Naphthenic acids, reaction products with diethylenetriamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 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):

40

Modified dose descriptor starting point:

NOAEC

Value:

42 mg/m³

Explanation for the modification of the dose descriptor starting point:

NA-DETA is likely to be readily bioavailable both for oral and inhalation routes. Based on the molecular mass and liphophilicity of major components of NA-DETA, it can be predicted that most of the inhalated Na-DETA will be deposited in the upper respiratory tract, resulting into the resorption in the gastro-intestinal tract. Comparable resorption for oral and inhalation routes assumed; Human body weight of 70 kg/person; Daily respiration volume for a worker of 10 m3.

AF for dose response relationship:

1

Justification:

Clear dose responce relation was demontrated; no effect was demonstrated at 100 mg/kg bw in OECD 422 study and at 6 mg/kg bw in subchronic toxicity study.

AF for differences in duration of exposure:

2

Justification:

Extrapolation from subchronic data to chronic exposure situation

AF for interspecies differences (allometric scaling):

4

Justification:

Rats were used in the proposed repeated dose toxicity studies

AF for other interspecies differences:

1

Justification:

The remaining factor is not justified; the target organ is liver and the metabolic overload as mode of action is apparent. Any species difference due to the different toxicodynamic profile is not likely.

AF for intraspecies differences:

5

Justification:

According to ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

The available data to generate the DNEL for NA-DETA does not cover the endpoint developmental toxicity. An OECD 414 study is proposed to fill the data gap. The provided DNEL is based on the repeated dose toxicity of naphthenic acid and should be revised in case that adverse effect occur in the planned OECD 414 study in the dose range of 10 mg/kg bw. All other endpoints are covered either by experimental data on NA-DETA or by read-across.

AF for remaining uncertainties:

1

Justification:

The toxicity variation of naphthenic acids of different sources (commercial vs. oil sands tailings) is considered to be the most critical point related to the hazard assessment of NA-DETA. Since NA-DETA is the reaction mass of the commercial naphthenic acid, the data on commercial naphthenic acid is likely to be more relevant for the NA-DETA. However, in absence of convincing data explaining the toxicity variations, the possible relation of NA-DETA to naphthenic acids of oil sands tailings cannot be rejected. For the derivation of the DNEL for NA-DETA, it is proposed to use the NOAEL of 6 mg/kg bw from subchronic toxicity study on naphthenic acid from oil sands tailings (instead of the NOAEL of 100 mg/kg bw from the OECD 422 study on the commercial naphthenic acid) to cover the uncertainties related to the toxicity variation of naphthenic acids. It is likely that the toxicity of NA-DETA is overestimated and the related risk as well. Such approach is sufficiently conservative to cover the possible potency difference of target and source substances.Further assessment factors related to the read-across uncertainty is considered to be not necessary.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Route of original study:

Oral

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 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):

40

Modified dose descriptor starting point:

NOAEL

Value:

6 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Comparable resorption for oral and dermal routes assumed

AF for dose response relationship:

1

Justification:

Clear dose responce relation was demontrated; no effect was demonstrated at 100 mg/kg bw in OECD 422 study and at 6 mg/kg bw in subchronic toxicity study.

AF for differences in duration of exposure:

2

Justification:

Extrapolation from subchronic data to chronic exposure situation

AF for interspecies differences (allometric scaling):

4

Justification:

Rats were used in the proposed repeated dose toxicity studies

AF for other interspecies differences:

1

Justification:

The remaining factor is not justified; the target organ is liver and the metabolic overload as mode of action is apparent. Any species difference due to the different toxicodynamic profile is not likely.

AF for intraspecies differences:

5

Justification:

According to ECHA REACH Guidance

AF for the quality of the whole database:

1

Justification:

The available data to generate the DNEL for NA-DETA does not cover the endpoint developmental toxicity. An OECD 414 study is proposed to fill the data gap. The provided DNEL is based on the repeated dose toxicity of naphthenic acid and should be revised in case that adverse effect occur in the planned OECD 414 study in the dose range of 10 mg/kg bw. All other endpoints are covered either by experimental data on NA-DETA or by read-across.

AF for remaining uncertainties:

1

Justification:

The toxicity variation of naphthenic acids of different sources (commercial vs. oil sands tailings) is considered to be the most critical point related to the hazard assessment of NA-DETA. Since NA-DETA is the reaction mass of the commercial naphthenic acid, the data on commercial naphthenic acid is likely to be more relevant for the NA-DETA. However, in absence of convincing data explaining the toxicity variations, the possible relation of NA-DETA to naphthenic acids of oil sands tailings cannot be rejected. For the derivation of the DNEL for NA-DETA, it is proposed to use the NOAEL of 6 mg/kg bw from subchronic toxicity study on naphthenic acid from oil sands tailings (instead of the NOAEL of 100 mg/kg bw from the OECD 422 study on the commercial naphthenic acid) to cover the uncertainties related to the toxicity variation of naphthenic acids. It is likely that the toxicity of NA-DETA is overestimated and the related risk as well. Such approach is sufficiently conservative to cover the possible potency difference of target and source substances.Further assessment factors related to the read-across uncertainty is considered to be not necessary.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 mg/kg bw/day

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 mg/cm²

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 mg/cm²

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:

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:

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