Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
22.9 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
37.5
Modified dose descriptor starting point:
LOAEC
Value:
460 mg/m³
AF for dose response relationship:
3
Justification:
LOAEC as point of departure
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The available data support that the registered substance is not acutely toxic when administered via oral or dermal routes. Furthermore, the skin and eye irritation potential of the registered substance is minimal and the substance is not believed to be a skin sensitizer. There is no evidence of local irritation or systemic effects following long-term exposure by any route of exposure based on the available data. All available data indicate the registered substance is not genotoxic, and since there is also no evidence of cumulative toxicity, it is not expected to be carcinogenic, and it is not expected to present a reproductive or developmental toxicity hazard. Hence, this substance does not meet the classification and labelling criteria for these health endpoints as defined by EU DSD/DPD 67/548/EEC or CLP EU Regulation 1272/2008 (GHS aligned) criteria. In addition,no adverse effects were observed for the above endpoints at the highest recommended concentration/doses tested indicating the registered substance is effectively non-hazardous following long-term exposure via the oral, dermal and inhalation routes, as well as short-term exposure via the dermal and oral routes. Therefore,the following DNELs were not derived:

1) Acute/short-term exposure-systemic effects dermal

2) Acute/short-term exposure-local effects dermal

3) Acute/short-term exposure-local effects inhalation

4) Long-term exposure-systemic effects dermal

5) Long-term exposure-local effects dermal

6) Long-term exposure-local effects inhalation

7) Long-term exposure-systemic effects inhalation

 

The reported LC50 for the registered substance is below 5 mg/L and it is therefore classified as R20, Harmful if inhaled in accordance with EU Dangerous Substance Directive 67/548/EEC and as a Category 4 inhalation hazard under EU CLP regulation 1272/2008 (GHS aligned). Therefore an acute/short-term exposure-systemic effects inhalation DNEL was calculated. This DNEL was established for the effects of peak exposures as outlined in Appendix R.8-8 of the ECHA document ‘Guidance on information requirements and chemical safety assessment Chapter R.8’ (ECHA 2008)

While substance-specific information on acute inhalation toxicity is not sufficiently robust to form the basis of a DNEL, one has been developed by analogy with 1-decene dimer, hydrogenated as discussed below under the Worker Acute Inhalation DNEL and General Population Acute Inhalation DNEL section. 

 

Regulatory classification and labeling for aspiration toxicity relies on the measured or calculated kinematic viscosity of a substance rather than results from toxicological studies with animals. The reported kinematic viscosity value for the registered substance at 40 °C is 5.2 cSt. This value meets the criteria for classification for aspiration toxicity under DSD and CLP regulations. Therefore, the registered substance is classified as Xn; R65 harmful (May cause lung damage if swallowed) under EU Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway). A quantitative DNEL is neither feasible nor appropriate for this endpoint.

 

 

Worker Acute Inhalation DNEL:

This DNEL was provided in accordance with Articles 10(b) and 14(1) of the REACH regulation based on an acute inhalation hazard identified in an OECD TG 403 equivalent study. However, as noted in the ECHA DNEL guidance document (ECHA, 2008), there is no established or generally accepted methodology for calculating an acute toxicity DNEL. Therefore the following DNEL was calculated based on ECHA DNEL guidance document (ECHA, 2008), in conjunction with expert judgment.

 

Dose Descriptor

The reported LC50 for the registered substance is below 5 mg/L and the substance is therefore classified as R20, Harmful if inhaled in accordance with EU Dangerous Substance Directive 67/548/EEC and as a Category 4 inhalation hazard under EU CLP regulation 1272/2008 (GHS aligned). Therefore an acute/short-term exposure-systemic effects inhalation DNEL was calculated.   While substance-specific information on acute inhalation toxicity is not available to form the basis of a DNEL for this substance, one has been developed by analogy with a structurally analogous substance as described in section R.6.2.2.1 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’, (ECHA, 2008). As described in Chapter R.6, the known value of a property for the source chemical can be used to estimate the unknown value of the same property for the registered substance by using the endpoint value of a source chemical.   

