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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14.81 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):
25
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
370.26 mg/m³
Explanation for the modification of the dose descriptor starting point:

Interspecies variation (rat to human) is accounted for by converting the rat NOAEL (No Observed Adverse Effect Level) to a human NAEL (No Adverse Effect Level) by applying a factor of 0.38 to account for the standard breathing volume of the rat for 8 hours, as per the ECHA Guidance (ECHA, 2012).  An additional conversion for workers of 6.7m3/10m3to account for caloric demand during light activity has been applied. The correction factors used to account for differences in the exposure conditions of experimental animals in a test study from those of human groups (EXPCOND) is 1.4 for workers (ECHA, 2012).

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
4.2 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):
100
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
420 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The correction factors used to account for differences in the exposure conditions of experimental animals in a test study from those of human groups (EXPCOND) are 1.0 for the general population and 1.4 for workers (ECHA, 2012). Correction factors of 1.0 for differences in bioavailability (ABS) are applied for the human groups, whilst those for differences in respiratory volume (sRV) and light activity at work (WORKER) are not considered appropriate

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high 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:
2.61 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):
50
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
130.44 mg/m³
Explanation for the modification of the dose descriptor starting point:

Interspecies variation (rat to human) is accounted for by converting the rat NOAEL (No Observed Adverse Effect Level) to a human NAEL (No Adverse Effect Level) by applying a factor of 0.38 to account for the standard breathing volume of the rat for 8 hours, as per the ECHA Guidance (ECHA, 2012). An additional conversion for workers of 6.7m3/10m3to account for caloric demand during light activity has been applied. The correction factors used to account for differences in the exposure conditions of experimental animals in a test study from those of human groups (EXPCOND) is 1.4 for workers (ECHA, 2012).

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
1.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The correction factors used to account for differences in the exposure conditions of experimental animals in a test study from those of human groups (EXPCOND) are 1.0 for the general population and 1.4 for workers (ECHA, 2012). Correction factors of 1.0 for differences in bioavailability (ABS) are applied for the human groups, whilst those for differences in respiratory volume (sRV) and light activity at work (WORKER) are not considered appropriate

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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):
200
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The correction factors used to account for differences in the exposure conditions of experimental animals in a test study from those of human exposure groups (EXPCOND) are 1.0 for the general population and 1.4 for workers (ECHA, 2012). Correction factors of 1.0 for differences in bioavailability (ABS) are applied for the human exposure groups, whilst those for differences in respiratory volume (sRV) and light activity at work (WORKER) are not considered appropriate.

AF for dose response relationship:
1
AF for differences in duration of exposure:
2
AF for interspecies differences (allometric scaling):
10
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

The available short- and long-term toxicological dataset for Distillation Residue Grade has been used to generate the relevant Derived No Effect Levels (DNELs) required for the risk characterisation exercise. The approach adopted is based on ECHA Guidance on information requirements and chemical safety assessment - Chapter R.8: Characterisation of dose [concentration]-response for human health (ECHA, 2012).

 

Longer-term repeated dose toxicity data are available from two studies which provide data on key target groups, namely males, unmated females, mated (pregnant) females and their offspring. Data for mated females can be used to determine if pregnant females represent a group of concern that may need to be specifically addressed in the determination of DNELs. These studies comprise:

1. An OECD TG408 Repeated Dose Oral Toxicity Study in which males and unmated females are exposed to the test substance during a 90-day period of growth and maturation

2. An OECD TG414 Prenatal Developmental Toxicity Study in which mated females are exposed to the test substance during pregnancy

Based on the available No Observed Adverse Effect Levels (NOAEL) generated from the data and the identified routes of exposure it has been concluded that no DNELacutevalues need to be derived since no acute toxicity effects have been observed in OECD studies assessing exposure via the oral and dermal routes. In order to be able to assess all potential risks to humans (in terms of the general population and workers) DNELlong-termvalues have been derived for all possible routes of exposure (i.e. oral, dermal and inhalation). The general population and worker DNELlong-termvalues for the oral route have been derived directly from the most relevant test NOAEL values. In contrast, the oral NOAEL values have been corrected to achieve the starting point values for the derivation of the dermal and inhalation DNELlong-termvalues.

 

Based on the available data the DNELs derived for systemic exposure are sufficiently precautionary to provide adequate protection for the local histopathological effects on the stomach surface identified in both the OECD studies.

In addition the NOAEL for maternal toxicity in pregnant females based on the oral route of exposure is higher than the corresponding long-term systemic toxicity for the general population indicating that they do not constitute a vulnerable population to repeated Distillation Residue Grade exposure. The absence of adverse effects on foetal development at the highest dose in the OECD TG414 study also means that the “unborn child” does not need to be considered to be a group of concern that would not be protected by DNELs derived for the general population.

These DNELs are considered to be conservative due to the use of the default assessment factors to cover issues such as interspecies differences, intraspecies differences, differences in duration of exposure, issues related to the dose-response relationship and the quality of the whole database in the absence of substance-specific data.