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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
0.69 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):
12.5
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
As the endpoint is reproductive toxicity, there is no adjustment for duration of exposure, as gestation is a finite measure.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default factor for worker
AF for intraspecies differences:
5
Justification:
Default factor for worker
AF for the quality of the whole database:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
AF for remaining uncertainties:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.45 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard extrapolation factor of 5x was used for the short-term DNEL from the long-term DNEL

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:
0.19 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):
50
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
As the endpoint is reproductive toxicity, there is no adjustment for duration of exposure, as gestation is a finite measure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default rat -> human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Default factor for worker
AF for the quality of the whole database:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
AF for remaining uncertainties:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.95 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard extrapolation factor of 5x was use for a short-term DNEL from a long-term

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

Long Term DNEL Derivation for 6PPD

The starting NOAEL was 7 mg/kg/day from an extended 1-generation reproductive toxicity study. In that study, females (and males, but moot to the derivation) were treated with 6PPD daily for 10 weeks of pre-breeding, 2 weeks of breeding followed by 21 days of gestation until parturition.  The NOAEL was based on dystocia (difficult delivery) which was observed in both the range-finder, which had a 2-week pre-treatment period and the main study with a 10 week pre-treatment period.  As the primary effect observed was part of gestation (parturition) no correction factors for duration of study are applied, as gestation is a fixed time period, and thus there is no adjustment for duration.

 

Modification of the dose descriptor:

General population long-term inhalation:

               NOAEL of 7 mg/kg/day * ECHA default bioavailability of animal oral of 50% to human inhalationof 100%, = 3.5 mg/kg/day. Divided by the standard respiratory volume of 1.35 m3kg bw/24 hr =     Adjusted NOAEC of 2.59 mg/m3

               Adjustment factors:   2.5 for remaining interspecies, 10 for intraspecies,Total Adjustment         factors = 25.   As the primary effect observed was part of gestation (parturition) correction      factors for duration of study are not applied, as gestation is a fixed time period, and thus      there is no adjustment for duration.

               General population long term inhalation DNEL =2.59 mg/m3/ 25 =0.10 mg/m3

 

General population long term oral/dermal:

               NOAEL of 7 mg/kg/day. There is no bioavailability difference between animal to human oral      exposures, sothe adjusted NOAEL = 7 mg/kg/day

               Adjustment factors:   4 for allometric scaling,2.5 for remaining interspecies, 10 for intraspecies,              Total Adjustment factors = 100.   As the primary effect           observed was part of gestation(parturition) correction               factors for duration of study are not applied, as gestation is a fixed timeperiod, and thus there is no adjustment for duration.

               General population long term inhalation DNEL = 7 mg/kg/day /100=0.07 mg/kg/day

 

 

 

Worker long term dermal:

               NOAEL of 7 mg/kg/day. There is no bioavailability difference between animal to human oral      exposures. A factor of 1.4 is applied for exposure conditions for anadjusted NOAEL = 9.8      mg/kg/day

               Adjustment factors:   4 for allometric scaling,2.5 for remaining interspecies, 5 for intraspecies,Total Adjustment factors = 50.   As the primary effect observed was part of gestation               (parturition) correction               factors for duration of study are not applied, as gestation is a fixed timeperiod, and thus there is no adjustment for duration.

               Worker long term oral/dermal DNEL = 9.8 mg/kg/day/50=0.19 mg/kg/day

 

               Worker long term inhalation:

               NOAEL of 7 mg/kg/day. ECHA default bioavailability of animal oral of 50% to human inhalation of 100%, = 3.5 mg/kg/day, / 0.38 m3 bw/8hr = 9.21, * 0.67 (respiratory volumes) * 1.4 (exposure   conditions) for anadjusted NOAEL = 8.6 mg/m3

               Adjustment factors:   2.5 for remaining interspecies, 5 for intraspecies,Total Adjustment           factors = 12.5.   As the primary effect observed was part of gestation (parturition) correction       factors for duration of study are not applied, as gestation is a fixed time         period, and thus there is no adjustment for duration.

               Worker long term oral/dermal DNEL = 8.6 mg/m3/12.5=0.69 mg/m3

 

Short Term DNEL Derivation for 6PPD

Short-Term DNEL values are derived based ECHA guidance suggesting that a five-fold difference in the short and long term DNEL is protective in the absence of other data suggesting a more restrictive need.

