Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
21.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor starting point:
NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
72
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
500 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
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

Workers - Hazard for the eyes

Additional information - workers

The major use of 1 -nitropropane is as a chemical intermediate for the manufacture of pharmaceutical products, pesticides, surfactants and resins. Other uses include propellant fuel, gasoline additives, and solvents. The predominant route of occupational exposure for 1 -nitropropane is inhalation. Products containing 1 -nitropropane are not widely used by consumers.

 

Dermal DNELs:

 

Dermal DNELs for acute short-term local effects and long-term exposure local effects were not derived for 1-nitropropane. No dermal studies examining the systemic toxicity of 1-nitropropane were found. Instead a route-to-route extrapolation is used from a repeat dose oral study. No classification or labeling is required for 1-nitropropane since it is not irritating to the skin and the LD50> 2000. Pharmacokinetic studies in monkeys indicate that 1-nitropropane is poorly absorbed from the skin (< 0.5% in 12 hrs). Also, 1 -nitropropane is not readily absorbed through the skin and volatilizes quickly from the skin's surface. Therefore, no acute dermal DNELs for local effects are necessary for this compound.

 

The following DNELs were derived using ECETOX guidance document entitled, “Guidance on Assessment Factors to Derive DNELs” Final draft. March 17th2010

 

WORKER DNELs

 

Dermal DNEL: Acute/Short-Term worker exposure systemic effects

 

A NOAEL from a oral 28 day study in rats was used to derive a dermal DNEL acute/short term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.5%

 

Therefore: 30 mg/kg/day ÷0.005 = 6000 mg/kg/day

 

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = 1

Intraspecies adjustment factor for worker population = 3

Exposure Duration (Subacute study) = N/A

 

Worker dermal DNEL Acute/Short-Term Exposure Systemic Effects = 6000 mg/kg/day/4*3 =500 mg/kg/day

 

 

Inhalation DNEL: Acute/Short-term worker exposure systemic effects

 

The NOEC of 50 ppm (182 mg/m3) was taken from a sub-acute inhalation study to derive an inhalation DNEL general population.

 

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

Adjustment for respiration rate = 6.7 m3/10m3

Allometric Scaling factor (rat) = 1 (Not applicable when setting an inhalation DNEL from an inhalation animal study)

Remaining Differences = 1

Subacute to Acute = N/A

Intraspecies variation for the general population = 3

inhalation DNELworker population = (182 mg/m3)(6/8)(6.7/10)(1/3) =30.5 mg/m3

 

 

Inhalation DNEL: Acute/short-term worker exposures: local effects

 

The NOEC of 25 ppm (91 mg/m3) was taken from a sub-acute inhalation study

Time adjustment for 6 hr/day exposure = (6 hr/day)/(8h/day)

Adjustment for respiration rate (8 hr) = (6.7 m3)/(10 m3) 

Time Adjustment for 5 day/week worker exposure = (7 days/week)/(5 days/week)

Allometric Scaling factor (rat) = 1 (not appropriate for local effects)

Remaining Differences = 1 

Sub acute to Acute = N/A

Intraspecies variation for the worker population = 3

Inhalation DNEL worker = (91 mg/m3)(6/8)(6.7/10)(7/5)(1/3) =21.3 mg/m3

 

 

Dermal DNEL: Long Term worker exposures: systemic Effects.

 

WORKER: Dermal DNEL for Chronic/Long-Term Exposure Systemic Effects

 

A NOAEL from a oral 28 day study in rats was used to derive a dermal DNEL chronic /long-term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.5%

 

Therefore: 30 mg/kg/day ÷.005 = 6000 mg/kg/day

 

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = 1

Intraspecies adjustment factor for worker population = 3

Exposure Duration (From Subacute study to Chronic) = 6

 

Worker dermal DNEL Acute/Short-Term Exposure Systemic Effects = 6000 mg/kg/day/4*3*6 =83 mg/kg/day

 

 

Inhalation DNEL: Long-term exposure systemic effects.

 

The NOEC of 50 ppm (182 mg/m3) was taken from a sub-acute inhalation study.

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

Adjustment for respiration rate (8 hr) = (6.7 m3)/(10 m3)  

Time Adjustment for 5 day/week worker exposure = (7 days/week)/(5 days/week)

Allometric Scaling factor (rat) = 1 (not applicable when setting an inhalation DNEL from an inhalation animal study)

Remaining Differences = 1

Subacute to chronic = 6

Intraspecies variation for the worker population = 3

inhalation DNELworker = (182 mg/m3)(6/8)(6.7/10)(7/5)(1/6)(1/3) =7.1 mg/m3

 

Inhalation DNEL: Long-term Exposure local effects:

 

The NOEC of 25 ppm (91 mg/m3) was taken from a sub-acute inhalation study

Time adjustment for 6 hr/day exposure = (6 hr/day)/(8h/day)

Adjustment for respiration rate (8 hr) = (6.7 m3)/(10 m3)

Time Adjustment for 5 day/week worker exposure = (7 days/week)/(5 days/week)

Allometric Scaling factor (rat) = 1 (not appropriate for local effects)

