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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
15 mg/m³
AF for dose response relationship:
1
Justification:
no additional AF required
AF for differences in duration of exposure:
1
Justification:
no additional AF required as this is a chronic study
AF for interspecies differences (allometric scaling):
2.5
Justification:
default for allometric scaling
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.32 mg/m³
Most sensitive endpoint:
neurotoxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
79 mg/m³
AF for dose response relationship:
1
Justification:
no additional AF required
AF for interspecies differences (allometric scaling):
2.5
Justification:
default for allometric scaling
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.64 mg/m³
Most sensitive endpoint:
carcinogenicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor:
NOAEC
AF for dose response relationship:
1
Justification:
no additional AF required
AF for differences in duration of exposure:
1
Justification:
no additional AF required
AF for interspecies differences (allometric scaling):
2.5
Justification:
default for allometric scaling
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.32 mg/m³
Most sensitive endpoint:
neurotoxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEC
AF for dose response relationship:
1
Justification:
no additional AF required
AF for interspecies differences (allometric scaling):
2.5
Justification:
default for allometric scaling
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Explanation for the modification of the dose descriptor starting point:
n/a
AF for dose response relationship:
1
Justification:
no additional AF required
AF for differences in duration of exposure:
1
Justification:
no additional AF required
AF for interspecies differences (allometric scaling):
2.5
Justification:
default for allometric scaling
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required
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:
DMEL (Derived Minimum Effect Level)
Value:
7.3 µg/cm²
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
other: LOAEL
AF for dose response relationship:
3
Justification:
recommended AF used as dose descriptor is LOAEL
AF for differences in duration of exposure:
1
Justification:
no additional AF required
AF for interspecies differences (allometric scaling):
1
Justification:
allometric scaling not relevant for local effects
AF for other interspecies differences:
1
Justification:
no additional AF required
AF for intraspecies differences:
2.5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
no additional AF required
AF for remaining uncertainties:
1
Justification:
no additional AF required
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Table 7-1: DN(M)ELs for workers

Exposure pattern

Route

Descriptors[1]

DNEL/DMEL*

Most sensitive endpoint

Acute - systemic effects

dermal (mg/kg bw /day)

DNEL

2.4

Repeat dose dermal

Inhalation (mg/m3)

DNEL

6.32

Acute neurotoxicity

Acute - local effects

Dermal (μg/cm2)

DMEL

7.3

Repeat dose dermal

Inhalation (mg/m3)

DNEL

6.32

Acute neurotoxicity

Long-term - systemic effects

Dermal (mg/kg bw /day)

DNEL

2.4

Repeat dose dermal

Inhalation (mg/m3)

DNEL

1.2

Chronic toxicity

Long-term – local effects

Dermal (μg/cm2)

DMEL

7.3

Repeat dose dermal

Inhalation (mg/m3)

DNEL

4.64

Chronic toxicity

* unit specified in column “Route”

Discussion

Acute Dermal –

As stated in ECHA, Chapter R-8.1.2.5 for dermal exposures route, exposures should be normally be assessed using the long term DNELs (see below).

Acute Inhalation - systemic and local

The inhalation NOELs (ppm iodomethane) were converted to mg/m3(1 ppm = 5.81 mg/m3) and corrected for duration of experimentalvshuman exposure and human resting respiration volumevsworker respiration volume(refer to Section 5.11.2),according to the guidance in Chapter R.8.

The critical NOAEL was taken from the acute inhalation neurotoxicity study where a NOAEL of 27 ppm was obtained.

Corrected NOAEL = ppm * 5.81 mg/m3* experimental duration (6 hrs) / human exposure duration (8 hrs) * human resting resp. volume (6.7 m3) / worker resp. volume (10 m3).

NOAECcorr= 79 mg/m3

Default assessment factors (ECHA, Chapter R-8.4.3.3) were applied.

Assessment factors = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database

Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5

DNEL derivation

DNEL = NOAELcorr / Assessment factor

Acute DNEL Local and Systemic=79 mg/m3/ 12.5 = 6.32 mg/m3

Long term dermal exposure

Local

No local dermal NOAEL was available, with evidence of dermal irritation (erythema/ desquamation) observed at every dose level treated. Therefore, the LOAEL of 30 mg/kg bw/day was converted to an mg/cm2dose, 0.11 mg/cm2(refer to Section 5.11.2),according to the guidance in Chapter R.8

NOAECcorr= 0.11 mg/cm2

Default assessment factors (ECHA, Chapter R-8.4.3.3) were applied.

Assessment factors = Interspecies * Intraspecies * Dose-response * Quality of whole database

Assessment factors = 1 * 5 * 3 *1

DNEL derivation

DNEL = NOAELcorr / Assessment factor

Acute / long term DNEL local = 0.11 mg/cm2/ 15 = 7.3 μg/cm2

Systemic

The dermal NOAEL following 28 days of dosing was 30 mg/kg bw/day.

Default assessment factors (ECHA, Chapter R-8.4.3.3) were applied.

Assessment factors = Interspecies * Intraspecies * Dose-response * Quality of whole database

Assessment factors = 2.5 * 5 * 1 *1

DNEL derivation

Acute / long term DNEL systemic= 30 mg/kg bw/day / 12.5 = 2.4 mg/kg bw/day

Long term exposure – inhalation systemic

Two studies, sub chronic inhalation study (90 day) and chronic (2 year study) have been used to establish DNEL for long term exposureviathe inhalatory route.

Assessment of mode of action

The identified endpoint and the observed effects have a threshold for both the sub chronic and chronic endpoints.

The inhalation NOELs (ppm iodomethane) were converted to mg/m3(1 ppm = 5.81 mg/m3) and corrected for duration of experimental vs human exposure and human resting respiration volumevsworker respiration volume, according to the guidance in Chapter R.8.

Corrected NOAEL = ppm * 5.81 mg/m3* experimental duration (6 hrs) / human exposure duration (8 hrs) * human resting resp. volume (6.7 m3) / worker resp. volume (10 m3).

Sub chronic NOAECcorr= 61 mg/m3(local and systemic)

Chronic NOAECcorr= 58 mg/m3(local)

Chronic NOAECcorr= 15 mg/m3(systemic)

Assessment factors

Default assessment factors (ECHA, Chapter R-8.4.3.3) were applied.

Assessment factor = Interspecies * Intraspecies * Exposure duration * Dose-response * Quality of whole database

Assessment factor (general) = 2.5 * 5 * 1 * 1 * 1 = 12.5

DNEL derivation

DNEL = NOAELcorr / Assessment factor

Subchronic DNEL Local and System= 61 mg/m3/ 12.5 = 4.88 mg/m3

Chronic DNEL Local=58 mg/m3/ 12.5 = 4.64 mg/m3

Chronic DNEL Systemic= 15 mg/m3/ 12.5 = 1.2 mg/m3

[1]   Values in IUCLID 5 are DNEL/DMEL/ not quantifiable

General Population - Hazard via inhalation route

Systemic 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

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

General Population - Hazard via dermal route

Systemic 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

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)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
insufficient hazard data available (further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population

No exposure to the general population, therefore no requirement to determine DNELs.

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