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Registration Dossier
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EC number: 241-924-6 | CAS number: 18016-43-8
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 8.3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 170
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1 410.52 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:
- DNEL (Derived No Effect Level)
- Value:
- 8.3 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 170
- Dose descriptor:
- NOAEC
- 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:
- hazard unknown (no further information necessary)
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 4.7 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 170
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 800 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - workers
Worker:
Based on the available data,” oleic acid, compound with N-(2-aminoethyl)ethane-1,2-diamine”, has to be considered as irritating to the skin (R38 according to Directive 67/548/EEC annex VI; Cat. 2 according to EC/1271/2008) and as irritating to the eye (R36; Cat. 2), respectively.As no dose response information for these local effects exists, the use of protective gloves and appropriate eye protection is mandatory whenever a potential for relevant ocular or dermal exposure exists.
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 (also covers local effects):
The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (RTC, 2013) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for systemic toxicity was at 800 mg/kg bw/day. As the substance was severely irritating to the skin, an additional safety factor is applied to cover for any potentially occurring local effects on the respiratory tract (see below).
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 1410.52 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.
- Additional safety factor to cover for potential local effects (irritation) and remaining differences: 10
- Intraspecies factor: 5
Standard factor as outlined in REACh Guidance document R.8
- Exposure duration: 3.4 (Batke et.al., 2011)
Within the ERASM project, time-extrapolation factors were evaluated with the database RepDoseg that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
- Dose-response: 1
Total AF = 1 x 10 x 5 x 3.4 x 1 = 170
Based on this calculation the resulting DNEL is 8.3 mg/m³.
Dermal long-term exposure – systemic effects:
The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (RTC, 2013) was identified as the appropriate starting point for DNEL derivation for long-term dermal exposure. The NOAEL for systemic toxicity was at 800 mg/kg bw/day.
There is no data available indicating that dermal uptake is considerably lower than oral uptake. The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction.
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: 3.4 (Batke et.al., 2011)
Within the ERASM project, time-extrapolation factors were evaluated with the database RepDoseg that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
- Dose-response: 1
- Remaining differences: 2.5
Standard factor as outlined in REACh Guidance document R.8
Total AF = 4 x 5 x 3.4 x 1 x 2.5 = 170
Based on this calculation the resulting DNEL is 4.7 mg/kg bw/day.
- Batke M, Escher S, Hoffmann-Doerr S, Melber C, MessingerH, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.
- Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247-S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.
- Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.
-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.
-ECHA (2008). REACh Guidance document R.8
-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.
-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs. Technical Report No. 110, October 2010.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.04 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 340
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 695.65 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:
- DNEL (Derived No Effect Level)
- Value:
- 2.04 mg/m³
DNEL related information
- Overall assessment factor (AF):
- 340
- Dose descriptor:
- NOAEC
- 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:
- hazard unknown (no further information necessary)
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.35 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 340
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 800 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:
- low hazard (no threshold derived)
Acute/short term exposure
- Hazard assessment conclusion:
- low hazard (no threshold derived)
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.35 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- Overall assessment factor (AF):
- 340
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 800 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
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- low hazard (no threshold derived)
Additional information - General Population
Consumer
Based on the available data,” oleic acid, compound with N-(2-aminoethyl)ethane-1,2-diamine”, has to be considered as irritating to the skin (R38 according to Directive 67/548/EEC annex VI; Cat. 2 according to EC/1271/2008) and as irritating to the eye (R36; Cat. 2), respectively.As no dose response information for these local effects exists, the use of protective gloves and appropriate eye protection is mandatory whenever a potential for ocular or dermal exposure to relevant quantities exists.
For the general population, all three possible routes of exposure (oral, dermal, inhalation) have to be taken into account.
Inhalation long-term exposure – (also covers local effects):
The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (RTC, 2013) was identified as the appropriate starting point for DNEL derivation for long-term exposure following inhalation. The NOAEL for systemic toxicity was at 800 mg/kg bw/day. As the substance was severely irritating to the skin, an additional safety factor is applied to cover for any potentially occurring local effects on the respiratory tract (see below).
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 695.65 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.
- Additional safety factor to cover for potential local effects (irritation) and remaining differences: 10
- Intraspecies factor: 10
Standard factor as outlined in REACh Guidance document R.8
- Exposure duration: 3.4 (Batke et.al., 2011)
Within the ERASM project, time-extrapolation factors were evaluated with the database RepDoseg that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
- Dose-response: 1
Total AF = 1 x 10 x 10 x 3.4 x 1 = 340
Based on this calculation the resulting DNEL is 2.04 mg/m³.
Dermal long-term exposure – systemic effects:
The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (RTC, 2013) was identified as the appropriate starting point for DNEL derivation for long-term dermal exposure. The NOAEL for systemic toxicity was at 800 mg/kg bw/day.
There is no data available indicating that dermal uptake is considerably lower than oral uptake. The oral systemic long-term NOAEL was therefore considered appropriate for derivation of a dermal systemic long-term DNEL without further correction.
The NOAEL of 800 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 (3.4) (AF = 4 x 10 x 3.4 x 1 x 2.5 = 340).
As a consequence, the resulting DNEL for long-term oral local and systemic effects is 2.35 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: 3.4 (Batke et.al., 2011)
Within the ERASM project, time-extrapolation factors were evaluated with the database RepDoseg that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
- Dose-response: 1
- Remaining differences: 2.5
Standard factor as outlined in REACh Guidance document R.8
Oral long-term exposure – systemic effects:
The NOAEL from an oral OECD Guideline 422 study (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) (RTC, 2013) was identified as the appropriate starting point for DNEL derivation for long-term oral exposure. The NOAEL for systemic toxicity was at 800 mg/kg bw/day.
The NOAEL of 800 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 (3.4) (AF = 4 x 10 x 3.4 x 1 x 2.5 = 340).
As a consequence, the resulting DNEL for long-term oral local and systemic effects is 2.35 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: 3.4 (Batke et.al., 2011)
Within the ERASM project, time-extrapolation factors were evaluated with the database RepDoseg that currently contains about 670 substances and 2200 studies on repeated-dose toxicity. It has been shown that as long as the material is soluble, the sub-acute to sub-chronic factor was 1.5, rather than 3 , the sub-acute to chronic factor was 3.4 and the sub-chronic to chronic factor was 1.4 (Batke et al, 2011). In addition females were exposed for a longer period of time (at least 42 days instead of 28 days), a factor of 3.4 therefore is sufficient.
- Dose-response: 1
- Remaining differences: 2.5
Standard factor as outlined in REACh Guidance document R.8
- Batke M, Escher S, Hoffmann-Doerr S, Melber C, Messinger H, Mangelsdorf I.(2011).Evaluation of time extrapolation factors based on the database RepDose. Toxicology Letters 205 (2011) 122– 129.
- Escher S and Mangelsdorf I. (2009). Evaluation of risk assessment factors for inter-species and time-extrapolation. Toxicol Lett 189:S247-S248. 46th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden.
- Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I. (2006).REPDOSE: A database on repeated dose toxicity studies of commercial chemicals – a multifunctional tool. Regul Toxicol Pharmacol 46:202-210.
-ECETOC (2003). Contact Sensitization: classification according to potency. Technical Report No. 87, April 2003.
-ECHA (2008). REACh Guidance document R.8
-ECETOC (2003). Derivation of Assessment factors for Human Health Risk Assessment. Technical Report No. 86, February 2003.
-ECETOC (2010). Guidance on Assessment Factors to Derive DNELs.Technical Report No. 110, October 2010.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
