D-glucono-1,5-lactone

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

59 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

13

Modified dose descriptor starting point:

NOAEC

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

50

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

Acute DNELs:

Worker: Production of the gluconates is in excess of 10 t/y. According to the REACh "Guidance on information requirements and chemical safety assessment, Part B: Hazard Assessment", above 10 t/y, the establishment of acute toxicity DNEL is unnecessary in most cases, as the DNEL based on long-term exposure is normally sufficient to ensure that adverse effects do not occur. Thus, as long term DNELs are available for gluconates and these substances are not classified for acute toxicity via any route of exposure, separate acute DNELs were not derived.

Long-term DNELs:

DNELs are based on the oral rat study (key study selected) entitled "Teratologic evaluation of FDA 71-72 (Glucono-Delta-Lactone). With respect to the most sensitive endpoint, although the study was for teratogenicity, the chemical was not found to be a teratogen or developmental toxicant; thus the most sensitive endpoint was selected as repeated dose toxicity.

Starting Dose for DNEL calculation:

594 mg/kg/day (based on NOAEL)

Modified dose for DNEL Calculation

Worker – Inhalation = 594 mg/kg/day x 1/0.38 x 6.7/10 x 70.5%/100% (adjustment for differences in absorption) = 738 mg/m3

Worker – Dermal = 594 mg/kg/day (no adjustment for absorption)

Assessment Factors (AF) –

Worker – Inhalation = 2.5 (for non-metabolic species differences) x 5 for (intraspecies difference); no scaling factor required (as per REACh guidance); no duration factor applied since exposure was for sensitive lifestage (in utero)

Worker – Dermal = 4 x 2.5 (species differences) x 5 for (intraspecies difference); no scaling factor required (as per REACh guidance); no duration factor applied since exposure was for sensitive lifestage (in utero)

Absorption assumed to be 70.5% for oral absorption (toxicokinetic statement). In the absence quantifiable data, inhalation absorption was assumed to be 100%. While the high molecular weight (178.14 g/mol) and high water solubility of D-glucono-δ-lactone do not favour its absorption via the dermal route of exposure, in the absence of quantifiable data, absorption via the dermal route was assumed to be the same as for oral absorption.

Final DNELs

Worker – Inhalation = 59 mg/m3

Worker – Dermal = 11.9 mg/kg/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

14.6 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

25

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.9 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

100

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

Acute DNELs - General Population: Similar to above for worker, assessment of acute systemic effects should default to the long term systemic DNELs. Also, gluconates are not classified as irritant or other endpoints; default to systemic DNEL for inhalation local effects.

Long-term DNELs:

DNELs are based on the oral rat study (key study selected) entitled "Teratologic evaluation of FDA 71-72 (Glucono-Delta-Lactone). With respect to most sensitive endpoint, although the study was for teratogenicity, the chemical was not found to be a teratogen or developmental toxicant; thus the most sensitive endpoint was selected as repeated dose toxicity.

Starting Dose for DNEL calculation:

594 mg/kg/day (based on NOAEL)

Modified dose for DNEL Calculation

General Population – Inhalation = 594 mg/kg/day x 1/1.15 x 70.5%/100% (adjustment for differences in absorption) = 364 mg/m3

General Population – Oral/Dermal = 594 mg/kg/day (no adjustment for absorption)

Assessment Factors (AF) –

General – Inhalation = 2.5 (for non-metabolic species differences) x 10 for (intraspecies difference); no scaling factor required (as per REACh guidance); no duration factor applied since exposure was for sensitive lifestage (in utero)

General Population – Oral/Dermal = 4 x 2.5 (species differences) x 10 for (intraspecies difference); no scaling factor required (as per REACh guidance); no duration factor applied since exposure was for sensitive lifestage (in utero)

Absorption

Same as for worker.

Final DNELs General Population – Inhalation = 14.6 mg/m3

General Population – Oral& Dermal = 5.9 mg/kg/d