5-methylheptan-3-one

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10.759 mg/m³

Most sensitive endpoint:

developmental toxicity / teratogenicity

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:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

264.474 mg/m³

Explanation for the modification of the dose descriptor starting point:

NOAEC=NOAELoral_rat/(AF1*AF2*AF3)=300/(0.38*2.0*1.5)=264.474 mg/m³. Three AF were used for the extrapolation from the oral to the inhalation route: 1) AF1=0.38 to convert oral NOAELrat_rat (in mg/kg bw/day) into inhalatory NOAECinhal_rat (in mg/m3) by using a default respiratory volume for the rat corresponding to the daily duration of human exposure (Table R. 8-2 p.20), 2) AF2=2.0 to correct for differences in absorption between routes (it is assumed that the absorption percentage for the starting route is half that of the end route in the case of oral-to inhalation extrapolation in the absence of substance specific data on absorption via the different routes. R8, p.19), 3) AF3=1.5 to correct for the difference between respiratory rates under standard conditions and under conditions of light activity for workers (Table R. 8-2 p.20). [1.5 from 10 m3 per worker divided by 6.7 m3 per person].

AF for dose response relationship:

1

Justification:

Default assessment factor, as a standard procedure, is 1. (R8, p.30).

AF for differences in duration of exposure:

2

Justification:

sub-chronic to chronic (Table R. 8-5 p.29)

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling (AS) from Oral_rat to Inhalation_human factor do not apply (Table R. 8-4 p.26) with the prefered approach (step 1.route-to-route extrapolation within one species, step 2. interspecies extrapolation within the same exposure route), which was used here (see right-hand side of the example R. 8-2 p. 59). The alternative approach is reverse (step 2. before step 1.) and allometric scaling would apply in this case (see left-hand side of the example R. 8-2 p. 59)

AF for other interspecies differences:

2.5

Justification:

The default value of 2.5 is used to correct for other interspecies differences because EAK is taken up via the mucuous membrane of the respiratory tract in the system (R8, p.24: If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

5

Justification:

For workers, as standard procedure for threshold effects, a default assessment factor of 5 is to be used (R8 p.28)

AF for the quality of the whole database:

1

Justification:

Assumption: good/standard quality of database, i.e. standard data requirements are fulfilled (R8, p. 31)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

53 mg/m³

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Dose descriptor starting point:

other: IOEL

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3 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:

300 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Default factor according to R8, p. 19; On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i. e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

When the starting point for the DNEL calculation is a NOAEL, the default assessment factor, as a standard procedure, is 1. (R8, p.30). A factor of 1 was chosen eventhough only 5 rats were used as the study complies to all other requirements from OECD

AF for differences in duration of exposure:

2

Justification:

Chronic to sub-chronic (Table R. 8-5 p.29)

AF for interspecies differences (allometric scaling):

4

Justification:

Allometric factor may be used according to Table R. 8.4 (Oral_rat to Dermal_human). Allometric factor taken from Table R. 8.3

AF for other interspecies differences:

2.5

Justification:

The default value of 2.5 is used to correct for other interspecies differences because EAK is taken up via the skin in the system (R8, p.24: If no substance-specific data are available, the standard procedure for threshold effects would be, as a default, to correct for differences in metabolic rate (allometric scaling) and to apply an additional factor of 2.5 for other interspecies differences, i.e. toxicokinetic differences not related to metabolic rate (small part) and toxicodynamic differences (larger part)

AF for intraspecies differences:

5

Justification:

For workers, as standard procedure for threshold effects, a default assessment factor of 5 is to be used (R8 p.28)

AF for the quality of the whole database:

1

Justification:

Assumption: good/standard quality of database, i.e. standard data requirements are fulfilled (R8, p. 31)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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

Acute systemic hazards via inhalation were not evaluated since acute local data (IOEL) available is more relevant than a derivation of the DNEL for acute systemic effect from a LC50.

As 5-methylheptan-3-one is not classified for acute toxicity via skin, short-term systemic exposure does not have to be evaluated according to the REACH "Guidance on information requirements and chemical safety assessment Chapter R.8: Characterization of dose [concentration]-response for human health".

As no information on dose-response for eye (local effect) and skin is available, no DNEL was derived for these endpoints. However, a qualitative approach to assessing and controlling the risks was followed (Guidance on information requirements and chemical safety assessment Part E: Risk Characterization). As 5-methyheptan-3-one was simultaneously classified with the H-phrases H319 (causes serious eye irritation, R36 according to Directive 67/548/EEC), H315 (causes skin irritation, R38 according to Directive 67/548/EEC) and H335 (STOT SE 3, R37 according to Directive 67/548/EEC) according to Regulation (EC) 1272/2008, it was allocated to the medium hazard category.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified