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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.16 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
350 mg/m³
Explanation for the modification of the dose descriptor starting point:

The study used for deriving this DNEL is an OECD guideline n° 422 study performed in April 2017. Rats were exposure daily by gavage to 0; 50; 150 and 500 mg/kg/day of the substance (Rhodiantal Original IBCH). A NOAEL for reproductive performance (mating, fertility and delivery) was considered to be 50 mg/kg/day based on the prolonged pre-coital and gestation times and the lower fertility and gestation indexes at 500 mg/kg/day, and on the lower number of corpora lutea, implantation sites and pups delivered, and the higher pre- and post-implantation loss from 150 mg/kg/day. This NOAEL was used as a point of departure for the derivation of the DNEL (NOAEL = 50 mg/kg/day).

Route to route extrapolation (modification of the starting point)

Corrected inhalation NAEC = 50 mg/kg/day * 70 / 10 = 350 mg/m3

(70 kg: mean human body weight - 10 m3: respiratory volume light activity for worker 8 hrs)

AF for differences in duration of exposure:
3
Justification:
Subacute to sub-chronic extrapolation (ECHA R8 guidance default value).
Sub-chronic study is sufficient to investigate the impact on the reproductive organs and on fertility.
AF for interspecies differences (allometric scaling):
4.5
Justification:
Study performed on rats (ECHA R8 guidance default value).
AF for other interspecies differences:
2.5
Justification:
ECHA R8 guidance default value for remaining differences.
AF for intraspecies differences:
5
Justification:
ECHA R8 guidance default value for workers.
AF for remaining uncertainties:
2
Justification:
The study used is an OECD 422 study (sreening test).
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:
0.16 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since no data regarding the adsorption rate of the substance by dermal route is available, the following hypothesis was assumed:

Oral adsorption rate = dermal adsorption rate

NOAEL (oral) (rat) = 50 mg/kg/day

NOAEL (dermal) (rat) = 50 mg/kg/day

AF for differences in duration of exposure:
3
Justification:
Subacute to sub-chronic extrapolation (ECHA default value).
Sub-chronic study is sufficient to investigate the impact on the reproductive organs and on fertility.
AF for interspecies differences (allometric scaling):
4.5
Justification:
Study performed on rats (ECHA R8 guidance default value).
AF for other interspecies differences:
2.5
Justification:
ECHA R8 guidance default value for remaining differences.
AF for intraspecies differences:
5
Justification:
ECHA R8 guidance default value for workers.
AF for remaining uncertainties:
2
Justification:
The study used is an OECD 422 study (sreening test).
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:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.29 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
175 mg/m³
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation (modification of the starting point)

Corrected inhalation NAEC = 50 mg/kg/day * 70 / 20 = 175 mg/m3

(70 kg: mean human body weight - 20 m3: respiratory volum for general population 24 hrs)

AF for differences in duration of exposure:
3
Justification:
Subacute to sub-chronic extrapolation (ECHA default value).
Sub-chronic study is sufficient to investigate the impact on the reproductive organs and on fertility.
AF for interspecies differences (allometric scaling):
4.5
Justification:
Study performed on rats (ECHA R8 guidance default value).
AF for other interspecies differences:
2.5
Justification:
ECHA R8 guidance default value for remaining differences.
AF for intraspecies differences:
10
Justification:
ECHA R8 guidance default value for general population.
AF for remaining uncertainties:
2
Justification:
The study used is an OECD 422 study
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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Since no data regarding the adsorption rate of the substance by dermal route is available, the following hypothesis was assumed:

Oral adsorption rate = dermal adsorption rate

NOAEL (oral) (rat) = 50 mg/kg/day

NOAEL (dermal) (rat) = 50 mg/kg/day

AF for differences in duration of exposure:
3
Justification:
Sub-acute to sub-chronic extrapolation (ECHA default value).
Sub-chronic study is sufficient to investigate the impact on the reproductive organs and on fertility.
AF for interspecies differences (allometric scaling):
4.5
Justification:
Study performed on rats (ECHA R8 guidance default value).
AF for other interspecies differences:
2.5
Justification:
ECHA R8 guidance default value for remaining differences.
AF for intraspecies differences:
10
Justification:
ECHA R8 guidance default value for general population.
AF for remaining uncertainties:
2
Justification:
The study used is an OECD 422 study.
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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No need to modify the strating point.

AF for differences in duration of exposure:
3
Justification:
Sub-acute to sub-chronic extrapolation (ECHA default value).
Sub-chronic study is sufficient to investigate the impact on the reproductive organs and on fertility.
AF for interspecies differences (allometric scaling):
4.5
Justification:
Study performed on rats (ECHA R8 guidance default value).
AF for other interspecies differences:
2.5
Justification:
ECHA R8 guidance default value for remaining differences.
AF for intraspecies differences:
10
Justification:
ECHA R8 guidance default value for general population.
AF for remaining uncertainties:
2
Justification:
The study used is an OECD 422 study.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

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