Registration Dossier
Registration Dossier
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EC number: 200-819-5 | CAS number: 74-88-4
Toxicological Summary
Administrative data
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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