2-hexyloxyethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

18.4 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

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:

9.3 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

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

18.5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12

Modified dose descriptor starting point:

NOAEL

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Worker-DNEL short-term for the inhalation route (local): Ethylene glycol hexyl ether is not classified for acute inhalation.

 

Worker-DNEL short-term for the inhalation route (systemic): Ethylene glycol hexyl ether is not classified for acute inhalation.

 

Worker-DNEL short-term for the dermal route (local): Medium hazard due to classification as skin corrosive Cat 1B – H314: causes severe skin burns and eye damage.  ≥ 5% Cat 1B; ≥ 1% but < 5% Cat 2; < 1% not classified.

 

Worker-DNEL short-term for the dermal route (systemic): The only endpoint assessed in the acute dermal toxicity study is mortality and only limited information on sub-lethal effects can be retrieved from those studies. Therefore, the relevant dose descriptor for short-term exposure via the dermal route is the NOAEL for systemic effects of 222 mg/kg bw/day from a 2-week dermal toxicity study in rabbits. A total assessment factor of 12 to correct for inter- and intra-species differences (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive the DNEL short-term for the dermal route of 18.5 mg/kg bw/day.

 

Worker-DNEL long-term for the inhalation route (local): No local effects were observed in repeated dose inhalation studies. Therefore, the DNEL for systemic effects is considered to be protective for potential local effects.

 

Worker-DNEL long-term for the inhalation route (systemic): The relevant dose-descriptor for long-term exposure via the inhalation route is the NOAEC of 41 ppm (245 mg/m³) from a 13-week vapor inhalation study in rats. The only test substance-related effect observed in this study was a dose-dependent increase in liver weights which was not reversed after 4 weeks of recovery in animals exposed to 71 ppm. No effects on red blood cells or histologic changes in the liver or kidney were noted up to the highest concentration tested (71 ppm or 425 mg/m3). Therefore, the NOAEC of 41 ppm has been used as the critical dose descriptor to derive the DNEL. This value has been corrected for exposure duration and a total assessment factor of 10 (according to the ECHA Guidance Document, Chapter R.8) has been applied to correct for intra-species differences and for extrapolating from sub-chronic to chronic exposure. The resulting DNEL long-term for the inhalation route is 3.1 ppm (18.4 mg/m³).

 

Worker-DNEL long-term for the dermal route (local): Medium hazard due to classification as skin corrosive Cat 1B – H314: causes severe skin burns and eye damage.  ≥ 5% Cat 1B; ≥ 1% but < 5% Cat 2; < 1% not classified.

 

Worker-DNEL long-term for the dermal route (systemic): The relevant dose descriptor for long-term exposure via the dermal route is the NOAEL for systemic effects of 222 mg/kg bw/day from a 2-week dermal toxicity study in rabbits. In this study no overt indications of treatment-related toxicity were observed up to the highest dose level of 444 mg/kg bw/day. However, two females of the high dose group died and the cause of death could not be determined from the evaluations performed in this study. The death may have resulted from stress due to the skin irritation and dosing procedures used. A total assessment factor of 24 to correct for inter- and intra-species differences (according to the ECHA Guidance Document, Chapter R.8) and for exposure duration has been applied to derive the DNEL long-term for the dermal route of 9.3 mg/kg bw/day. The use of a reducedassessment factor of 2 for exposure duration can be justified based on the ECETOC report (2010) on DNEL derivation which 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. For ethylene glycol hexyl ether, a 14-day and a 90-day inhalation study in rats are available. Both studies show similar effects and a similar NOAEC was identified in both studies.As no difference was observed in the NOAEC from sub-acute to sub-chronic study a reduced assessment factor of 2 is considered to be sufficiently protective to correct for exposure duration from a sub-acute study to chronic exposure.

Worker-Eye Exposure: Medium hazard due to classification as Eye Damage Cat 1 – H318: causes serious eye damage.  ≥ 3% Cat 1; ≥ 1% but < 3% Cat 2; < 1% not classified.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

20

Modified dose descriptor starting point:

NOAEC

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:

4.63 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

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.24 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

80

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.49 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

General population-DNEL short-term for inhalation route (local): Ethylene glycol hexyl ether is not classified for acute inhalation.

General population-DNEL short-term for inhalation route (systemic): Ethylene glycol hexyl ether is not classified for acute inhalation.

General population-DNEL short-term for dermal route (local): Medium hazard due to classification as skin corrosive Cat 1B – H314: causes severe skin burns and eye damage.  ≥ 5% Cat 1B; ≥ 1% but < 5% Cat 2; < 1% not classified.

