Octylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.6 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):

30

Modified dose descriptor starting point:

NOAEC

Value:

137.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

only reliable guideline study with repeated exposure available

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

default value (subacute to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

not necessary, scaling factor 4 used for calculation of inhalation concentration from oral NOAEL

AF for other interspecies differences:

1

Justification:

not necessary for inhalation concentration

AF for intraspecies differences:

5

Justification:

default value

AF for the quality of the whole database:

1

Justification:

default value

AF for remaining uncertainties:

1

Justification:

default value (no remaining uncertainties)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

26.85 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: adoption of the work place limit value of structurally related amines

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

53.7 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

other: adoption of the work place limit value of structurally related amines

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.65 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):

120

Modified dose descriptor starting point:

NOAEL

Value:

78 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

only reliable guideline study with repeated exposure available

AF for dose response relationship:

1

Justification:

default value

AF for differences in duration of exposure:

6

Justification:

default value (subacute to chronic)

AF for interspecies differences (allometric scaling):

4

Justification:

default value (allometric scaling rat)

AF for other interspecies differences:

1

AF for intraspecies differences:

5

Justification:

default value

AF for the quality of the whole database:

1

Justification:

default value

AF for remaining uncertainties:

1

Justification:

default value (no uncertainties)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

N-octylamine is acutely toxic upon all resorption routes. Regarding toxicokinetics, n-octylamine is metabolised via oxidative deamination by MAO (monoamine oxidase) to NH₃and octanal which is further metabolised via aldehyde dehydrogenase and subsequently ß-oxidation. There is no potential for bioaccumulation of n-octylamine.

The acute oral LD₅₀in rats is approx. 315  mg/kg bw, the dermal LD₅₀ was between 200 and 2000 mg/kg bw, and the inhalation LC_{50 (rat, 4 hours)} was 1.6 mg/L. N-octylamine is corrosive to the skin and eyes, and irritating to the respiratory tract. The latter is due to the alkalinity of the free base, which is a common feature of all primary alkylamines, all having an unshared electron pair. Due to corrosivity and for reasons of animal welfare, the possibilities to conduct repeated dose studies are very limited. Therefore, the systemic toxicity of n-octylamine was examined in a combined OECD TG 422 oral rat study using the hydrochloride salt. The NOAEL was 100 mg/kg bw/day for male and female systemic toxicity, and for reproduction and developmental toxicity in this study. N-octylamine lacked genotoxicity in bacterial and mammalian cells in vitro, no micronuclei were observed in vivo in mice after single oral exposure to n-octylamine hydrochloride.

The following DNELs were not derived using the procedure set out in the Guidance Document R8:

- DNELs for dermal exposure, since no sufficient data are available for this; moreover, skin contact should be avoided due to irritation and local cytotoxic effects on the skin and the high systemic toxicity after dermal exposure.

- DNELs for local or systemic effects upon inhalation since there is not sufficient data in order to assess this.

- DNELs for the general population since there is no designed exposure of the general public to this material.

For acute inhalation exposure at the work place a DNEL of 10 ppm [53.7 mg/m³(short term value; local effects)] is proposed, which is twice of the proposed long term Limit Value- Eight hours (5 ppm; 26.85 mg/m³). These proposals are based on the following assumptions

-      the local effects prevail over systemic effects;

-      local effects depend on alkalinity, and are therefore comparable between short and medium size alkylamines in the range C1 to C13;

-      existing Limit Values (as ppm) can therefore directly be read across between alkylamines;

-      most alkylamines have a Limit Value-Eight hours of 5 ppm

-      the short term value (15 minutes) factor is 2, based on the dominance of corrosive effects;

-      for several alkylamines, Limit Values exist since many years worldwide and have proven to warrant safe conditions;

-      re-assessment of Limit Values have been conducted by authorities in several countries

-      bad odour and immediate recognition of skin, eye, or throat irritation provide warnings (thus limiting exposure duration) if the Limit Value would be exceeded

For chronic inhalation exposure, a DNEL of 5 ppm (26.85 mg/m³) could be proposed, according to the rational given above. This would protect against local skin, eye, and respiratory effects, and also against systemic effects. The uptake would be up to 268.5 mg/person within an 8-hour work shift, or 2.74 mg/kg bw/day (7 days/week).

Alternatively, a chronic DNEL could be derived from the results obtained in the subchronic rat study mentioned above. The NOAEL was 100 mg octylamine-hydrochloride/kg bw/day, the highest tested dose. Conversion of the oral NOAEL to the inhalation route, and combination with an overall assessment factor of 30 (5 for intraspecies differences; 6 for extrapolation subacute > chronic), and correction for the molecular weight difference would result in a DNEL of 0.854 ppm (4.58 mg octylamine/m³). This would be only approx. 1/6 of the DNEL of 5 ppm which was suggested based on occupational exposure experience with alkylamines, thus suggesting overprotection against systemic effects. This approach is considered to be very conservative as in the oral study underlying this R2R extrapolation no adverse effects were observed up to the highest concentration tested.

Also, a DNEL for systemic effects after dermal exposure can be derived: Starting point: NOAEL (28d oral, rat, 1-octylamine hydrochloride) = 100 mg/kg bw for systemic effects = 78 mg/kg 1-octylamine, factors according to guidance R.8 for adjustment to chronic exposure (6), workers (5) and allometric scaling for Rat (4). 6*5*4=120.

 

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Additional information - General Population

DNELs not derived because not considered to be relevant: the general public is no target population.