As summarized in the acute toxicity endpoint summary of this CSR (Section 5.2.3), five studies on structurally similar substances (analogues) were used to characterize the hazards associated with acute inhalation exposure to the registered substance. Fourstudies were identified for 1-decene dimer, hydrogenated and one study was identified for 1-dodecene dimer, hydrogenated. These data indicate the occurrence of mortality in rats exposed for 4 hr to test substance and together support an acute inhalation LC50 for aerosol exposure to the registered substance in the range above 1mg/L and below 5mg/L. In the studies where more detailed pathology observations were performed at concentrations close to or above the LC50, the observed mortality appears to involve localized tissue effects possibly resulting from deposition of the test material in the lungs from aerosol exposure. Localized lung inflammation and the observation of lung redness is therefore regarded as a key determinant of toxicity. No additional relevant information to help refine the point of departure could be acquired from longer-term repeat dose studies conducted at lower concentrations, as these did not report any adverse findings. Therefore an acute inhalation DNEL for workers for lung inflammation was calculated. This DNEL was established for the effects of peak exposures and therefore calculated only for a specified fraction of the daily exposure duration (15 minutes) as described in Appendix R.8-8 in the ECHA document Guidance on information requirements and chemical safety assessment Chapter R.8’ (ECHA, 2008).   Out of the available acute inhalation data, the LOAEC of 0.5 mg/L following 4h exposure of rats to the structural analogue 1-decene dimer, hydrogenated provided the basis for establishing a quantitative DNEL for the registered substance. Treatment at this dose level, the lowest tested among all five key or supporting studies, caused no mortality, though it did cause an incidence of focal lesions and redness in the lung that were observed to be dose-dependent and were prevalent in deceased animals from this and other studies upon necropsy. 1 -Decene dimer, hydrogenated is analogous to the registered substance through a number of unifying considerations including structural similarity, physical chemical properties, and manufacturing processes (as described in the read-across justification provided in the endpoint summary). Therefore, this substance serves as a reliable and adequate source chemical for calculating a quantitative DNEL for the registered substance. 

 

Modification of dose descriptor

The LOAEC of 0.5 mg/L (Exxon, 1995) was used as the dose descriptor for calculating an acute inhalation DNEL for workers. 

This dose descriptor was modified for differences in respiratory function for humans at rest and humans undertaking light work according to the guidance outlined in the ECHA document ‘Guidance on information requirements and chemical safety assessment Chapter R.8’ (ECHA, 2008).

(LC50) *(breathing rate adjustment)

0.5 mg/L*(6.7m3/10m3) =0.34 mg/L

The dose descriptor was further modified for exposure duration according to Haber’s law as advised in Appendix R.8-8 of the ECHA document “Guidance on information requirements and chemical safety assessment Chapter R.8”. The Haber’s constant was derived using 4 hr data (using the corrected dose descriptor of 0.78 mg/L) and the default regression coefficient (n) value of 3.

(c^n) x t = k

(0.34mg/L) ^3 x 4h = 0.16 mg3*h/L3

Rearranging the modified Haber's law calculation and using the constant value to derive a concentration for the 15 minute (0.25 hour) time period yields: -

(c^n) x t = k

 c = 3√ (k / t)

 c = 3√ (0.16 mg3*h/L3/ 0.25h)

 c = 0.86 mg/L

The duration of exposure of 0.25h is appropriate for the assessment of human peak exposures.

Based on this methodology, the modified dose descriptor is 0.86 mg/L

 

Assessment factor

accounting for differences in

Default value
systemic effects

Chosen values   worker

Interspecies

correction for differences in metabolic rate per body weight

AS

1

remaining differences

2.5

2.5

Intraspecies

worker

5

5

general population

10

Exposure duration

subacute to subchronic

3

1

subchronic to chronic

2

subacute to chronic

6

Dose-response

issues related to reliability of the dose-response incl. LOAEL/NOAEL extrapolation and severity of effect

1

3

Quality of database

Issues related to completeness and consistency of the available data

1

1

Issues related to the reliability of the alternative data

1

1

 

 

Total AF

37.5

 

 

Corrected LOAEC

860 mg/m3

 

 

rDNEL

22.9 mg/m3

DNELacuteInhalation: 0.86 mg/L / (37.5) = 0.0229 mg/L (22.9 mg/m3), 15 min TWA (general pop)

