TROYSOL LAC

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.248 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

75

Dose descriptor starting point:

NOAEC

Value:

37 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

18.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

For the given human exposure route there is a dose descriptor for the same route in experimental animals but there are differences in respiratory volumes between experimental animals (at rest) and humans (light activity).

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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) 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:

The default value for the relatively homogenous group "worker" is used.

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

Route of original study:

By inhalation

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

repeated dose toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Most sensitive endpoint:

acute toxicity

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.8 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):

300

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

840 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming a four times higher absorption via the oral route (starting route) as compared to the dermal route (end 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) 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:

The default value for the relatively homogenous group "worker" is used.

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:

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (2010).

 

Acute, systemic, DNEL

The test item is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

   

Acute/short term DNEL for local effects

The inhalation DNEL for short term local effects does not need to be derived as this DNEL is covered by the derived inhalation DNEL for long term local effects. Furthermore, the test item is not classified and labelled for acute inhalation toxicity, according to Regulation (EC) No 1272/2008 (CLP).

 

Skin irritation: The test item is classified for skin irritation cat. 2, according to Regulation (EC) No 1272/2008 (CLP) and thus associated to the low hazard band.

 

Sensitization: However, the test item is not classified and labelled as skin sensitizer according to Regulation (EC) No 1272/2008 (CLP).

Eye irritation:The test item is classified for eye irritation cat.1 according to Regulation (EC) No 1272/2008 (CLP) and thus associated to the medium hazard band.

Long term, DNEL for local effects

Since no threshold value could be derived in the repeated dose toxicity study, a qualitative risk assessment was carried out. The test item is classified for STOT SE cat. 3 according to Regulation (EC) No 1272/2008 (CLP) and is therefore attributable to the low hazard band. Since the substance concentration in preparation is lower than 10% for industrial and professional use, local effects are not considered as no classification is required for this diluted mixtures (Regulation (EC) No 1272/2008 (CLP)).

Long term, systemic DNEL

Occupational exposure to the test item occurs by inhalation exposure. Two long-term DNELs are calculated for workers. Unless otherwise indicated, the "quality of whole database factor", “remaining uncertainties” and "dose-response factor" are considered to amount each to a value of 1.

Exposure by inhalation

 

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

The sub-acute (four-week) inhalation toxicity study is selected for DNEL derivation as it is the relevant repeated dose study which is equivalent to the OECD guideline 412. In this study, the NOAEC (systemic) in rats is 37 mg/m³, the highest dose tested.

 

Step 2: Modification into a correct starting point

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived. This worker DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

Relevant dose descriptor (NOAEC): 37 mg/m³

Duration of exposure used in study: 6 h (5 days per week)

Duration of exposure of the worker: 8 h (5 days per week)

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:

= 37 mg/m³x 6 h/8 h x 6.7 m³/10 m³= 18.6 mg/m³

 

Step 3: Use of assessment factors: 75

AF for differences in duration of exposure: 6

AF for other interspecies differences: 2.5

AF for intraspecies differences: 5

 

In conclusion, long term systemic inhalation DNEL, workers = 0.248 mg/m³.

 

Dermal exposure

 

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

There are no relevant experimental data on repeated dermal exposure. Thus, the OECD TG 407 study (2008), performed with the main compound is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the NOAEL (systemic) in rats is 100 mg/kg bw/day.

 

Step 2: Modification of the starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. The oral NOAEL rat is converted into a dermal NOAEL rat. Based on the physico-chemical properties of Troysol LAC (log Kow: 8.2 and water solubility: 0.2 mg/L) a 4 times higher absorption via the oral route (starting route) as compared to the dermal route (end route) is assumed as a worst case.

Relevant dose descriptor (NOAEL): 100 mg/kg bw/day

Absorption (oral, animal): 100%

Absorption (dermal, human): 25%

 

Dermal NOAEL for workers:

= 100 mg/kg bw/d x 100% / 25% = 400 mg/kg bw/d based on the main compound (98.3%).

For the mixture (46.5% main compound), the dermal NOAEL for workers is 840 mg/kg bw/d.

 

Step 3: Use of assessment factors: 300

AF for differences in duration of exposure: 6

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

 

In conclusion, long term systemic dermal DNEL (workers) for the mixture = 2.8 mg/kg bw/day.

 

References

(not included as endpoint study record)

 

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. ECHA-2010-G-19-EN.

 

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. ECHA-14-G-06-N.

 

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.044 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Dose descriptor starting point:

NOAEC

Value:

37 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

6.61 mg/m³

Explanation for the modification of the dose descriptor starting point:

For the given human exposure route there is a dose descriptor for the same route in experimental animals but there are differences in the exposure duration between experimental animals and humans.

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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) 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:

10

Justification:

The default value for the relatively homogenous group "general population" is used.

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

Route of original study:

By inhalation

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

Most sensitive endpoint:

acute toxicity

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.4 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):

600

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

840 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated dermal exposure. A conservative approach is used assuming a four times higher absorption via the oral route (starting route) as compared to the dermal route (end 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) 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:

10

Justification:

The default value for the more heterogenous group "general population" is used.

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

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

0.35 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):

600

Dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

210 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation is necessary since a repeated dose oral toxicity study is 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:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) 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:

10

Justification:

The default value for the more heterogenous group "general population" is used.

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

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (2010).

 

Acute, systemic, DNEL

The test item is not classified and labelled for acute systemic toxicity, according to Regulation (EC) No 1272/2008 (CLP), based on the test data for acute oral, dermal and inhalation toxicity.

   

Acute/short term DNEL for local effects

The DNEL for local effects is not considered to be derived for consumers as the substance concentration in preparation is only 0.7% which does not lead to classification according to Regulation (EC) No 1272/2008 (CLP).

 

Long term DNEL (local)

The DNEL for local effects is not considered to be derived for consumers as the substance concentration in preparation is only 0.7% which does not lead to classification according to Regulation (EC) No 1272/2008 (CLP).

Long term DNEL(systemic)

Occupational exposure to the test item occurs by inhalation exposure. Altogether four long-term DNELs are calculated for general population. Unless otherwise indicated, the "quality of whole database factor", “remaining uncertainties” and "dose-response factor" are considered to amount each to a value of 1.

 

Exposure by inhalation

 

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

The sub-acute (four-week) inhalation toxicity study is selected for DNEL derivation as it is the relevant repeated dose study which is equivalent to the OECD guideline 412. In this study, the NOAEC in rats is 37 mg/m³, the highest dose tested.

 

Step 2: Modification into a correct starting point

Using a conservative approach, a DNEL for general population (long-term inhalation exposure) is derived. This DNEL is considered to ensure an appropriate level of protection with regard to acute inhalation exposure (no high peaks of exposure expected).

Relevant dose descriptor (NOAEC): 37 mg/m³

Duration of exposure used in study: 6 h (5 days per week)

Duration of exposure of the general population: 24 h (5 days per week)

 

Corrected inhalatory NOAEC for general population:

= 37 mg/m³x 6 h/24 h x 5 d/7 d = 6.61 mg/m³

 

Step 3: Use of assessment factors: 150

AF for differences in duration of exposure: 6

AF for other interspecies differences: 2.5

AF for intraspecies differences: 10

 

In conclusion, long term systemic inhalation DNEL, general population = 0.044 mg/m³.

Dermal exposure

 

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

There are no relevant experimental data on repeated dermal exposure. Thus, the OECD TG 407 study (2008), performed with the main compound is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the NOAEL (systemic) in rats is 100 mg/kg bw/d.

                     

Step 2: Modification of the starting point:

Using a conservative approach, a DNEL general population (long-term dermal exposure) is derived. The oral NOAEL rat is converted into a dermal NOAEL rat. Based on the physico-chemical properties of Troysol LAC (log Kow: 8.2 and water solubility: 0.2 mg/L) a four times higher absorption via the oral route (starting route) as compared to the dermal route (end route) is assumed as a worst case.

Relevant dose descriptor (NOAEL): 100 mg/kg bw/day

Absorption (oral, animal) = 100%

Absorption (dermal, human) = 25%

 

Dermal NOAEL for general population:

= 100 mg/kg bw/d x 100 %/ 25% = 400 mg/kg bw/dbased on the main compound (98.3%)

For the mixture (46.5% main compound), the dermal NOAEL for general population is 840 mg/kg bw/d.

 

Step 3: Use of assessment factors: 600

AF for differences in duration of exposure: 6

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 10

 

In conclusion, long term systemic dermal DNEL (general population) for the mixture = 1.4 mg/kg bw/day.

 

Oral exposure (systemic)

 

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

No route to route extrapolation is necessary since a GLP and guideline conform repeated dose oral toxicity study is available (OECD TG 407). In this study, the NOAEL (systemic) in rats is 100 mg/kg bw/d.

                     

Step 2: Modification of the starting point:

No modification is necessary.

 

Relevant dose descriptor (NOAEL): 100 mg/kg bw/d 

 

Oral NOAEL for general population:

= 100 mg/kg bw/dbased on the main compound (98.3%)

For the mixture (46.5% main compound), the oral NOAEL for general population is 210 mg/kg bw/d.

 

Step 3: Use of assessment factors: 600

AF for differences in duration of exposure: 6

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

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 10

 

In conclusion, long term systemic oral DNEL (general population) for the mixture = 0.35 mg/kg bw/day.

  

References

(not included as endpoint study record)

 

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. ECHA-2010-G-19-EN.

 

- ECHA (2014). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. ECHA-14-G-06-N.

 

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.