Butyronitrile

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):

25

Dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

13.22 mg/m³

Explanation for the modification of the dose descriptor starting point:

The most sensitive endpoint was the 90-day oral study where the rat NOAEL was 15 mg/kg/day for males and 25 mg/kg/day for females. As it is not reasonable to set sex-specific DNEL’s in a work environment, the 15 mg/kg/day value is used for both sexes.

The oral dose was converted to inhalation by dividing by 0.38 m³/kg BW ( for an 8 hour exposure) = 39.47 mg/m³. The was corrected for default bioavailability (100% oral to 50% inhalation) by dividing by 2, = 19.74 mg/m³.  This was corrected for light work by multiplying by 0.67, = 13.22 mg/m³.

AF for dose response relationship:

1

Justification:

Default value

AF for differences in duration of exposure:

2

Justification:

correction for subchronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

No scaling for inhalation

AF for other interspecies differences:

2.5

Justification:

Default value

AF for intraspecies differences:

5

Justification:

Default value

AF for the quality of the whole database:

1

Justification:

Default value

AF for remaining uncertainties:

1

Justification:

Default value

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:

no hazard identified

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:

0.14 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):

100

Dose descriptor starting point:

NOAEL

Value:

15 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

14.07 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The most sensitive endpoint was the 90-day oral study where the rat NOAEL was 15 mg/kg/day for males and 25 mg/kg/day for females. As it is not reasonable to set sex-specific DNEL’s in a work environment, the 15 mg/kg/day value is used for both sexes.

The oral dose was converted from a 7 day exposure in the rat study to a 5 day work wee exposure by multiplying by 1.4 (15*1.4= 21 mg/kg/day). This was corrected for light work by multiplying by 0.67 (21* 0.67 = 14.07.

AF for dose response relationship:

1

Justification:

Default value

AF for differences in duration of exposure:

2

Justification:

subchronic to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default value

AF for other interspecies differences:

5

Justification:

Default value

AF for intraspecies differences:

2.5

Justification:

Default value

AF for the quality of the whole database:

1

Justification:

Default value

AF for remaining uncertainties:

1

Justification:

Default value

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Explanation for the modification of the dose descriptor starting point:

No DNEL for acute/short-term exposure via dermal route is needed, because the acute systemic toxicity of N-Butyronitrile by dermal route is low (LD50 > 2000 mg/kg bw). The long-term systemic DNEL is sufficient to ensure that acute systemic effects do not occur, provided high-peak acute exposure can be avoided.

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

DNEL Derivations for n-Butyronitrile (NBN)

 

General Population: As NBN is only used as in industrial product, with limited uses and is available to the general population, DNEL values for the general population were not calculated.

 

Workers:

Long-term

Inhalation

- The most sensitive endpoint was the 90-day oral study where the rat NOAEL was 15 mg/kg/day for males and 25 mg/kg/day for females. As it is not reasonable to set sex-specific DNEL’s in a work environment, the 15 mg/kg/day value is used for both sexes.

- The oral dose was converted to inhalation by dividing by 0.38 m³/kg BW ( for an 8 hour exposure) = 39.47 mg/m³. The was corrected for default bioavailability (100% oral to 50% inhalation) by dividing by 2, = 19.74 mg/m³.  This was corrected for light work by multiplying by 0.67, = 13.22 mg/m³.

- For the assessment factors, the following were used: 1 for interspecies (no allometric scaling for inhalation), 5 for intraspecies, 2 for subchronic to chronic and 2.5 for remaining interspecies for a total of 25. 13.22/25 = 0.53 mg/m³.

Dermal:

-- The most sensitive endpoint was the 90-day oral study where the rat NOAEL was 15 mg/kg/day for males and 25 mg/kg/day for females. As it is not reasonable to set sex-specific DNEL’s in a work environment, the 15 mg/kg/day value is used for both sexes.

- The oral dose was converted from a 7 day exposure in the rat study to a 5 day work wee exposure by multiplying by 1.4 (15*1.4= 21 mg/kg/day). This was corrected for light work by multiplying by 0.67 (21* 0.67 = 14.07.

- Adjustment factors were 5 for intraspecies, 4 for allometric scaling, 2.5 for remaining interspecies and 2 for subchronic to chronic (100 total).  

- The DNEL is 14.07/100 = 0.14 mg/kg/day

 

Oral: 

Oral DNEL’s are not developed for workers.

Acute DNEL’s

- According to REACH Appendix R.8-8, Acute Toxicity, an acute DNEL is only developed if the long-term DNEL is not adequate for worker protection and there is evidence of a “peak exposure”.  NBN is a industrial chemical is that normally used in closed systems. Any sort of exposure is highly discouraged, so there should never be a “peak exposure” situation, and the long-term DNEL should be protective.

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 (no further information necessary)

Additional information - General Population

N-Butyronitrile is used exclusively in industry so exposure to the general population is not a valid parameter.