Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
By inhalation
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:
0.95 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
262.5
Modified dose descriptor starting point:
LOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No dermal sub-chronic/chronic study available. Dermal and oral uptake considered to be equivalent (REACH Guidance R8.4.2) so route to route extrapolation factor =1 applied.

The LOAEL in the chronic mouse study was established to be 250 mg/kg/d, based on the increase incidence in hepatocellular carcinoma with increasing beta-myrcene dose significantly higher than both the concurrent and the NTP historical control. In addition, the time to observation of first hepatocellular carcinoma was also dose-related.  In addition, beta-myrcene is not consider as a genotoxic carcinogen as it does not exert any mutagenic or clastogenic properties.

AF for dose response relationship:
3
Justification:
ECHA default assessment factor when the starting point for the DNEL calculation is a LOAEL
AF for differences in duration of exposure:
1
Justification:
ECHA default assessment factor of 1 applied for chronic.exposure
AF for interspecies differences (allometric scaling):
7
Justification:
ECHA default factor. Allometric scaling factor for mice compared to humans.
AF for other interspecies differences:
2.5
Justification:
Additional ECHA default factor of 2.5 for other interspecies differences; systemic effects.
AF for intraspecies differences:
5
Justification:
ECHA default factor
AF for the quality of the whole database:
1
Justification:
ECHA default assessment factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements.
AF for remaining uncertainties:
1
Justification:
ECHA default factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.48 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
525
Modified dose descriptor starting point:
LOAEL
DNEL value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Conservative read-across from a chronic oral gavage carcinogenicity study (NTP, 2010) in mice with beta-myrcene. the LOAEL in the chronic mouse study was established to be 250 mg/kg/d, based on the increase incidence in hepatocellular carcinoma with increasing beta-myrcene dose significantly higher than both the concurrent and the NTP historical control. In addition, the time to observation of first hepatocellular carcinoma was also dose-related.  In addition, beta-myrcene is not consider as a genotoxic carcinogen as it does not exert any mutagenic or clastogenic properties.

AF for dose response relationship:
3
Justification:
ECHA default assessment factor when the starting point for the DNEL calculation is a LOAEL.
AF for differences in duration of exposure:
2
Justification:
ECHA default assessment factor of 2 applied when extrapolating duration of exposure from sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
7
Justification:
ECHA default factor. Allometric scaling factor for mice compared to humans.
AF for other interspecies differences:
2.5
Justification:
Additional ECHA default factor of 2.5 for other interspecies differences; systemic effects.
AF for intraspecies differences:
10
Justification:
ECHA default factor for general population
AF for the quality of the whole database:
1
Justification:
ECHA default assessment factor for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements.
AF for remaining uncertainties:
1
Justification:
ECHA default factor
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