Phosphoric acid, 2-ethylhexyl ester

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

36.73 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110 "Guidance on Assessment Factors to Derive a DNEL"

Overall assessment factor (AF):

6

Modified dose descriptor starting point:

NOAEC

Value:

220.39 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study was available, therefore standard route to route extrapolation was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8.

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic (ECHA approach)

AF for interspecies differences (allometric scaling):

1

Justification:

Not required: allometric scaling was taken into account during route-to-route extrapolation

AF for other interspecies differences:

1

Justification:

Allometry is generally accepted in the scientific community when the parent chemical or a stable metabolite is the toxic entity that is metabolically detoxified and when renal excretion is the predominant route of elimination (ECETOC Technical Report No. 110)

AF for intraspecies differences:

3

Justification:

ECETOC Technical Report 110

AF for the quality of the whole database:

1

Justification:

Default

AF for remaining uncertainties:

1

Justification:

Not applicable

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.42 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110 "Guidance on Assessment Factors to Derive a DNEL"

Overall assessment factor (AF):

24

Modified dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal study is available therefore standard route to route extrapolation was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8, assuming 100 % dermal absorption.

AF for dose response relationship:

1

Justification:

Default (ECHA)

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic (ECHA approach)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (ECHA)

AF for other interspecies differences:

1

Justification:

Allometry is generally accepted in the scientific community when the parent chemical or a stable metabolite is the toxic entity that is metabolically detoxified and when renal excretion is the predominant route of elimination (ECETOC Technical Report No. 110)

AF for intraspecies differences:

3

Justification:

ECETOC Technical Report 110

AF for the quality of the whole database:

1

Justification:

Default

AF for remaining uncertainties:

1

Justification:

Not applicable

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium 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

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye).

The hazard statement H314: Causes severe skin burns and eye damage, is applicable.

An in-vivo skin irritation/corrosion study showed the substance to be corrosive.

 

Short-term systemic effects

DNELs for short-term systemic effects were not derived as acute toxicity testing was not conducted by either dermal or inhalation routes due to the corrosivity of the substance. Therefore, no adequate data is available for deriving DNELs for short-term systemic effects. It is considered that dermal effects will be characterised by local tissue damage rather than by systemic effects due to uptake via the skin and inhalation is not considered to be a significant route of exposure. 

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.

 

Short-term local effects

A DNEL for short-term local dermal effects was not derived as the skin irritation/corrosion study, which showed corrosion, does not give suitable dose-response information required to derive a DNEL. For corrosive substances, appropriate PPE should be used by all workers. As a result, direct dermal contact occurs only infrequently/accidentally.

A DNEL for short-term local inhalation systemic effects was not derived as no acute toxicity testing has been conducted via the inhalation route. The substance has a vapour pressure of 0.085 Pa at 25°C and is not considered to be volatile. Inhalation is not considered to be a significant route of exposure if used in a well ventilated area.

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.

 

Long-term system effects

A DNEL was derived for long-term inhalation and dermal systemic effects by route-to-route extrapolation from an oral NOAEL (see justification).

 

Inhalation DNEL long-term systemic

The corrected dose descriptor of 220.39 mg/m³ for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8. The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC (for workers 8h exposure) was performed using the following equation:

 

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

 

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

 

Variables were based on worst case assumptions for absorption (i.e. the absorption percentage for the oral route is half that for the inhalation route). The inclusion of this factor means that 50% absorption was assumed for oral absorption and 100% absorption assumed for inhalation. This leads to the most conservative corrected dose descriptor.

Default parameters for rats and human (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle.

