4,4',4''-(1-methylpropanyl-3-ylidene)tris[6-tert-butyl-m-cresol]

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.53 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:

88.16 mg/m³

Explanation for the modification of the dose descriptor starting point:

Exposure data available only from oral exposure data.

AF for dose response relationship:

1

Justification:

Table R8-6

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic Table R8-6

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies variation is accounted for in extrapolation

AF for intraspecies differences:

5

Justification:

worker Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

2.5

Justification:

Table R8-6

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.5 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):

100

Modified dose descriptor starting point:

NOAEL

Value:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Exposure data available only from oral exposure data.

AF for dose response relationship:

1

Justification:

Table R-6

AF for differences in duration of exposure:

2

Justification:

Sub-chronic to chronic. Table R-6

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human. Table R-3

AF for intraspecies differences:

5

Justification:

Worker. Table R-6

AF for the quality of the whole database:

1

Justification:

Table R-6

AF for remaining uncertainties:

2.5

Justification:

Table R-6

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 mg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

5

Dose descriptor:

other: NOAEL

AF for dose response relationship:

1

Justification:

Not applicable to sensitisation

AF for differences in duration of exposure:

1

Justification:

Not applicable to sensitisation

AF for interspecies differences (allometric scaling):

1

Justification:

mouse to human Table R8-3

AF for intraspecies differences:

5

Justification:

Workers. Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

1

Justification:

Table R8-6

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Inhalation NOAEL

 

Based on formulae in R. 8-3, as a worst case it is assumed 100% adsorption orally to rats and by inhalation to human are equivalent. The granulometry data for this substance indicates that the substance is not respirable by humans; the vapour pressure of the substance is extremely low indicating the substance is non-volatile. Target endpoints are also assumed to be equivalent.

 

For workers (8h exposure/d)

 

NOAEC (inhal) = 50 * 1/0.38 m³/kg/d * 100/100 * 6.7m³/10m³

 

NOAEC (inhal) = 88.16 mg/m³

 

 

Dermal NOAEL

 

Based on Appendix R. 8-2, Example B.5, as a worst case it is assumed that 100% adsorption orally to rats and by dermal adsorption to human are equivalent.

 

NOAEL (dermal) = 50 * 100/100

 

NOAEL (dermal) = 50 mg/kg/day.

 

 

Derivation of DNEL For Dermal Sensitisation

 

Data available from the LLNA endpoint established that the substance is a dermal sensitiser. EC3≤5%.

 

Based on Appendix R.8-10 of ECHA Guidance Chapter R8, the EC3 value expressed in µg/cm²can be considered the LOAEL according to the formula

 

EC3 [%] * 250 [µg/cm²/%] = EC3 [µg/cm²]

 

5 [%] * 250 [µg/cm²/%] = 1250 [µg/cm²]

 

Sensitising LOAEL = 1.250 mg/cm²

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.87 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:

43.48 mg/m³

Explanation for the modification of the dose descriptor starting point:

Exposure data available only from oral exposure data.

AF for dose response relationship:

1

Justification:

Table R8-6

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic Table R8-6

AF for interspecies differences (allometric scaling):

1

Justification:

Interspecies variation is accounted for in extrapolation

AF for intraspecies differences:

10

Justification:

consumer Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

2.5

Justification:

Table R8-6

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:

DNEL (Derived No Effect Level)

Value:

0.25 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:

50 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Exposure data available only from oral exposure data.

AF for dose response relationship:

1

Justification:

Table R8-6

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic Table R8-6

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human. Table R-3

AF for intraspecies differences:

10

Justification:

consumer Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

2.5

Justification:

Table R8-6

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.125 mg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

10

Dose descriptor:

other: NOAEL

AF for dose response relationship:

1

Justification:

Not applicable to sensitisation

AF for differences in duration of exposure:

1

Justification:

Not applicable to sensitisation

AF for interspecies differences (allometric scaling):

1

Justification:

bodyweight not relevent to sensitisation

AF for intraspecies differences:

10

Justification:

consumer Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

1

Justification:

Table R8-6

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 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:

50 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Table R8-6

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic Table R8-6

AF for interspecies differences (allometric scaling):

4

Justification:

Rat to human. Table R-3

AF for intraspecies differences:

10

Justification:

consumer Table R8-6

AF for the quality of the whole database:

1

Justification:

Table R8-6

AF for remaining uncertainties:

2.5

Justification:

Table R8-6

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

Inhalation NOAEL

Based on formulae in R. 8-3, as a worst case it is assumed 100% adsorption orally to rats and by inhalation to human are equivalent. The granulometry data for this substance indicates that the substance is not respirable by humans; the vapour pressure of the substance is extremely low indicating the substance is non-volatile. Target endpoints are also assumed to be equivalent.

 

For general population (24h exposure/d)

NOAEC (inhal) = 50 * 1/1.15 m³/kg/d * 100/100

NOAEC (inhal) = 43.48 mg/m³

 

 

Dermal NOAEL

 

Based on Appendix R. 8-2, Example B.5, as a worst case it is assumed that 100% adsorption orally to rats and by dermal adsorption to human are equivalent.

 

NOAEL (dermal) = 50 * 100/100

 

NOAEL (dermal) = 50 mg/kg/day.

 

 

Derivation of DNEL for Dermal Sensitisation

 

Data available from the LLNA endpoint established that the substance is a dermal sensitiser. EC3≤5%.

 

Based on Appendix R.8-10 of ECHA Guidance Chapter R8, the EC3 value expressed in µg/cm²can be considered the LOAEL according to the formula

 

EC3 [%] * 250[µg/cm²/%] = EC3 [µg/cm²]

 

5 [%] * 250 [µg/cm²/%] = 1250 [µg/cm²]

 

Sensitising LOAEL = 1.250 mg/cm²