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Description of key information

Acute Oral Toxicity: LD50 = 2050 mg/Kg

Acute Dermal Toxicity: LD50 = 5000 mg/Kg

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
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
No exact guideline or method detailed in report.
GLP compliance:
not specified
Remarks:
pre-GLP report
Test type:
fixed dose procedure
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
Test material was described with the generic name "alpha-methylcinnamaldehyde". As manufactured by Innospec, the product met the criteria of > 80% trans-isomer, supporting that the test material was the isomer better described as CAS 15174-47-7.
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
Compound No. RIFM 72-257
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
1.64, 2.05, 2.56, 3.20, 5.00 g/Kg
No. of animals per sex per dose:
10 animals per dose, no sex details given
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 2 050 mg/kg bw
95% CL:
> 1.83 - < 2.27
Mortality:
On day 1 post oral exposure mortality was observed as follows:
1.64 g/Kg - 2 rats dead
2.05 g/Kg - 4 rats dead
2.56 g/Kg - 8 rats dead
3.20 g/Kg - 10 rats dead
5.00 g/Kg - 10 rats dead
Clinical signs:
The animals which died experienced sluggishness prior to death

Table 1. Distribution of Mortality

Dose

(g/Kg)

Observation Day

Mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1.64

2

0

0

0

0

0

0

0

0

0

0

0

0

0

2/10

2.05

4

0

0

0

0

0

0

0

0

0

0

0

0

0

4/10

2.56

8

0

0

0

0

0

0

0

0

0

0

0

0

0

8/10

3.20

10

0

0

0

0

0

0

0

0

0

0

0

0

0

10/10

5.00

10

0

0

0

0

0

0

0

0

0

0

0

0

0

10/10

Interpretation of results:
other: Not classified
Remarks:
Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures
Conclusions:
Based on observed mortality, the acute oral LD50 of Alpha methyl cinnamic aldehyde was determined to be 2050 mg/Kg (95% confidence interval = 1830 – 2270 mg/Kg).
Executive summary:

In a key fixed dose oral toxicity study, the test material (Alpha methyl cinnamic aldehyde) was orally administered to rats (10/dose) at doses of 1.64, 2.05, 2.56. 3.20, or 5.0 g/Kg.

 

All animals treated at ≥3.20 g/Kg died on day one. At 1.64 g/Kg, 2/10 animals died while 4/10 and 8/10 animals died post exposure to the test material at doses of 2.05 and 2.56 g/Kg, respectively.

 

The acute oral LD50 of Alpha methyl cinnamic aldehyde was therefore determined to be 2050 mg/Kg (95% confidence interval = 1830 – 2270 mg/Kg).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 050 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
No guideline or method detailed in report.
GLP compliance:
no
Remarks:
Pre-GLP study.
Test type:
fixed dose procedure
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
Test material was described with the generic name "alpha-methylcinnamaldehyde". As manufactured by Innospec, the product met the criteria of > 80% trans-isomer, supporting that the test material was the isomer better described as CAS 15174-47-7.

Compound No.: RIFM 72-257
Clear liquid
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
Not specified
Duration of exposure:
Not specified
Doses:
5 gm/Kg bw
No. of animals per sex per dose:
10 animals
Control animals:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 5000 mg/Kg bw

Table 1. Distribution of Mortality

Dose

(g/Kg)

Observation Day

Mortality

1

2

3

4

5

6

7

8

9

10

11

12

13

14

5.0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0/10

Interpretation of results:
other: Not classified
Remarks:
Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures
Conclusions:
The acute dermal LD50 of Alpha methyl cinnamic aldehyde was determined to be >5000 mg/Kg.
Executive summary:

In a key acute dermal toxicity study, the test material (Alpha methyl cinnamic aldehyde) was dermally administered to rabbits (10/dose) at a dose of 5000 mg/Kg (5 g/Kg).

 

No mortality was observed through the study period.