General population-DNEL short-term for dermal route (systemic): The only endpoint assessed in the acute dermal toxicity studies is mortality and only limited information on sub-lethal effects can be retrieved from those studies. Therefore, the relevant dose descriptor for short-term exposure via the dermal route is the NOAEL for systemic effects of 222 mg/kg bw/day from a 2-week dermal toxicity study in rabbits. A total assessment factor of 24 to correct for inter- and intra-species differences (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive the DNEL short-term for the dermal route of 9.25 mg/kg bw/day.

General population-DNEL short-term for oral route (systemic): The only endpoint assessed in the acute oral toxicity studies is mortality and only limited information on sub-lethal effects can be retrieved from those studies. No repeated dose study via the oral route is available for ethylene glycol hexyl ether. Therefore, the NOAEC of 245 mg/m3 from the 90-day inhalation study in rats has been converted into a systemic dose of 19.4 mg/kg bw and is used as critical dose descriptor to derive the long-term DNEL for oral exposure. A total assessment factor of 40 to correct for inter- and intra-species differences (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive a DNEL short-term for the oral route of 0.49 mg/kg bw/day. 

General population-DNEL long-term for inhalation route (local): No local effects were observed in repeated dose inhalation studies. Therefore, the DNEL for systemic effects is considered to be protective for potential local effects.

General population-DNEL long-term for inhalation route (systemic): The relevant dose-descriptor for long-term exposure via the inhalation route is the NOAEC of 41 ppm (245 mg/m³) from a 13-week vapor inhalation study in rats. The only test substance-related effect observed in this study was a dose-dependent increase in liver weights which was not reversed after 4 weeks of recovery in animals exposed to 71 ppm. No effects on red blood cells or histologic changes in the liver or kidney were noted up to the highest concentration tested (71 ppm or 425 mg/m3). Therefore, the NOAEC of 41 ppm has been used as the critical dose descriptor to derive the DNEL. This value has been corrected for exposure duration and a total assessment factor of 20 (according to the ECHA Guidance Document, Chapter R.8) has been applied to correct for intra-species differences and for extrapolating from sub-chronic to chronic exposure. The resulting DNEL long-term for the inhalation route is 0.5 ppm (2.9 mg/m³).

General population-DNEL long-term for dermal route (local): Medium hazard due to classification as skin corrosive Cat 1B – H314: causes severe skin burns and eye damage.  ≥ 5% Cat 1B; ≥ 1% but < 5% Cat 2; < 1% not classified.

General population-DNEL long-term for dermal route (systemic): The relevant dose descriptor for long-term exposure via the dermal route is the NOAEL for systemic effects of 222 mg/kg bw/day from a 2-week dermal toxicity study in rabbits. In this study no overt indications of treatment-related toxicity were observed up to the highest dose level of 444 mg/kg bw/day. However, two females of the high dose group died and the cause of death could not be determined from the evaluations performed in this study. The death may have resulted from stress due to the skin irritation and dosing procedures used. A total assessment factor of 48 to correct for inter- and intra-species differences (according to the ECHA Guidance Document, Chapter R.8) and for exposure duration has been applied to derive the DNEL long-term for the dermal route of 4.6 mg/kg bw/day. The use of a reducedassessment factor of 2 for exposure duration can be justified based on the ECETOC report (2010) on DNEL derivation which 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. For ethylene glycol hexyl ether, a 14-day and a 90-day inhalation study in rats are available. Both studies show similar effects and a similar NOAEC was identified in both studies.As no difference was observed in the NOAEC from sub-acute to sub-chronic study a reduced assessment factor of 2 is considered to be sufficiently protective to correct for exposure duration from a sub-acute study to chronic exposure.  

General population-DNEL long-term for oral route (systemic): No repeated dose study via the oral route is available for ethylene glycol hexyl ether. Therefore, the NOAEC of 245 mg/m3 from the 90-day inhalation study in rats has been converted into a systemic dose of 19.4 mg/kg bw and is used as critical dose descriptor to derive the long-term DNEL for oral exposure.A total assessment factor of 80 (according to the ECHA Guidance Document, Chapter R.8) has been applied to derive a DNEL long-term for the dermal route of 0.24 mg/kg bw/day.

General population-Eye Exposure: Medium hazard due to classification as Eye Damage Cat 1 – H318: causes serious eye damage.  ≥ 3% Cat 1; ≥ 1% but < 3% Cat 2; < 1% not classified.