Benzylamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14.7 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEC

Value:

264.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by the inhalation route available.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

1

Justification:

There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.

AF for intraspecies differences:

3

Justification:

The (ECETOC) default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach of the DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

44.1 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

3

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

DNEL related information

DNEL derivation method:

other: VCI (2010)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

3

DNEL extrapolated from long term DNEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.3 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

72

Modified dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by the dermal route available.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

6

Justification:

The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

1

Justification:

Interspecies differences including toxicokinetics are fully covered by the allometric scaling. There is no additional evidance for species differences including toxicodynamics. Therefore, no additional factor is used.

AF for intraspecies differences:

3

Justification:

The (ECETOC) default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

The information related to acute/short-term and long-term exposure hazards via the different exposure routes has been commented/discussed above. For exposure hazards, where a more detailed discussion is appropriate, additional information is provided below.

 

Local effects via inhalation route

 

Long term exposure

The worker-DNEL long-term for inhalation route - local below was calculated with a LOAEL obtained in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422, BASF SE, 2013) performed with Benzylamine and compared with the above generic DNEL of 1 mg/m³ in order to justify the selection on the basis of the most conservative approach.

Hazard assessment conclusion: DNEL (Derived No Effect Level) = 5.9 mg/m³

Most sensitive endpoint: repeated dose toxicity (OECD 422); Route of original study: Oral

 

DNEL related information

DNEL derivation method: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF): 3

Dose descriptor starting point (after route to route extrapolation): NOAEC = 17.6 mg/m³

 

AF for dose response relationship: 1

Justification: The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure: 1

Justification: When comparing subacute to chronic exposure duration, irritation responses are considered to be mostly concentration dependent; no duration-based difference between subacute and chronic exposure is assumed.

AF for interspecies differences (allometric scalling): 1

Justification: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences: 1

Justification: There is no additional evidence for species differences including toxicodynamics (ECETOC). Therefore, no additional factor is used.

AF for intraspecies differences: 3

Justification: The (ECETOC) default value for the relatively homogenous group "worker" is used.

AF for the quality of the whole database: 1

Justification: The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties: 1

 

Justification: The approach of the DNEL derivation is conservative. No further assessment factors are required.

Justification and comments: The worker-DNEL long-term for inhalation route - local is derived from the LOAEL for local effects of 30 mg/kg bw/day, obtained in the key subacute oral repeated dose study in Wistar rats (BASF SE, 2013), where histological lesions in the stomach occurred down to the lowest dose level tested (30 mg/kg bw/d). The NOAECcorr is calculated as follows: NOAECcorr = 30 mg/kg bw/day*(1/0.38 m³/kg bw/d)*(6.7 m³ (8h)/10 m³ (8h))/3 = 17.6 mg/m³, with: 30 mg/kg bw/day: LOAEL (local effects), (1/0.38 m³/kg bw/d): correction factor for sRVrat, (6.7 m³ (8h)/10 m³ (8h)): correction factor for physical activity, 3: factor for LOAEL-to-NOAEL extrapolation.

 

Acute/short term exposure

The worker-DNEL acute for inhalation route - local of 3 mg/m³ has been set at three times of the corresponding long-term DNEL derived by the recommended VCI DNEL of 1 mg/m³ for test substances classified with R34 (causes burns) according to Directive 67/548/EEC.

 

With regard to local effects after acute inhalation exposure a Protective Action Criteria 1 (PAC-1) value of 2 mg/m³ is published for Benzylamine. The PAC-1 value is the airborne concentration of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory effects. These effects are not disabling and are transient and reversible upon cessation of exposure. The PAC-1 value is a conservative value with regard to the acute exposure situation at the workplace as workers represent a more homogenous and less susceptible population group than the general population and peak exposure of workers is limited to 15 min whereas the PAC-1 value covers peak exposure up to 60 min.

 

The worker-DNEL acute for inhalation route - local of 3 mg/m³ derived on the basis of the generic DNEL of 1 mg/m³ (VCI, 2010) for workers is in the same range as the PAC-1 value of 2 mg/m³ for the general population group, and is, in view of the different underlying exposure durations, considered as the more conservative value. Therefore the selection of the worker-DNEL acute inhalation route - local of 3 mg/m³ is justified.

 

Conclusion

On this basis, the worker-DNEL long-term for inhalation route - local and the worker-DNEL acute for inhalation route - local are set at 1 and 3 mg/m³, respectively.

 

References:

- VCI (Verband der Chemischen Industrie e.V.) (2010). Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität. Published 21.01.2010.

- PAC (Protective Action Criteria). Rev. 27, February 2012. 2012.http://www.atlintl.com/DOE/teels/teel.html.

- ECHA (2012). ECHA Guidance on IR/CSR Part E

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

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

Benzylamine is neither marketed to the general public nor intentionally added to consumer products. Also, consumer products do not contain substances from which Benzylamine is intended to be released. Thus the derivation of general population DNELs is not required.