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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
3.8 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEC
Value:
566.5 mg/m³
Value:
284.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL generation plugin)

AF for dose response relationship:
3
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL generation plugin)
AF for intraspecies differences:
5
Justification:
Default (DNEL generation plugin)
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.17 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Value:
350 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL generation plugin)

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL generation plugin)
AF for intraspecies differences:
5
Justification:
Default (DNEL generation plugin)
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
161 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
45

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

A. Inhalation route (long term)

Dose descriptor: 50 ppm as an inhalation NOAEC

Basis for dose descriptor: 90-day (5 days/week) inhalation study in mice

Reference: NTP, 2006, TOX-81 - Toxicity studies of alpha-pinene

Modification of dose descriptor: NOAEC mouse (mg/m3) = (NOAEC (ppm) x MW) / Vmol = (50 x 136.24) / 24.05 = 283.24 mg/m3

Corrected NOAEC inhalation worker = NOAEC mouse inhalation x (Mouse Exposure condition (6h) / Worker Exposure condition (8 h)) x (General Pop Respiratory volume (6.7 m3/person) / Worker Respiratory volume (10 m3/person)) = 283.24 x (6/8) x (6.7/10) = 142.33 mg/m3

ASSESSMENT FACTORS

AF

Rationale/Source

Interspecies

17.5

Chapter R8, ECHA

Intraspecies

5

Chapter R8, ECHA

Duration (subchronic to chronic)

2

Chapter R8, ECHA

Human Respiratory Volume / Female Mouse Respiratory Volume = 0.2 / 1.467

(With Human Respiratory Volume = 0.2 L/min/kg bw; Female Mouse Respiratory Ventilation = 2.2 L/h and female mouse BW = 0.025 kg. Thus, Female Mouse Respiratory Ventilation = 2.2 / (60 x 0.025) = 1.467 L/min/kg bw.)

0.136

 
 Total AF  23.8  

Calculation of DNEL: 142.33 / 23.8 = 5.98 mg/m3

B. Dermal Route (acute local effects)

Dose descriptor: EC3 value

Basis for dose descriptor: LLNA study in mice with beta-pinene

Reference: Pelcot, 2010, Evaluation of skin sensitization potential in mice using the local lymph node assay (LLNA)

Modification of dose descriptor: EC3 = 29 x 250 = 7250 µg/cm²

ASSESSMENT FACTORS

AF

Rationale/Source

Interspecies

1

The EC3 value has been demonstrated to closely correlate with the NOEL from human sensitization tests (Api et al., 2008)

Intraspecies

5

Chapter R8, ECHA

Vehicle or matrix effect

3

Matrix for the product not the same as the experimental conditions and may be designed to enhance penetration

Exposure considerations

 3

Taking into account site of body exposed for workers, dermal integrity, effect of occlusion and environmental conditions 
 Total AF

 45

  

Calculation of DNEL: 7250 / 45 = 161 µg/cm²

References: Api et al., Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients, 2008, Regulatory Toxicology and Pharmacology 52:3–23

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.674 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEC
Value:
566.5 mg/m³
Value:
101.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL generation plugin)

AF for dose response relationship:
3
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
2
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL generation plugin)
AF for intraspecies differences:
10
Justification:
Default (DNEL generation plugin)
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.417 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL generation plugin)

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL generation plugin)
AF for intraspecies differences:
10
Justification:
Default (DNEL generation plugin)
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
81 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
Overall assessment factor (AF):
90

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.417 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL generation plugin)

AF for dose response relationship:
1
Justification:
Default (DNEL generation plugin)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL generation plugin)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL generation plugin)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL generation plugin)
AF for intraspecies differences:
10
Justification:
Default (DNEL generation plugin)
AF for the quality of the whole database:
1
Justification:
Default (DNEL generation plugin)
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

