N-(2-ethylhexyl)-8,9,10-trinorborn-5-ene-2,3-dicarboximide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

9.3 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):

17.5

Dose descriptor starting point:

NOAEL

Value:

32.5 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

162.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Derivation of an inhalation DNEL_systemicfor a worker population

Modification of a starting point - Conversion of oral NOAEL from the dog chronic toxicity study to inhalation NOAEC concentration

According to Chapter R.8: Characterisation of dose [concentration]-response for human health, Example R 8.2 Workers; Use of allometric scaling (table R. 8-3); scaling has been used in the absence of default standard respiratory volume values for dogs.

NOAEL dog = 32.5 mg/kg bw/day

Divide by AS factor for dogs - 1.4 = 23.2 mg/kg bw/day

Multiply by 70 kg human body weight = 1625 mg/person/day

Divide by default human breathing volume for workers (8h and light activity -10 m³)

= 162.5 mg/m³

NOAEC worker (8h) - 162.5 mg/m³

AF for dose response relationship:

1

Justification:

The starting point is a NOAEL derived in a GLP study in which the dose increments were 4-fold . Serious systemic effects were not identified in the toxicity studies but rather changes associated with an increased workload to the liver.

AF for differences in duration of exposure:

1

Justification:

The NOAEL was obtained from a 1-year dietary study in dogs.

AF for interspecies differences (allometric scaling):

1.4

Justification:

Table R.8-3, allometric scaling for Dog

AF for other interspecies differences:

2.5

Justification:

R.8.4.3.1. page 24, Interspecies difference 2.5 ‘for remaining differences’

AF for intraspecies differences:

5

Justification:

R.8.4.3.1. page 28, default assessment factor of 5 for workers

AF for the quality of the whole database:

1

Justification:

R.8.4.3.1. page 31, 1 is the default factor to be applied to a good quality database taking into account completeness.

AF for remaining uncertainties:

1

Justification:

Not applicable for MGK 264

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:

5.4 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor:

NOAEC

Value:

135 mg/m³

AF for dose response relationship:

1

Justification:

R.8.4.3.1. page 30, the starting point for the DNEL is a NOAEC

AF for differences in duration of exposure:

2

Justification:

R.8.4.3.1. page 29, NOAEC is from a sub-chronic study

AF for interspecies differences (allometric scaling):

1

Justification:

R.8.4.3.1. page 25, Allometric scaling is not required for effects not dependent on metabolic rate or systemic absorption

AF for other interspecies differences:

2.5

Justification:

R.8.4.3.1. page 27, Interspecies difference 2.5 ‘for remaining uncertainties’

AF for intraspecies differences:

5

Justification:

R.8.4.3.1. page 28, default assessment factor of 5 for workers

AF for the quality of the whole database:

1

Justification:

R.8.4.3.1. page 31, 1 is the default factor to be applied to a good quality database taking into account completeness.

AF for remaining uncertainties:

1

Justification:

Not applicable for MGK 264

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:

1.86 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):

17.5

Dose descriptor starting point:

NOAEL

Value:

32.5 mg/kg bw/day

Modified dose descriptor starting point:

other: Not required as NOAEL is a systemic effect level

AF for dose response relationship:

1

Justification:

The starting point is a NOAEL derived in a GLP study in which the dose increments were 4-fold . Serious systemic effects were not identified in the toxicity studies but rather changes associated with an increased workload to the liver.

AF for differences in duration of exposure:

1

Justification:

R.8.4.3.1. page 29, NOAEL is from a chronic 1 year study and therefore a lower factor may be used

AF for interspecies differences (allometric scaling):

1.4

Justification:

Table R.8-3, allometric scaling for Dog

AF for other interspecies differences:

2.5

Justification:

R.8.4.3.1. page 24, Interspecies difference 2.5 ‘for remaining differences’

AF for intraspecies differences:

5

Justification:

R.8.4.3.1. page 28, default assessment factor of 5 for workers

AF for the quality of the whole database:

1

Justification:

R.8.4.3.1. page 31, 1 is the default factor to be applied to a good quality database taking into account completeness.

AF for remaining uncertainties:

1

Justification:

Not applicable for MGK 264

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

DNELs for the general population have not been derived as there will be no exposure to the general population from the MGK 264 use assessed in this regiatration dossier.