1-phenoxypropan-2-ol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

25.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

5

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

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:

42 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

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

Additional information - workers

No DNELs for acute exposure have been derived for phenoxypropanol (PPh) as this substance is not classified for acute toxicity by any route and no acute effects have been observed in the repeated exposure studies. Phenoxypropanol did not show any adverse effects regarding sensitisation, mutagenicity or reproductive toxicity. Therefore, no DNELs have been derived for these endpoints. No DNELs have been derived for local effects as no quantitative assessment is possible due to the lack of dose-response data for skin- and eye-irritation.

Worker-DNEL long-term for the inhalation route:

Phenoxypropanol has a very low vapour pressure (0.002 kPa at 20°C) and has a boiling point of 243°C. Therefore, it is highly unlikely that exposure of workers occurs via the inhalation route. Aerosol formation could be possible under conditions of elevated temperature. No vapour or aerosol inhalation toxicity studies have been conducted with PPh. Therefore, the NOAEL of 146 mg/kg bw/day from the 90-day oral study in rats has been used as the critical dose descriptor to derive the DNEL for inhalation exposure. The systemic NOAEL has been converted into an inhalation concentration of 129 mg/m³.An intra-species factor of 5 (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive a DNEL long-term for the inhalation route of exposure of 25.7 mg/m³. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified. No assessment factor has been applied for exposure duration as three repeated dose studies are available for the oral route which showed similar effects and resulted in similar NOAELs. As no significant difference was observed in the NOAELs from the 28-day to the 90-day oral study, no change of the NOAEL is expected going from sub-chronic to chronic exposure. The ECETOC report (2010) on DNEL derivation concludes that - for chemicals with a short half-life - the extension of the exposure duration to more than 28 days is unlikely to have a significant effect on the NOAEL.

Worker-DNEL long-term for the dermal route:

The relevant dose descriptor for long-term exposure via the dermal route is the NOAEL of 1000 mg/kg bw/day from a 28-day dermal toxicity study in rabbits. A total assessment factor of 24, based on the allometric factor of 2.4, the intra-species factor of 5 (according to the ECHA Guidance Document, Chapter R.8) and a factor of 2 for duration of the study has been applied to derive a DNEL long-term for the dermal route of exposure of 42 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified. A reduced assessment factor of 2 has been applied for exposure duration as two repeated dose studies via the dermal route are available for PPh (14-day and 28-day study) and both studies have shown similar effects and the same NOAEL. As no difference was observed in the NOAEL from the 14-day to the 28-day study, no change of the NOAEL is expected going from sub-acute to chronic exposure. The ECETOC report (2010) on DNEL derivation concludes that - for chemicals with a short half-life - the extension of the exposure duration to more than 28 days is unlikely to have a significant effect on the NOAEL. The ERASM project (Mangelsdorf et al 2010) has identified equivalent extrapolation factors for extrapolation from sub-acute to sub-chronic studies and sub-chronic to chronic studies.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

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:

21 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

48

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.65 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

No DNELs for acute exposure have been derived for phenoxypropanol (PPh) as this substance is not classified for acute toxicity by any route and no acute effects have been observed in the repeated exposure studies. Phenoxypropanol did not show any adverse effects regarding sensitisation, mutagenicity or reproductive toxicity. Therefore, no DNELs have been derived for these endpoints. No DNELs have been derived for local effects as no quantitative assessment is possible due to the lack of dose-response data for skin- and eye-irritation.

General population-DNEL long-term for inhalation route:

Phenoxypropanol has a very low vapour pressure (0.002 kPa at 20°C) and has a boiling point of 243°C. Therefore, it is highly unlikely that exposure occurs via the inhalation route. Aerosol formation could be possible under conditions of elevated temperature. However, no consumer uses of PPh under these conditions are known to us. No vapour or aerosol inhalation toxicity studies have been conducted with PPh and no DNEL for the inhalation route has been derived as inhalation exposure to PPh is unlikely.

General population-DNEL long-term for dermal route:

The relevant dose descriptor for long-term exposure via the dermal route is the NOAEL of 1000 mg/kg bw/day from a 28-day dermal toxicity study in rabbits.A total assessment factor of 48, based on the allometric factor of 2.4, the intra-species factor of 10 (according to the ECHA Guidance Document, Chapter R.8) and a factor of 2 for duration of the study has been applied to derive a DNEL long-term for the dermal route of exposure of 21 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified. A reduced assessment factor of 2 has been applied for exposure duration as two repeated dose studies via the dermal route are available for PPh (14-day and 28-day study) and both studies have shown similar effects and the same NOAEL. As no difference was observed in the NOAEL from the 14-day to the 28-day study, no change of the NOAEL is expected going from sub-acute to chronic exposure. The ECETOC report (2010) on DNEL derivation concludes that - for chemicals with a short half-life - the extension of the exposure duration to more than 28 days is unlikely to have a significant effect on the NOAEL. The ERASM project (Mangelsdorf et al 2010) has identified equivalent extrapolation factors for extrapolation from sub-acute to sub-chronic studies and sub-chronic to chronic studies.

General population-DNEL long-term for oral route:

The relevant dose descriptor for long-term exposure via the oral route is the NOAEL of 146 mg/kg bw/day from a 90-day drinking water study in rats.A total assessment factor of 40,based on the allometric factor of 4 and the intra-species factor of 10 (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive a DNEL long-term for the oral route of exposure of 3.65 mg/kg bw/day. No interspecies factor for remaining differences has been applied. According to the ECETOC report (2010) on DNEL derivation the factor for remaining differences is already covered by the allometric factor and the factor for intra-species differences. This is supported by the results of the ERASM project (Mangelsdorf et al 2010) which indicates that no additional factor for remaining differences is justified. No assessment factor has been applied for exposure duration as three repeated dose studies are available for the oral route which showed similar effects and resulted in similar NOAELs. As no significant difference was observed in the NOAELs from the 28-day to the 90-day oral study, no change of the NOAEL is expected going from sub-chronic to chronic exposure. The ECETOC report (2010) on DNEL derivation concludes that - for chemicals with a short half-life - the extension of the exposure duration to more than 28 days is unlikely to have a significant effect on the NOAEL.