Tributylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.3 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):

25

Dose descriptor starting point:

NOAEL

Value:

75 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

132.2 mg/m³

Explanation for the modification of the dose descriptor starting point:

The modified dose descriptor starting point was calculated according to the method recommended by the Guidance on Information Requirements and Chemical Safety Assessment R.8 (see example R.8 -2: 75 * 1/0.38 * 6.7/10).

AF for dose response relationship:

1

Justification:

standard factor

AF for differences in duration of exposure:

2

Justification:

standard factor for subchronic to chronic extrapolation

AF for interspecies differences (allometric scaling):

1

Justification:

standard starting point was an air concentration

AF for other interspecies differences:

2.5

Justification:

standard factor for remaining interspecies differences

AF for intraspecies differences:

5

Justification:

standard factor

AF for the quality of the whole database:

1

Justification:

standard factor

AF for remaining uncertainties:

1

Justification:

standard factor

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: based on long term value with an exceedance factor of 2 for the acute exposure

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

15.2 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:

15.2 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

acute toxicity

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Systemic effects

With the 90 -day oral study in rats a valid study became available for the evaluation of systemic toxicity after repeated exposure. A NOAEL of 75 mg/kg bw/d was derived from this study which can be used as basis for the derivation of inhalative systemic DNELs after route-to-route extrapolation.

For the inhalation route the modified dose descriptor starting point (132.2 mg/m³) was calculated according to the method recommended by the Guidance on Information Requirements and Chemical Safety Assessment R.8 (see example R.8 -2: 75 * 1/0.38 * 6.7/10). Applying an overall assessment factor of 25 (factor 5 for intraspecies variability, factor 2.5 for remaining interspecies variability and factor 2 for subchronic to chronic extrapolation) results in a long-term systemic inhalation DNEL of 5.3 mg/m³. No additional factor for route-to-route extrapolation was applied, as 100% absorption was assumed for both routes.

No adequate data are available for the derivation of an acute systemic inhalation DNEL. However, a DNEL of 10.6 mg/m³could be derived by applying an exceedance factor of 2 for acute effects. Numerically, such a value would also result on basis of the NOAEL of the 90-day study with an overall assessment factor of 12.5 (i.e. same basis as for the long-term DNEL without time-extrapolation factor), which would be a very conservative approach for an acute DNEL. This value is well below the inhalation LC50 of 500 mg/m³ and below the DNEL for local effects which has proven to be safe under workplace conditions.

Due to the high toxicity after acute dermal exposure (Acute Tox 2, H310: Fatal in contact with skin) a qualitative assessment of the systemic toxicity after dermal exposure according to the Guidance on Information Requirements and Chemical Safety Assessment, Part E is performed in the CSR (high hazard).

Local effects

No adequate inhalation studies are available for tri-n-butylamine to assess its local effects. In general, alkylamines are caustic, and local effects prevail over systemic effects after inhalation exposure, i.e. it is not possible to reach concentrations which produce systemic toxicity . Therefore,it is proposed to compare existing MAK-values for alkylamines. These take experimental results and human experience at the workplace into consideration. Irritation in humans is expected to occur at 10 ppm and above. This is largely based on the pKa value, and therefore there is only little difference between primary, secondary, and tertiary saturated linear or branched alkylamines. As a result MAK values range from 2 to 5 ppm. For TnBA a conservative MAK value of 2 ppm is proposed for local effects after inhalation exposure. This value is considered conservative because it was established for primary butylamines on the basis of mucous membrane irritation (i.e. RD50 values for respiratory depression in mice). In contrats to monobutylamine, TnBA was not sufficiently irritating to reach a 50% respiratory depression. By definition MAK values are derived to provide a long-term worker protection, and therefore they can also be used as a worker long-term inhalation DNEL value.

It should be noted that tributylamine caused pulmonary irritation (tRD50 = 96 ppm) in mice. Sensory irritation was minor, unlike findings with other alkylamines. The authors proposed a TLV in the range 1 to 2.2 ppm (Nielsen and Yamagiwa, 1989).

A DNEL for local effects after acute and long-term inhalation exposure of 15.2 mg/m3 results considering a conversion factor (1 ppm = 7.70 mg/m³ (20°C)).

Tributylamine is classified as skin irritant (Skin Irrit. 2; H315: Causes skin irritation), but no dose-response data are available, which would allow derivation of a DNEL for local effects. Therefore, a qualitative risk characterisation according to the Guidance on Information Requirements and Chemical Safety Assessment, Part E is performed in the CSR for these effects (low hazard).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

No data derived, considered to be not relevant, as the general public is no target population.