Ethylenediaminetetraacetonitrile

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.4 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEC

Value:

220 mg/m³

Explanation for the modification of the dose descriptor starting point:

systemic effects present in 6-wk oral study

AF for dose response relationship:

1

Justification:

NOAEL availabale

AF for differences in duration of exposure:

4

Justification:

from 6-week to subchronic (2) and from subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

already in sRV

AF for other interspecies differences:

2.5

Justification:

systemic effects

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

well performed study available

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.75 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

750 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

systemic effects present in 6-wk oral study

AF for dose response relationship:

1

Justification:

NOAEL available

AF for differences in duration of exposure:

4

Justification:

from 6-week to subchronic (2) and from subchronic to chronic (2)

AF for interspecies differences (allometric scaling):

4

Justification:

standard factor

AF for other interspecies differences:

2.5

Justification:

systemic effects

AF for intraspecies differences:

5

Justification:

workers

AF for the quality of the whole database:

1

Justification:

well performed study

AF for remaining uncertainties:

1

Justification:

no remaining uncertainties

Acute/short term exposure

DNEL related information

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

This dossier is a registration of a well contained transported isolated intermediate. As such exposure is not likely. However, because toxicity data are available on repeated exposure, DNELs for worker exposure (long term, systemic, inhalation and dermal) have been calculated.

Dermal Worker-DNEL-long-term systemic

There is no data available on systemic toxicity following repeated dermal exposures. However, a DNEL for dermal route can be derived by route-to-route extrapolation from an oral NOAEL of 250 mg/kg bw/day from a 6 -week study in rat. Since it is generally accepted that substances with log Pow ranging from 0.1 to 6 penetrate the skin easily, it is to be expected that EDTN will not penetrate the skin to a large extent. As such it is expected that

dermal absorption will be lower than oral absorption, a conservative factor of 1/3 was used for oral-to-dermal extrapolation.

Thus calculated: dermal absorption is 1; oral absorption 3. Corrected dermal NOAEL = oral NOAEL x [absorption (oral-rat) / absorption (dermal-human)]. This will be: 250 x 3/1 = 750 mg/kg

Assessment factors:

- Interspecies (allometric scaling): 4

- Interspecies (remaining differences): 2.5 (systemic effects)

- Intraspecies for workers: 5

- Exposure duration 6 -week to subchronic (2) and from subchronic to chronic (2): 4

This results in a total assessment factor of 200, indicating a DNEL of 750/200 = 3.75 mg/kg bw/day.

Inhalation Worker-DNEL-long-term systemic

There is no data available on systemic toxicity following repeated inhalation exposures. However, a DNEL for the inhalation route can be derived by route-to-route extrapolation from an oral NOAEL of 250 mg/kg bw/day from a 6 -week study in rat.

- Corrected inhalatory NOAEC = oral NOAEL x (1/sRVrat)x(ABSoral-rat/ABSinh-human)x(sRVhuman/wRV) =

250 mg/kg bw/day x (1/0.38m³) x (1/2) x (6.7m³/10m³ = 220 mg/m³

ABS: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume

- Interspecies (allometric scaling): 1 (not needed, already in sRV)

- Interspecies (remaining differences): 2.5 (systemic effects)

- Intraspecies for workers: 5

- Exposure duration 6 -week to subchronic (2) and from subchronic to chronic (2): 4

This results in a total assessment factor of 50, indicating a DNEL of 220/50 = 4.4 mg/m³.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified