Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral route: Weight of evidence: All studies available show  oral LD50 at least equal to or higher than 2000 mg/kg bw in rats.

Acute toxicity, dermal route: Weight of evidence: All studies available show dermal LD50 equal to or higher than 5000 mg/kg bw in rabbits.

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
Study period:
1975
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
Standard acute method (limit test)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
None
Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
None
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
10 animals
Control animals:
not specified
Details on study design:
Animals were observed for mortality and clinical signs of toxicity for 14 days.
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No
Body weight:
No data
Gross pathology:
No data
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Remarks:
CLP Implementation.
Conclusions:
The oral LD50 for l-limonene is higher than 5000 mg/kg bw in rats therefore it is not classified according the CLP Regulation (EC) N° 1272/2008.
Executive summary:

In an acute oral toxicity study, 10 rats were given a single oral dose of l-limonene at 5000 mg/kg bw. Animals were then observed for mortality and clinical signs of toxicity for 14 days. No deaths and clinical signs of toxicity occurred during the observation period.

 

The oral LD50 for l-limonene is higher than 5000 mg/kg bw in rats therefore it is not classified according to the CLP Regulation (EC) N° 1272 /2008.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1972
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue for which there is available information (Klimish=4).
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See cross reference to justification of read-across.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Principles of method if other than guideline:
Not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Based on the read-across from the analogue substance d-limonene.
Interpretation of results:
GHS criteria not met
Remarks:
CLP Implementation.
Conclusions:
Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 5000 mg/kg bw in rats and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 5000 mg/kg bw in rats and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which there is available information (Klimish =4).
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See cross reference to justification of read-across.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Limit test:
no
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
5 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 4 800 - <= 6 500
Remarks on result:
other: Based on the read-across from the analogue substance d-limonene.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
6 600 mg/kg bw
Based on:
test mat.
95% CL:
>= 5 500 - <= 7 900
Remarks on result:
other: Based on the read-across from the analogue substance d-limonene.
Interpretation of results:
GHS criteria not met
Remarks:
CLP Implementation.
Conclusions:
Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 5000 mg/kg bw in mice and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 5000 mg/kg bw in mice and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which there is available information (Klimish=4).
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
See cross reference to justification of read-across.
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
4 400 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 400 - <= 5 900
Remarks on result:
other: Based on the read-across from the analogue substance d-limonene.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
5 200 mg/kg bw
Based on:
test mat.
95% CL:
>= 3 900 - <= 7 000
Remarks on result:
other: Based on the read-across from the analogue substance d-limonene.
Interpretation of results:
GHS criteria not met
Remarks:
CLP implementation.
Conclusions:
Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 2000 mg/kg bw in rats and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).
Executive summary:

Based on the read-across from the analogue substance d-limonene, the oral LD50 for l-limonene is estimated to be higher than 2000 mg/kg bw in rats and therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Several low quality (Klimish =4) studies are presented in a weight of evidence approach, results are consistent with each other and all of them lead to the same classification of the substance.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Low quality (Klimish =4) studies are presented in a weight of evidence approach, results are consistent with each other and all of them lead to the same classification of the substance.

Additional information

A weight of evidence approach was adopted with data on l-limonene and d-limonene.

The oral LD50 was found to be greater than 5000 mg/kg bw in rats for l-limonene.

Three additional studies, old and briefly described, performed with d-limonene, demonstrated oral LD50 at least higher than 4400 mg/kg bw in rats or mice.

One acute dermal toxicity study was available for each substance d-limonene and l-limonene, all showing LD50 values >5000 mg/kg bw. Although these studies were old and briefly described, they all show consistent results. Morevover, the low dermal toxicity is consistent with and confirmed by the low oral toxicity.

No study was strictly designed in order to fulfill criteria for deriving classification of the substance for acute inhalation toxicity.

Nevertheless, two tests were available performed with d-limonene and l-limonene, in which groups (4/dose) of male BALB/cA mice were exposed (head only) to vapors at concentration range of 197-1599 and 316 -2421 ppm (measured) for 30 min. These tests were designed to measure the effects of these substances on respiratory rate of mouse. Out of 56 animals studied, one died at each of the 2 highest concentrations of S-(-)-limonene concentrations, after 2 and 4 min, respectively, while one mouse exposed to 1198 ppm R-(+)-limonene died after 18 min of exposure. There was no concentration or time-dependent effect of death and none of the deaths is considered to be exposure related. Based on Haber's law, calculated values of LC50 for inhalation for 4-hour derived exposure were higher than 1.11 mg/L and 1.68 mg/L for d-limonene and l-limonene, respectively, based on the absence of treatment-related observed deaths.

For further information on read-across justification, see section 13: point "read-across approach"

Justification for classification or non-classification

Harmonized classification:

No harmonized classification for acute toxicity is available according to the Regulation (EC) No 1272/2008.

Self classification:

Oral and dermal LD50 are higher than 2000 mg/kg bw in rats and rabbits, respectively, therefore l-limonene does not need to be classified according to the CLP Regulation (1272/2008).

No acute inhalation toxcity study was available, designed specifically to address the classification purpose. Tests were available on d-limonene and l-limonene, giving possibilities to calculate LC50 value for 4-h exposure of higher than 1.11 and 1.68 mg/L, based on mortality observation following 30 minutes of exposure. Based on the absence of treatment-related deaths in these tests, and based on LD50 values showing low toxicity by oral and dermal routes, it is not deemed to be necessary to classify l-limonene for acute inhalation toxicity.