 

Type

Worker

General Population

Long Term Inhalation

0.69 mg/m3

0.10 mg/m3

Short Term Inhalation

3.45 mg/m3

0.50 mg/m3

Long Term Oral/Dermal*

0.19 mg/kg/day

0.07 mg/kg/day

Short Term Oral/Dermal

0.95 mg/kg/day

0.35 mg/kg/day

*Oral worker values are not derived

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.1 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):
25
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
As the endpoint is reproductive toxicity, there is no adjustment for duration of exposure, as gestation is a finite measure.
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
Justification:
Default factor for the general population
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.5 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard extrapolation factor of 5x was used for the short-term DNEL from the long-term DNEL

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:
0.07 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):
100
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
As the endpoint is reproductive toxicity, there is no adjustment for duration of exposure, as gestation is a finite measure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for the general population
AF for other interspecies differences:
2.5
Justification:
Default factor for the general population
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.35 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard extrapolation factor of 5x was used for the short-term DNEL from the long-term DNEL

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:
0.07 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):
100
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
As the endpoint is reproductive toxicity, there is no adjustment for duration of exposure, as gestation is a finite measure.
AF for interspecies differences (allometric scaling):
4
Justification:
default rat -> humanDefault factor for the general population
AF for other interspecies differences:
2.5
Justification:
Default factor for the general population
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
AF for remaining uncertainties:
1
Justification:
Comprehensive data are available: acute, sub-acute, sub-chronic and chronic toxicity studies.
Acute/short 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
DNEL extrapolated from long term DNEL
Explanation for the modification of the dose descriptor starting point:

The standard extrapolation factor of 5x was used for the short-term DNEL from the long-term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Long Term DNEL Derivation for 6PPD

The starting NOAEL was 7 mg/kg/day from an extended 1-generation reproductive toxicity study. In that study, females (and males, but moot to the derivation) were treated with 6PPD daily for 10 weeks of pre-breeding, 2 weeks of breeding followed by 21 days of gestation until parturition.  The NOAEL was based on dystocia (difficult delivery) which was observed in both the range-finder, which had a 2-week pre-treatment period and the main study with a 10 week pre-treatment period.  As the primary effect observed was part of gestation (parturition) no correction factors for duration of study are applied, as gestation is a fixed time period, and thus there is no adjustment for duration.

 

Modification of the dose descriptor:

General population long-term inhalation:

               NOAEL of 7 mg/kg/day * ECHA default bioavailability of animal oral of 50% to human inhalationof 100%, = 3.5 mg/kg/day. Divided by the standard respiratory volume of 1.35 m3kg bw/24 hr =     Adjusted NOAEC of 2.59 mg/m3

               Adjustment factors:   2.5 for remaining interspecies, 10 for intraspecies,Total Adjustment         factors = 25.   As the primary effect observed was part of gestation (parturition) correction      factors for duration of study are not applied, as gestation is a fixed time period, and thus      there is no adjustment for duration.

               General population long term inhalation DNEL =2.59 mg/m3/ 25 =0.10 mg/m3

 

General population long term oral/dermal:

               NOAEL of 7 mg/kg/day. There is no bioavailability difference between animal to human oral      exposures, sothe adjusted NOAEL = 7 mg/kg/day

               Adjustment factors:   4 for allometric scaling,2.5 for remaining interspecies, 10 for intraspecies,              Total Adjustment factors = 100.   As the primary effect           observed was part of gestation(parturition) correction               factors for duration of study are not applied, as gestation is a fixed timeperiod, and thus there is no adjustment for duration.

               General population long term inhalation DNEL = 7 mg/kg/day /100=0.07 mg/kg/day

 

 

 

Worker long term dermal:

               NOAEL of 7 mg/kg/day. There is no bioavailability difference between animal to human oral      exposures. A factor of 1.4 is applied for exposure conditions for anadjusted NOAEL = 9.8      mg/kg/day

               Adjustment factors:   4 for allometric scaling,2.5 for remaining interspecies, 5 for intraspecies,Total Adjustment factors = 50.   As the primary effect observed was part of gestation               (parturition) correction               factors for duration of study are not applied, as gestation is a fixed timeperiod, and thus there is no adjustment for duration.

               Worker long term oral/dermal DNEL = 9.8 mg/kg/day/50=0.19 mg/kg/day

 

               Worker long term inhalation:

               NOAEL of 7 mg/kg/day. ECHA default bioavailability of animal oral of 50% to human inhalation of 100%, = 3.5 mg/kg/day, / 0.38 m3 bw/8hr = 9.21, * 0.67 (respiratory volumes) * 1.4 (exposure   conditions) for anadjusted NOAEL = 8.6 mg/m3

               Adjustment factors:   2.5 for remaining interspecies, 5 for intraspecies,Total Adjustment           factors = 12.5.   As the primary effect observed was part of gestation (parturition) correction       factors for duration of study are not applied, as gestation is a fixed time         period, and thus there is no adjustment for duration.

               Worker long term oral/dermal DNEL = 8.6 mg/m3/12.5=0.69 mg/m3

 

Short Term DNEL Derivation for 6PPD

Short-Term DNEL values are derived based ECHA guidance suggesting that a five-fold difference in the short and long term DNEL is protective in the absence of other data suggesting a more restrictive need.

 

Type

Worker

General Population

Long Term Inhalation

0.69 mg/m3

0.10 mg/m3

Short Term Inhalation

3.45 mg/m3

0.50 mg/m3

Long Term Oral/Dermal*

0.19 mg/kg/day

0.07 mg/kg/day

Short Term Oral/Dermal

0.95 mg/kg/day

0.35 mg/kg/day

*Oral worker values are not derived