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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
18
Dose descriptor starting point:
NOAEC
Value:
550 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
276.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Adjustment factor for 6 hr/day exposure to 8 hour day = (6 h/d)/(8 h/d) 

 

 Inhalation rate adjustment = 6.7 m3for 8 hr/10 m3for 8 hr. 

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
92.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEC
Value:
550 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
276.4 mg/m³
Explanation for the modification of the dose descriptor starting point:

Adjustment factor for 6 hr/day exposure to 8 hour day = (6 h/d)/(8 h/d) 

 

 Inhalation rate adjustment = 6.7 m3for 8 hr/10 m3for 8 hr. 

AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
1
Justification:
Does not apply
AF for other interspecies differences:
1
Justification:
Not applicable
AF for intraspecies differences:
3
Justification:
Standard assessment factor for the worker population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
27
Dose descriptor:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.6 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
Overall assessment factor (AF):
9
Dose descriptor starting point:
LOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11.4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
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:
1.1 mg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
other: NOAEL
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

WORKER DNEL CALCULATIONS FOR DETA

 

For occupational exposures, diethylene triamine (DETA) is produced, distributed, stored and consumed in a closed system. Workers may be exposed to DETA during certain operations such as maintenance, transfer, or sampling. DETA has a low volatility and does not have a tendency to rapidly form vapors. The corrosivity and sensitizing potential will require workers, in such instances, to protect themselves from dermal exposure by using personal protective equipment.

DERMAL DNEL- SHORT TERM EXPOSURE SYSTEMIC EFFECTS

A dermal DNEL short term systemic effects may not be appropriate since workers diethylene triamine would be handled in closed systems. Workers who could be potential exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, we will not derive a DNEL for this endpoint. 

INHALATION DNEL-ACUTE/SHORT-TERM EXPOSURE SYSTEMIC EFFECTS

Acute inhalation studies did not demonstrate any adverse effects when rats were exposed to air saturated with DETA at ambient temperatures.

The derivation of an inhalation DNEL for acute/short term exposure systemic effects was derived from a sub-acute rat study where the NOEAL was estimated at 550 mg/m3. Exposures lasted 6 hrs/day, 5 days/week. The inhalation DNEL for acute exposures systemic effects has the following adjustments:

 

Adjustment factor for 6 hr/day exposure to 8 hour day = (6 h/d)/(8 h/d)

Inhalation rate adjustment = 6.7 m3for 8 hr/10 m3for 8 hr.

Allometric Adjustment = Does not apply

Remaining Differences = 1

Intraspecies variation for the worker population = 3

Adjustment for duration = 1

The starting point for the derivation of the inhalation DNEL is the NOEAL of 550 mg/m3

Therefore: [(550 mg/m3)(6/8)(6.7/10)]/(3) =92.1 mg/m3

 

DERMAL DNEL ACUTE/SHORT TERM EXPOSURE LOCAL EFFECTS

A dermal DNEL short term local effects for workers may not be appropriate since diethylene triamine would be handled in closed systems. Workers who could be potential exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, we will not derive a DNEL for this endpoint.  Substance is classified as H314, H317 and H318.

INHALATION DNEL ACUTE/SHORT TERM EXPOSURE LOCAL EFFECTS

The derivation for an inhalation DNEL for short-term local effects was taken from an acute inhalation study where the NOEAL was 70 mg/m3for lethality as DETA aerosol. This was considered as a LOAEL for short term local effects given observations on gross pathology on the lungs indicating some atelectasis of the lungs.

Adjustment factor for 4 hour exposure to 8 hr/day = (4 h/d)/(8 h/d)

Inhalation rate adjustment = 6.7 m3for 8 hr day/10 m3for 8 hr day

Allometric factor = Not applicable

Remaining interspecies differences = 1

Intraspecies variation for the worker population =  3

Adjustment from LOEAL to NOEAL = 3

 

Therefore: 70 mg/m3*4/8*6.7/10/(3)(3) =2.6 mg/m3  (as aerosol)

DERMAL DNEL LONG-TERM EXPOSURE SYSTEMIC EFFECTS

The derivation of an dermal DNEL for short-term and long term systemic effects for workers was derived from the chronic study where the NOEAL was achieved by painting 40 mg of DETA to an area of 12 cm2 on the back of a rat 6 days/week for the lifetime of the animal. 

