Methyl 2-benzoylbenzoate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.367 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):

75

Dose descriptor starting point:

NOAEL

Value:

31.25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

27.55 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL from an OECD 422 oral study was converted to an inhalatory NOAEC according to the following formula. Absorption via the oral route was considered to be less effective by a factor of 2 as a worst case assumption. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 31.25 mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 0.5

AF for dose response relationship:

1

Justification:

NOAEL from an OECD 422 oral study was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

already considered during route to route extrapolation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

default factor for workers

AF for the quality of the whole database:

1

Justification:

reliable guideline (under GLP) study available

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.104 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):

300

Dose descriptor starting point:

NOAEL

Value:

31.25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

31.25 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The same absorption rate is assumed for dermal as for oral uptake

AF for dose response relationship:

1

Justification:

NOAEL from an OECD 422 oral study was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

default factor for workers

AF for the quality of the whole database:

1

Justification:

reliable guideline (under GLP) study available

AF for remaining uncertainties:

1

Justification:

default

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.184 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):

150

Modified dose descriptor starting point:

NOAEC

Value:

27.55 mg/m³

Explanation for the modification of the dose descriptor starting point:

The NOAEL from an OECD 422 oral study was converted to an inhalatory NOAEC according to the following formula. Absorption via the oral route was considered to be less effective by a factor of 2 as a worst case assumption. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 31.25 mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 0.5

AF for dose response relationship:

1

Justification:

NOAEL from an OECD 422 oral study was used as starting point.

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

1

Justification:

already considered during route to route extrapolation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

default factor for the general population

AF for the quality of the whole database:

1

Justification:

reliable guideline (under GLP) study available

AF for remaining uncertainties:

1

Justification:

default

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 (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.052 mg/kg bw/day

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Value:

31.25 mg/kg bw/day

AF for dose response relationship:

1

Justification:

NOAEL from an OECD 422 oral study was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

this factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

default factor for the general population

AF for the quality of the whole database:

1

Justification:

reliable guideline (under GLP) study available

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.052 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):

600

Modified dose descriptor starting point:

NOAEL

Value:

31.25 mg/kg bw/day

AF for dose response relationship:

1

Justification:

NOAEL from an OECD 422 oral study was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure

AF for interspecies differences (allometric scaling):

4

Justification:

this factor describes the differences in metabolic rate between rats and humans based on body weight and is generally applicable to renally excreted substances.

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

default factor for the general population

AF for the quality of the whole database:

1

Justification:

reliable guideline (under GLP) study available

AF for remaining uncertainties:

1

Justification:

defaults

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

Additional information - General Population

A combined repeated dose toxicity study/reproduction/developmental toxicity screening test (OECD 422) was conducted to obtain information on the toxicity of the test item RCX 14-672 after repeated daily administration of RCX 14-672 by oral gavage to Wistar rats at dose levels of 31.25, 125, or 500 mg/kg bw/day. Test item related differences were found in liver and kidney weights at 500 mg/kg bw/day in both sexes and at 125 mg/kg bw/day in males, in correlation with the histopathological changes. The test item administration was associated with hepatocellular hypertrophy of the liver, and degeneration in the cortical/corticomedullary tubules of the kidney in the mid and the high dose in both sexes. The incidence and severity suggested dose relationship in both alterations. Under the conditions of this study, the no observed adverse effect level (NOAEL) for RCX 14-672 is considered to be 31.25 mg/kg bw/day for the parental/adult generation. The NOEL of this study (31.25 mg/kg bw) has been used to derive the DNELs for workers and the general population using the default approach as described in the ECHA Guidance Documents.