Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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):
30
Modified dose descriptor starting point:
NOAEC
DNEL value:
4.41 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC = NOAEL /[sRV*time] *ABSoral-rat/ABSresp.-human *no/light work = 5 mg/kg bw/d /[0.8L/min/kg bw rat *8*60 min] *50%/100% *6.7m3/10m3
AF for dose response relationship:
1
Justification:
GLP compliant, OECD test guideline study with 3 doses.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
See correction to NOAEC.
AF for other interspecies differences:
1
Justification:
No evidence for species differences for substance-related reduced food consumption and body weight.
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.04 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):
120
Modified dose descriptor starting point:
NOAEL
DNEL value:
5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

NOAEL = oral NOAEL *ABSoral-rat/ABSdermal-human = 5 mg/kg bw/d *1 (absorption).

AF for dose response relationship:
1
Justification:
GLP compliant, OECD test guideline study with 3 doses.
AF for differences in duration of exposure:
6
Justification:
From subacute to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
From rat to man.
AF for other interspecies differences:
1
Justification:
No evidence for species differences for substance-related reduced food consumption and body weight.
AF for intraspecies differences:
5
Justification:
Default.
AF for the quality of the whole database:
1
Justification:
Default.
AF for remaining uncertainties:
1
Justification:
Default.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
medium hazard (no threshold derived)

Additional information - workers

Toxicokinetic and acute toxicity

There is are no toxicokinetic studies available. Since it is likely that 1-vinyl-imidazole will be orally absorbed and in the absence of substance-specific inhalation or dermal absorption data, the default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation and 50% for oral and dermal absorption. Concerning acute toxicity the substance is moderate toxic after single ingestion (LD50 (oral, rat) = 1040 mg/kg bw) and of low toxicity after dermal exposure (LD50 (dermal, rat) > 2000 mg/kg bw). It is not skin irritating, but severe irritant to the eyes. There was no skin sensitization observed  in an LLNA and no mutagenic potential in vitro (Ames test, in vitro CA test, HPRT test).

Long-term systemic effects

For anticipated occupational exposure to 1-Vinylimidazole, CAS 1072 -63 -5 systemic long-term DNELs for inhalation and dermal contact were derived.

Point of departure

The starting point for the systemic long-term inhalation and dermal DNEL is a NOAEL of 5 mg/kg bw/d, obtained from a oral Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test in Wistar Rats (OECD TG 422 with exposure via gavage; 2013, RL1).

The NOAEL for general parental toxicity is 5 mg/kg bw/d, based on adverse clinical symptoms and decreased body weights/body weight gain. There was no specific target organ toxicity up to the highest dose of 35 mg/kg bw/d, as the effects observed in liver and kidney were considered to be adaptive, but not adverse (organ weights, histopathology). The NOAEL for fertility/reproductive toxicity is 35 mg/kg bw/d, which is the highest dose tested. The NOAEL for developmental toxicity in the F1 offspring is 5 mg/kg bw/d, as decreased pup weights, perinatal mortality, and dissecting aneurysms in the great vessels of the heart were noted at 15 mg/kg bw/d and above.

The repeated dose toxicity is considered to be the most sensitive endpoint for the DNEL derivation, because there an assessment factor for the exposure duration needed, which is not necessary, if the developmental toxicity is considered to be the starting point for the DNEL derivation.

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:
DNEL (Derived No Effect Level)
Value:
0.02 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):
240
Dose descriptor starting point:
NOAEL
AF for dose response relationship:
1
Justification:
GLP compliant, OECD test guideline study with 3 doses.
AF for differences in duration of exposure:
6
Justification:
Default for sub-acute to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Default.
AF for other interspecies differences:
1
Justification:
No evidence for species differences for substance-related reduced food consumption and body weight.
AF for intraspecies differences:
10
Justification:
Default for general population.
AF for the quality of the whole database:
1
Justification:
Default.
AF for remaining uncertainties:
1
Justification:
Default.
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

Because there are no consumer uses for 1-Vinylimidazole, CAS 1072-63-5, no consumer DNELs were derived; exept for the oral LT systemic DNEL for the MvE assessment. The justification for the point of departure is comparable to the PoD for the systemic LT DNELs for workers (see "Additional information - Workers").