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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
912.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
11 400 mg/m³
Explanation for the modification of the dose descriptor starting point:

Chronic and sub-chronic dietary studies were conducted in rodents with various glycerides and fatty acids which are representative of the REVODS category members and covering the fatty acid chain length of C8 to C18. In these studies, no treatment-related effects were seen in the test animals due to supplementation of the diet with these substances and consequently, the no observed effect levels for these studies were the respective highest tested dose levels. For perspective, the highest free standing NOAEL from the long term studies is 18.5% in diet from the 47-week study with coconut oil, equivalent to 9250 mg/kg bw/day (Harkins, 1968). This NOAEL is supported by free standing NOAELs from other chronic and sub-chronic studies (Morin, 1967; Nolen, 1981; Speijers, 2009; Coquet, 1977 and Manorama and Rukmini, 1991).

The tocopherols, in general, contribute less to the composition of deodorizer distillates than the phytosterols and sterol esters. The sterols and sterol esters are generally poorly absorbed from the gastro-intestinal tract and slowly absorbed through the skin. As a result, inspite of their relative greater extent of absorption through oral well as dermal routes, overall contribution of the tocopherols to the systemic dose of the deodorizer distillates could be considered to be low. On the other hand, major constituents of the deodorizer distillates are glycerides and fatty acids of C8 to C18 chain length. Systemic absorption of the shorter chain fatty acids is greater than the longer chain counterparts. Therefore, C8-C12 fatty acids could be considered to show higher degree of systemic absorption compared to the longer chains. With this in mind, coconut oil (rich in C12 and C14 fatty acids) as a representative of the constituent glycerides, C8 -18 and C18 -unsatd.’ would be appropriate and studies conducted with coconut oil as test substance can be regarded as major contributor in the evaluation of repeated dose exposure.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
insufficient hazard data available (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:
1 300 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
64 800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Chronic and sub-chronic dietary studies were conducted in rodents with various glycerides and fatty acids which are representative of the REVODS category members and covering the fatty acid chain length of C8 to C18. In these studies, no treatment-related effects were seen in the test animals due to supplementation of the diet with these substances and consequently, the no observed effect levels for these studies were the respective highest tested dose levels. For perspective, the highest free standing NOAEL from the long term studies is 18.5% in diet from the 47-week study with coconut oil, equivalent to 9250 mg/kg bw/day (Harkins, 1968). This NOAEL is supported by free standing NOAELs from other chronic and sub-chronic studies (Morin, 1967; Nolen, 1981; Speijers, 2009; Coquet, 1977 and Manorama and Rukmini, 1991).

The tocopherols, in general, contribute less to the composition of deodorizer distillates than the phytosterols and sterol esters. The sterols and sterol esters are generally poorly absorbed from the gastro-intestinal tract and slowly absorbed through the skin. As a result, inspite of their relative greater extent of absorption through oral well as dermal routes, overall contribution of the tocopherols to the systemic dose of the deodorizer distillates could be considered to be low. On the other hand, major constituents of the deodorizer distillates are glycerides and fatty acids of C8 to C18 chain length. Systemic absorption of the shorter chain fatty acids is greater than the longer chain counterparts. Therefore, C8-C12 fatty acids could be considered to show higher degree of systemic absorption compared to the longer chains. With this in mind, coconut oil (rich in C12 and C14 fatty acids) as a representative of the constituent glycerides, C8 -18 and C18 -unsatd.’ would be appropriate and studies conducted with coconut oil as test substance can be regarded as major contributor in the evaluation of repeated dose exposure.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Not required additionally
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
136.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
3 420 mg/m³
Explanation for the modification of the dose descriptor starting point:

Chronic and sub-chronic dietary studies were conducted in rodents with various glycerides and fatty acids which are representative of the REVODS category members and covering the fatty acid chain length of C8 to C18. In these studies, no treatment-related effects were seen in the test animals due to supplementation of the diet with these substances and consequently, the no observed effect levels for these studies were the respective highest tested dose levels. For perspective, the highest free standing NOAEL from the long term studies is 18.5% in diet from the 47-week study with coconut oil, equivalent to 9250 mg/kg bw/day (Harkins, 1968). This NOAEL is supported by free standing NOAELs from other chronic and sub-chronic studies (Morin, 1967; Nolen, 1981; Speijers, 2009; Coquet, 1977 and Manorama and Rukmini, 1991).

