Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
other: RD50
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
30

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/m³
Most sensitive endpoint:
sensitisation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
30
Dose descriptor:
other: RD50
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.56 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
30

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Inhalation:

The available acute inhalation studies with aerosols and vapour derived from different peracetic acid solutions suffered from the difficulty of generating and maintaining a stable atmosphere of peracetic acid and accurate measurement of the composition of the test atmosphere and particle size of the aerosol. The reported LC50 values should, therefore, be treated with circumspection. The 4h-LC50 values ranged from 76 to >241 mg/m³ based on peracetic acid. A common finding of those studies was local irritation of the respiratory tract, which seems more pronounced with aerosols than vapours, so that peracetic acid is consequently classified with STOT SE 3.

In order to determine a threshold level reflecting the irritation potency, the RD50 of 5.4 ppm (approx. 17 mg/m³) is taken into account, which was derived Gagnaire (2002). RD50 values have been successfully shown to predict safe industrial exposures if sensory irritation is the most sensitive endpoint as developed by the American Conference of Governmental Industrial Hygienists (ACGIH 2006; Kuwabara, 2007).

According to this, it also has been demonstrated for a wide range of chemicals that at 0.1 times the RD50, humans would experience a slight discomfort and at 0.03 times the RD50 (RD50/30) no effects have been encountered.

As the most prominent effects of peracetic acid are due to the corrosive properties which is more a dose-dependent rather than a time-dependent effect, the use of the RD50 as a starting point for derivation of the DNEL for the inhalation route (acute and long-term, systemic and local) is justified. Thus, the DNEL is derived as follows:

DNEL = RD50 / AF = 17 mg/m³ / 30 = 0.56 mg/³

Dermal:

Due to the corrosive properties dermal contact will result in local effects at the site of first contact. It was also found that due to its high reactivity and rapid degradation, peracetic acid is not expected to enter the body and become systemically available after dermal application. As all systemic observations and effects after single or repeated exposure were seen after oral application these are considered to be secondary to a locally irritating/corrosive effect. Hence, a DNEL for systemic effects, long-term and acute, are not derived.

However, peracetic acid at concentrations ≥ 10 % is categorised in the “high hazard” band according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Part E, Table E.3-1.

References:

ACGIH. TLVs and BEIs, Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 2006.

Yu Kuwabara, George V. Alexeeff, Rachel Broadwin, and Andrew G. Salmon, Evaluation and Application of the RD50 for Determining Acceptable Exposure Levels of Airborne Sensory Irritants for the General Public; Environ Health Perspect. 2007 November; 115(11): 1609–1616.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
60
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
60

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
60
Dose descriptor:
other: RD50
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on the method by the American Conference of Governmental Industrial Hygienists (ACGIH, 2006) using the determined RD50 as most sensitive endpoint.
Overall assessment factor (AF):
60
Dose descriptor starting point:
other: RD50

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
AF for dose response relationship:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for differences in duration of exposure:
1
Justification:
Corrosive effects are not regarded as time-dependent, so an AF is not necessary according to ECHA Guidance R.8 (ECHA, 2012)
AF for interspecies differences (allometric scaling):
1
Justification:
Corrosive effects are independent of the basal metabolic rate and equal in different species, so an AF is not necessary according to ECHA Guidance R.8 (ECHA, 2012)
AF for other interspecies differences:
1
Justification:
Corrosive effects are independent of the basal metabolic rate and equal in different species, so an AF is not necessary according to ECHA Guidance R.8 (ECHA, 2012)
AF for intraspecies differences:
10
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for the quality of the whole database:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for remaining uncertainties:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
AF for dose response relationship:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for interspecies differences (allometric scaling):
1
Justification:
Corrosive effects are independent of the basal metabolic rate and equal in different species, so an AF is not necessary according to ECHA Guidance R.8 (ECHA, 2012)
AF for other interspecies differences:
1
Justification:
Corrosive effects are independent of the basal metabolic rate and equal in different species, so an AF is not necessary according to ECHA Guidance R.8 (ECHA, 2012)
AF for intraspecies differences:
10
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for the quality of the whole database:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)
AF for remaining uncertainties:
1
Justification:
According to ECHA Guidance R.8 (ECHA, 2012)