A. Inhalation route (systemic - long term)

Dose descriptor: 50 ppm as an inhalation NOAEC

Basis for dose descriptor: 90-day(5 days/week) inhalation study in mice

Reference: NTP, 2006, TOX-81 - Toxicity studies of alpha-pinene

Modification of dose descriptor: NOAEC mouse (mg/m3) = (NOAEC (ppm) x MW) / Vmol = (50 x 136.24) / 24.05 = 283.24 mg/m3

Corrected NOAEC inhalation GP = NOAEC mouse inhalation x (Mouse Exposure condition (6 h a day and 5 days a week) x General Population Exposure condition (24 h a day and 7 days a week)) = 283,24 x (6/24) x (5/7) = 50.58 mg/ m3

ASSESSMENTFACTORS

AF

Rationale/Source

Interspecies

17.5

Chapter R8, ECHA

Intraspecies

10

Chapter R8, ECHA

Duration (subchronic to chronic)

2

Chapter R8, ECHA

Human Respiratory Volume / Female Mouse Respiratory Volume = 0.2 / 1.467

(With Human Respiratory Volume = 0.2 L/min/kg bw; Female Mouse Respiratory Ventilation = 2.2 L/h and female mouse BW = 0.025 kg. Thus, Female Mouse Respiratory Ventilation = 2.2 / (60 x 0.025) = 1.467 L/min/kg bw.)

0.136

 
 Total AF  47.6  

Calculation of DNEL: 50.58 / 47.6 = 1.06 mg/m3

B. Oral Route (systemic - long term)

Dose descriptor: 50 ppm as an inhalation NOAEC

Basis for dose descriptor: 90-day(5 days/week) inhalation study in mice

Reference: NTP, 2006, TOX-81 - Toxicity studies of alpha-pinene

Modification of dose descriptor: NOAEC mouse (mg/m3) = (NOAEC (ppm) x MW) / Vmol = (50 x 136.24) / 24.05 = 283.24 mg/m3

NOAEL mouse oral/dermal GP = NOAEC mouse inhalation x Mouse Respiratory Volume for 6 hours of exposure = 283.24 x 0.29 = 82.14 mg/kg/day

Corrected NOAEL oral/dermal GP = NOAEL mouse oral/dermal x (Exposure condition mouse (6 h per day and 5 days per week) / Exposure condition GP (24 h per day and 7 days per week) = 82.14 x (6/24) x (5/7) = 14.66 mg/ kg/ day

ASSESSMENT FACTORS

AF

Rationale/Source

Interspecies

17.5

Chapter R8, ECHA

Intraspecies

10

Chapter R8, ECHA

Duration (subchronic to chronic)

2

Chapter R8, ECHA

Human Respiratory Volume / Female Mouse Respiratory Volume = 0.2 / 1.467

(With Human Respiratory Volume = 0.2 L/min/kg bw; Female Mouse Respiratory Ventilation = 2.2 L/h and female mouse BW = 0.025 kg. Thus, Female Mouse Respiratory Ventilation = 2.2 / (60 x 0.025) = 1.467 L/min/kg bw.)

0.136

 
 Total AF  47.6  

Calculation of DNEL: 14.66 / 47.6 = 0.31 mg/kg/day

C. Dermal Route (local effects - acute)

Dose descriptor: EC3 value

Basis for dose descriptor: LLNA study in mice with beta-pinene

Reference: Pelcot, 2010, Evaluation of skin sensitization potential in mice using the local lymph node assay (LLNA)

Modification of dose descriptor:EC3 = 29 x 250 = 7250 µg/cm²

ASSESSMENT FACTORS

AF

Rationale/Source

Interspecies

1

The EC3 value has been demonstrated to closely correlate with the NOEL from human sensitization tests (Api et al., 2008)

Intraspecies

10

Chapter R8, ECHA

Vehicle or matrix effect

3

Matrix for the product not the same as the experimental conditions and may be designed to enhance penetration

Exposure considerations

 3

Taking into account site of body exposed for workers, dermal integrity, effect of occlusion and environmental conditions 
 Total AF

 90

  

Calculation of DNEL: 7250/ 90 = 81 µg/cm²

References: Api et al., Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients, 2008, Regulatory Toxicology and Pharmacology 52:3–23