Diisononyl adipate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.9 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Modified dose descriptor starting point:

NOAEC

Value:

222.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL from the oral one-generation study was converted to an inhalation NOAEC according to the following formula. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 170mg/kg b.w. / 0.384 m³/kg b.w. x 0.67 x 0.75 / 1 = 222.5 mg/m³. Based on toxicokinetic data absorption was considered to be 75% after oral exposure and 100% after inhalation.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

already included in route to route extrapolation

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

5

Justification:

Default factor for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

NOAEL is already worst case due to wide spacing of doses (factor of 10). No additional factor for use of a read across substance was applied.

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:

12.8 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Value:

1 275 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For the risk assessment 75% absorption is chosen for the oral route and 10% for the dermal route, based on LogPow > 4, MW and water solubility

AF for dose response relationship:

1

Justification:

NOAEL used as starting point

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

5

Justification:

Default factor for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

NOAEL is already worst case due to wide spacing of doses (factor of 10). No additional factor for use of a read across substance was applied.

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

Additional information - workers

Acute toxicity

A DNEL acute should be established for substances if an acute hazard toxicity (leading to C&L) has been identified and a potential for high peak exposures exists. Since DEHA is not classified for acute toxicity, a DNEL acute is not required.

Local effects

Since no local effects were described, the DNELs are based on the systemic effects only.

LONG -TERM DNEL

The long-term DNEL is based on the most critical NOAEL of 170mg/kg seen in the one-generation study (reduced body weight gain in maternal animals and offspring). The selection follows the precautionary principle, since no effects on body or organ weights were observed in further subchronic and chronic studies up to 630mg/kg (DEHA) and 500mg/kg (DINA). For DEHA, blood and urine parameteres were only assessed in a 28 -day repeated dose, but no changes were observed up to 1000mg/kg.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.2 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:

110.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL from the oral one-generation study was converted to an inhalation NOAEC according to the following formula. NOAEC = NOAEL / resp. volume (rat) x (absorption (oral) / absorption (inhal.)) = 170mg/kg b.w. / 1.15m³/kg b.w. x 0.75 / 1 = 110.9 mg/m³. Based on toxicokinetic data absorption was considered to be 75% after oral exposure and 100% after inhalation.

AF for dose response relationship:

1

Justification:

NOAEL used as starting point

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in route to route extrapolation

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

10

Justification:

Default factor for consumers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

NOAEL is already worst case due to wide spacing of doses (factor of 10). No additional factor for use of a read across substance was applied.

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:

6.4 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

1 275 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

For the risk assessment 75% absorption is chosen for the oral route and 10% for the dermal route, based on LogPow > 4, MW and water solubility

AF for dose response relationship:

1

Justification:

NOAEL used as starting point

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

10

Justification:

Default factor for consumer

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

NOAEL is already worst case due to wide spacing of doses (factor of 10). No additional factor for use of a read across substance was applied.

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.85 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:

170 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

not required, no difference in oral absorption between rats and human is expected

AF for dose response relationship:

1

Justification:

NOAEL used as starting point

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

Default factor for remaining differences

AF for intraspecies differences:

10

Justification:

Default factor for consumers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

NOAEL is already worst case due to wide spacing of doses (factor of 10). No additional factor for use of a read across substance was applied.

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

Acute toxicity

A DNEL acute should be established for substances if an acute hazard toxicity (leading to C&L) has been identified and a potential for high peak exposures exists. Since DEHA is not classified for acute toxicity, a DNEL acute is not needed.

Local effects

Since no local effects were described, the DNELs are based on the systemic effects only

LONG -TERM DNEL

The long-term DNEL is based on the most critical NOAEL of 170mg/kg seen in the one-generation study (reduced body weight gain in maternal animals and offspring). The selection follows the precautionary principle, since no effects on body or organ weights were observed in further subchronic and chronic studies up to 630mg/kg (DEHA) and 500mg/kg (DINA). For DEHA, blood and urine parameteres were only assessed in a 28 -day repeated dose, but no changes were observed up to 1000mg/kg.