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

Inhalation:

The available acute inhalation studies with aerosols and vapour derived from different peracetic acid solutions suffered from the difficulty of generating and maintaining a stable atmosphere of peracetic acid and accurate measurement of the composition of the test atmosphere and particle size of the aerosol. The reported LC50 values should, therefore, be treated with circumspection. The 4h-LC50 values ranged from 76 to >241 mg/m³ based on peracetic acid. A common finding of those studies was local irritation of the respiratory tract, which seems more pronounced with aerosols than vapours, so that PAA is consequently classified with STOT SE 3.

In order to determine a threshold level reflecting the irritation potency, the RD50 of 5.4 ppm (approx. 17 mg/m³) is taken into account, which was derived by Gagnaire (2002). RD50 values have been successfully shown to predict safe industrial exposures if sensory irritation is the most sensitive endpoint as developed by the American Conference of Governmental Industrial Hygienists (ACGIH 2006; Kuwabara, 2007).

According to this, it also has been demonstrated for a wide range of chemicals that at 0.1 times the RD50, humans would experience a slight discomfort and at 0.03 times the RD50 (RD50/30) no effects have been encountered.

As the most prominent effects of peracetic acid are due to the corrosive properties which is more a dose-dependent rather than a time-dependent effect, the use of the RD50 as a starting point for derivation of the DNEL for the inhalation route (acute and long-term, systemic and local) is justified.

To reflect the intraspecies difference among the general population compare worker, an additional assessment factor of two is applied. Thus, the DNEL is derived as follows:

DNEL = RD50 / AF = 17 mg/m³ / (30* 2) = 0.28 mg/³

Dermal:

Due to the corrosive properties dermal contact will result in local effects at the site of first contact. It was also found that due to its high reactivity and rapid degradation, peracetic acid is not expected to enter the body and become systemically available after dermal application. As all systemic observations and effects after single or repeated exposure were seen after oral application these are considered to be secondary to a locally irritating/corrosive effect. Hence, a DNEL for systemic effects, long-term and acute, are not derived.

Oral:

Due to the corrosive properties of peracetic acid oral contact will result in local effects at the site of first contact. All systemic observations and effects after single or repeated exposure are considered to be secondary to a locally irritating/corrosive effect as peracetic acid is not expected to become systemically available due to its high reactivity and rapid degradation. However, a NOAEL of 12.5 mg/kg bw/day was estimated in a developmental study based on statistically significant reductions in water and food consumption throughout the entire treatment period and significant reduction in terminal body weight, corrected body weight and body weight gain from days 5 to 20, respectively.

The DNEL for then oral route is derived based on the procedure described ECHA Guidance R.8 (ECHA, 2012) by application of relevant assessment factors (AF) as follows:

Long-term DNEL Assessment Factors (Oral)

Long-term DNEL Assessment Factors (Oral)

Assessment Factor

General population

Differences in metabolic rate per b. w. (allometric scaling)

1*

Interspecies remaining differences (toxicodynamic and toxicokinetic)

1**

Intraspecies differences

10

Duration extrapolation

(sub-acute/sub-chronic/chronic)

1**

Issues related to dose-response

1

Quality of whole database

1

Overall AF

100

* corrosive effects are independent of the basal metabolic rate, so allometric scaling is not applied

**corrosive effect are not regarded as time-dependent or species-dependent

Thus, the DNEL for systemic-affects after oral exposure is 0.125 mg/kg bw/d.

References:

ACGIH. TLVs and BEIs, Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists; 2006.

Yu Kuwabara, George V. Alexeeff, Rachel Broadwin, and Andrew G. Salmon, Evaluation and Application of the RD50 for Determining Acceptable Exposure Levels of Airborne Sensory Irritants for the General Public; Environ Health Perspect. 2007 November; 115(11): 1609–1616.