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.8 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
LOAEC
Value:
460
AF for dose response relationship:
3
Justification:
LOAEC as point of departure
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The available data support that the registered substance is not acutely toxic when administered via oral or dermal routes. Furthermore, the skin and eye irritation potential of the registered substance is minimal and the substance is not believed to be a skin sensitizer. There is no evidence of local irritation or systemic effects following long-term exposure by any route of exposure based on the available data. All available data indicate the registered substance is not genotoxic, and since there is also no evidence of cumulative toxicity, it is not expected to be carcinogenic, and it is not expected to present a reproductive or developmental toxicity hazard. Hence, this substance does not meet the classification and labelling criteria for these health endpoints as defined by EU DSD/DPD 67/548/EEC or CLP EU Regulation 1272/2008 (GHS aligned) criteria. In addition,no adverse effects were observed for the above endpoints at the highest recommended concentration/doses tested indicating the registered substance is effectively non-hazardous following long-term exposure via the oral, dermal and inhalation routes, as well as short-term exposure via the dermal and oral routes. Therefore,the following DNELs were not derived:

1) Acute/short-term exposure-systemic effects dermal

2) Acute/short-term exposure-local effects dermal

3) Acute/short-term exposure-local effects inhalation

4) Long-term exposure-systemic effects dermal

5) Long-term exposure-local effects dermal

6) Long-term exposure-local effects inhalation

7) Long-term exposure-systemic effects inhalation

 

The reported LC50 for the registered substance is below 5 mg/L and it is therefore classified as R20, Harmful if inhaled in accordance with EU Dangerous Substance Directive 67/548/EEC and as a Category 4 inhalation hazard under EU CLP regulation 1272/2008 (GHS aligned). Therefore an acute/short-term exposure-systemic effects inhalation DNEL was calculated. This DNEL was established for the effects of peak exposures as outlined in Appendix R.8-8 of the ECHA document ‘Guidance on information requirements and chemical safety assessment Chapter R.8’ (ECHA 2008)

While substance-specific information on acute inhalation toxicity is not sufficiently robust to form the basis of a DNEL, one has been developed by analogy with 1-decene dimer, hydrogenated as discussed below under the Worker Acute Inhalation DNEL and General Population Acute Inhalation DNEL section. 

 

Regulatory classification and labeling for aspiration toxicity relies on the measured or calculated kinematic viscosity of a substance rather than results from toxicological studies with animals. The reported kinematic viscosity value for the registered substance at 40 °C is 5.2 cSt. This value meets the criteria for classification for aspiration toxicity under DSD and CLP regulations. Therefore, the registered substance is classified as Xn; R65 harmful (May cause lung damage if swallowed) under EU Dangerous Substances Directive 67/548/EEC and as Category 1 for aspiration toxicity (H304: May be fatal if swallowed and enters airway). A quantitative DNEL is neither feasible nor appropriate for this endpoint.

 

 

General Population Acute Inhalation DNEL

 This DNEL was provided in accordance with Articles 10(b) and 14(1) of the REACH regulation based on an acute inhalation hazard identified in an OECD TG 403 equivalent study. However, as noted in the ECHA DNEL guidance document (ECHA, 2008), there is no established accepted methodology for calculating an acute toxicity DNEL. Therefore the following DNEL was determined based on expert judgment in conjunction with the ECHA DNEL guidance document.

 

Dose Descriptor

The reported LC50 for the registered substance is below 5 mg/L and the substance is therefore classified as R20, Harmful if inhaled in accordance with EU Dangerous Substance Directive 67/548/EEC and as a Category 4 inhalation hazard under EU CLP regulation 1272/2008 (GHS aligned). Therefore an acute/short-term exposure-systemic effects inhalation DNEL was calculated.

 

While substance-specific information on acute inhalation toxicity is not available to form the basis of a DNEL for this substance, one has been developed by analogy with a structurally analogous substance as described in section R.6.2.2.1 of the ECHA document ‘Guidance on Information requirements and chemical safety assessment Chapter R.6: QSARS and grouping of chemicals’, (ECHA, 2008). As described in this document, the known value of a property for the source chemical can be used to estimate the unknown value of the same property for the registered substance by using the endpoint value of a source chemical. 

