4-Octanol, 3-amino-

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

29 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):

9

Modified dose descriptor starting point:

NOAEC

Value:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study available for the substance. NOAEC calcultated from NOAEL obtained in an oral study.

AF for dose response relationship:

1

Justification:

there is a clear dose response and the effect drving the NOAEL is not severe

AF for differences in duration of exposure:

3

Justification:

conversion from a subchronic study to a chronic study

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

Justification:

there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

AF for intraspecies differences:

3

Justification:

based on the guidance by ECETOC and SCOEL on intra-worker variability

AF for the quality of the whole database:

1

Justification:

all studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high 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:

8.3 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):

36

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A repeated dose toxicity study for the dermal route is not available

AF for dose response relationship:

1

Justification:

there is a clear dose response and the effect drving the NOAEL is not severe

AF for differences in duration of exposure:

3

Justification:

conversion from a subchronic study to a chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling rat to human

AF for other interspecies differences:

1

Justification:

there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

AF for intraspecies differences:

3

Justification:

based on the guidance by ECETOC and SCOEL on intra-worker variability

AF for the quality of the whole database:

1

Justification:

all studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Acute / Short term exposure - Systemic effects

It is not considered to be necessary to calculate acute dermal and inhalation DNELs for octanolamine.

Octanolamine has a low volatility and is not anticipated to be present in aerosols at significant concentrations during manufacture or use. Therefore it is very unlikely that a worker would receive an acute inhalation exposure. It is also corrosive and this will subsequently limit the possibility for a worker to receive an acute dermal exposure to this substance as part of the normal manufacturing and use processes due the need for personal protective equipment during handling. If an acute dermal exposure were to occur, the corrosivity would ensure that the worker was immediately aware of the exposure and result in the cleaning of the exposure site. This will significantly limit the degree of absorption and systemic exposure and thus the potential for systemic toxicity.

Once formulated into a metalworking fluid, octanolamine will be at a low concentration, further limiting the opportunity for an acute exposure in the work force.

Acute / Short term, Long term - local effects

Dermal

Octanolamine is corrosive. As such it must be handled by workers using sufficient protective equipment to prevent accidental skin contact. Therefore it is not considered necessary to calculate a DNEL for local effects following acute or chronic dermal exposure.

Inhalation

There are no inhalation toxicity data available for the calculation of an Inhalation DNEL for local effects. The corrosivity of this substance will likely mean that vapors would be irritating however the vapour pressure is low minimizing the potential for inhalation exposure to vapour. Risk management measures employed while handling the concentrated form will also limit the potential for inhalation exposure.

Long term Exposure - systemic effects

The long-term exposure DNELS for systemic effects (dermal and inhalation) were calculated as follows:

Dermal DNEL:

The NOAEL of 150 mg/kg bw/day from the 90 -day repeat dose oral study in the rat was taken as the starting point.

The corrected human dermal NOAEL = oral NOAEL(rat) * (Oral Rat Absorption / Dermal human absorption)

Based on the in vitro dermal penetration data, the higher absorption level of 50% associated with 0.5% 3 -amino-4 -octanol solution will be taken as the value for dermal penetration. This is considered to be more conservative since it appears that higher concentrations lead to a lower degree of dermal penetration.

Oral absorption in the rat is taken as 100% in the absence of evidence to the contrary.

Therefore the corrected NOAEL for human dermal absorption = 150* (100/50) = 300 mg/kg bw/day.

