Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
18
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
LOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 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:
350 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:
2 100 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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Worker DNELs for Nitroethane

 

The major use of nitroethane is as a chemical intermediate for the manufacture of other chemicals. Nitroethane is also used as a solvent for polymers in coatings and inks.  The predominant route of occupational exposure for nitroethane is inhalation. Products containing nitroethane are not widely used by consumers. The following DNELs were derived using ECETOC guidance document entitled, “Guidance on Assessment Factors to Derive DNELs”, Final draft. March 17th2010.

 

Inhalation DNEL: Long-term worker exposures, systemic effects.

The LOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic 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)  

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

Remaining differences = 1

LOAEL to NOAEL = 3 (based on severity of the effects)

Sub-chronic to chronic = 2

Intraspecies variation for the worker population = 3

Inhalation DNEL/long-term, systemic effects = (300 mg/m3)(6/8)(6.7/10)(1/2)(1/3)(1/3) = 8.4 mg/m3

 

Inhalation DNEL: Acute/Short-term worker exposures, systemic effects

The LOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic inhalation study to derive an inhalation DNEL/worker 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

LOAEL to NOAEL = 3 (based on slight severity of the effects)

Sub-chronic to acute = N/A

Intraspecies variation for the worker population = 3

Inhalation DNEL/short-term, systemic effects = (300 mg/m3)(6/8)(6.7/10)(1/3)(1/3) = 17 mg/m3

 

 Inhalation DNEL: Long-term worker exposures, local effects:

The NOAEC of 100 ppm (300 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)

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

Remaining differences = 1

Sub-chronic to chronic = 2

Intraspecies variation for the worker population = 3

Inhalation DNEL/long-term, local effects = (300 mg/m3)(6/8)(6.7/10)(1/2)(1/3) = 25 mg/m3

 

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

The NOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic 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) 

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

Remaining differences = 1 

Sub-chronic to acute = N/A

Intraspecies variation for the worker population = 3

Inhalation DNEL/short-term, local effects = (300 mg/m3)(6/8)(6.7/10)(1/3) = 50 mg/m3

 

Dermal DNELs:

Dermal DNELs for acute short-term local effects and long-term exposure local effects were not derived for nitroethane. No dermal studies examining the systemic toxicity of nitroethane were found. Instead a route-to-route extrapolation is used from a repeat dose oral study using 1-nitropropane as a surrogate for read across. No classification or labelling is required for skin and eye irritation or dermal toxicity since it is not irritating to the skin and the dermal LD50 is greater than 2000. Pharmacokinetic studies in monkeys indicate that 1-nitropropane is poorly absorbed from the skin (~0.12% in 72 hrs). Also, nitroethane 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: Long-term worker exposures, systemic effects.

A NOAEL from an oral 28 day study in rats exposed to 1-nitropropanewas used as a surrogate for read across to nitroethane to derive a dermal DNEL chronic /long-term exposure systemic effects.

Dose Modification:

Percutaneous absorption from non-human primate = 0.12%

Therefore: 30 mg/kg/day ÷.0012 = 25’000 mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining differences = 1

Intraspecies adjustment factor for worker population = 3

Exposure duration (From sub-acute study to Chronic) = 6

Dermal DNEL/long-term, systemic effects = 25’000 mg/kg/day/4*3*6 = 350 mg/kg/day

 

Worker Dermal DNEL: Acute/short-term worker exposure, systemic effects

A NOAEL from an oral 28 day study in rats exposed to 1-nitropropane was used as a surrogate for read across to nitroethane to derive a dermal DNEL acute/short term exposure systemic effects.

Dose Modification:

Percutaneous absorption from non-human primate = 0.12%

Therefore: 30 mg/kg/day ÷ 0.0012 = 25’000 mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining differences = 1

Intraspecies adjustment factor for worker population = 3

Exposure Duration (Subacute study) = N/A

Dermal DNEL/short-term, systemic effects = 25’000 mg/kg/day/4*3 = 2’100 mg/kg/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
LOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
75
Modified dose descriptor starting point:
LOAEC

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
10
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15 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:
210 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:
1 250 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:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General Population DNELs for Nitroethane

The major use of nitroethane is as a chemical intermediate for the manufacture of other chemicals. Nitroethane is used as a solvent for polymers in coatings and inks.  The predominant route of occupational exposure for nitroethane is inhalation. Products containing nitroethane are not widely used by consumers. The following DNELs were derived using ECETOC guidance document entitled, “Guidance on Assessment Factors to Derive DNELs”, Final draft. March 17th 2010.

 

Inhalation DNEL: Long-term general population exposure, systemic effects.

The LOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic inhalation study.

 

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

Adjustment from 5 days/week to 7 days/week = (5 days/7 days) 

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

Remaining differences = 1

LOAEL to NOAEL = 3 (based on slight severity of the effects)

Sub-chronic to chronic = 2

Intraspecies variation for the general population = 5

Inhalation DNEL/long-term, systemic= (300 mg/m3)(6/24)(5/7)(1/2)(1/3)(1/5) =2 mg/m3

 

Inhalation DNEL: Acute/Short-term general population exposure, systemic effects

The LOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic inhalation study to derive an inhalation DNEL/general population.

 

Time adjustment for 6 hr/8 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

LOAEL to NOAEL = 3 (based on slight severity of the effects)

Sub-chronic to acute = N/A

Intraspecies variation for the general population = 5

Inhalation DNEL/short-term, systemic = (300 mg/m3)(6/24)(1/5)(1/3) =5 mg/m3

 

Inhalation DNEL: Long-term general population exposure, local effects:

The NOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic inhalation study

 

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

Adjustment from 5 days/week to 7 days/week = (5 day/7 days)

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

Remaining Differences = 1

Sub-chronic to chronic = 2

Intraspecies variation for the general population = 5

Inhalation DNEL general population = (300 mg/m3)(6/24)(5/7)(1/2)(1/5) =5 mg/m3

 

Inhalation DNEL: Acute/short-term exposure, local effects

The NOAEC of 100 ppm (300 mg/m3) was taken from a sub-chronic inhalation study

 

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

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

Remaining differences = 1 

Sub-chronic to acute = N/A

Intraspecies variation for the general population = 5

Inhalation DNEL/short-term, local effects = (300 mg/m3)(6/24)(1/5) =15 mg/m3

 

Dermal DNELs:

Dermal DNELs for acute short-term local effects and long-term exposure local effects were not derived for nitroethane. No dermal studies examining the systemic toxicity of nitroethane were found. Instead a route-to-route extrapolation is used from a repeat dose oral study using 1-nitropropane as a surrogate for read across. No classification or labelling is required for skin and eye irritation or dermal toxicity since it is not irritating to the skin and the dermal LD50 is greater than 2000. Pharmacokinetic studies in monkeys indicate that 1-nitropropane is poorly absorbed from the skin (~0.12% in 72 hrs). Also, nitroethane 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: Long-term general population exposure, systemic effects.

A NOAEL from an oral 28 day study in rats exposed to 1-nitropropanewas used as a surrogate for read across to nitroethane to derive a dermal DNEL chronic /long-term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.12%

Therefore: 30 mg/kg/day ÷.0012 = 25’000 mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining differences = 1

Intraspecies adjustment factor for general population = 5

Exposure duration (from sub-acute study to chronic) = 6

 

Dermal DNEL/short-term, systemic = 25’000 mg/kg/day/4*5*6 =210 mg/kg/day

 

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

Read across to nitroethane to derive a dermal DNEL acute/short term exposure systemic effects.

 

Dose Modification:

Percutaneous absorption from non-human primate = 0.12%

Therefore: 30 mg/kg/day ÷ 0.0012 = 25’000 mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining differences = 1

Intraspecies adjustment factor for the general population = 5

Exposure duration (sub-acute study) = N/A

 

Dermal DNEL/short-term, systemic = 25’000 mg/kg/day/4*5 =1’250 mg/kg/day