Iodine

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

Dose descriptor starting point:

NOAEL

Value:

0.01 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

0.07 mg/m³

Explanation for the modification of the dose descriptor starting point:

A chronic NOAEL in humans has been set at 0.01 mg/kg bw/day and is the dose descriptor starting point.

Inhalation correction starting point: Inhalation NOAEL = Oral NOAEL x Standard worker human body weight (70 kg)/ Breathing volume for workers in 8 hours assuming light activity (10 m³). Inhalation NOAEL = 0.07 mg/m^3.

Interspecies differences: 1 (NOAEL is based on a human study); Intraspecies differences: 1 (The NOAEL was obtained from a children study, already considered a sensitive subpopulation, ATSDR indicates that the NOAEL would also applicable to elderly who may represent another sensitive subpopulation); Differences in duration of exposure: 1 (Study on chronic effects); Issue related to dose-response: 1 (Starting point NOAEL); Quality of whole database: 1 (A large set of information is available for the substance).

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

AF for intraspecies differences:

1

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Explanation for the modification of the dose descriptor starting point:

The short-term DNEL for local effects is considered sufficiently protective for short-term systems effects based on precedence of hazards.

Irritation is likely to occur at lower concentrations than systemic effects.

Local effects

Long term exposure

Hazard assessment conclusion:

insufficient hazard data available (further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal 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

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1

Dose descriptor starting point:

NOAEL

Value:

0.01 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

0.01 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

A chronic NOAEL in humans has been set at 0.01 mg/kg bw/day and is the dose descriptor starting point.

Dermal correcting starting point: Dermal NOAEL = Oral NOAEL x No default factor (1). Dermal NOAEL = 0.01 mg/kg bw/day. The factor of 1 is provided on page 25 of Chapter R8 as dermal absorption is not higher than oral absorption, and that no factor should be introduced when performing oral-to-dermal extrapolation.

Overall assessment factors: Interspecies differences: 1 (NOAEL is based on a human study); Intraspecies differences: 1 (The NOAEL was obtained from a children study, already considered a sensitive subpopulation, ATSDR indicates that the NOAEL would also applicable to elderly who may represent another sensitive subpopulation); Differences in duration of exposure: 1 (Study on chronic effects); Issue related to dose-response: 1 (Starting point NOAEL); Quality of whole database: 1 (A large set of information is available for the substance)

No oral-to-dermal extrapolation has been applied even though an assumed absorption rate of 1% in humans is available. As it is difficult to apply an exact figure for dermal absorption, a further adjustment compared to oral absorption is difficult to apply. Therefore, a very precautinary approach has been applied in the derivation of DNEL for systemic effects via dermal route of exposure. Further, the irritative properties of Iodine could at higher exposure levels affect dermal absorption, making adjustment of absorption figure very problematic.

AF for dose response relationship:

1

AF for differences in duration of exposure:

1

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

1

AF for intraspecies differences:

1

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

Acute Exposure

The information available is inappropriate to derive an acute Derived No Effect Level (DNEL) for systemic and local effects. There is no information of thresholds at which sub-lethal toxicity occurs from studies. The in vitro skin irritation study does not yield any information that can be used to derive a DNEL for the observed skin irritation effects (local irritation). There is also insufficient information available from the acute dermal toxicity study to determine a DNEL for skin irritation.

With respect to setting a systemic DNEL for acute dermal exposure, the same value as the DNEL for long term exposure has been set. This is based on ECHA Guidance on chemical safety assessment (Chapter R8) which recommends that in the first tier, that acute dermal exposures should be compared against the corresponding long term DNEL.

 Similarly for eye irritation, a DNEL cannot be derived as this classification has been determined from the in vitro skin irritation data and published data. Therefore a qualitative risk assessment has been conducted to determine appropriate risk mitigation measures to cover this effect.It is noted that there are workplace exposure limits available for iodine in European member states that report short term exposure limits (STELs) and Time Weighted Averages (TWAs) of 0.1 ppm (equivalent to 1 mg/m₃). According to the American Conference of Industrial Hygienists (ACGIH) humans can work at an air iodine concentration of 0.1 part per million; work is impossible at 0.3 part per million; and concentrations of 1 part per million were highly irritating.

Therefore, 1 mg/m³is set as a short term DNEL for inhalation effects. This DNEL covers both local and systemic effects via acute inhalation exposure, as respiratory irritation is likely to occur at lower concentrations than systemic effects.

 

Repeated exposure

In a work environment, the dermal and inhalation routes are the relevant exposure pathways. As a suitable dose descriptor was not available via these routes for long term exposure, the NOAEL (oral) has been adjusted to a correct starting point for the dermal and inhalation routes. The calculations used to determine the correct starting point are provided below.

Dermal Correct Starting Point:

Dermal NOAEL = Oral NOAEL x No default factor (1)

Dermal NOAEL = 0.01 mg/kg bw/day

The factor of 1 is provided on page 25 of Chapter R8 as dermal absorption is not higher than oral absorption, and that no factor should be introduced when performing oral-to-dermal extrapolation.

Inhalation Correct Starting Point:

Inhalation NOAEL = Oral NOAEL x Standard worker human body weight (70 kg)/ Breathing volume for workers in 8 hours assuming light activity (10 m³).

Inhalation NOAEL = 0.07 mg/m³

These values when divided by an overall AF of 1 result in a long term dermal DNEL of 0.01 mg/kg bw/day and a long term inhalation DNEL of 0.07 mg/m3.

 

General Population - Hazard via inhalation route

Systemic 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

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

General Population - Hazard via dermal route

Systemic 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

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

General Population - Hazard via oral route

Systemic 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected