Registration Dossier

Administrative data

Description of key information

The test item is not an acute toxic substance via the oral route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
No detailed information is available on the test method.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sunflower-seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20-45%
- Amount of vehicle (if gavage):0.2-0.5 mL/kg bw
- Justification for choice of vehicle: because of low solubility of the substance



Doses:
20-45% solution in the vehicle
No. of animals per sex per dose:
6 animals/sex/dose
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 15 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 4 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
The test substance had a LD50 of 4000 mg/kg bw given as a single oral dose.
Executive summary:

The study has been performed in order to describe the toxic propreties of the test substance in guinea pigs after a single dose.

Each group of 6 males and 6 females of guinea pigs were administered the substance through a stomach tube. The substance was administered in the form of a 20 - 45% solution in sunflower-seed oil (0.02 - 0.05 mL per kg bw) and a single dose was given.

The animals were observed within 15 days.

No differences in the sex sensitivity of these animals were observed. The LD50 was found to be 4000 mg/kg bw, and so the test substance can be referred to as a low-toxic compound.

According to the regulation 1272/2008 on CLP, the substance does not need to be classified as an acute toxic.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
No detailed information is available on the test method.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: White/CD-1
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sunflower-seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20-45%
- Amount of vehicle (if gavage):0.2-0.5 mL/kg bw
- Justification for choice of vehicle: because of low solubility of the substance



Doses:
20-45% solution in the vehicle
No. of animals per sex per dose:
6 animals/sex/dose
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 15 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 4 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
The test substance had a LD50 of 4000 mg/kg bw given as a single oral dose.
Executive summary:

The study has been performed to assess the toxic properties of the test substance in mice after a single dose.

Each group of 6 males and 6 females of White/CD-1 mice were administered the substance through a stomach tube. The substance was administered in the form of a 20 - 45% solution in sunflower-seed oil (0.02 - 0.05 mL per kg bw) and a single dose was given.

The animals were observed within 15 days.

No differences in the sex sensitivity of these animals were observed. The LD50 was found to be 4000 mg/kg bw, and so the test substance can be referred to as a low-toxic compound.

According to the regulation 1272/2008 on CLP, the substance does not need to be classified as an acute toxic.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No detailed information is available on the test method.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
2.56, 3.20, 4.0 and 5.0 g/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
There are no further details available.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
7 800 mg/kg bw
Based on:
test mat.
95% CL:
>= 7 410 - <= 8 190
Mortality:
2.56 g/kg bw: 0/10
3.20 g/kg bw: 2/10
4.0 g/kg bw: 7/10
5.0 g/kg bw: 9/10
Clinical signs:
The animals which died experienced sluggishness prior to death.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
The oral LD50 was 7.8 g/kg with 95% confidence limits 7.41 and 8.19 g/kg. The substance does not need to be classified according to Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

In the current study a standard acute method was used to determine the acute oral toxicity of the test item. 10 animals/dose at 2.56, 3.20, 4.0 and 5.0 g test substance/kg bw were dosed once and observed for 14 days. The respective mortalities were 0, 2, 7 and 9. The animals which died experienced sluggishness prior to death.

The oral LD50 was found to be 7.8 g/kg (95% confidence limits: 7.41 and 8.19 g/kg).

This is above the cutoff value of 2000 mg/kg bw of the CLP Regulation and therefore, the substance does not need to be classified.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
No detailed information is available on the test method.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Albino
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sunflower-seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20-45%
- Amount of vehicle (if gavage):0.2-0.5 mL/kg bw
- Justification for choice of vehicle: because of low solubility of the substance



Doses:
20-45% solution in the vehicle
No. of animals per sex per dose:
6 animals/sex/dose
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 15 days
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 4 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
The test substance had a LD50 of 4000 mg/kg bw in rats given as a single oral dose.
Executive summary:

The study has been performed to assess the toxic properties of the test substance in rats after 1 oral dose.

Each group of 6 males and 6 females of albino rats were administered the substance through a stomach tube. The substance was administered in the form of a 20 - 45% solution in sunflower-seed oil (0.02 - 0.05 mL per kg bw) and a single dose was given.

The animals were observed for 15 days.

No differences in the sex sensitivity of these animals were observed. The LD50 was found to be 4000 mg/kg bw, and so the test substance can be referred to as a low-toxic compound.

According to the regulation 1272/2008 on CLP, the substance does not need to be classified as an acute toxic.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read-across from benzyl cinnamate to ethyl cinnamate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section 13 of the IUCLID dossier.
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 426 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 936 - <= 3 023
Remarks on result:
other: Corrected for MW
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
Read-across was done from an appropriate source substance. Based on the result, and on the structural, chemical and toxicological similarities between the source and the target substance, the LD50 for the target substance was calculated to be 2426 mg/kg bw with 19/20 confidence limits of 1936 to 3023 mg/kg bw.
Executive summary:

Read across was done from an appropriate source substance. The oral LD50 of the source substance was determined in rats in an oral (gavage) acute toxicity test. No OECD guideline was followed and the study was not GLP.

The rats were fed 2.0, 2.25, 3.0 or 5.0 g/kg of the source substance dissolved in corn oil, via a rigid stomach tube. 10 animals per dose were used. Following the administration of each dose level the animals were observed for 14 days for signs of toxicity.

8/10 animals dosed with 5 g/kg died within 24 hours post-dosing, the remaining 2 showed a normal increase in body weight at the end of the 14 days observation period. All surviving animals ate well and gained body weight in a normal way.

Animals dosed with 5 g/kg bw showed CNS effects 18 hours post-dosing. Animals dosed at the three lower levels did not show any symptoms prior to death and behaved as normal laboratory animals.

The oral LD50 for the source substance was calculated to be 3.28 g/kg bw with 19/20 confidence limit of 2.62 to 4.1 g/kg bw.

Based on the result, and on the structural, chemical and toxicological similarities between source and target substance, the LD50 for the target substance was calculated to be 2426 mg/kg bw with 19/20 confidence limit of 1936 to 3023 mg/kg bw.

As the LD50 > 2,000 mg/kg bw, the test item is not to be classified as acute toxic according to the CLP regulation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 426 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

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
No data on the test method available.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
No data available.
Type of coverage:
not specified
Vehicle:
not specified
Doses:
5.00 g/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/10
Clinical signs:
none reported
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
The dermal LD50 is > 5000 mg/kg bw and therefore, the substance does not need to be classified according to CLP regulation.
Executive summary:

In the current study a standard acute method was used to determine the acute dermal toxicity of the test item, however, no data are available concerning type and duration of dermal coverage. 10 animals were dosed once and observed for 14 days.

At a dose of 5.00 g/kg bw no animal died and no clinical signs were reported.

It can be concluded that the LD50 is > 5000 mg/kg bw as at this dose 0 out of 10 animals died. This is above the cutoff value of 2000 mg/kg bw of the CLP Regulation and therefore, the substance does not need to be classified.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
Read-across from benzyl cinnamate to ethyl cinnamate is considered justified based on strong similarities with regard to chemical structure and metabolic pathways. A full read-across justification including comparison of toxicological profiles is included in section 13 of the IUCLID dossier.
Reason / purpose:
read-across source
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 217 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Corrected for MW
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008
Conclusions:
Read-across was done from an appropriate source substance. Based on the result, and on the structural, chemical and toxicological similarities between the source and target substance, the LD50 for the target substance was calculated to be > 2217 mg/kg bw.
Executive summary:

Read-across was done from an appropriate source substance. In the acute dermal toxicity study the source substance was applied once to the clipped backs of rabbits, on both abraded and intact clipped skin areas. The dose levels were 1, 2 or 3 g/kg bw. The animals were covered with a rubber sleeve which fit snuggle around the animal. The animals were placed in an animal holder and exposed for a period of 24 hours.

After the exposure period of 24 hours, the rubber sleeves were removed and the skin reactions were recorded. Each animal was thoroughly wiped down and returned to its own metabolism cage to be observed for the following 14 days.

Examination of the treated backs after 24 hours showed moderate erythema but no edema or eschar formation and 24 hours later the treated backs showed a decrease in the degree of erythema. 48 hours after exposure the treated backs were normal.

The animals consumed their daily ration, gained weight and behaved normal. No animals died during the test and the animals did not show any clinical signs of toxicity, nor any significant differences between their initial and final haematogram. From these data an LD50 > 3000 mg/kg bw for the source substance could be deduced.

Based on the result, and on the structural, chemical and toxicological similarities between the source and target substance, and taking into account the difference in molecular weight range between both substances, the LD50 for the target substance was calculated to be > 2217 mg/kg bw.

This is above the cutoff value of 2000 mg/kg bw of the CLP Regulation and therefore, the substance does not need to be classified.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 217 mg/kg bw

Additional information

Acute oral toxicity

For the acute oral toxicity endpoint there are 3 studies available, 2 studies on the test substance itself and 1 study performed with an appropriate source substance for read across.

In the first study on the test substance itself (1973), 10 animals were dosed once and observed for 14 days. The oral LD50 was found to be 7.8 g/kg bw with 95% confidence limits of 7.41 and 8.19 g/kg bw.

The second study (1973) comprises data on 3 different species. The toxic properties of the substance were assessed in albino rats, White/CD-1 mice and guinea pigs.

Groups of 6 male and 6 female animals were fed through a stomach tube. The substance was administered in the form of a 20 - 45% solution in sunflower-seed oil (0.02 - 0.05 mL per kg bw) and a single dose was given. The animals were observed for 15 days.

No differences in the sex sensitivity of these animals were observed and the LD50 was found to be 4000 mg/kg bw for all species.

The last study was done on an apprpriate read-across source substance. The oral LD50 of the source substance was determined in rats in an oral (gavage) acute toxicity test. Rats were fed 2.0, 2.25, 3.0 or 5.0 g/kg bw of the source substance dissolved in corn oil via a rigid stomach tube. 10 animals wer used per dose and were observed for 14 days.

The oral LD50 for the source substance was calculated to be 3.28 g/kg bw with 19/20 confidence limit of 2.62 to 4.1 g/kg bw.

Based on the result, and on the structural, chemical and toxicological similarities between the source and the target substance, and taking into account the difference in molecular weight between the source and target substance, the LD50 for the target substance was calculated to be 2426 mg/kg bw with 19/20 confidence limit of 1936 to 3023 mg/kg bw.

Taken together and being conservative, the LD50 of the test substance is considered to be 2426 mg/kg bw, and the test item is not to be classified as acute toxic according to the CLP regulation.

Acute dermal toxicity

For the acute dermal toxicity endpoint there are 2 studies available, 1 on the test substance itself and 1 on an appropriate source substance for read across.

In the study on the substance itself (1973) the acute dermal toxicity was tested in 10 animals which were dosed once and observed for 14 days.

At a dose of 5.00 g/kg bw no animal died and no clinical signs were reported. It can be concluded that the LD50 is > 5000 mg/kg bw as at this dose 0 out of 10 animals died.

In the study on the source substance the acute dermal toxicity was assessed by applying the source substance once to the clipped backs of rabbits, on both abraded and intact clipped skin areas. The doses used were 1, 2 or 3g/kg bw. The animals were covered with a rubber sleeve and in an animal holder exposed for 24 hours.

After exposure, the rubber sleeves were removed and the skin reactions were recorded. Each animal was thoroughly wiped down and returned to its own metabolism cage to be observed for the following 14 days.

No animals died during the test and the animals did not show any toxicity signs, and so the LD50 > 3000 mg/kg bw for the source substance.

Based on the result, and on the structural, chemical and toxicological similarities between the source and target substance, and taking into account the difference in molecular weight between the source and target substance, the LD50 for the target substance was calculated to be > 2217 mg/kg bw.

Taken together and being conservative, the LD50 of the test substance is considered to be > 2217 mg/kg bw, and the test item is not to be classified as acute toxic according to the CLP regulation.

Justification for classification or non-classification

Acute oral toxicity

According to the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) the substance is not considered to be classified as acute toxic because the LD50 is 2426 mg/kg bw, which is > 2000 mg/kg bw (Table 3.1.1).

Acute dermal toxicity

According to the EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) the substance is not considered to be classified as acute toxic because the LD50 is 2217 g/kg bw, which is > 2000 mg/kg bw (Table 3.1.1).