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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
34.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 4.7 mg/kg bw/day from the maternal toxicity of the developmental toxicity study in rats by the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study.Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies. From the available toxicokinetic information it can be concluded that the availability is similar for all exposure routes and no correction is needed. Correction of the starting point: A route to route extrapolation from oral to inhalation and an interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012. The NOAEL oral, rat is divided by 0.38 (12.4 mg/m3) and the correction for light to medium activity for workers 6.7/10 m3.: 8.3 mg/m3 is applied. As the exposure duration and frequency was 24 h/day and 7 d/week in the rat study correction factors of 24/8 and 7/5 are applied to this value:34.9 mg/m3.
AF for dose response relationship:
1
Justification:
see above the NOAEL is a conservative assumption and no target organ toxicity was observed up to the highest dose tested in several studies
AF for differences in duration of exposure:
1
Justification:
No duration correction is applied as the NOAEL values did not decrease with study duration and were consistent between the repeated dose and generation studies
AF for interspecies differences (allometric scaling):
1
Justification:
With the correction of the route to route extrapolation the allometric scaling factor between rats and humans was included
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8.
AF for intraspecies differences:
5
Justification:
The intraspecies factor for workers of 5 is applied in the absence of specific information.
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies.
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
34.9 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 4.7 mg/kg bw/day from the maternal toxicity of the developmental toxicity study in rats by the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study.Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies. From the available toxicokinetic information it can be concluded that the availability is similar for all exposure routes and no correction is needed. Correction of the starting point: A route to route extrapolation from oral to inhalation and an interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012. The NOAEL oral, rat is divided by 0.38 (12.4 mg/m3) and the correction for light to medium activity for workers 6.7/10 m3.: 8.3 mg/m3 is applied. As the exposure duration and frequency was 24 h/day and 7 d/week in the rat study correction factors of 24/8 and 7/5 are applied to this value:34.9 mg/m3.
AF for dose response relationship:
1
Justification:
see above the NOAEL is a conservative assumption and no target organ toxicity was observed up to the highest dose tested in several studies
AF for interspecies differences (allometric scaling):
1
Justification:
With the correction of the route to route extrapolation the allometric scaling factor between rats and humans was included
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8.
AF for intraspecies differences:
5
Justification:
The intraspecies factor for workers of 5 is applied in the absence of specific information.
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 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
Modified dose descriptor starting point:
NOAEL
Value:
19.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 4.7 mg/kg bw/day from the maternal toxicity of the developmental toxicity study in rats by the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study.Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies. From the available toxicokinetic information it can be concluded that the availability is similar for all exposure routes and no correction is needed. An adjustment factor for route to route extrapolation from oral to dermal absorption is not needed.. As the exposure duration and frequency was 24 h/day and 7 d/week in the rat study correction factors of 24/8 and 7/5 are applied to the NOAEL value:yielding 19.7 mg/kg bw/day as acorrected startoing point
AF for dose response relationship:
1
Justification:
see above the NOAEL is a conservative assumption and no target organ toxicity was observed up to the highest dose tested in several studies
AF for differences in duration of exposure:
1
Justification:
No duration correction is applied as the NOAEL values did not decrease with study duration and were consistent between the repeated dose and generation studies
AF for interspecies differences (allometric scaling):
4
Justification:
An interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012 by using a factor of 4 for rat to humans
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8.
AF for intraspecies differences:
5
Justification:
The intraspecies factor for workers of 5 is applied in the absence of specific information.
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Value:
1.2
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

See above under the derivation of the DNELs.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.16 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
Modified dose descriptor starting point:
NOAEC
Value:
4.1 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 4.7 mg/kg bw from the maternal toxicity of the developmental toxicity study in rats via the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study. .Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies. From the available toxicokinetic information it can be concluded that the availability is similar for all exposure routes and no correction is needed. Corection of the starting point: A route to route extrapolation from oral to inhalation and an interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012. The NOAEL oral, rat is divided by 1.15 m3/kg bw : 4.1 mg/m3 (24 h).
AF for dose response relationship:
1
Justification:
see above the NOAEL is a conservative assumption and no target organ toxicity was observed up to the highest dose tested in several studies
AF for differences in duration of exposure:
1
Justification:
No duration correction is applied as the NOAEL values did not decrease with study duration and were consistent between the repeated dose and generation studies
AF for interspecies differences (allometric scaling):
1
Justification:
The allometric scaling for rat to human has already been included in the route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8
AF for intraspecies differences:
10
Justification:
The intraspecies factor for workers of 10 is applied in the absence of specific information
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.48
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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
Modified dose descriptor starting point:
NOAEL
Value:
4.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The NOAEL of 4.7 mg/kg bw/day from the maternal toxicity of the developmental toxicity study in rats by the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study.Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies. From the available toxicokinetic information it can be concluded that the availability is similar for all exposure routes and no correction is needed. An adjustment factor for route to route extrapolation from oral to dermal absorption is not needed and the NOAEL of the oral study can be used as a starting point
AF for dose response relationship:
1
Justification:
see above the NOAEL is a conservative assumption and no target organ toxicity was observed up to the highest dose tested in several studies
AF for differences in duration of exposure:
1
Justification:
No duration correction is applied as the NOAEL values did not decrease with study duration and were consistent between the repeated dose and generation studies.
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies extrapolation: An interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012 by using a factor of 4 for rat to humans
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8.
AF for intraspecies differences:
10
Justification:
The intraspecies factor for the general population a factor of 10 is applied in the absence of specific information
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies. This yields a dermal DNEL of 0.05 mg/kg bw/day.
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies. This yields a dermal DNEL of 0.05 mg/kg bw/day.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
Value:
0.15
DNEL related information
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 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
Modified dose descriptor starting point:
NOAEL
Value:
4.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
not needed routes are identical
AF for dose response relationship:
1
Justification:
The NOAEL of 4.7 mg/kg bw/day from the maternal toxicity of the developmental toxicity study in rats by the oral route is chosen as a conservative starting point for systemic toxicity. Note that in the repeated dose toxicity studies higher NOAEL values were obtained, 7 mg/kg bw in the 28-day study and ca. 10 mg/kg bw in the 90-day study.Only light general toxicity, reduction in body weight gain and food consumption and no target organ toxicity was observed in all available studies.
AF for differences in duration of exposure:
1
Justification:
No duration correction is applied as the NOAEL values did not decrease with study duration and were consistent between the repeated dose and generation studies.
AF for interspecies differences (allometric scaling):
4
Justification:
Interspecies extrapolation: An interspecies extrapolation using allometric scaling is performed according to the TNG R8 version 2.1, 2012 by using a factor of 4 for rat to humans.
AF for other interspecies differences:
2.5
Justification:
As no information on human toxicity are available an additional assessment factor of 2.5 for remaining differnces is applied according to ECHA, 2012, R8.
AF for intraspecies differences:
10
Justification:
The intraspecies factor for the general population a factor of 10 is applied in the absence of specific information.
AF for the quality of the whole database:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies.
AF for remaining uncertainties:
1
Justification:
No additional factors for dose response and qualtity of the data base is applied as the effects observed were light and consistent results were obtained from the different studies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - General Population

From rhe use of the substance as industrial biocide (assessed in the Dossier provided under the biocidal products directive) and intermediate in the chemical industry no exposure of the general population should occur. Indirect exposure through the environment is also improbable due to the handling and raedy biodegradability of the substance.