Dimethyl(propyl)amine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

7.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

357 mg/m³

Modified dose descriptor starting point:

NOAEC

Value:

180 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEC of 100ppm (app. 357mg/m³) was corrected for differences in experimental conditions (6h/8h) and increased respiratory volume due to light activity (6.7/10).

AF for dose response relationship:

1

Justification:

NOAEC identified

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

not required

AF for other interspecies differences:

2.5

Justification:

default factor

AF for intraspecies differences:

5

Justification:

default for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.2 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

15

Dose descriptor:

NOAEC

Value:

63 mg/m³

AF for dose response relationship:

1

Justification:

NOAEC identified

AF for differences in duration of exposure:

3

Justification:

In the repeated dose study according to OECD 422, males were exposed for 34 days and females for 59 days. No difference in the severity of local effects was observed. Because of this and the already longer exposure time, the factor from subacute to subchronic was reduced to 1.5, but the factor of 2 for subchronic to chronic was conservatively maintained. This results in an overall assessment factor of 3 for differences in duration.

AF for interspecies differences (allometric scaling):

1

Justification:

not required

AF for other interspecies differences:

1

Justification:

Local effects are based on direct chemical/pH reactivity of the test substance. Additionally, irritating effects were only observed in the upper part of the respiratory tract. Therefore, differences in deposition, airflow patterns, clearance rates, and protective mechanisms were not considered and the default factor can be reduced to 1.

AF for intraspecies differences:

5

Justification:

default factor for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

none

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.2 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEC

Value:

357 mg/m³

Modified dose descriptor starting point:

NOAEL

Value:

104 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The NOAEC for systemic toxicity via inhalation was converted to a dermal NOAEL. The NOAEC was multiplied with the respiratory volume of rats for the exposure period of 6h (0.29 m³/ kg bw).

Since the dermal absorption is assumed to be similar to the inhalation absorption, extrapolation from inhalation to dermal route was performed assuming that 100 % of the amount applied is systemically available and thus, no further modification of the starting point was needed.

AF for dose response relationship:

1

Justification:

NOAEL identified

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in route to route extrapolation, when considering the respiratory volume of experimental animals during the exposure period and the resulting dose.

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

default for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

none

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)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

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:

DNEL (Derived No Effect Level)

Value:

0.97 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Modified dose descriptor starting point:

NOAEL

Value:

145 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

An OECD 422 (BASF, 2019) sub-acute inhalation toxicity study for Dimethylpropylamine is available. The NOAEC for systemic toxicity was identified to be 500 mg/m³.

The NOAEC for systemic toxicity via the inhalation route was adjusted to an NOAEL via the oral route. The NOAEC (500 mg/m³) was multiplied with the respiratory volume of rats for the exposure period of 6h (0.29 m³/ kg bw).

The resulting corrected NOAEL equals to 145 mg/kg bw.

Since the oral absorption is assumed to be similar to the inhalation absorption (irritating effects can influence absorption), extrapolation from inhalation to oral route was performed assuming that 100 % of the amount applied is systemically available and thus, no further modification of the starting point was needed.

AF for dose response relationship:

1

Justification:

NOAEL identified

AF for differences in duration of exposure:

6

Justification:

Subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in route to route extrapolation, when considering the respiratory volume of experimental animals during the exposure period and the resulting dose.

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

10

Justification:

default for general population

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

none

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:

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

Additional information - General Population

Dimethylpropylamine is used in industrial or professional settings only. There are no consumer uses. Hence, there is no exposure of the general population.