Cyclohexyldimethylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.53 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):

50

Dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

26.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

The oral (gavage) developmental toxicity study in the rat (OECD 414) is considered to provide the critical endpoint for DNEL derivation; a NOAEL of 30 mg/kg bw/d was obtained for maternal toxicity based on reduced body weight and food consumption (most likely a result of reduced palatability of the test substance rather than systemic toxicity). As this study is a recent guideline compliant study conducted over a sensitive exposure period it is considered more appropriate for systemic DNEL derivation than the available repeat dose inhalation study.

The NOAEL is modified to obtained the NOAEC as follows:

assuming that inhalation absorption is twice oral absorption = 30 mg/kg bw/d /2 = 15 mg/kg bw/d

taking into account the standard respiratory volume for the rat (8 h exposure) = 15 mg/kg bw/d / 0.38 m³/kg/d = 39.5 mg/m³

taking into account the respiratory volume of the worker (8 h exposure) = 39.5 mg/m³ * (6.7 m³/10 m³) = 26.5 mg/m³

AF for dose response relationship:

1

Justification:

ECHA default factor when the starting point is a NOAEL/NOAEC

AF for differences in duration of exposure:

1

Justification:

An AF for duration of exposure is not considered necessary; animals were dosed during a sensitive time period (Days 3 to 19 of gestation). The NOAEL obtained in the 90-day repeated dose toxicity study is higher (100 mg/kg bw/d) and application of an AF for duration of exposure to this value would result in a DNEL higher than that obtained using the developmental NOAEL. Therefore correction for duration of exposure is not considered necessary.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default factor when the starting point is derived from a rat study

AF for other interspecies differences:

2.5

Justification:

ECHA default value

AF for intraspecies differences:

5

Justification:

ECHA default value for workers

AF for the quality of the whole database:

1

Justification:

ECHA default:comprehensive database

AF for remaining uncertainties:

1

Justification:

ECHA default: no significant 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:

8.3 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor:

NOAEC

Value:

104 mg/m³

AF for dose response relationship:

1

Justification:

ECHA default factor when the starting point is a NOAEC

AF for differences in duration of exposure:

1

Justification:

A factor of 1 is selected on the basis that effects seen in the repeated dose inhalation study were limited to local effects of irritation in the nasal epithelium and are therefore concentration-dependent rather than time-dependent.

AF for interspecies differences (allometric scaling):

1

Justification:

An AF for interspecies differences is not required when setting a local inhalation DNEL based on an inhalation study

AF for other interspecies differences:

2.5

Justification:

Required based on irritant effects noted in respiratory tract (nasal epithelium)

AF for intraspecies differences:

5

Justification:

ECHA default value for workers

AF for the quality of the whole database:

1

Justification:

Whilst the starting point study is not guideline compliant, it was conducted to GLP and is considered to be of sufficient quality with regard to assessment of local irritation

AF for remaining uncertainties:

1

Justification:

ECHA default value: no significant remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.3 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Dose descriptor starting point:

NOAEC

Value:

104 mg/m³

AF for dose response relationship:

1

Justification:

ECHA default factor when the starting point is a NOAEC

AF for interspecies differences (allometric scaling):

1

Justification:

A factor of 1 is selected on the basis that effects seen in the repeated dose inhalation study were limited to local effects of irritation in the nasal epithelium and are therefore concentration-dependent rather than time-dependent.

AF for other interspecies differences:

2.5

Justification:

Required based on irritant effects noted in respiratory tract (nasal epithelium)

AF for intraspecies differences:

5

Justification:

ECHA default value for workers

AF for the quality of the whole database:

1

Justification:

Whilst the starting point study is not guideline compliant, it was conducted to GLP and is considered to be of sufficient quality with regard to assessment of local irritation

AF for remaining uncertainties:

1

Justification:

ECHA default value: no significant remaining uncertainties

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.6 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):

50

Dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

0.6 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The oral (gavage) developmental toxicity study in the rat (OECD 414) is considered to provide the critical endpoint for DNEL derivation; a NOAEL of 30 mg/kg bw/d was obtained for maternal toxicity based on reduced body weight and food consumption (most likely a result of reduced palatability of the test substance rather than systemic toxicity). As there is no information on the extent of oral or dermal absorption, dermal absorption is considered equal to oral absorption (ECHA guidance) and the starting point is not modified.

AF for dose response relationship:

1

Justification:

ECHA default factor when the starting point is a NOAEL

AF for differences in duration of exposure:

1

Justification:

An AF for duration of exposure is not considered necessary; animals were dosed during a sensitive time period (Days 3 to 19 of gestation). The NOAEL obtained in the 90-day repeated dose toxicity study is higher (100 mg/kg bw/d) and application of an AF for duration of exposure to this value would result in a DNEL higher than that obtained using the developmental NOAEL. Therefore correction for duration of exposure is not considered necessary.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default value when using a rat study for derivation of the starting point

AF for other interspecies differences:

2.5

Justification:

ECHA default value

AF for intraspecies differences:

5

Justification:

ECHA default value for workers

AF for the quality of the whole database:

1

Justification:

ECHA default value: comprehensive and good quality database

AF for remaining uncertainties:

1

Justification:

ECHA default value: no significant 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:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

The substance is classified for acute oral, dermal and inhalation toxicity and as corrosive to skin, effects seen in the toxicology studies are indicative of local effects of irritation. There was no clear evidence for systemic toxicity and local effects are expected to dominate following exposure, however DNELs for systemic and local toxicity have been derived where appropriate.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

There will be no exposure of the general public as the substance is only used in industrial settings, therefore DNELs for the general population are not required and have not been derived.