 

Corrected inhalatory N(L)OAEC= 250mg/kg bw/day x (1 / 0.38 m³/kg/d) x (1 / 2) x (6.7 m³(8h) / 10 m³(8h)) = 220.39 mg/m³

 

Default parametrs:

sRVrat (8 h) : 0.38m³/kg bw

sRVhuman (8 h) : 6.7 m³/ person

wRV (8 h): 10 m³/ person

 

Conversion of corrected inhalatory NOAEC into a long-term DNEL (inhalation) of workers:

 

DNEL (inhalation)= Inhalatory NOAEC / Overall assessment factor = 220.26 mg/m³/ 6 = 36.73 mg/m³

 

Dermal DNELlong-term Systemic

The dose descriptor for dermal exposure was not modified from the oral NOAEL, in the absence of dermal absorption data it is assumed that the dermal NOAEL is equivalent to the oral NOAEL, i.e. 250 mg/kg bw/day.

 

Conversion of corrected dermal NOAEL into a dermal DNEL long-term for workers:

 

Dermal DNEL = Dermal NOAEL / Overall assessment factor = 250 mg/kg bw/day / 24 =10.42 mg/kg bw/day

 

Long-term local effects

No DNEL can be derived for long-term dermal local effects as no long-term dermal study has been conducted as the substance is corrosive. It is considered that dermal effects will be characterised by local tissue damage. For corrosive substances, appropriate PPE should be used by all workers. Therefore, repeated substantial daily dermal exposure is unlikely.

A DNEL for long-term local inhalation effects was not derived as no acute toxicity testing has been conducted via the inhalation route. The substance has a vapour pressure of 0.085 Pa at 25°C and is not considered to be volatile. Inhalation is not considered to be a significant route of exposure if used in a well ventilated area.

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.87 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110 "Guidance on Assessment Factors to Derive a DNEL"

Overall assessment factor (AF):

10

Modified dose descriptor starting point:

NOAEC

Value:

108.7 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study was available, therefore standard route to route extrapolation was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8.

AF for dose response relationship:

1

Justification:

Default

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic (ECHA approach)

AF for interspecies differences (allometric scaling):

1

Justification:

Not required: allometric scaling was taken into account during route-to-route extrapolation

AF for other interspecies differences:

1

Justification:

Allometry is generally accepted in the scientific community when the parent chemical or a stable metabolite is the toxic entity that is metabolically detoxified and when renal excretion is the predominant route of elimination (ECETOC Technical Report No. 110)

AF for intraspecies differences:

5

Justification:

ECETOC Technical Report No. 110

AF for the quality of the whole database:

1

Justification:

Default

AF for remaining uncertainties:

1

Justification:

Default

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110 "Guidance on Assessment Factors to Derive a DNEL"

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal study is available therefore standard route to route extrapolation was conducted in accordance with ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R8, assuming 100 % dermal absorption.

AF for dose response relationship:

1

Justification:

Default (ECHA)

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic (ECHA approach)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (ECHA)

AF for other interspecies differences:

1

Justification:

ECETOC - Allometry is generally accepted in the scientific community when the parent chemical or a stable metabolite is the toxic entity that is metabolically detoxified and when renal excretion is the predominant route of elimination.

AF for intraspecies differences:

5

Justification:

ECETOC Technical Report No. 110

AF for the quality of the whole database:

1

Justification:

Default (ECHA)

AF for remaining uncertainties:

1

Justification:

Not applicable.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

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:

6.25 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC Technical Report No. 110 "Guidance on Assessment Factors to Derive a DNEL"

Overall assessment factor (AF):

40

Modified dose descriptor starting point:

NOAEL

Value:

250 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default (ECHA)

AF for differences in duration of exposure:

2

Justification:

Subchronic to chronic (ECHA approach)

AF for interspecies differences (allometric scaling):

4

Justification:

Default (ECHA)

AF for other interspecies differences:

1

Justification:

ECETOC - Allometry is generally accepted in the scientific community when the parent chemical or a stable metabolite is the toxic entity that is metabolically detoxified and when renal excretion is the predominant route of elimination.

AF for intraspecies differences:

5

Justification:

ECETOC Technical Report No. 110

AF for the quality of the whole database:

1

Justification:

Default

AF for remaining uncertainties:

1

Justification:

Default

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

The substance is classified for human health as corrosive to the skin (and assumed corrosive to the eye).

The hazard statement H314: Causes severe skin burns and eye damage, is applicable.