 

The acute dermal LD50 of Alpha methyl cinnamic aldehyde was therefore determined to be >5000 mg/Kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Additional information

Acute Oral Toxicity

In a key fixed dose oral toxicity study (Toxicological Resources, 1973a), the test material (Alpha methyl cinnamic aldehyde) was orally administered to rats (10/dose) at doses of 1.64, 2.05, 2.56. 3.20, or 5.0 g/Kg. All animals treated at ≥3.20 g/Kg died on day one. At 1.64 g/Kg, 2/10 animals died while 4/10 and 8/10 animals died post exposure to the test material at doses of 2.05 and 2.56 g/Kg, respectively. The acute oral LD50 of Alpha methyl cinnamic aldehyde was therefore determined to be 2050 mg/Kg (95% confidence interval = 1830 – 2270 mg/Kg).

Supporting oral toxicity data is also available from structural analogues cinnamic aldehyde (CAS# 104-55-2) and amyl cinnamic aldehyde (CAS# 78605-96-6).

In a supporting read across acute oral toxicity study (Jenner et al. 1964), the test material (Cinnamic aldehyde; CAS# 104-55-2) was administered via oral intubation to groups of young adult Osborne-Mendel rats (10/sex). Animals were fasted for approximately 18 hours prior to treatment and had access to water at all times. The food was replaced in cages as soon as animals received their respective doses. All animals were maintained under close observation for recording toxic signs and the time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks; in a few cases, where no acute toxic signs were seen, the animals were observed for only one week. LD50'S were computed by the method of Litchfield & Wilcoxon (1949). The acute oral LD50 of cinnamic aldehyde was determined to be 2220 mg/Kg (95% C.I: 1910 – 2600 mg/Kg).

 

In a supporting read across acute oral toxicity study (Jenner et al., 1964), the test material (Amyl cinnamic aldehyde; CAS# 78605-96-6) was administered via oral intubation to groups of young adult Osborne-Mendel rats (10/sex). Animals were fasted for approximately 18 hours prior to treatment and had access to water at all times. The food was replaced in cages as soon as animals received their respective doses. All animals were maintained under close observation for recording toxic signs and the time of death. Such observation was continued until animals appeared normal and showed weight gain. The usual observation period was 2 weeks; in a few cases, where no acute toxic signs were seen, the animals were observed for only one week. LD50'S were computed by the method of Litchfield & Wilcoxon (1949). The acute oral LD50 of amyl cinnamic aldehyde was determined to be 3730 mg/Kg (95% C.I: 3190 – 4370 mg/Kg).

Acute Dermal Toxicity

In a key acute dermal toxicity study (Toxicological Reseources, 1973b), the test material (Alpha methyl cinnamic aldehyde) was dermally administered to rabbits (10/dose) at a dose of 5000 mg/Kg (5 g/Kg). No mortality was observed through the study period. The acute dermal LD50 of Alpha methyl cinnamic aldehyde was therefore determined to be >5000 mg/Kg.

 

Supporting dermal toxicity data is also available from a structural analogue cinnamic aldehyde (CAS# 104-55-2).

 

In a peer reviewed study according to OECD guideline 402 (RCC/Notox, 1994) the acute dermal toxicity LD50 of cinnamaldehyde was deternined to be >2000mg/Kg, based on absence of mortality observed at this dose.

Acute Inhalation Toxicity

Inhalation is not the primary or secondary route of exposure. Two studies on the primary (oral) and secondary (dermal) routes of exposure are available.

Justification for classification or non-classification

Based on an acute oral LD50 of 2050 mg/Kg and an acute dermal LD50 of >5000 mg/Kg, Cyprinal (alpha methyl cinnamic aldehyde) is not classified for acute lethality by the oral or dermal routes of exposure under EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. For non-EU countries, the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) defines a fifth category for acute toxicity for chemicals with oral LD50 values between 2000 and 5000 mg/Kg bw. Based on the results of one acute oral toxicity study, alpha methyl cinnamic aldehyde meets the criteria for a Category 5 classification under UN GHS for acute oral toxicity.