Potassium iodide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.07 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):

1

Modified dose descriptor starting point:

NOAEC

Value:

0.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

As per ECHA Guidance R.8 Appendix R.8-2.: Corrected inhalatory NOAEC = oral NOAEL x ABSoral-human/ABSinh-human x average human bw /wRV = 0.01 x 100/100 x 70/10 = 0.07 mg/m3 Available data indicate that iodide is well absorbed orally therefore it is assumed that human oral absorption = 100% and that as a worst case human inhalation absorption = 100% as per ECHA Guidance R.8.4.2.

AF for dose response relationship:

1

Justification:

Default value for NOAEL as per ECHA Guidance R.8.4.3.1

AF for differences in duration of exposure:

1

Justification:

Chronic human studies were used to determine the oral NOAEL, which is equal to the WHO TDI. ECHA Guidance R.8.4.3.1 states that, if an adequate chronic toxicity study is available, this is the preferred starting point and no assessment factor for duration extrapolation is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for other interspecies differences:

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for intraspecies differences:

1

Justification:

A low AF is justified as studies used to determine oral NOAEL included sensitive subpopulations i.e. elderly and children. ECHA Guidance Appendix R. 8-15, Section 7.A.1.3 states that there can be cases where the sample (i.e. the population) in a good quality human study is so heterogeneous and well characterised for different 'aspects' of intraspecies variation that the use of a lower than standard AF i.e. 1-2, is justified.

AF for the quality of the whole database:

1

Justification:

Oral NOAEL is based on WHO TDI, which was determined using high quality human studies as assessed using the criteria in ECHA Guidance Appendix R. 8-15

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 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):

1

Modified dose descriptor starting point:

NOAEL

Explanation for the modification of the dose descriptor starting point:

As per ECHA Guidance R.8 Appendix R.8-2.: Corrected dermal NOAEL = oral NOAEL x ABSoral-human/ABSderm-human = 0.01 x 100/1 = 1 mg/kg bw/day. Assuming human oral absorption = 100% (worst case). Dermal absorption of iodide is considered to be negligible (Louk A. R. M. Pechtold et al., 2001) therefore human dermal absorption of 1% is assumed.

AF for dose response relationship:

1

Justification:

Default value for NOAEL as per ECHA Guidance R.8.4.3.1

AF for differences in duration of exposure:

1

Justification:

Chronic human studies were used to determine the oral NOAEL, which is equal to the WHO TDI. ECHA Guidance R.8.4.3.1 states that, if an adequate chronic toxicity study is available, this is the preferred starting point and no assessment factor for duration extrapolation is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for other interspecies differences:

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for intraspecies differences:

1

Justification:

A low AF is justified as studies used to determine oral NOAEL included sensitive subpopulations i.e. elderly and children. ECHA Guidance Appendix R. 8-15, Section 7.A.1.3 states that there can be cases where the sample (i.e. the population) in a good quality human study is so heterogeneous and well characterised for different 'aspects' of intraspecies variation that the use of a lower than standard AF i.e. 1-2, is justified.

AF for the quality of the whole database:

1

Justification:

Oral NOAEL is based on WHO TDI, which was determined using high quality human studies as assessed using the criteria in ECHA Guidance Appendix R. 8-15

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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

Because the dermal route and inhalation route are not likely exposure route to human the DNEL of systemic effects for these two routs are unnecessary to be derived.

The existing data show the iodide is not skin/eye irritant, so the DNEL of local effects for skin is also unnecessary to be derived.

In addition, due to same reason of unlikely exposure by inhalation, the DNEL of local effects for inhalation is unnecessary.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.035 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):

1

Modified dose descriptor starting point:

NOAEC

Value:

0.035 mg/m³

Explanation for the modification of the dose descriptor starting point:

As per ECHA Guidance R.8 Appendix R.8-2.: Corrected inhalatory NOAEC = oral NOAEL x ABSoral-human/ABSinh-human x average human bw /gpRV = 0.01 x 100/100 x 70/20 = 0.035 mg/m3 Available data indicate that iodide is well absorbed orally therefore it is assumed that human oral absorption = 100% and that as a worst case human inhalation absorption = 100% as per ECHA Guidance R.8.4.2.