An in-vivo skin irritation/corrosion study showed the substance to be corrosive.

 

Short-term systemic effects

DNELs for short-term systemic effects were not derived as acute toxicity testing was not conducted by either dermal or inhalation routes due to the corrosivity of the substance. Therefore, no adequate data is available for deriving DNELs for short-term systemic effects. It is considered that dermal effects will be characterised by local tissue damage rather than by systemic effects due to uptake via the skin and inhalation is not considered to be a significant route of exposure.

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.

 

Short-term local effects

A DNEL for short-term local dermal effects was not derived as the skin irritation/corrosion study, which showed corrosion, does not give suitable dose-response information required to derive a DNEL. For corrosive substances, appropriate risk management measures are applied for consumer products.

A DNEL for short-term local inhalation systemic effects was not derived as no acute toxicity testing has been conducted via the inhalation route. The substance has a vapour pressure of 0.085 Pa at 25°C and is not considered to be volatile. Inhalation is not considered to be a significant route of exposure if used in a well ventilated area.

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.

 

Long-term systemic effects

A DNEL has been derived for long-term inhalation and dermal systemic effects by route-to-route extrapolation from an oral NOAEL (see justification).

 

Inhalation DNEL long-term systemic

The corrected dose descriptor of 108.70 mg/m³for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8. The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC (for consumer 24h exposure) was performed using the following equation:

 

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-rat) x (ABSinh-rat / ABSinh-human)

 

Where:

ABS: Absorption

sRV: standard Respiratory Volume

 

Variables were based on worst case assumptions for absorption (i.e. the absorption percentage for the oral route is half that for the inhalation route). The inclusion of this factor means that 50% absorption was assumed for oral absorption and 100% absorption assumed for inhalation. This leads to the most conservative corrected dose descriptor.

Default parameters for rats and human (for 24 hour exposure) were used for the modification of starting point under the allometric scaling principle.

 

Corrected inhalatory N(L)OAEC= 250mg/kg bw/day x (1 / 1.15 m³/kg/d) x (1 / 2) x (1 / 1)=108.7mg/m³ 

 

Default parametrs:

sRVrat (24 h) : 1.15m³/kg bw

 

Conversion of corrected inhalatory NOAEC into a long-term DNEL (inhalation) for the general population:

 

DNEL (inhalation)= Inhalatory NOAEC / Overall assessment factor = 108.70 mg/m³/ 10 =10.87 mg/m³

 

Dermal DNEL ling-term Systemic

The dose descriptor for dermal exposure was not modified from the oral NOAEL, in the absence of dermal absorption data it is assumed that the dermal NOAEL is equivalent to the oral NOAEL, i.e. 250 mg/kg bw/day.

 

Conversion of corrected dermal NOAEL into a dermal DNEL long-term for workers:

 

Dermal DNEL = Dermal NOAEL / Overall assessment factor = 250 mg/kg bw/day / 40 = 6.25 mg/kg bw/day

 

 

Oral DNEL long-term Systemic

A DNEL was derived for systemic effects via the oral route based on the NOAEL from the subacute oral toxicity study.

 

Conversion of oral NOAEL into a long-term DNEL (oral) for the general population:

Oral DNEL= oral NOAEL / Overall assessment factor = 250 mg/kg bw/d / 40 = 6.25 mg/kg bw/d

 

Long-term local effects

No DNEL can be derived for long-term dermal local effects as no long-term dermal study has been conducted as the substance is corrosive. It is considered that dermal effects will be characterised by local tissue damage. For corrosive substances, appropriate risk management measures are applied to consumer products.

 

A DNEL for long-term local inhalation effects was not derived as no acute toxicity testing has been conducted via the inhalation route. The substance has a vapour pressure of 0.085 Pa at 25°C and is not considered to be volatile. Inhalation is not considered to be a significant route of exposure if used in a well ventilated area.

 

If the substance is used in concentrations below the limit for corrosivity, operational conditions and risk management measures prescribed for long-term effects will resolve any risk due to short-term exposure.