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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.8 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):
10
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study by inhalation is available. Therefore an oral-to-inhalation extrapolation is done. The default factor of 2 was included.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for time extrapolation from subchronic to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
included in route to route extrapolation
AF for intraspecies differences:
5
Justification:
default value (worker)
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
40
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No repeated dose toxicity study with dermal application is available. Therefore an oral-to-dermal extrapolation is done.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for time extrapolation from subchronic to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default value for correction for differences in metabolic rate (rat to humans)
AF for intraspecies differences:
5
Justification:
default value (worker)
AF for the quality of the whole database:
1
Justification:
GLP Guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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 considerations

The primary route of anticipated industrial exposure to the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is via skin contact. Given its low vapour pressure at room temperature, inhalation of the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is not likely to be high. However, exposition to aerosols or droplets of an inhalable size cannot be ruled out. 

 

The reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is harmful after single ingestion (Smyth et al., 1969) and corrosive after single skin contact (BASF SE, 2011). It is not possible to derive a local DNEL based on the available data. However, because of its corrosivity the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen should be attributed to the medium hazard class according to the ECHA Guidance on information requirement and chemical safety assessment, Part E: Risk Characterisation. Appropriate qualitative risk management measures and operational conditions should therefore be implemented when developing exposure scenarios.

The reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen did not show any adverse effects regarding mutagenicity.

 

Point of departure

The starting point is a NOAEL of 100 mg/kg bw/day obtained in male and non-pregnant female Wistar rats from a OECD TG 408 study (Subchronic Repeated Dose Toxicity Study) under GLP conditions (BASF SE, 2017), in which no treatment-related adverse findings were observed up to a dose level of 100 mg/kg bw/day in male animals exposed for a total of 90 days. Therefore, the NOAEL of 100 mg/kg bw/day is considered reliable for the purpose of DNEL derivation.

 

DNEL DERIVATION - WORKER

In general, the derivation of DNEL is based on the above described NOAEL, which is modified as described in R8 (ECHA, May 2008) and ECETOC Guidance on Assessment Factors to Derive DNELs (ECETOC, 2010).

 

The following factors were also taken into account:

- The conversion factors form the oral to inhalation route is 0.38 m³/kg, and exposure adaptation factor of the respiration volume for light activity 6.7 m³/10 m³;

- The intraspecies variation factor is assumed to be 5 (worker);

 

- Inhalation route – Long-term exposure (systemic)

For derivation of the worker inhalation DNEL, a route to route extrapolation of the above NOAEL was performed, and different assessment factors were applied.

NB: it is recalled that a qualitative approach has to be implemented to deal with the corrosivity of the reaction product of 2,4 -dinitrotoluene and 2,6-dinitrotoluene and hydrogen.

- Dermal route (systemic)

The DNELs for dermal long term exposure of workers are also derived from the above mentioned NOAEL.

NB: it is recalled that a qualitative approach has to be implemented to deal with the corrosivity of the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.2 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):
20
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
43.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

No repeated dose toxicity study by inhalation is available. Therefore an oral-to-inhalation extrapolation is done. The default factor of 2 was included.

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for time extrapolation from subchronic to chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
included in route to route extrapolation
AF for other interspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
GLP guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
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:
DNEL (Derived No Effect Level)
Value:
1.3 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):
80
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No repeated dose toxicity study with dermal application is available. Therefore an oral-to-dermal extrapolation is done.

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for time extrapolation from subchronic to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default value for correction for differences in metabolic rate (rat to humans)
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
GLP Guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
1.3 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):
80
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for time extrapolation from subchronic to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
default value for correction for differences in metabolic rate (rat to humans)
AF for intraspecies differences:
10
Justification:
default value (general population)
AF for the quality of the whole database:
1
Justification:
GLP Guideline study
AF for remaining uncertainties:
1
Justification:
Toxicodynamic differences between humans and rats are not assumed. Therefore the assessment factor for remaining differences is set to 1.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

General considerations

The primary route of anticipated industrial exposure to thereaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is via skin contact. Given its low vapourpressure at room temperature, inhalation of the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is not likely to be high. However, exposition to aerosols or droplets of an inhalable size cannot be ruled out. 

 

The reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen is harmful after single ingestion (Smyth et al., 1969) and corrosive after single skin contact (BASF SE, 2011). It is not possible to derive a local DNEL based on the available data. However, because of its corrosivity the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen should be attributed to the medium hazard class according to the ECHA Guidance on information requirement and chemical safety assessment, Part E: Risk Characterisation. Appropriate qualitative risk management measures and operational conditions should therefore be implemented when developing exposure scenarios.

The reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen did not show any adverse effects regarding mutagenicity.

 

Point of departure

The starting point is a NOAEL of 100 mg/kg bw/day obtained in male and non-pregnant female Wistar rats from a OECD TG 408 study (Subchronic Repeated Dose Toxicity Study) under GLP conditions (BASF SE, 2017), in which no treatment-related adverse findings were observed up to a dose level of 100 mg/kg bw/day in male animals exposed for a total of 90 days. Therefore, the NOAEL of 100 mg/kg bw/day is considered reliable for the purpose of DNEL derivation.

 

DNEL DERIVATION - General Population

In general, the derivation of DNEL is based on the above described NOAEL, which is modified as described in R8 (ECHA, May 2008) and ECETOC Guidance on Assessment Factors to Derive DNELs (ECETOC, 2010).

 

The following factors were also taken into account:

- The conversion factors form the oral to inhalation route is 1.15 m³/kg

- The intraspecies variation factor is assumed to be 10 (gernal population);

 

- Inhalation route – Long-term exposure (systemic)

For derivation of the worker inhalation DNEL, a route to route extrapolation of the above NOAEL was performed, and different assessment factors were applied.

NB: it is recalled that a qualitative approach has to be implemented to deal with the corrosivity of the reaction product of 2,4 -dinitrotoluene and 2,6-dinitrotoluene and hydrogen.

- Dermal route - Long-term exposure (systemic)

The DNELs for dermal long term exposure of workers are also derived from the above mentioned NOAEL.

NB: it is recalled that a qualitative approach has to be implemented to deal with the corrosivity of the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen.

- Oral route - Long-term exposure (systemic)

The DNELs for oral long term exposure of workers are also derived from the above mentioned NOAEL.

NB: it is recalled that a qualitative approach has to be implemented to deal with the corrosivity of the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen.