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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
36
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC

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:
5.25 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:
31.5 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:
medium hazard (no threshold derived)

Additional information - workers

ISOPROPYLHYDROXYLAMINE

N-isopropylhydroxylamine (IPHA) is a primary alkylhydroxylamine that has shown excellent performance as a shortstop for styrene-butadienepolymerization. It is also used as an oxygen scavenger and metal passivator to inhibit corrosion in boiler water systems.

The following DNELs were derived using ECETOC guidance document entitled, “Guidance on Assessment Factors to Derive DNELs” Final draft. March 17th 2010.

WORKER POPULATION: 

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

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

 Dose Modification:

Corrected dermal NOAEL = Oral NOAEL x Abs (oral rat)/Abs (dermal human) = [ 100%/Abs 7.4 % = 13.5]

Dermal Absorption taken from Dermwin the predicted relative dermal absorption of aqueous solution of IPHA ranged from 3.5% to 7.4%.

Therefore: 20 mg/kg/day x 13.5 = 270 mg/kg/day

Worker adjustment 7 day/week to 5 day week = 7/5

Modified Dose: (270 mg/kg/day x 7)/5 = 378mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = N/A

Intraspecies adjustment factor for the worker population = 3

Exposure Duration (Subacute study) = N/A

WorkerPopulation dermal DNEL Acute/Short-Term Exposure Systemic Effects = 378 mg/kg/day/(4*3) =31.5 mg/kg/day

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

The NOEL of 20 mg/kg was taken from a sub-chronic study to derive an inhalation DNEL/worker population.

Modification Factors:

Physiological Parameters = 0.38 m3/kg bw (See Table R. 8.2)

Inhalation adjustment = (20 mg/kg)/(0.38 m3/kg bw) = 52.6 mg/m3

Then 52.6 mg/m3x (6.7 m3/10 m3) = 35.3 mg/m3

Then (35.3 mg/m3) x (7/5) = 49.4 mg/m3

Assessment factors:

Assessment factor for route-to-route extrapolation when considering oral to inhalation. = 2

Remaining Differences = N/A

Subchronic to Acute = N/A

Intraspecies variation for the worker population = 3

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

(49.4 mg/m3)/(2 x 3) =8.2 mg/m3

 

Dermal DNEL: Long-Term worker population exposure systemic effects

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

Dose Modification:

Corrected dermal NOAEL = Oral NOAEL x Abs (oral rat)/Abs (dermal human) = [ 100%/Abs 7.4 % = 13.5]

Dermal Absorption taken from Dermwin the predicted relative dermal absorption of aqueous solution of IPHA ranged from 3.5% to 7.4%.

Therefore: 20 mg/kg/day x 13.5 = 270 mg/kg/day

Worker adjustments 7 day/week to 5 day week = 7/5

               

Modified Dose: (270 mg/kg/day) x (8/24) (7/5) = 378 mg/kg/day

Assessment factors:

Allometric scaling from rat to human = 4

Remaining Difference = N/A

Intraspecies adjustment factor for the worker population = 3

Exposure Duration (Subacute to Chronic study) = 6

Worker Population dermal DNEL Acute/Short-Term Exposure Systemic Effects = 378 mg/kg/day/(4*3*6)= 5.25 mg/kg/d

 

Inhalation DNEL: /Long-term worker population exposure systemic effects

The NOEL of 20 mg/kg was taken from a sub-chronic oral study to derive an inhalation DNEL/worker population.

Modification Factors:

Physiological Parameters = 0.38 m3/kg bw (See Table R. 8.2)

Inhalation adjustment = (20 mg/kg)/(0.38 m3/kg bw) = 52.6 mg/m3

Then 52.6 mg/m3 x (6.7 m3/10 m3) = 35.3 mg/m3

Then (35.3 mg/m3) x (7/5) =49.4 mg/m3

Assessment factors:

Assessment factor for route-to-route extrapolation when considering oral to inhalation. = 2

Remaining Differences = N/A

Subchronic to Acute = 6

Intraspecies variation for the worker population = 3

Inhalation DNEL: Acute/Short-term workerpopulation exposure systemic effects =

(49.4 mg/m3)/(2 x 3 x 6) =1.4 mg/m3

General Population - Hazard via inhalation 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

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:
no hazard identified
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

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

N-isopropylhydroxylamine (IPHA) is for used in industry as a shortstop for styrene-butadienepolymerization. It is also used as an oxygen scavenger and metal passivator to inhibit corrosion in boiler water systems. It is mainly for industrial uses and some minor professional uses. No consumer uses have been identified.

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