Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
other: NOAEL
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:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Additional information - workers

Short term exposure worker (systemic effects)

It is not possible to derive a DNEL for acute effects based on the available data. The acute toxicity of 2-ethylhexanoic acid, the source substance of the read across approach (for read across justification please refer to IUCLID chapter 13) is low with respect to the oral, dermal and inhalative routes of exposure. There is no acute risk to be expected from inhalation since an inhalation hazard test showed no mortality and no clinical signs after 8h exposure to saturated vapor. Furthermore, there are no uses with inhalable aerosol formation.

Long term exposure worker (systemic effects)

The DNELs for inhalation and dermal long term exposure are derived from the NOAEL (100 mg/kg bw) obtained in the oral reproductive and developmental toxicity studies (see chapter “toxicity for reproduction”).

 

Long term worker (systemic, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 100 mg/kg bw (OECD 414/415; oral; rat)

The dose at which no adverse effects were observed in pups (developmental toxicity)

Step 2) modification of the starting point

1/0.38

Route to route (8h exposure)

 

1/1

Absorption oral to inhal. (complete absorption after oral uptake assumed according to toxicokinetic study)

 

6.7 m³/10 m³

Correction to light work

Step 3) Assessment factors

 

 

Exposure duration

1

No extrapolation of exposure duration since the NOAEL is from a reproductive toxicity study

Interspecies

1

No interspecies extrapolation for inhal.

Intraspecies

5

Default assessment factor for worker; as proposed in the REACh Guidance

Remaining differences

2.5

Default assessment factor as proposed in the REACh Guidance

Dose response

1

 

Quality of database

1

 

DNEL

Value

For workers

100 mg/kg x 1 x 0.67 / (0.38 x 1 x 1 x 5 x 2.5 x 1 x 1) =14 mg/m³

 

 

Long term worker (systemic, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 100 mg/kg bw (OECD 414/415; oral; rat)

The dose at which no adverse effects were observed in pups (developmental toxicity)

Step 2) modification of the starting point

1/1

No correction factor for dermal absorption according to pharmacokinetic study

Step 3) Assessment factors

 

 

Exposure duration

1

No extrapolation of exposure duration since the NOAEL is from a reproductive toxicity study

Interspecies

4

Allometric scaling from rat to human

Intraspecies

5

Default assessment factor for worker; as proposed in the REACh Guidance

Remaining differences

2.5

Default assessment factor as proposed in the REACh Guidance

Dose response

1

 

Quality of database

1

 

DNEL

Value

For workers

100 mg/kg / (1 x 4 x 5 x 2.5 x 1 x 1) =2 mg/kg bw/d

 

Long/short term exposure worker (local effects)

Sodium 2 -ethylhexanoate is in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 not classified for skin, eye or respiratory irritation. The performed tests for skin and eye irritation with the source substance 2 -ethylhexanoic acid (similar to OECD guideline 404 and 405) are indicating a slightly irritating potential. The tests are not providing dose-response data that could be used for the derivation of a DNEL. According to the REACH guidance on information requirements and chemical safety assessment, Part E: Risk Characterisation, a qualitative risk characterisation should be performed for this endpoint. In order to guarantee "adequately control of risks", it is necessary to stipulate risk management measures that prevent skin and eye exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Short term exposure consumer (systemic effects)

Same considerations as for the worker.

Long term exposure consumer (systemic effects)

The DNELs for oral, inhalation and dermal long term exposure are derived from the NOAEL (100 mg/kg bw) obtained in the oral reproductive and developmental toxicity studies with 2 -ethylhexanoic acid, the source substance of the read across approach (see chapter “toxicity for reproduction” and chapter 13 for read across justification).

Long term consumer (systemic, oral)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 100 mg/kg bw (OECD 414/415; oral; rat)

The dose at which no adverse effects were observed in pups (developmental toxicity)

Step 2) modification of the starting point

1/1

No correction factor for oral absorption according to pharmacokinetic study

Step 3) Assessment factors

 

 

Exposure duration

1

No extrapolation of exposure duration since the NOAEL is from a reproductive toxicity study

Interspecies

4

Allometric scaling from rat to human

Intraspecies

10

Default assessment factor for consumer; as proposed in the REACh Guidance

Remaining differences

2.5

Default assessment factor as proposed in the REACh Guidance

Dose response

1

 

Quality of database

1

 

DNEL

Value

For consumer

100 mg/kg / (1 x 4 x 10 x 2.5 x 1 x 1) =1 mg/kg bw/d

 

Long term consumer (systemic, inhalation)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 100 mg/kg bw (OECD 414/415; oral; rat)

The dose at which no adverse effects were observed in pups (developmental toxicity)

Step 2) modification of the starting point

1/1.15

Route to route (24h exposure)

 

1/1

Absorption oral to inhal. (complete absorption after oral uptake according to toxicokinetic study)

Step 3) Assessment factors

 

 

Exposure duration

1

No extrapolation of exposure duration since the NOAEL is from a reproductive toxicity study

Interspecies

1

No interspecies extrapolation for inhal.

Intraspecies

10

Default assessment factor for consumer; as proposed in the REACh Guidance

Remaining differences

2.5

Default assessment factor as proposed in the REACh Guidance

Dose response

1

 

Quality of database

1

 

DNEL

Value

For consumer

100 mg/kg x 1 / (1.15 x 1 x 1 x 10 x 2.5 x 1 x 1) =3.5 mg/m³

 

 

Long term consumer (systemic, dermal)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 100 mg/kg bw (OECD 414/415; oral; rat)

The dose at which no adverse effects were observed in pups (developmental toxicity)

Step 2) modification of the starting point

1/1

No correction factor for dermal absorption according to pharmacokinetic study

Step 3) Assessment factors

 

 

Exposure duration

1

No extrapolation of exposure duration since the NOAEL is from a reproductive toxicity study

Interspecies

4

Allometric scaling from rat to human

Intraspecies

10

Default assessment factor for consumer; as proposed in the REACh Guidance

Remaining differences

2.5

Default assessment factor as proposed in the REACh Guidance

Dose response

1

 

Quality of database

1

 

DNEL

Value

For consumer

100 mg/kg / (1 x 4 x 10 x 2.5 x 1 x 1) =1 mg/kg bw/d

 

Long/short term exposure consumer (local effects)

Same considerations as for the worker.