An Assessment Factor of 36 was applied. This is made up of the following factors as prescribed by the CSA/CSR guidance documents:

4 = Allometric scaling rat to human

1 = Remaining differences - there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

3 = intra species (worker) based on the guidance by ECETOC and SCOEL on intra-worker variability

3 = conversion from a sub-chronic study to a chronic study

1 = Dose response - there is a clear dose response and the effect driving the NOAEL is not severe

1 = Quality of the database - all the studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

Dermal DNEL = 300/36 = 8.3 mg/kg bw/day

Inhalation DNEL:

Although Octanolamine is not volatile and thus will not have a tendency to form vapors, when used as a metalworking fluid additive it is feasible that aerosols of metalworking fluid will be generated above the machines working the metal. If these machines are not enclosed it is possible that a worker could inhale the mists and subsequently be exposed to octanolamine. Therefore an Inhalation DNEL has been calculated as follows:

The same NOAEL of 150 mg/kg bw/day was used (see above)

The corrected human inhalation NOAEL was calculated as prescribed by the guidance. i.e.

Human corrected Inhalation NOAEL = rat oral NOAEL* (1/sRVrat)*(ABSoral rat/ABS human inhal)*(sRVhuman/wRV)

= 150*(1/0.38)*(100/100)*(6.7/10)

= 264.5 mg/m3

Note: The value for oral absorption was taken as 100%. This is justified in the toxicokinetic statement where it is argued that due to the low molecular weight and LogPow of 1.3, octanolamine is believed to be absorbed well from the gastrointestinal tract. The value used for human inhalation absorption was taken as 100% since it is also likely to be absorbed well through the respiratory epithelia.

Assessment factor of 9 applied:

It was derived according to the guidance as follows:

1 = remaining differences (justification as above)

3 = intra species (worker) (justification as above)

3 = conversion from a sub-chronic study to a chronic study.

1 = Dose response - there is a clear dose response and the effect driving the NOAEL is not severe

1 = Quality of the database - all the studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

Inhalation DNEL = 264.5 / 9 = 29 mg/m³

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14.69 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):

18

Modified dose descriptor starting point:

NOAEC

Value:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

No inhalation study available for the substance. NOAEC calcultated from NOAEL obtained in an oral study.

AF for dose response relationship:

1

Justification:

there is a clear dose response and the effect drving the NOAEL is not severe

AF for differences in duration of exposure:

3

Justification:

conversion from a subchronic study to a chronic study

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

Justification:

there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

AF for intraspecies differences:

6

Justification:

based on the ECETOC report about variabilty within a population

AF for the quality of the whole database:

1

Justification:

ll studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high 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:

4.17 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal study available for the substance. NOAEL calculated from NOAEL obtained in an oral study.

AF for dose response relationship:

1

Justification:

there is a clear dose response and the effect drving the NOAEL is not severe

AF for differences in duration of exposure:

3

Justification:

conversion from a subchronic study to a chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling rat to human

AF for other interspecies differences:

1

Justification:

there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

AF for intraspecies differences:

6

Justification:

based on the ECETOC report about variabilty within a population

AF for the quality of the whole database:

1

Justification:

ll studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.08 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECETOC

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

150 mg/kg bw/day

AF for dose response relationship:

1

Justification:

there is a clear dose response and the effect drving the NOAEL is not severe

AF for differences in duration of exposure:

3

Justification:

conversion from a subchronic study to a chronic study

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling rat to human

AF for other interspecies differences:

1

Justification:

there were no effects observed at the top dose level therefore there appears to be no justification for an additional factor of 2.5

AF for intraspecies differences:

6

Justification:

based on the ECETOC report about variabilty within a population

AF for the quality of the whole database:

1

Justification:

all studies are new and to OECD guidelines (excluding the dermal repeat dose screen) thus the quality of the database is considered to be sufficient.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

The substance is used as an additive in metalworking fluid and paint and coatings, present at levels of approximately 0.1%. Due to the low amount of octanolamine in the metal working fluid and paints and coatings, it is not anticipated that there will be indirect consumer exposure via the handling of manufactured goods.

Indirect exposure via the environment:

Octanolamine is readily biodegradable and so once in the environment following discharge through waste water treatment facilities, it will degrade quickly, minimising/eliminating the potential for indirect exposure via the environment or food. It is not volatile and so it is highly unlikely that the general population could be exposed via the presence of vapours in the air.