2-(2-heptadec-8-enyl-2-imidazolin-1-yl)ethanol

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.46 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):

75

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

35 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point is a NOAEL of 20 mg/kg. This oral rat NOAEL was converted into human inhalatory worker NOAEC by correction for differences in exposure route (÷0.38) and respiratory rate between rat and human (*6.7/10). The corrected NOAEC for humans is 20 ÷ 0.38 * (6.7/10) = 35 mg/m3.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.

AF for differences in duration of exposure:

6

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, an assessment factor for allometric scaling should not be applied as the correction for interspecies differences has already been accounted for in the modification of the dose descriptor in regards to route-to-route extrapolation from an oral NOAEL to an inhalatory NOAEC.

AF for other interspecies differences:

2.5

Justification:

Interspecies extrapolation is treated with a factor of 2.5 for “remaining differences”.

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. This results in recommended default assessment factor of 10 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 5 is recommended.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, assessment for additional remaining uncertainties are not required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14 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):

2.5

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

35 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point is a NOAEL of 20 mg/kg. This oral rat NOAEL was converted into human inhalatory worker NOAEC by correction for differences in exposure route (1/0.38) and respiratory rate between rat and human (*6.7/10). The corrected NAEC for humans is 20 * (1/0.38) * (6.7/10) = 35 mg/m3.

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEC, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.

AF for interspecies differences (allometric scaling):

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, an assessment factor for allometric scaling should not be applied as the correction for interspecies differences has already been accounted for in the modification of the dose descriptor in regards to route-to-route extrapolation from an oral NOAEL to an inhalatory NOAEC.

AF for other interspecies differences:

2.5

Justification:

Interspecies extrapolation is treated with a factor of 2.5 for “remaining differences”.

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. This results in recommended default assessment factor of 10 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 5 is recommended.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

AF for remaining uncertainties:

0.2

Justification:

The value of 0.2 for the extrapolation of effect levels following subacute expsosure to effect levels following acute exposure is considered conservative. The principle applies for systemic effects in case of sensitisers or irritant/corrosive substances. The test substance is corrosive with an unknown threshold concentration for the induction of the effect. By ignoring the unknown risk for corrosivity, it is considered acceptable to use the data from repeated dose toxicity studies (35d (m) - 49d (f)) to derive a safe exposure dose/concentration for systemic short-tem effects.

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:

0.06 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):

300

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.

AF for differences in duration of exposure:

6

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a factor allowing for differences in the experimental exposure duration and the duration of exposure for the worker and scenario under consideration needs to be considered taking into account that a) in general the experimental NOAEL will decrease with increasing exposure times and b) other and more serious adverse effects may appear with increasing exposure times. Consequently, to end up with the most conservative DNEL for repeated dose toxicity, chronic exposure is the ‘worst case’. So, as only a sub-acute toxicity study is available, default assessment factor of 6 is to be applied, as a standard procedure.

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.25. This results in a default allometric scaling factor for the rat when compared with humans, namely 4.

AF for other interspecies differences:

2.5

Justification:

Interspecies extrapolation is treated with a factor of 2.5 for “remaining differences”.

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. This results in recommended default assessment factor of 10 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 5 is recommended.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

AF for remaining uncertainties:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, assessment for additional remaining uncertainties are not required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2 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):

10

Dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

20 mg/kg bw/day

AF for dose response relationship:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, for the dose-response relationship, consideration should be given to the uncertainties in the dose descriptor (NOAEL, benchmark dose…) as the surrogate for the true no-adverse-effect-level (NAEL). In this case the starting point for the DNEL calculation is a NOAEL, derived from a study which is of good quality and without uncertainties. Therefore the default assessment factor, as a standard procedure, is 1.

AF for interspecies differences (allometric scaling):

4

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, allometric scaling extrapolates doses according to an overall assumption that equitoxic doses (when expressed in mg/kg bw/day) scale with body weight to the power of 0.25. This results in a default allometric scaling factor for the rat when compared with humans, namely 4.

AF for other interspecies differences:

2.5

Justification:

Interspecies extrapolation is treated with a factor of 2.5 for “remaining differences”.

AF for intraspecies differences:

5

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, a default assessment factor for the general population is based on the distributions of human data for various toxicokinetic and toxicodynamic parameters. This results in recommended default assessment factor of 10 for the general population. As the worker population is more homogeneous (i.e. younger, healthier, protected from exposures), a default assessment factor of 5 is recommended.

AF for the quality of the whole database:

1

Justification:

In accordance with ECHA Guidance on information requirements and chemical safety assessment – Chapter 8: Characterisation of dose [concentration]-response for human health, the evaluation of the total toxicological database should include an assessment whether the available information as a whole meets the tonnage driven data requirements necessary to fulfil the REACH requirements, or whether there are data gaps (completeness of the database). Furthermore, the hazard data should be assessed for the reliability and consistency across different studies and endpoints and taking into account the quality of the testing method, size and power of the study design, biological plausibility, dose-response relationships and statistical association (adequacy of the database). When taking into account the standard information requirements and the completeness and consistency of the database the default assessment factor of 1, to be applied for good/standard quality of the database, is recommended.

AF for remaining uncertainties:

0.2

Justification:

The value of 0.2 for the extrapolation of effect levels following subacute expsosure to effect levels following acute exposure is considered conservative. The principle applies for systemic effects in case of sensitisers or irritant/corrosive substances. The test substance is corrosive with an unknown threshold concentration for the induction of the effect. By ignoring the unknown risk for corrosivity, it is considered acceptable to use the data from repeated dose toxicity studies (35d (m) - 49d (f)) to derive a safe exposure dose/concentration for systemic short-tem effects.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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

The acute exposure limit is derived from subacute data because local effects (corrosion of skin and airways) do not allow to derive the acute effect data without harm to the animal. Similarly, as it is justified to extrapolate subacute effect levels to chronic effect levels by applying a correction factor, it is reasonable to use the principle to extrapolate from subacute to shorter exposure periods as well. The value of 0.2 for the extrapolation of effect levels following subacute expsosure to effect levels following acute exposure is considered conservative. The principle applies for systemic effects in case of sensitisers or irritant/corrosive substances.

CAS 95-38-5 is corrosive with an unknown threshold concentration for the induction of the effect. By ignoring the unknown risk for corrosivity, it is considered acceptable to use the data from repeated dose toxicity studies (35d (m) - 49d (f)) to derive a safe exposure dose/concentration for systemic short-tem effects.

 

CAS 95-38-5 is often used in mixtures with an acidic component. CAS 95-38-5 is positively charged at neutral pH and therefore dermal penetration is low. In case exposure is to a positively charged chemical the dermal DNEL is considered to be 10x higher than the uncharged molecule in compliance with REACH guidance.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

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:

no hazard identified

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

A DNEL has not been derived for the General Population. The substance is exclusively used in industrial and professional sectors. Used substance is collected (e.g. as metal working fluid) and disposed under controlled conditions. Release to the environment is avoided by training of the workforce, handling procedures and collection of used solutions for recycling or disposal. Therefore exposure of the General Population is practically absent.