Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.056 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
125
Modified dose descriptor starting point:
NOAEC
Value:
882 mg/m³
Explanation for the modification of the dose descriptor starting point:
All data were based on oral repeated dose toxicity studies; there were no inhalation repeated toxicity dose studies.
AF for dose response relationship:
1
Justification:
Started from NOAEC
AF for differences in duration of exposure:
2
Justification:
Started from subchronic toxicity
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling was already applied in modification from NOAEL to NOAEC
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Default ECHA factor
AF for the quality of the whole database:
2
Justification:
Additional uncertainty by read across
AF for remaining uncertainties:
2.5
Justification:
Additional safety factor for the lower female reproductive NOAEL of 200 mg/kg based on read-across with a-methylstyrene
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
500
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
All data were based on oral repeated dose toxicity studies; there were no dermal repeated dose toxicity studies.
AF for dose response relationship:
1
Justification:
Started from NOAEL
AF for differences in duration of exposure:
2
Justification:
Started from subchronic toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA factor for rat
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Default ECHA factor
AF for the quality of the whole database:
2
Justification:
Additional uncertainty by read across
AF for remaining uncertainties:
2.5
Justification:
Additional safety factor for the lower female reproductive NOAEL of 200 mg/kg based on read-across with a-methylstyrene
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Weight of evidence for Depanol I was obtained from subchronic and chronic toxicity testing with d-limonene in rats and subchronic toxicity testing in mice. The three studies were conducted according to older standards, however in combination they covered all needed study parameters. In addition, other studies are available for d-limonene demonstrating its safety. In all studies, NOAEL was above 500 mg/kg bw, taking into account that the kidney findings in male rats were not of relevance for humans. Supporting information was also available from 6-month dog studies, confirming that the nephropathology was specific to male rats.

Two year carcinogenicity studies were available in rats and mice with d-limonene. In rats, hyperplasia and adenomas were seen in male rats associated with cytoplasmic alfa 2µ-globulin granules in the renal tubuli. In mice, no hyperplasia or tumours were observed. These findings in male rats have meanwhile been accepted not to be relevant for humans.

For the reproductive toxicity, read across from source chemical alpha-methylstyrene tested in an OECD 422 study, demonstrated systemic toxicity at 200 mg/kg bw, without reproductive toxicity. At the dose of 1000 mg/kg, maternal toxicity was more extensive, and loss of offspring in two dams and lower body weight and viability of pups were observed at 1000 mg/kg bw. These effects however were considered to be secondary to maternal systemic toxicity.

No teratogenicity was observed for source chemicals alpha-methylstyrene (in rats) and for d-limonene (in rats, mice and rabbits). Some foetal toxicity was observed with both source chemicals at maternally toxic doses in rats, which was considered a secondary effect, however in mice and rabbits there was no foetal toxicity even at maternally toxic doses. Developmental NOAEL was at least 591 mg/kg bw.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.74 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
250
Modified dose descriptor starting point:
NOAEC
Value:
435 mg/m³
Explanation for the modification of the dose descriptor starting point:
All data were based on oral repeated dose toxicity studies; there were no inhalation repeated dose toxicity studies.
AF for dose response relationship:
1
Justification:
Started from NOAEC
AF for differences in duration of exposure:
2
Justification:
Started from subchronic toxicity
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling was already applied in modification from NOAEL to NOAEC
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default ECHA factor
AF for the quality of the whole database:
2
Justification:
Additional safety factor for read-across
AF for remaining uncertainties:
2.5
Justification:
Additional safety factor for the lower female reproductive NOAEL of 200 mg/kg based on read-across with a-methylstyrene
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 000
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
All data were based on oral repeated dose toxicity studies; there were no dermal repeated dose toxicity studies.
AF for dose response relationship:
1
Justification:
Started from NOAEL
AF for differences in duration of exposure:
2
Justification:
Started from subchronic toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA factor for rat
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default ECHA factor
AF for the quality of the whole database:
2
Justification:
Additional safety factor for read-across
AF for remaining uncertainties:
2.5
Justification:
Additional safety factor for the lower female reproductive NOAEL of 200 mg/kg based on read-across with a-methylstyrene
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 000
Modified dose descriptor starting point:
NOAEL
Value:
500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
All data were based on oral repeated dose toxicity studies.
AF for dose response relationship:
1
Justification:
Started from NOAEL
AF for differences in duration of exposure:
2
Justification:
Started from subchronic toxicity
AF for interspecies differences (allometric scaling):
4
Justification:
Default ECHA factor for rat
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Default ECHA factor
AF for the quality of the whole database:
2
Justification:
Additional safety factor for read-across
AF for remaining uncertainties:
2.5
Justification:
Additional safety factor for the lower female reproductive NOAEL of 200 mg/kg based on read-across with a-methylstyrene
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Weight of evidence for Depanol I was obtained from subchronic and chronic toxicity testing with d-limonene in rats and subchronic toxicity testing in mice. The three studies were conducted according to older standards, however in combination they covered all needed study parameters. In addition, other studies are available for d-limonene demonstrating its safety. In all studies, NOAEL was above 500 mg/kg bw, taking into account that the kidney findings in male rats were not of relevance for humans. Supporting information was also available from 6-month dog studies, confirming that the nephropathology was specific to male rats.

Two year carcinogenicity studies were available in rats and mice with d-limonene. In rats, hyperplasia and adenomas were seen in male rats associated with cytoplasmic alfa 2µ-globulin granules in the renal tubuli. In mice, no hyperplasia or tumours were observed. These findings in male rats have meanwhile been accepted not to be relevant for humans.

For the reproductive toxicity, read across from source chemical alpha-methylstyrene tested in an OECD 422 study, demonstrated systemic toxicity at 200 mg/kg bw, without reproductive toxicity. At the dose of 1000 mg/kg, maternal toxicity was more extensive, and loss of offspring in two dams and lower body weight and viability of pups were observed at 1000 mg/kg bw. These effects however were considered to be secondary to maternal systemic toxicity.

No teratogenicity was observed for source chemicals alpha-methylstyrene (in rats) and for d-limonene (in rats, mice and rabbits). Some foetal toxicity was observed with both source chemicals at maternally toxic doses in rats, which was considered a secondary effect, however in mice and rabbits there was no foetal toxicity even at maternally toxic doses. Developmental NOAEL was at least 591 mg/kg bw.