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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.3 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12
Dose descriptor starting point:
NOAEL
Value:
90 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
78.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation: NOAEL (OECD414, oral, rat) = 90 mg/kg bw/d with adverse findings in the higher dose of 230 mg/kg bw/d; /2 (absorption inhalation/oral); /0.38 m3/kg bw (rat SRV, corrected for 8h exposure); *6.7 m3/10 m3 (light/no work).

AF for dose response relationship:
1
Justification:
GLP compliant, OECD guideline studies
AF for differences in duration of exposure:
1
Justification:
default for prenatal developmental toxicity study
AF for interspecies differences (allometric scaling):
1
Justification:
oral to inhalation route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
GLP compliant OECD guideline studies
AF for remaining uncertainties:
1
Justification:
default
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)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.8 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
90 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
90 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route-to-route extrapolation: NOAEL (OECD414, oral, rat) = 90 mg/kg bw/d with adverse findings in the higher dose of 230 mg/kg bw/d; *1 (default factor for extrapolation from oral to dermal).

AF for dose response relationship:
1
Justification:
GLP compliant, OECD guideline studies
AF for differences in duration of exposure:
1
Justification:
default for prenatal developmental toxicity study
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat-to-human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
GLP compliant, OECD guideline studies
AF for remaining uncertainties:
1
Justification:
default
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

According to the REACH “Guidance on information requirements and chemical safety assessment”, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.


- Kinetics (absorption figures for oral, dermal and inhalation route of exposure): No data on absorption are available. According to Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, it is proposed in the absence of route-specific information on the starting route, to include a default factor of 2 in the case of oral-to-inhalation extrapolation. This approach will be taken forward to DNEL derivation. For dermal absorption, based on the physico-chemical properties of the substance (log Kow < 0 and high water solubility), and based on the estimated Kp, low dermal uptake is expected. However, as in the acute dermal toxicity study mortality and clinical effects were observed, dermal absorption cannot be excluded. Therefore a default factor of 1 in the case of oral-to-dermal extrapolation is included.


- Acute toxicity: 1-Methylimidazole is classified for acute oral and dermal toxicity. Testing for acute inhalation toxicity was not necessary because the substance is classified as corrosive to the skin.


- Irritation/corrosion and sensitisation: The substance is classified as corrosive to the skin and eye. Testing for skin sensitisation was not necessary because the substance is classified as corrosive to the skin.


- Mutagenicity: 1-Methylimidazole did not cause gene mutations in Salmonella typhimurium (Ames test). 1-Methylimidazole is not mutagenic in the HPRT locus assay in CHO cells and is considered not to have a chromosome-damaging (clastogenic) effect nor to induce numerical chromosomal aberrations (aneugenic activity) under in vitro conditions in V79 cells in the absence and the presence of metabolic activation.


 


Though the substance is classified for acute toxicity (oral and dermal), no short-term DNELs were derived because the long-term DNELs were considered to ensure sufficient protection to prevent peak exposure. As oral and dermal exposure is expressed as amount (per kg bw) per day, acute oral and dermal exposure peaks (in mg/kg bw/day) will not be higher than a calculated total exposure per day (chronic; in mg/kg bw/day). Therefore, practically relevant peak exposures via the oral and dermal routes do not occur for 1-methylimidazole.


Though the substance is classified as corrosive to the skin and eye, no data are available from which a DNEL for local effects can be derived.


 


For the DNEL derivation, the endpoint prenatal developmental toxicity is considered to be the most sensitive endpoint. In a prenatal developmental toxicity study, maternal and prenatal developmental toxicity was observed in rats at 230 mg/kg bw/d per gavage.


Regarding repeated dose toxicity, an oral OECD408 was performed in rats with a NOAEL of 90 mg/kg bw/d with only non-adverse findings (increase of relative liver weights in males and females of the mid and/or high dose group; dose dependent, minimal to slight centrilobular liver hypertrophy in males and females of all test groups without correlating findings in clinical chemistry). With the endpoint repeated dose toxicity as the point of departure the long-term systemic DNELs would be slightly higher compared to the derived DNEL:
Worker – long-term systemic inhalation
- NOAEC = NOAEL (90d, oral, rat) /0.384 m3/kg bw *abs.oral/abs.inhal. *no work/slight work = 90 mg/kg bw/d /0.384 m3/kg bw *50%/100% *6.7 m3/10m3 = 78.5 mg/m3
- DNEL (inhalation) = NOAEC / (1*2*1*1*5*1*1) = 78.5 mg/m3 / 10 = 7.9 mg/m3
- Assessment factors: Dose response, duration, interspecies, other interspecies, intraspecies, database, remaining uncertainties.
- Justification for using 1 instead of 2.5 for the other interspecies factor:
ECHA GD R.8., section 8.4.3.1: "For effects on the skin, eye or GI tract, where the mechanism of effect is direct chemical/pH reactivity, no further kinetic considerations apply. Furthermore, in terms of dynamics, one might assume that animals and humans will respond to the insult in the same way. In this case, the default factor for remaining uncertainties of 2.5 could be reduced to 1." The corrosiveness of 1-methylimidazole - as a basic aqueous solution - is most probably responsible for the acute toxicity after oral and dermal administration and also for the observed effects in the repeated dose toxicity studies above 90 mg/kg bw/d (DRF, additional OECD414 high dose) (IUCLID section 7.5 and 7.8). The observed systemic effects in the 90d-study were considered as non-adverse, but adaptive: increase of relative liver weights in males and females of the mid and/or high dose group; dose-dependent, minimal to slight centrilobular liver hypertrophy in males and females of all test groups without correlating findings in clinical chemistry. Metabolome analysis revealed no clear evidence for any organ specific toxicological modes of action. Additionally, weak effects on liver enzyme induction may be discussed for treatment of rats with 1-methylimidazole, but compared to known potent enzyme inducers such as typical ligands of the AhR or CAR, observed effects are negligible (IUCLID section 7.9.3). Thus, an additional assessment factor for interspecies differences is not justified.


Worker – long-term systemic dermal
- NOAEL (dermal) = NOAEL (90d, oral, rat) *1 (oral -> dermal)
- DNEL (dermal) = 90 mg/kg / (1*2*4*1*5*1*1) = 2.25 mg/kg bw/d
- Assessment factors: Dose response, duration, interspecies, other interspecies, intraspecies, database, remaining uncertainties.
- Justification for using 1 instead of 2.5 for the other interspecies factor: see above.

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

Additional information - General Population

The substance has no consumer uses. But for an assessment man via environment, an oral systemic long-term DNEL was derived for the general population:


DNEL = NOAEL (dev.tox, oral, rat) / 1*1*4*2.5*10*1*1 = 90 mg/kg bw/d / 100 = 0.9 mg/kg bw/d


- Assessment factors: Dose response, duration, interspecies, other interspecies, intraspecies, database, remaining uncertainties.