Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.115 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):
25
Dose descriptor starting point:
NOAEC
DNEL value:
52.89 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
52.89 mg/m³
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
1.5 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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Worker:

Based on the available data 2-Propyn-1-ol, compd. with methyloxirane (Golpanol PAP), has to be considered as harmful if swallowed (R22 according to Directive 67/548/EEC annex VI; Cat. 4 according to EC/1271/2008) and as posing the risk of serious damage to the eye (R41; Cat. 1), respectively.

The primary routes of anticipated industrial and professional exposure are via inhalation and skin contact. In industrial settings, ingestion is not an anticipated route of exposure, but has to be considered for the general population (see below).

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (BASF, 2017) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for systemic toxicity was at 30 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 8-hour standard inhalation volume of rats versus humans, and for differences between the 8-hour inhalation volume of workers in rest versus workers in light activity, by multiplying with the corresponding factors (x 1/0.38 m³/kg/d x 6.7 m³/10 m³). The resulting corrected starting point for inhalation DNEL derivation for workers is equal to 52.89 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8  

 - Intraspecies factor: 5

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 2

Standard factor as outlined in REACh Guidance document R.8

- Dose-response: 1

Total AF = 1 x 2.5 x 5 x 2 x 1 = 25

Based on this calculation the resulting DNEL is 2.115 mg/m3

Dermal long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (BASF, 2017) was identified as the appropriate starting point for DNEL derivation for long-term exposure following dermal uptake. The NOAEL for systemic toxicity was at 30 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation. As the acute data shows that acute dermal toxicity is considerably lower than acute oral toxicity (no mortality at 2000 mg/kg after dermal exposure vs. mortality at 464 mg/kg after oral exposure) and based on the toxicokinetic assessment which came to the conclusion that dermal absorption is negligible, the NOAEL can be corrected at least by a factor of 5 based on the available data which resulted in a corrected starting point for DNEL derivation for worker of 150 mg/kg bw/day.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 4

Recommended for the rat in REACh Guidance document R.8 for allometric scaling

  - Intraspecies factor: 5

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 2

Standard factor as outlined in REACh Guidance document R.8 

- Dose-response: 1

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8

Total AF = 4 x 5 x 2 x 1 x 2.5 = 100

Based on this calculation the resulting DNEL is 1.5 mg/kg bw/day.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.521 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):
50
Dose descriptor starting point:
NOAEC
DNEL value:
26.086 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
26.086 mg/m³
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.75 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.15 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information
Explanation for the modification of the dose descriptor starting point:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion
Justification:
see discussion

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Consumer

Based on the available data 2-Propyn-1-ol, compd. with methyloxirane (Golpanol PAP), has to be considered as harmful if swallowed (R22 according to Directive 67/548/EEC annex VI; Cat. 4 according to EC/1271/2008) and as posing the risk of serious damage to the eye (R41; Cat. 1), respectively.

For the general population, all three possible routes of exposure (oral, dermal, inhalation) have to be taken into account.

Inhalation long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (BASF, 2017) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for systemic toxicity was at 30 mg/kg bw/day.

This point of departure was modified to get the correct starting point for DNEL derivation. As a first step, route-to-route extrapolation was performed as recommended in the "Guidance on information requirements and chemical safety assessment, Chapter R.8, p. 26 f.:

The oral rat NOAEL was converted into the inhalative human NOAEC corrected for differences between the 24-hour standard inhalation volume of rats versus humans by multiplying with the corresponding factor (x 1/1.15 m³/kg/d). The resulting corrected starting point for inhalation DNEL derivation for the general population is equal to 26.086 mg/m³.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 1

Besides the applied allometric scaling factors no additional interspecies factor for remaining differences has been used based on the fact that concerning inhalation, rodents like the rat are in general more sensitive compared to human as the rat's ventilation frequency is higher. Also anatomical differences as well as air flow patterns between rodents and humans have to be taken into account.

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8  

- Intraspecies factor: 10

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 2

Standard factor as outlined in REACh Guidance document R.8

- Dose-response: 1

Total AF = 1 x 2.5 x 10 x 2 x 1 = 50

Based on this calculation the resulting DNEL is 0.521 mg/m3.

Dermal long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (BASF, 2017) was identified as the appropriate starting point for DNEL derivation for long-term exposure following dermal uptake. The NOAEL for systemic toxicity was at 30 mg/kg bw/day.

This point of departure was modified to get the corrected starting point for DNEL derivation. As the acute data shows that acute dermal toxicity is considerably lower than acute oral toxicity (no mortality at 2000 mg/kg after dermal exposure vs. mortality at 464 mg/kg after oral exposure) and based on the toxicokinetic assessment which came to the conclusion that dermal absorption is negligible, the NOAEL can be corrected at least by a factor of 5 based on the available data which resulted in a corrected starting point for DNEL derivation for the general population of 150 mg/kg bw/day.

The NOAEL of 150 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. Subsequently, the following assessment factors are taken into account for the final DNEL calculation for the oral route: interspecies differences (4), remaining differences (1), intraspecies differences (10), exposure duration (2) (AF = 4 x 10 x 2 x 1 x 2.5 = 200

As a consequence, the resulting DNEL for long-term oral local and systemic effects is 0.75 mg/kg bw/d for the general population.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 4

Recommended for the rat in REACh Guidance document R.8 for allometric scaling

- Intraspecies factor: 10

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 2

Standard factor as outlined in REACh Guidance document R.8

- Dose-response: 1

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8

Oral short-term –systemic effects:

The long-term oral DNEL for systemic effects will also be sufficiently protective for short-term oral systemic effects. Furthermore, the hazard is considered low and based on the available data calculation of a meaningful DNEL is not possible. 

Oral long-term exposure – systemic effects:

The NOAEL from an oral OECD Guideline 408 study (BASF, 2017) was identified as the appropriate starting point for DNEL derivation for long-term exposure following oral uptake. The NOAEL for systemic toxicity was at 30 mg/kg bw/day.

The NOAEL of 30 mg/kg bw/day was considered appropriate as point of departure for DNEL derivation. Subsequently, the following assessment factors are taken into account for the final DNEL calculation for the oral route: interspecies differences (4), remaining differences (1), intraspecies differences (10), exposure duration (2) (AF = 4 x 10 x 2 x 1 x 2.5 = 200.

As a consequence, the resulting DNEL for long-term oral local and systemic effects is 0.15 mg/kg bw/d for the general population.

For DNEL derivation, the following assessment factors (AF) were applied to the corrected starting point:

- Interspecies factor: 4

Recommended for the rat in REACh Guidance document R.8 for allometric scaling

- Intraspecies factor: 10

Standard factor as outlined in REACh Guidance document R.8  

- Exposure duration: 2

Standard factor as outlined in REACh Guidance document R.8  

- Dose-response: 1

- Remaining differences: 2.5

Standard factor as outlined in REACh Guidance document R.8