 

Dose in mg/kg = 40 mg/.35 kg = 114 mg/kg

Allometric Scaling factor (rat) = 4

Remaining Differences = 1

Intraspecies variation for the worker population = 3

Adjustment for duration of exposure = 1

The calculated NOAEL (114 mg/kg/day) from a chronic rat dermal study was used as a starting point to derive the dermal DNEL.

Therefore [(114 mg/kg/day)(6/5)] /(4 x 1 x 3) = 11.4mg/kg/day

INHALATION DNEL LONG-TERM EXPOSURE SYSTEMIC EFFECTS

The derivation of an inhalation DNEL for long term exposure systemic effects was derived from a sub-acute rat study where the NOEAL was estimated at 550 mg/m3. Exposures lasted 6 hrs/ day, 5 days/week. The inhalation DNEL for long term systemic effects has the following adjustments:

 

Adjustment factor for 6 hr/day exposure to 8 hr/day = (6 h/d)(8 h/d)

Inhalation rate adjustment = 6.7 m3for 8 hr day/ 10 m3for 8 hr day

Adjustment for duration from subacute to chronic = 6

Intraspecies variation for the worker population = 3

Allometric factor = Does not apply

Remaining Differences = 1

 

The starting point for the derivation of the inhalation DNEL is the NOEAL of 550 mg/m3

Therefore: [(550 mg/m3)(6/8)(6.7/10)]/(6)(1)(3) =15.4 mg/m3

 

DERMAL DNEL LONG-TERM EXPOSURE LOCAL EFFECTS

The derivation of a dermal DNEL for acute short-term exposures local effects for workers was taken from a chronic study where the NOEAL was estimated from a skin painting study in rats where 40 mg of DETA was applied to 12 cm2 on the dorsal surface. Therefore the following adjustments apply:

 

Amount per surface area (mg/cm2) = 40 mg/12 cm2= 3.33 mg/cm2

Intra-species variation for the worker population= 3

Allometric factor = Not applicable

Remaining differences = 1

Adjustment for duration of exposure = 1

 

The starting point for the derivation of the dermal DNEL is the NOEAL of 3.33 mg/cm2

Therefore (3.33 mg/cm2)/(3) = 1.1 mg/cm2

 

INHALATION DNEL LONG-TERM EXPOSURE LOCAL EFFECTS

The derivation for a inhalation DNEL for long term local effects was taken from an acute inhalation study where the NOEAL was 70 mg/m3for lethality as DETA aerosol. This was considered as a LOAEL for short term local effects given observations on gross pathology on the lungs.

 

Adjustment factor for 4 hour exposure to 8 hr/day = (4 h/d)/(8 h/d)

Inhalation rate adjustment = 6.7 m3for 8 hr day/10 m3for 8 hr day

Adjustment from LOEAL to NOEAL = 3

Adjustment from Acute to chronic = 3

 

Local effects on the respiratory tract appear to be more related to concentration rather than duration. The 3 fold adjustment from acute to chronic (above) addresses the accumulative subclinical damage at low levels of exposure.  

 

Intraspecies variation for the worker population = 3

Allometric Adjustment = Not Applicable

Remaining Differences =  1

 

The starting point for the derivation of the inhalation DNEL is the acute inhalation NOEAL of 70 mg/m3for lethality which was taken as an acute LOAEL due to local effects on the lung.

Therefore: (70 mg/m3)(4/8)(6.7/10)/(3)(3)(3) =0.87 mg/m3 (as aerosol)

 

Skin Sensitization Potential

A DNEL for skin sensitization has not been derived. The justification is that there is a limited potential for exposures during manufacturing and use. DETA is manufacture in a closed system and personal protective equipment would be used for any worker at risk of contact. The sensitizaition potential of DETA was evaluated by the Guinea Pig Maximization Test and the LLNA. Based on the results of the LLNA, DETA is classified as a moderate sensitizer (from Table R. 8 -24 of the guidance). Therefore, risk management measures such as labeling and personal protective equipment are considered suffiicient to prevent allergic reactions in workers.

References

[1] ECETOC (2010) Guidance on Assessment Factors to Derive DNELs. Technical Report in Draft)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
27.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.88 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.88 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
exposure based waiving
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

GENERAL POPULATION DNEL CALCULATIONS FOR DETA

 

For exposures to the general population, diethylene triamine (DETA) has few uses. Consumers may be exposed to DETA infrequent and intermittent exposures through the use of epoxies.  

DERMAL DNEL- SHORT TERM EXPOSURE SYSTEMIC EFFECTS

Acute data are not available for a sound derivation of the dermal DNEL for short-term exposure systemic effects.  Therefore, the chronic study will be used. .

The derivation of a dermal DNEL for short-term exposure systemic effects for the general population was derived from the chronic study where the NOEAL was achieved by painting 40 mg of DETA to an area of 12 cm2 on the back of a rat 6 days/week for the lifetime of the animal. 

 

Dose in mg/kg = 40 mg/.35 kg = 114 mg/kg

Allometric Scaling factor (rat) = 4

Remaining Differences = 1

Intraspecies variation for the general population = 5

Adjustment for duration of exposure = 1

The calculated NOAEL (114 mg/kg/day) from a chronic rat dermal study was used as a starting point to derive the dermal DNEL.

The dermal DNEL for short-term exposure systemic effects is:

Therefore [(114 mg/kg/day)(6/7)]/(4)(5) =4.88 mg/kg bd wt

 

INHALATION DNEL-ACUTE/SHORT-TERM EXPOSURE SYSTEMIC EFFECTS

Acute inhalation studies did not demonstrate any adverse effects when rats were exposed to air saturated with DETA at ambient temperatures.

The derivation of a general population inhalation DNEL for acute/short term exposure systemic effects was derived from a sub-acute rat study where the NOEAL was estimated at 550 mg/m3. Exposures lasted 6 hrs/day, 5 days/week. The inhalation DNEL for acute exposures systemic effects has the following adjustments:

 

Adjustment factor for 6 hr/day exposure to 24 hour day = (6 h/d)/(24 h/d)

Allometric Adjustment = Does not apply

Remaining Differences = 1

Intraspecies variation for the general population = 5

Adjustment for duration = 1

The starting point for the derivation of the inhalation DNEL is the NOEAL of 550 mg/m3

Therefore: [(550 mg/m3)(6/24)]/(5) = 27.5 mg/m3

 

DERMAL DNEL LONG-TERM EXPOSURE SYSTEMIC EFFECTS

The derivation of a dermal DNEL for short-term and long term systemic effects for the general population was derived from the chronic study where the NOEAL was achieved by painting 40 mg of DETA to an area of 12 cm2 on the back of a rat 6 days/week for the lifetime of the animal. 

 

Dose in mg/kg = 40 mg/.35 kg = 114 mg/kg

Allometric Scaling factor (rat) = 4

Remaining Differences = 1

Intraspecies variation for the general population = 5

Adjustment for duration of exposure = 1

The calculated NOAEL (114 mg/kg/day) from a chronic rat dermal study was used as a starting point to derive the dermal DNEL.

Therefore [(114 mg/kg/day)(6/7)] /(4 x 5) = 4.88mg/kg/day

INHALATION DNEL LONG-TERM EXPOSURE SYSTEMIC EFFECTS

The derivation of an inhalation DNEL for long term exposure systemic effects was derived from a sub-acute rat study where the NOEAL was estimated at 550 mg/m3. Exposures lasted 6 hrs/ day, 5 days/week. The inhalation DNEL for long term systemic effects has the following adjustments:

 

Adjustment factor for 6 hr/day exposure to 24 hr/day = (6 h/d)(24 h/d) 

Adjustment for duration from subacute to chronic = 6

Intraspecies variation for the general population = 5

Allometric factor = Does not apply

Remaining Differences = 1

The starting point for the derivation of the inhalation DNEL is the NOEAL of 550 mg/m3

Therefore: [(550 mg/m3)(6/24)]/(6)(5) = 4.6mg/m3