Benzene, 1,4-bis(1-methylethyl)-, homopolymer

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

882 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming 100 % absorption via the inhalation route (end route) and 50 % absorption via the oral route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: starting point - subchronic (NOAEL oral derived from an OECD 408 study) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

Intraspecies differences of worker are considered to be fully covered by the selected factor.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

100 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

10 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Due to the physico-chemical properties (logPow, water solubility) dermal absorption (end route) is assumed to be 10 % of oral absorption (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: starting point subchronic, NOAEL oral derived to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for other interspecies differences.

AF for intraspecies differences:

5

Justification:

Intraspecies differences of worker are considered to be fully covered by the selected factor.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the assessment factors (AF) for "quality of whole database factors", "dose-response factors" and "remaining uncertainties" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

DNEL long-term inhalation

According to ECHA REACH guidance document R8 (2012), if the calculated DNEL inhalation is above the general dust limit (10 mg/m³), then, the general dust limit (10 mg/m³) should be considered as the DNEL long-term inhalation. As the calculated DNEL long-term inhalation for CCPIB was determined to be35.28 mg/m³ (see below *), the DNEL considered for risk characterization is the general dust limit of 10 mg/m³.

*DNEL (long-term inhalation) derivation:

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of 1000 mg/kg bw/day, assessed in the key repeated dose oral toxicity study (OECD 408, 2016) is identified as the relevant dose descriptor and starting point.

In order to derive the worker DNEL (long-term inhalation exposure), the NOAEC was initially calculated:

Step 2: Modification into a correct starting point (route to route modification):

Using a conservative approach, an inhalation NOAEC value was derived from an oral NOAEL value.

Relevant dose descriptor (NOAEL): 1000 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Corrected inhalatory NOAEC for workers

= 1000 mg/kg bw/d × 0.5 × (1 / 0.38 m³/kg bw/d) × (6.7 m³/10 m³)

= 882 mg/m³

Step 3: Use of assessment factors: 25

Intraspecies AF (worker): 5

Exposure duration (duration extrapolation): 2

Interspecies differendes: 2.5

DNEL (long-term inhalation)= 882 mg/m³ : 10 = 35.28 mg/m³

As the value of the DNEL obtained above is higher than the dust limit, the DNEL (long-term inhalation) applied is 10 mg/m³ (the general dust limit).

DNEL long-term dermal

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of 1000 mg/kg bw/day, assessed in the key repeated dose oral toxicity study (OECD 408, 2016) is identified as the relevant dose descriptor and starting point.

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physicochemical properties of CCPIB (log Kow and water solubility) a dermal absorption of 10 % is assumed as a worst case scenario.

In conclusion, dermal NOAEL = oral NOAEL × 100 : 10 = 10000 mg/kg bw/d.

Step 3: Use of assessment factors: 100

Allometric scaling (rat to human): 4

Intraspecies AF (worker): 5

Interspecies differences: 2.5

Exposure duration AF: 2

In conclusion, long term systemic dermal DNEL, workers = 10000: 100 = 100 mg/kg bw/day.

DNEL systemic acute and DNEL local acute/ systemic

Short-term DNELs are not required as the acute toxicity of the test item is low. The test substance is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on test data of acute oral and dermal toxicity. Inhalation toxicity is also considered as low and skin sensitization potential was not observed in the available sensitisation study (OECD 406).

Respiratory irritation: No study testing the respiratory effects of the test material is available. However, since the test material showed no eye irritation, mucosal damage via inhalation route is not likely to occur. Therefore, no adverse effects on respiratory system are expected and no local DNEL (long-term-inhalation) was derived.

Skin and eye irritation/corrosion: Results of a skin and eye irritation studies showed that CCBIP is not irritating to skin and eyes: Therefore, no qualitative risk assessment is required.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.5 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEC

Value:

375 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming 100 % absorption via the inhalation route (end route) and 50 % absorption via the oral route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: starting point - subchronic (NOAEL oral derived from an OECD 408 study) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for interspecies differences.

AF for intraspecies differences:

10

Justification:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

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:

DNEL (Derived No Effect Level)

Value:

50 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Value:

10 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. Due to the physico-chemical properties (logPow , water solubility) dermal absorption (end route) is assumed to be 10 % of oral absorption (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: starting point subchronic, NOAEL oral derived to chronic (end point)

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for interspecies differences.

AF for intraspecies differences:

10

Justification:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

irritation (respiratory tract)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

200

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A route to route extrapolation was not required since an OECD 408 study was available.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: starting point subchronic, NOAEL oral derived to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Recommended AF for interspecies differences.

AF for intraspecies differences:

10

Justification:

Intraspecies differences of general population are considered to be fully covered by the selected factor.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the assessment factors (AF) for "quality of whole database factors", "dose-response factors" and "remaining uncertainties" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

DNEL long-term inhalation

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of 1000 mg/kg bw/day, assessed in the key repeated dose oral toxicity study (OECD 408, 2016) is identified as the relevant dose descriptor and starting point.

In order to derive the worker DNEL (long-term inhalation exposure), the NOAEC was initially calculated:

Step 2: Modification into a correct starting point (route to route modification):

Using a conservative approach, an inhalation NOAEC value was derived from an oral NOAEL value.

Relevant dose descriptor (NOAEL): 1000 mg/kg bw/day

Allometric scaling: 4

Body weight: 60 kg

Standard respiratory volume of humans (sRVhuman) for 24 hours: 20 m³

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat / ABSinh-human): 0.5

Corrected inhalatory NOAEC for general population

= (1000 mg/kg bw/day / 4) × 60 kg / 20 m3/day × 0.5

= 375 mg/m³

Calculation of the general population DNEL:

Corrected inhalatory NOAEC for general population: 375 mg/m³

Assessment factors applied : 50

Interspecies differences: 2.5

Exposure duration (subchronic to chronic): 2

Intraspecies differences (general population): 10

General population DNEL (long-term inhalation exposure)

= 375 mg/m³ / 50

= 7.5 mg/m³

DNEL long-term dermal

Step 1: Selection of the relevant dose descriptor (starting point):

The NOAEL of 1000 mg/kg bw/day, assessed in the key repeated dose oral toxicity study (OECD 408, 2016) is identified as the relevant dose descriptor and starting point.

Step 2: Modification into a correct starting point:

Based on the phys-chem properties of CCPIB (log Kow and water solubility) a dermal absorption of 10 % is assumed as a worst case scenario.

In conclusion, dermal NOAEL = oral NOAEL × 100 : 10 = 10000 mg/kg bw/d.

Step 3: Use of assessment factors: 80

Interspecies AF (allometric scaling, rat to human): 4

Intraspecies AF (general population): 10

Exposure duration (duration extrapolation) AF: 2

In conclusion, long term systemic dermal DNEL, workers = 10000 : 80 = 125 mg/kg bw/day

DNEL long-term oral

DNEL long-term oral is based a NOAEL value of 1000 mg/kg bw/d obtained in a repeated dose oral toxicity study (OECD 408, 2016).

The following AF were applied:

Interspecies AF (allometric scaling, rat to human): 4

Interspecies differences: 2.5

Intraspecies AF (general population): 10

Exposure duration (duration extrapolation) AF: 2

In conclusion, long term systemic oral DNEL, general population = 1000 : 200 = 5 mg/kg bw/d

DNEL systemic acute and DNEL local acute/ systemic

Short-term DNELs are not required as the acute toxicity of the test item is low. The test substance is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on test data of acute oral and dermal toxicity. Inhalation toxicity is also considered as low and skin sensitization potential was not observed in the available sensitisation study (OECD 406).

Respiratory irritation: No study testing the respiratory effects of the test material is available. However, since the test material showed no eye irritation, mucosal damage via inhalation route is not likely to occur. Therefore, no adverse effects on respiratory system are expected and no local DNEL (long-term-inhalation) was derived.

Skin and eye irritation/corrosion: Results of a skin and eye irritation studies showed that CCBIP is not irritating to skin and eyes: Therefore, no qualitative risk assessment is required.