms and mortalities were monitored.
GLP compliance:
not specified
Test type:
other: modified design based on standard method but limited to group size of four rabbits due to insufficient test material
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data provided in report
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
Four rabbits dosed at 2 g/kg bw, no details available for duration of exposure or nature of the bandaging used or any wash-off procedures.
Insufficient test material available to treat a full group and consequently only four animals were tested.
Duration of exposure:
No data
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
4 rabbits
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities were observed
Clinical signs:
other: No clinical signs observed
Gross pathology:
No data
Other findings:
No data

No additional results

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for rabbits was greater than 2.0 g/kg. According to Regulation (EC) No. 1272/2008, no classification is warranted, based on the absence of signs of toxicology and mortalities in a group of four rabbits.
Executive summary:

In a study conducted by Moreno (1973), the dermal LD50value was derived for amyl cinnamic aldehyde in a group of four rabbits.

The dermal LD50 for rabbits was greater than 2000 mg/kg bw. According to Regulation (EC) No. 1272/2008, no classification is warranted.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The test was conducted similarly to OECD test guideline No. 402 with minor deviations: occlusive dressing, number of animal tested is not standard, no details on test animals and conditions, no data on gross pathology.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(occlusive dressing, number of animal tested is not standard, no details on test animals and conditions, no data on gross pathology)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: albino
Sex:
female
Details on test animals or test system and environmental conditions:
No data available
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 12 cm wide and covering the entire circumference of the rabbits
- % coverage:
- Type of wrap if used: rubber sheeting and the ends taped to the rabbits


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no details given
- Time after start of exposure: 24 h
Duration of exposure:
The animals were exposed for 24 h

Doses:
One animal was treated at 1000 mg/kg bw, one animal at 2000 mg/kg bw level and three animals were treated at 3000 mg/kg bw
No. of animals per sex per dose:
In total 5 female albino rabbits were treated
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: after 24h of tretament, the rubber sheets were removed and the animals were observed during 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
Statistics:
No information. statistics not required for limit test
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Remarks on result:
other: no animals died at this dose
Mortality:
no animals died
Clinical signs:
other: No information
Gross pathology:
No information
Other findings:
Moderate erythema was apparent. Occassional sloughing was seen but this was in large part due to damage caused by the removal of the tape from the skin and is not believed to be treatment related. All rabbits appeared normal by the end of the test period
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 for female rabbits exposed to HCA was greater than 3000 mg/kg bw and there were no signs of reaction to treatment at the limit dose.
Executive summary:

Female albino rabbits were exposed to undiluted hexyl cinnamic aldehyde for 24 hours (area exposure of 12 cm) at doses of 1000 (1 animal), 2000 (1 animal) or 3000 (3 animals) mg/kg bw under an occlusive coverage.  Animals were observed for 7 days. No animals died at any dose level tested. Moderate erythema was seen with all compounds.  All rabbits appeared normal by the end of the test period. The acute dermal LD50 was therefore found to be > 3000 mg/kg bw. The substance is not classified for acute dermal toxicity according to the CLP Regulation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch reliability score = 2 for sole study available

Additional information

In an acute oral toxicity study, groups of fasted rats (5 males and 5 females/dose) were given a single oral dose of amyl cinnamic aldehyde and observed for 14 days. Deaths occurred between 4 hours and 5 days post dosing. Animals dying during the study showed signs of depression and porphyrin-like deposits around the eyes. The acute oral LD50 was calculated to be 3730 mg/kg bw. The substance is therefore not classified for acute oral toxicity according to the CLP Regulation.

In an acute dermal toxicity study, four albino rabbits were exposed to undiluted amyl cinnamic aldehyde at a dose level of 2000 mg/kg bw under an occlusive bandage.   None of the treated rabbits died. No clinical signs or dermal changes were observed.  All rabbits appeared normal throughout the observation period. The acute dermal LD50 was therefore found to be > 2000 mg/kg bw. The substance is not classified for acute dermal toxicity according to the CLP Regulation.

The same investigator conducted a similar study with the read across substance, hexyl cinnamaldehyde. Female albino rabbits were exposed to undiluted hexyl cinnamic aldehyde for 24 hours (area exposure of 12 cm) at doses of 1000 (1 animal), 2000 (1 animal) or 3000 (3 animals) mg/kg bw under an occlusive coverage.  Animals were observed for 7 days. No animals died at any dose level tested. Moderate erythema was seen with all compounds.  All rabbits appeared normal by the end of the test period. The acute dermal LD50 was therefore found to be > 3000 mg/kg bw. The substance is not classified for acute dermal toxicity according to the CLP Regulation.

In a limit acute inhalation toxicity study, groups of young adult Sprague-Dawley rats (5/sex)were exposed by inhalation route to aerosol of the read-across substance hexyl cinnamic aldehyde (HCA) for 4 hours (whole body) at concentration of  5.00 mg/L (nominal, corresponding to 2.12 mg/L analytical).  Animals were observed for 14days. There were no mortalities under the test conditions. The only changes that were considered possibly to be attributable to treatment were a minimal loss of body weight on the days immediately following treatment and enlarged bronchial lymph nodes at the terminal kill, multiple grey-green foci on the lungs and occasional pulmonary congestion. The acute oral LC50 of the test material was found to be >2.12 mg/L. The absence of mortality at the tested exposure level indicates that the acute LC50 is likely to be <5 mg/L; classification for acute inhalation toxicity is therefore not required according to the CLP Regulation.

Justification for selection of acute toxicity – oral endpoint

Only one study available for this endpoint

Justification for selection of acute toxicity – inhalation endpoint

Only one study available for this endpoint

Justification for selection of acute toxicity – dermal endpoint

Only one study available for this endpoint

Justification for classification or non-classification

The results of the acute oral and dermal toxicity studies performed with amyl cinnamic aldehyde do not trigger classification according to the CLP Regulation. The results of an acute inhalation toxicity study performed with the read-across substance hexyl cinnamic aldehyde similarly do not indicate classification according to the CLP Regulation and consequently no classification is proposed for inhalation toxicity hazard for amyl cinnamic aldehyde.