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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2010. Guidance on assessment factors to derive a DNEL. Technical Report No. 110, Brussels.
Overall assessment factor (AF):
6
Modified dose descriptor starting point:
NOAEC
Value:
6.03 mg/m³
Explanation for the modification of the dose descriptor starting point:
no extrapolation
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
not needed for inhalation effects (ECHA, R.8, 2010)
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Justification:
individual variability (ECETOC, 2010)
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Local effects

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC, 2010. Guidance on assessment factors to derive a DNEL. Technical Report No. 110, Brussels.
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Fails criteria of Guidelines on Route-to-Route Extrapolation of Toxicity Data when Assessing Health Risks of Chemicals, by the Intergovernmental Group on Health Risks from Chemicals (IGHRC, 2006).
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
AF for intraspecies differences:
3
Justification:
individual variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Worker DNELs

 

For PACM, the mode-of-action is a threshold toxicant. This determination is based on the findings that, in repeated dose oral toxicity studies, systemic toxicity has a NOAEL. Furthermore, PACM is not mutagenic nor is it predicted to be carcinogenic, characteristics which are associated with non-threshold modes of action.

 

Assessment factors were adopted according to ECETOC's Technical Report No. 110 (2010) and according to the REACH technical guidance document R.8, 2010

Short-term exposure worker (systemic effects)

Inhalation and dermal

 

It is not possible to derive a DNEL for acute effects based on the available data. The acute toxicity of PACM is moderate with respect to the oral route of exposure. Concerning the dermal and inhalative exposure routes the acute toxicity is rather low.

Long/short term exposure worker (local effects)

As PACM is a corrosive substance, local dermal effects are qualitatively assessed, due to lack of dose-response information and the irritating and sensitising properties of the substance. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee ‘adequate control of risks’, it is necessary to stipulate risk management measures that prevent skin and eye corrosion.

 

 

Long-term exposure worker (systemic effects)

Inhalation

Long-term-inhalation, systemic (based on the 90 days inhalation study in rats, read across, DM-PACM, CAS 6864-37-5)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC:

12 mg/m3

at 48 mg/m3: body weight development was impaired, local irritative effects observed for the skin and upper airways (nasal mucosa) and target organ toxicity indicative of a mild anemic effect as well as effects on the liver, and kidneys were seen.

Step 2) Modification of starting point

6/8

 

 

 

6.7 m3/10 m3

 

 

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default worker exposure (8 hrs/day, 5 days/week);

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Modified dose-descriptor

12.0 x 6.7 x 6 / (10 x 8) = 6.03 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is needed in case of inhalation exposure

Intraspecies

3

Default assessment factor [ECETOC]

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study [REACh guidance R8]

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

6.03 / (1 x 3 x 2 x 1 x 1) = 1.0 mg/m3

 

 

Dermal

Long-term-dermal, systemic effects (based on the 90 days oral study in rats, read across, DM-PACM, CAS 6864-37-5)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL:

2.5 mg/kg bw

Liver, white and red blood cells, kidneys, adrenal glands and heart were the target organs for toxic effect showing also histopathological alterations. At the high dose level (60 mg/kg bw/day) body weight development/food consumption were clearly impaired and the general state of health was poor. While the toxic effects at the mid dose of 12 mg/kg bw/day were generally less pronounced, a NOAEL was achieved at 2.5 mg/kg bw/day.

Step 2) Modification of starting point

Not applicable (bioavailability oral = dermal) 

Step 3) Assessment factors

 

Interspecies

4

Assessment factor for allometric scaling

Intraspecies

3

Default assessment factor [ECETOC]

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study [REACh guidance R8]

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

2.50 / (4 x 3 x 2 x 1 x 1) = 0.10 mg/kg bw

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.21 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: ECETOC, 2010. Guidance on assessment factors to derive a DNEL. Technical Report No. 110, Brussels.
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
2.14 mg/m³
Explanation for the modification of the dose descriptor starting point:
no extrapolation
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
individual variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC, 2010. Guidance on assessment factors to derive a DNEL. Technical Report No. 110, Brussels.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
fails criteria of Guidelines on Route-to-Route Extrapolation of Toxicity Data when Assessing Health Risks of Chemicals, by the Intergovernmental Group on Health Risks from Chemicals (IGHRC, 2006)
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
individual variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low 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:
0.06 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC, 2010. Guidance on assessment factors to derive a DNEL. Technical Report No. 110, Brussels.
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
2.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
fails criteria of Guidelines on Route-to-Route Extrapolation of Toxicity Data when Assessing Health Risks of Chemicals, by the Intergovernmental Group on Health Risks from Chemicals (IGHRC, 2006)
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
individual variability
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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

Consumer DNELs

 

DNELs are generally not derived for the consumer in the general population, as there is no known or anticipated direct exposure to this industrial chemical. These are categorised in the risk analysis as low risk due to dilution effects. Nevertheless, there might be an indirect exposure of man via the environment. To take this into account, DNELs for systemic effects were calculated for inhalative, oral, and dermal exposure routes.

 

 

Inhalation

Long-term-inhalation, systemic/local effects (based on the 90 days inhalation study in rats, read across, DM-PACM, CAS 6864-37-5)

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC:

12 mg/m3

at 48mg/m3: body weight development was impaired, local irritative effects observed for the skin and upper airways (nasal mucosa) and target organ toxicity indicative of a mild anemic effect as well as effects on the liver, testes and kidneys were seen.

Step 2) Modification of starting point

6/24 and 5/7

 

Correction of exposure duration in study (6 hrs/day, 5 days/week) to default consumer exposure (24 hrs/day, 7 days/week)

Modified dose-descriptor

12.0 x 6 x 5 / (24 x 7) = 2.14 mg/m3

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is needed in case of inhalation exposure

Intraspecies

5

Default assessment factor [ECETOC]

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study [REACh guidance R8]

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

2.14 / (1 x 5 x 2 x 1 x 1) =0.21 mg/m3

 

 

Dermal/oral

Long-term-dermal/oral, systemic/local effects (based on the 90 days oral study in rats, read across, DM-PACM, CAS 6864-37-5

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL:

2.5 mg/kg bw

Liver, white and red blood cells, kidneys, adrenal glands and heart were the target organs for toxic effect showing also histopathological alterations. At the high dose level (60 mg/kg bw/day) body weight development/food consumption were clearly impaired and the general state of health was poor. While the toxic effects at the mid dose of 12 mg/kg bw/day were generally less pronounced, a NOAEL was achieved at 2.5 mg/kg bw/day.

Step 2) Modification of starting point

Not applicable (bioavailability oral = dermal) 

Step 3) Assessment factors

 

Interspecies

4

Assessment factor for allometric scaling

Intraspecies

5

Default assessment factor [ECETOC]

Exposure duration

2

Extrapolation to chronic exposure based on a sub-chronic toxicity study [REACh guidance R8]

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

2.50 / (4 x 5 x 2 x 1 x 1) =0.06 mg/kg bw

 

 

Short-term exposure consumer

Inhalation and Dermal

 

Same considerations as for the worker.

 

 

Long/short term exposure consumer (local effects)

 

Same considerations as for the worker.