2-piperazin-1-ylethylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

12.5

Modified dose descriptor starting point:

NOAEC

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15 µg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor:

NOAEC

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

80 µg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor starting point:

NOAEC

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.33 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

300

Dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

NOAEL used from dermal 28 day study

AF for differences in duration of exposure:

6

Justification:

Subacute to Chronic adjustment factor per guidance

AF for interspecies differences (allometric scaling):

4

Justification:

Standard adjustment factor per guidance

AF for other interspecies differences:

2.5

Justification:

Standard adjustment factor per guidance

AF for intraspecies differences:

5

Justification:

Worker population

AF for the quality of the whole database:

1

Justification:

Data base considered sufficient

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

WORKER DNELS FOR AMINOETHYL PIPERAZINE (AEP)

Most aminoethyl piperazine (AEP) is manufactured and used as an intermediate in closed systems. Workers may be exposed to AEP during certain operations such as maintenance, transfer, or sampling. AEP is not volatile and will not have a tendency to form vapors. The corrosivity and sensitizing potential will require workers, in such instances, to protect themselves from dermal exposure by using personal protective equipment.

The following DNELs were derived using ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter 8: Characterization of Dose [Concentration]-Response for Human Health, May 2008.

Worker Dermal DNEL Short- term exposure systemic effects

 

A dermal DNEL (short term systemic effect) is not appropriate since aminoethyl piperazine would be handled in closed systems. Workers who could be potentially exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, no DNEL will be derived for this endpoint. 

 

Worker Inhalation DNEL Short-Term Exposure Systemic Effects

 

The derivation for a worker inhalation DNEL for short-term exposure systemic effects was derived from an OECD 414 Prenatal Develoopmental Toxicology Study in rabbits. The dose was administered orally via gavage. The NOAEL was 75 mg/kg/day at the mid dose. Therefore, a route-to-route extrapolation was necessary to derive the inhalation DNEL.

 

Adjustment to the starting point for route-to-route extrapolation 75 mg/kg bd/day/0.38 = 197 mg/m³then 197 mg/m³x 6.7/10 = 132 mg/m³(NAEC).

 

Other adjustment factors

Subacute to chronic adjustment factor = 1

Remaining Differences = 2.5

Intraspecies differences for Workers = 5

 

Worker inhalation DNEL short-term systemic effects = 132 mg/m³/(2.5)(5) = 10.6 mg/m³

 

Worker Dermal DNEL Short-term Exposure Local Effects

A dermal DNEL (short term local effect) is not appropriate since aminoethyl piperazine would be handled in closed systems. Workers who could be potentially exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, no DNEL will be derived for this endpoint. 

Worker

Inhalation Exposure

Long-term Local Effects

The NOEC for the long-term local effects was taken from a 90 day rat inhalation study. Exposures occured 6 hrs/day, 5 days/week, for 90 days. The NOEC for local effects in the subchronic study was 0.2 mg AEP/m3. The study included a two-week probe study (used for short-term) effects. The NOEC in the probe (2 -week) study was 0.53 mg/m3.

Inhalation exposure for long-term local effects:

Adjustment for worker day:

0.2 mg/m3 x 6 hr/8 hr = 0.15 mg AEP/m3

 

Adjustment factors according to REACH guidance:

 

1 = Remaining differences

5   = Worker exposures

2   =  Subchronic to Chronic exposure

 

The resulting DNEL would be

 

(0.15 mg AEP)/(5 x 2) = 0.015 mg/m3  or 15 ug/m3.

Inhalation exposure

Short-term local effects

 

0.53 mg/m3 x 6hr/8hr = 0.4 mg AEP/m3

 

Adjustment factor according to REACH guidance:

 

1 = Remaining differences

5   = Worker exposures

 

The resulting DNEL would be:

 

(0.4 mg AEP)/(5) = 0.08 mg/m3  or 80 ug/day

Worker Dermal DNEL Long term exposure systemic effects

 

A dermal DNEL (short term systemic effect) is not appropriate since aminoethyl piperazine would be handled in closed systems. Workers who could be potentially exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, no DNEL will be derived for this endpoint. 

 

Worker Inhalation DNEL Long-Term Exposure Systemic Effects

The derivation for a worker inhalation DNEL for long-term exposure systemic effects was derived from an OECD 414 Prenatal Developmental Toxicity Study. The dose was administered orally via gavage. The NOAEL was 75 mg/kg/day at the mid-dose. Therefore, a route-to-route extrapolation was necessary to derive the inhalation DNEL.

 

Adjustment to the starting point for route-to-route extrapolation 75 mg/kg bd/day/0.38 = 197 mg/m³then 197 mg/m³x 6.7/10 = 132 mg/m³(NAEC).

 

Other adjustment factors

Remaining Differences = 2.5

Intraspecies differences for Workers = 5

 

Worker inhalation DNEL long-term systemic effects = 132 mg/m³/(2.5)(5) = 10.6 mg/m³

 

Worker Dermal DNEL Long-term Exposure Local Effects

A dermal DNEL (short term local effect) is not appropriate since aminoethyl piperazine would be handled in closed systems. Workers who could be potentially exposed would be using PPE due to the corrosive nature of the material and the potential for skin sensitization. Therefore, no DNEL will be derived for this endpoint. 

 

 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. AEP is manufacture in a closed system and personal protective equipment would be used for any worker at risk of contact. The sensitizaition potential of AEP was evaluated by the Guinea Pig Maximization Test . The test material was evaluated by using the highest concentration that produced only mild irrtation for epicutaneous induction and the highest concentration not producing irritation was used for epicutaneous induction. The maximum concentration used was: 5% for the intradermal induction, 50% for epicutaneous induction, and 25% for epicutaneous induction phase. Five of the 20 guinea pigs had a positive response. The potency of AEP is less than moderate based on Table R. 8 -24 of the guidance. Therefore, risk management measures such as labeling and personal protective equipment are considered sufficient to prevent allergic reactions in workers.

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

Most sensitive endpoint:

repeated dose toxicity

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

No consumers uses are supported for aminoethyl piperazine. Therefore, no DNELS will calculated for the general population.