Constitutional isomers of penta-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hexa-O-allyl-β-D-fructofuranosylα-D-glucopyranoside; Constitutional isomers of hepta-O-allyl-β-D-fructofuransoylα-D-glucopyranoside

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.16 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

Modified dose descriptor starting point:

NOAEC

Value:

987.36 mg/m³

Explanation for the modification of the dose descriptor starting point:

corrected starting point (worker, inhalative) = oral NAEL * 1/sRVrat* sRVhuman/wRV *7/5 = 400 mg/kg bw/d/0.38 m3/kg bw/d*6.7m3/10m3*7/5 = 987.36 mg/m3/d

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable

AF for other interspecies differences:

2.5

Justification:

rat to human

AF for intraspecies differences:

5

Justification:

worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

186.67 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

Modified dose descriptor starting point:

NOAEL

Value:

56 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected (high molecular weight, poor water solubility and log Kow>4). Therefore a factor of 0.01 (1% absorption) was introduced for the difference in absorption . corrected starting point (worker, dermal) = oral NAEL * 7/5 /0.01 = 400mg/kg bw/d/0.01 *7/5 = 56000 mg/kg bw/d

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

rat to human

AF for intraspecies differences:

5

Justification:

worker

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

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

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

Additional information - workers

The long-term DNELs are based on a 28 -day oral gavage study performed in rats. The NOAEL in this study was found to be 400 mg/kg bw/d for male and female rats.

Route to route extrapolation (oral to inhalative) was performed according to the ECHA guidance document R.8 (characterization of dose[concentration]-response for human health). The exposure of the test animals was based on 7 days a week. For workers, the expected exposure duration is only 5 days a week. Therefore, a factor of 7/5 was introduced for workers due to the reduced exposure duration (working time of 5 days a week).

For workers:

corrected starting point (worker, inhalative) = oral NAEL * 1/sRV_rat* sRV_human/wRV *7/5

= 400 mg/kg bw/d/0.38 m³/kg bw/d*6.7m³/10m³*7/5 = 987.36 mg/m³/d

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected (high molecular weight, poor water solubility and log K_ow>4). Therefore a factor of 0.01 (1% absorption) was introduced for the difference in absorption .

corrected starting point (worker, dermal) =oral NAEL * 7/5 /0.01 = 400 mg/kg bw/d/0.01 *7/5 = 5600 mg/kg bw/d

For the calculation of the DNEL, the following assessment factors were applied on the corrected starting points:

Dermal DNEL: Allometric scaling factor 4; interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 =300

Inhalation DNEL: Interspecies factor 2.5; intraspecies factor 5; exposure duration factor 6; dose-response factor 1; quality of the database 1 =75

Taken together, the resulting dermal DNELfor workers is 186.67 mg/kg bw/d, theinhalative DNEL is 13.16 mg/m³, respectively.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.32 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:

347.8 mg/m³

Explanation for the modification of the dose descriptor starting point:

corrected starting point (GP, inhalative) = oral NAEL * 1/sRVrat= 400 mg/kg bw/d/1.15 m3/kg/d = 347.8 mg/m3/d

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Not applicable

AF for other interspecies differences:

2.5

Justification:

rat to human

AF for intraspecies differences:

10

Justification:

general public

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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:

DNEL (Derived No Effect Level)

Value:

66.67 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:

40 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected. Therefore, a factor of 0.01 (1% absorption) for the difference in absorption was introduced. corrected starting point (GP, dermal) = oral NAEL/0.01 = 40000 m3/kg/d

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

rat to human

AF for intraspecies differences:

10

Justification:

General public

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

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

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:

DNEL (Derived No Effect Level)

Value:

0.67 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:

400 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Not applicable

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat

AF for other interspecies differences:

2.5

Justification:

rat to human

AF for intraspecies differences:

10

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

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

The long-term DNELs are based on a 28 -day oral gavage study performed in rats. The NOAEL in this study was found to be 400 mg/kg bw/d for male and female rats.

Route to route extrapolation (oral to inhalative) was performed according to the ECHA guidance document R.8 (characterization of dose[concentration]-response for human health).

The calculation of the corrected starting points for the general population was as follows:

For the general population (GP): corrected starting point (GP, inhalative) = oral NAEL * 1/sRV_rat= 400 mg/kg bw/d/1.15 m³/kg/d

= 347.8 mg/m³/dn

Due to the physicochemical properties of the test substance, only limited dermal absorption is expected. Therefore, a factor of 0.01 (1% absorption) for the difference in absorption was introduced.

corrected starting point (GP, dermal) =oral NAEL/0.01 = 40000 m³/kg/d

The DNEL calculation for the general population was performed equally as for the workers. In deviation to that, the assessment factor for intraspecies variability was set to 10 to account for more variability in the general population.

Resulting from this considerations, the DNELs calculated were 66.67 mg/kg bw/d, 0.66 mg/kg bw/d and 6.96 mg/m³for dermal exposure, oral exposure and inhalation, respectively.