AF for dose response relationship:

1

Justification:

Default value for NOAEL as per ECHA Guidance R.8.4.3.1

AF for differences in duration of exposure:

1

Justification:

Chronic human studies were used to determine the oral NOAEL, which is equal to the WHO TDI. ECHA Guidance R.8.4.3.1 states that, if an adequate chronic toxicity study is available, this is the preferred starting point and no assessment factor for duration extrapolation is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for other interspecies differences:

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for intraspecies differences:

1

Justification:

A low AF is justified as studies used to determine oral NOAEL included sensitive subpopulations i.e. elderly and children. ECHA Guidance Appendix R. 8-15, Section 7.A.1.3 states that there can be cases where the sample (i.e. the population) in a good quality human study is so heterogeneous and well characterised for different 'aspects' of intraspecies variation that the use of a lower than standard AF i.e. 1-2, is justified.

AF for the quality of the whole database:

1

Justification:

Oral NOAEL is based on WHO TDI, which was determined using high quality human studies as assessed using the criteria in ECHA Guidance Appendix R. 8-15

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 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):

1

Modified dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

As per ECHA Guidance R.8 Appendix R.8-2.: Corrected dermal NOAEL = oral NOAEL x ABSoral-human/ABSderm-human = 0.01 x 100/1 = 1 mg/kg bw/day. Assuming human oral absorption = 100% (worst case). Dermal absorption of iodide is considered to be negligible (Louk A. R. M. Pechtold et al., 2001) therefore human dermal absorption of 1% is assumed.

AF for dose response relationship:

1

Justification:

Default value for NOAEL as per ECHA Guidance R.8.4.3.1

AF for differences in duration of exposure:

1

Justification:

Chronic human studies were used to determine the oral NOAEL, which is equal to the WHO TDI. ECHA Guidance R.8.4.3.1 states that, if an adequate chronic toxicity study is available, this is the preferred starting point and no assessment factor for duration extrapolation is needed.

AF for interspecies differences (allometric scaling):

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for other interspecies differences:

1

Justification:

Oral NOAEL was determined from human studies. ECHA Guidance R.8.1.2.8 states that no inter-species AF is needed when human data are used for derivation of DNEL.

AF for intraspecies differences:

1

Justification:

A low AF is justified as studies used to determine oral NOAEL included sensitive subpopulations i.e. elderly and children. ECHA Guidance Appendix R. 8-15, Section 7.A.1.3 states that there can be cases where the sample (i.e. the population) in a good quality human study is so heterogeneous and well characterised for different 'aspects' of intraspecies variation that the use of a lower than standard AF i.e. 1-2, is justified.

AF for the quality of the whole database:

1

Justification:

Oral NOAEL is based on WHO TDI, which was determined using high quality human studies as assessed using the criteria in ECHA Guidance Appendix R. 8-15

AF for remaining uncertainties:

1

Justification:

There are no remaining uncertainties

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

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:

0.01 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.01 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Because the dermal route and inhalation route are not likely exposure route to human the DNEL of systemic effects for these two routs are unnecessary to be derived. The existing data show the iodide is not skin/eye irritant, so the DNEL of local effects for skin is also unnecessary to be derived. In addition, due to same reason of not likely exposure by inhalation, the DNEL of local effects for inhalation is unnecessary. The acute and long-term DNELs of systemic effects by oral for consumers have been derived. Because the TDI of iodide has been estimated by WHO (using human data - NOAELhuam 0.01 mg/kg bw, and AF 1 ). Therefore the DNEL oral for consumers is used same with the TDI, 0.01 mg/kg bw.