The tocopherols, in general, contribute less to the composition of deodorizer distillates than the phytosterols and sterol esters. The sterols and sterol esters are generally poorly absorbed from the gastro-intestinal tract and slowly absorbed through the skin. As a result, inspite of their relative greater extent of absorption through oral well as dermal routes, overall contribution of the tocopherols to the systemic dose of the deodorizer distillates could be considered to be low. On the other hand, major constituents of the deodorizer distillates are glycerides and fatty acids of C8 to C18 chain length. Systemic absorption of the shorter chain fatty acids is greater than the longer chain counterparts. Therefore, C8-C12 fatty acids could be considered to show higher degree of systemic absorption compared to the longer chains. With this in mind, coconut oil (rich in C12 and C14 fatty acids) as a representative of the constituent glycerides, C8 -18 and C18 -unsatd.’ would be appropriate and studies conducted with coconut oil as test substance can be regarded as major contributor in the evaluation of repeated dose exposure.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Not required additionally, considering that the POD is a very conservative ADI
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
insufficient hazard data available (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:
462.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
46 300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Chronic and sub-chronic dietary studies were conducted in rodents with various glycerides and fatty acids which are representative of the REVODS category members and covering the fatty acid chain length of C8 to C18. In these studies, no treatment-related effects were seen in the test animals due to supplementation of the diet with these substances and consequently, the no observed effect levels for these studies were the respective highest tested dose levels. For perspective, the highest free standing NOAEL from the long term studies is 18.5% in diet from the 47-week study with coconut oil, equivalent to 9250 mg/kg bw/day (Harkins, 1968). This NOAEL is supported by free standing NOAELs from other chronic and sub-chronic studies (Morin, 1967; Nolen, 1981; Speijers, 2009; Coquet, 1977 and Manorama and Rukmini, 1991).

The tocopherols, in general, contribute less to the composition of deodorizer distillates than the phytosterols and sterol esters. The sterols and sterol esters are generally poorly absorbed from the gastro-intestinal tract and slowly absorbed through the skin. As a result, inspite of their relative greater extent of absorption through oral well as dermal routes, overall contribution of the tocopherols to the systemic dose of the deodorizer distillates could be considered to be low. On the other hand, major constituents of the deodorizer distillates are glycerides and fatty acids of C8 to C18 chain length. Systemic absorption of the shorter chain fatty acids is greater than the longer chain counterparts. Therefore, C8-C12 fatty acids could be considered to show higher degree of systemic absorption compared to the longer chains. With this in mind, coconut oil (rich in C12 and C14 fatty acids) as a representative of the constituent glycerides, C8 -18 and C18 -unsatd.’ would be appropriate and studies conducted with coconut oil as test substance can be regarded as major contributor in the evaluation of repeated dose exposure.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Not required additionally
Acute/short term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
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:
92.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
9 250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Chronic and sub-chronic dietary studies were conducted in rodents with various glycerides and fatty acids which are representative of the REVODS category members and covering the fatty acid chain length of C8 to C18. In these studies, no treatment-related effects were seen in the test animals due to supplementation of the diet with these substances and consequently, the no observed effect levels for these studies were the respective highest tested dose levels. For perspective, the highest free standing NOAEL from the long term studies is 18.5% in diet from the 47-week study with coconut oil, equivalent to 9250 mg/kg bw/day (Harkins, 1968). This NOAEL is supported by free standing NOAELs from other chronic and sub-chronic studies (Morin, 1967; Nolen, 1981; Speijers, 2009; Coquet, 1977 and Manorama and Rukmini, 1991).

The tocopherols, in general, contribute less to the composition of deodorizer distillates than the phytosterols and sterol esters. The sterols and sterol esters are generally poorly absorbed from the gastro-intestinal tract and slowly absorbed through the skin. As a result, inspite of their relative greater extent of absorption through oral well as dermal routes, overall contribution of the tocopherols to the systemic dose of the deodorizer distillates could be considered to be low. On the other hand, major constituents of the deodorizer distillates are glycerides and fatty acids of C8 to C18 chain length. Systemic absorption of the shorter chain fatty acids is greater than the longer chain counterparts. Therefore, C8-C12 fatty acids could be considered to show higher degree of systemic absorption compared to the longer chains. With this in mind, coconut oil (rich in C12 and C14 fatty acids) as a representative of the constituent glycerides, C8 -18 and C18 -unsatd.’ would be appropriate and studies conducted with coconut oil as test substance can be regarded as major contributor in the evaluation of repeated dose exposure.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
1
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
Not required additionally
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

See the discussion under worker DNEL.

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