Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.2 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):
25
Dose descriptor starting point:
NOAEL
Value:
45 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
78.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The administration of 2-methylbut-3-yn-2-ol by gavage to male and female Wistar rats for 3 months caused signs of systemic toxicity manifested next to others on kidneys of male animals at dose levels beyond 45 mg/kg bw/d. Increased absolute and relative kidney weights of males were regarded as treatment-related as there as both a macroscopic (enlarged, discoloration) and a histological correlate (increased eosinophilic droplets graded moderate to severe). Additionally, increased basophilic tubules and tubular casts were seen in these test groups. Findings in the kidney of male animals were assessed as treatment-related and adverse. Therefore, the starting point for DNEL derivation was set to 45 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
default value according to ECHA REACH Guidance: normal dose response relationship
AF for differences in duration of exposure:
2
Justification:
default value according to ECHA REACH Guidance: extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
default value according to ECHA REACH Guidance: allometric scaling is not applied, because the ventilation rate directly depends on the basal metabolic rate
AF for other interspecies differences:
1
Justification:
default value according to ECHA REACH Guidance: no further interspecies differences expected
AF for intraspecies differences:
5
Justification:
default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
default value according to ECHA REACH Guidance: modern guideline study
AF for remaining uncertainties:
2.5
Justification:
default value according to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.2 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.4 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 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):
100
Dose descriptor starting point:
NOAEL
Value:
45 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
45 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The administration of 2-methylbut-3-yn-2-ol by gavage to male and female Wistar rats for 3 months caused signs of systemic toxicity manifested next to others on kidneys of male animals at dose levels beyond 45 mg/kg bw/d. Increased absolute and relativekidneyweights ofmaleswere regarded as treatment-related as there as both a macroscopic (enlarged, discoloration) and a histological correlate (increased eosinophilic droplets graded moderate to severe). Additionally, increased basophilic tubules and tubular casts were seen in these test groups. Findings in the kidney of male animals were assessed as treatment-related and adverse. Therefore, the starting point for DNEL derivation was set to 45 mg/kg bw/d.

AF for dose response relationship:
1
Justification:
default value according to ECHA REACH Guidance: normal dose response relationship
AF for differences in duration of exposure:
2
Justification:
default value according to ECHA REACH Guidance: extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
default value according to ECHA REACH Guidance: allometric scaling from rat to human
AF for other interspecies differences:
1
Justification:
default value according to ECHA REACH Guidance: no further interspecies differences expected
AF for intraspecies differences:
5
Justification:
default value according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
default value according to ECHA REACH Guidance: modern guideline study
AF for remaining uncertainties:
2.5
Justification:
default value according to ECHA REACH Guidance
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

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