Remaining Differences = 1

Sub acute to Chronic = 6

Intraspecies variation for the worker population = 3

Inhalation DNEL worker = (91 mg/m3)(6/8)(6.7/10)(7/5)(1/6)(1/3) =3.6 mg/m3

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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:
9.1 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:
DNEL (Derived No Effect Level)
Value:
0.76 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Dose descriptor:
NOAEC
Acute/short 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):
5
Dose descriptor starting point:
NOAEC

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
300 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:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL

General Population - Hazard for the eyes

Additional information - General Population

CONSUMER DNELs

 

Dermal DNELs:Acute short-term local effects and long term exposure local effects. were not derived for 1-nitropropane. No dermal studies examining the systemic toxicity of 1-nitropropane were found. No classification or labeling is required for 1-nitropropane since it is not irritating to the skin and the LD50> 2000. Pharmacokinetic studies in monkeys indicate that 1-nitropropane is poorly absorbed from the skin (< 0.5% in 12 hrs). Also, 1 -nitropropane is not readily absorbed through the skin and volatilizes quickly from the skin's surface. Therefore, no acute dermal DNELs for local effects are necessary for this compound.

 

Dermal DNEL: Acute/Short-Term general population exposure systemic effects

A NOAEL from an oral 28 day study in rats was used to derive a dermal DNEL acute/short term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.5%

 

Therefore: 30 mg/kg/day ÷0.005 = 6000 mg/kg/day

 

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = 1

Intraspecies adjustment factor for general population = 5

Exposure Duration (Subacute study) = N/A

 

General Population: dermal DNEL Acute/Short-Term Exposure Systemic Effects = 6000 mg/kg/day/4*5 =300 mg/kg/day

 

Inhalation DNEL: Acute/Short-term exposure systemic effects

The NOEC of 50 ppm (182 mg/m3) was taken from a sub-acute inhalation study to derive an inhalation DNEL general population.

 

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

Allometric Scaling factor (rat) = 1 (Not applicable when setting an inhalation DNEL from an inhalation animal study)

Remaining Differences = 1

Subacute to acute = N/A

Intraspecies variation for the general population = 5

inhalation DNELgeneral population = (182 mg/m3)(6/24)(1/5) =9.1 mg/m3

 

Oral DNEL: Acute/Short-term exposure systemic effects

 

The NOEL of 30 mg/kg/day was taken from a subacute oral study to derive an oral DNEL general population acute short term exposure systemic effects.

 

Allometric Scaling factor (rat) = 4

Remaining differences = 1

Intraspecies differences for general population = 5

Subacute to Acute = N/A

oral DNEL general population = (30 mg/kg/day)(1/4)(1/5) =1.5 mg/kg/day

 

 

Inhalation DNEL: Acute/short-term exposures: local effects

 

The NOEC of 25 ppm (91 mg/m3) was taken from a 28 day sub-acute inhalation study

 

Time adjustment for 6 hr/day exposure = (6 hr/day)/(24h/day)

Allometric Scaling factor (rat) = 1 (not appropriate for local effects)

Remaining Differences = 1

Subacute to Acute = N/A

Intraspecies variation for the general population = 5

inhalation DNEL general population = (91 mg/m3)(6/24)(1/5) =4.55 mg/m3

 

Dermal DNEL: Long Term general population exposures: systemic effects.

 

A NOAEL from a oral 28 day study in rats was used to derive a dermal DNEL chronic /long-term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.5%

 

Therefore: 30 mg/kg/day ÷.005 = 6000 mg/kg/day

 

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = 1

Intraspecies adjustment factor for general population = 5

Exposure Duration (From Subacute study to Chronic) = 6

 

General Population: dermal DNEL Acute/Short-Term Exposure Systemic Effects = 6000 mg/kg/day/4*5*6 =50 mg/kg/day

 

Inhalation DNEL: Long-term exposure systemic effects.

 

The NOEC of 50 ppm (182 mg/m3) was taken from a sub-acute inhalation study.

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

Allometric Scaling factor (rat) = 1 (Not applicable when setting an inhalation DNEL from an inhalation animal study)

Remaining Differences = 1

Subacute to chronic = 6

Intraspecies variation for the general population = 5

inhalation DNELgeneral population = (182 mg/m3)(6/24)(1/6)(1/5) =1.5 mg/m3

 

Oral DNEL: Long-term, Exposure systemic effects

 

The NOEL of 30 mg/kg/day was taken from a subacute oral study

Allometric Scaling factor (rat) = 4

Remaining differences = 1

Intraspecies differences for general population = 5

Subacute to Chronic study = 6

oral DNEL gen pop = (30 mg/kg/day)(1/4)(1/6)(1/5) =0.25 mg/kg/day

 

Inhalation DNEL: Long-term Exposure local effects

 

The NOEC of 25 ppm (91 mg/m3) was taken from a 28 day sub-acute inhalation study

 

Time adjustment for 6 hr/day exposure = (6 hr/day)/(24h/day)

Allometric Scaling factor (rat) = 1 (not appropriate for local effects)

Remaining Differences = 1

Subacute to Chronic = 6

Intraspecies variation for the general population = 5

inhalation DNEL general population = (91 mg/m3)(6/24)(1/6)(1/5) =0.76 mg/m3