Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
1.05 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):
37.5
Dose descriptor starting point:
NOAEL
Value:
16 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
39.5 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in two generation study.
To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:
Corrected starting point for the inhalative route for workers:
= NOAEL(oral) * (1/0.38 m³/kg bw/day) * (ABSoral-rat/ABSinh-human) * 6.7 m³ (8h) /10 m³ (8h)* (7 days exposure rat/5 days exposure worker)
= 16 mg/kg bw/day * (1/0.38 m³/kg bw/day) * (1/1) * 0.67 m³ * 1.4= 39.5 mg/m³

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)


In rats and mice, myclobutanil is rapidly absorbed; comparing urinary excretion after oral and intravenous administration of a single low dose suggests that bioavailability is important in rats, reaching 100%. Therefore, no correction for oral absorption is required.
Thus, the corrected starting point for workers was 39.5 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
3
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
allometric factors are accounted for in modification of the starting point
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance.
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
The whole database is comprehensive and good quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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
Most sensitive endpoint:
acute toxicity
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 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):
50
Dose descriptor starting point:
NOAEL
Value:
3.09 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
17.3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in chronic repeated dose toxicity study in dogs.
To correct the interspecies difference between dog and human the no observed effect level has to be corrected as follows:
Corrected starting point for the dermal route for workers:


Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) * (7 days exposure dog/5 days exposure worker) = 3.09 mg/kg bw/day * (1/0.25) * 1.4 = 17.3 mg/kg bw/day. Based on dermal absorption data a dermal absorption value of 25% is considered.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was rat.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
Default value for workers according to ECHA REACH Guidance.
AF for the quality of the whole database:
1
Justification:
Whole database is comprehensive and good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

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:
DNEL (Derived No Effect Level)
Value:
0.19 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):
75
Dose descriptor starting point:
NOAEL
Value:
16 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
13.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

The calculation of the DNEL is based on an oral NOAEL observed in a two generation study with rats.
To correct the interspecies difference between rat and human the no observed effect level has to be corrected as follows:

Corrected starting point for the inhalative route for general population:
= NOAELoral * (1/1.15 m³/kg bw/day (24h)) * (ABSoral-rat / ABSinh-human)
= 16 mg/kg bw/day * (1/1.15 m³/kg bw/day) * (1/1) = 13.9 mg/m³

(ABSoral-rat = oral absorption in rats, ABSinh-human = inhalation absorption rate in humans)


In rats and mice, myclobutanil is rapidly absorbed; comparing urinary excretion after oral and intravenous administration of a single low dose suggests that bioavailability is important in rats, reaching 100%. Therefore, no correction for oral absorption is required.
Thus, the corrected starting point for general population was 13.9 mg/m³ for inhalation.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
3
Justification:
The DNEL is based on a subchronic study.
AF for interspecies differences (allometric scaling):
1
Justification:
allometric factors are accounted for in modification of the starting point
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH guidance
AF for the quality of the whole database:
1
Justification:
Whole database is comprehensive and good quality.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
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
Most sensitive endpoint:
acute toxicity
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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:
3.09 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
12.36 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Dermal NOAEL = oral NOAEL*ABS(oral)/ABS(dermal) = 3.09 mg/kg bw/day *(1/0.25) = 12.36 mg/kg bw/day. Based on dermal absorption studies the dermal absorption is considered to be 25%.

AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal was rat
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH guidance.
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH guidance.
AF for the quality of the whole database:
1
Justification:
Whole database is comprehensive and good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.031 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:
3.09 mg/kg bw/day
AF for dose response relationship:
1
Justification:
The dose descriptor starting point is based on a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
The experimental animal is a rat.
AF for other interspecies differences:
2.5
Justification:
Default value according to ECHA REACH guidance
AF for intraspecies differences:
10
Justification:
Default value for general population according to ECHA REACH guidance
AF for the quality of the whole database:
1
Justification:
Whole database is comprehensive and good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population