 

As summarized in the acute toxicity endpoint summary of this CSR (Section 5.2.3), five studies on structurally similar substances (analogues) were used to characterize the hazards associated with acute inhalation exposure to the registered substance. Fourstudies were identified for 1-decene dimer, hydrogenated and one study was identified for 1-dodecene dimer, hydrogenated. These data indicate the occurrence of mortality in rats exposed for 4 hr to test substance and together support an acute inhalation LC50 for aerosol exposure to the registered substance in the range above 1mg/L and below 5mg/L. In the studies where more detailed pathology observations were performed at concentrations close to or above the LC50, the observed mortality appears to involve localized tissue effects possibly resulting from deposition of the test material in the lungs from aerosol exposure. Localized lung inflammation and the observation of lung redness is therefore regarded as a key determinant of toxicity. No additional relevant information to help refine the point of departure could be acquired from longer-term repeat dose studies conducted at lower concentrations, as these did not report any adverse findings. Therefore an acute inhalation DNEL for workers for lung inflammation was calculated. This DNEL was established for the effects of peak exposures and therefore calculated only for a specified fraction of the daily exposure duration (15 minutes) as described in Appendix R.8-8 in the ECHA document Guidance on information requirements and chemical safety assessment Chapter R.8’ (ECHA, 2008). Out of the available acute inhalation data, the LOAEC of 0.5 mg/L following 4h exposure of rats to the structural analogue 1-decene dimer, hydrogenated provided the basis for establishing a quantitative DNEL for the registered substance. Treatment at this dose level, the lowest tested among all five key or supporting studies, caused no mortality, though it did cause an incidence of focal lesions and redness in the lung that were observed to be dose-dependent and were prevalent in deceased animals from this and other studies upon necropsy.1 -Decene dimer, hydrogenated is analogous to the registered substance through a number of unifying considerations including structural similarity, physical chemical properties, and manufacturing processes (as described in the read-across justification provided in the endpoint summary). Therefore, this substance serves as a reliable and adequate source chemical for calculating a quantitative DNEL for the registered substance. 

 

Out of the available acute inhalation data, the LOAEC of 0.46 mg/L following 4h exposure of rats to the structural analogue 1-decene dimer, hydrogenated provided the basis for establishing a quantitative DNEL for the registered substance. Treatment at this dose level, the lowest tested among all five key or supporting studies, caused no mortality, though did cause an incidence of focal lesions in the lung that were prevalent in deceased animals from other studies upon necropsy. 1-Decene dimer, hydrogenated is analogous to the registered substance through a number of unifying considerations including structural similarity, physical chemical properties, and manufacturing processes (as described in the read-across justification provided in the endpoint summary). Therefore, this substance serves as a reliable and adequate source chemical for calculating a quantitative DNEL for the registered substance. 

 

Modification of dose descriptor

The LOAEC of 0.5 mg/L (Exxon, 1995) was used as the dose descriptor for calculating an acute inhalation DNEL for the general population. 

The dose was modified for exposure duration according to Haber’s law as advised in Appendix R.8-8 of the ECHA document “Guidance on information requirements and chemical safety assessment Chapter R.8”. The Haber’s constant was derived using 4 hr data and the default regression coefficient (n) value of 3.

(c^n) x t = k

(0.5 mg/L) ^3 x 4 = 0.5 mg3*h/L3

Rearranging the modified Haber's law calculation and using the constant value to derive a concentration for the 15 minute (0.25 hour) time period yields: -

(c^n) x t = k

 c = 3√ (k / t)

 c = 3√ (0.5 mg3*h/L3/ 0.25h)

 c = 1.26 mg/L

The duration of exposure is appropriate for the assessment of human peak exposures.

Based on this methodology, the modified dose descriptor is 1.26 mg/L

 

Assessment factor

accounting for differences in

Default value
systemic effects

Chosen values -- general population

Interspecies

correction for differences in metabolic rate per body weight

AS

1

remaining differences

2.5

2.5

Intraspecies

worker

5

10

general population

10

Exposure duration

subacute to subchronic

3

1

subchronic to chronic

2

subacute to chronic

6

Dose-response

issues related to reliability of the dose-response incl. LOAEL/NOAEL extrapolation and severity of effect

1

3

Quality of database

Issues related to completeness and consistency of the available data

1

1

Issues related to the reliability of the alternative data

1

1

 

 

Total AF

75

 

 

LOAEC

500 mg/m3

 

 

Corrected LOAEC

1260 mg/m3

 

 

DNEL

16.8 mg/m3

 

 

DNELacuteInhalation: 1.26 mg/L / (75) = 0.0168 mg/L (16.8 mg/m3), 15 min TWA (general pop)