Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Modified dose descriptor starting point:
NOAEC
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:
1 000 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
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

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance, using the assessment factors as proposed by ECETOC (ECETOC, Technical Report No. 86, 2003). In case no substance specific data were available, read-across from an appropriate read-across candidate was used. In this situation, a correction for molecular weight was used since it was assumed that the toxicity is exerted by the number of molecules rather than by the amount of substance expressed in weight. No assessment factor was used to correct for uncertainties that may occur when read-across is used. The reason is that the read-across substances used appear to have higher toxic potential than zinc bis(dibenzyldithiocarbamate) (ZBEC). This becomes clear in the read-across justification available in the current dossier.

Kinetics

No toxicokinetic data on ZBEC are available. The approach used for the different routes of exposure for DNEL derivation is described below.

Oral absorption

No long-term substance-specific data on ZBEC which could be used for DNEL derivation are available. Therefore the information on its long-term toxicity has been derived by read-across from its three structural analogues, zinc dibutyldithiocarbamate, (ZDBC), zinc bis(diethyldithiocarbamate) (ZDEC) and zinc bis(dimethyldithiocarbamate) (ZDMC). A default value of 50% for oral absorption, recommended by Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment was used in case of route-to-route extrapolation if DNELs were calculated based on the data on ZDBC or ZDEC, as no substance-specific data on oral absorption are available for these substances. For ZDMC, 60% oral absorption was determined in the GLP-compliant study with rats. Therefore this value for used to determined the internal dose of ZDMC in DNEL derivation when the ZDMC-specific data were used. The use of default value of 50% for oral absorption in case of route-to-route extrapolation if the data from ZDBC or ZDEC are used represents a worst-case approach, as it represents lower internal dose.  

Inhalation absorption

As no data are available on inhalation absorption, the default value of 100%, as set in Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, will be used for DNEL derivation in case of oral-to-respiratory route extrapolation.

Dermal absorption

Regarding dermal absorption, an available in vitro study on structural analogue ZDMC indicated 0.1% dermal absorption. As ZBEC is a larger molecule than ZDMC, it is expected that its dermal absorption will not exceed this value. Based on this, the dermal absorption percentage used fore the DNEL derivation is set to 0.1% for ZBEC.

Acute toxicity

ZBEC is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.

ZBEC is not irritating to the skin, eyes and respiratory tract and not sensitising. Therefore, no DNELs are derived for these endpoints.

Long-term toxicity

Regarding repeated dose toxicity studies, a 17-week diet study with rats is available for a structural analogue of ZBEC, ZDBC (zinc bis(dibutyldithiocarbamate)). A NOAEL of 41 mg/kg bw/day (males) and 47 mg/kg bw/day (females) was established in this study based on increased relative liver and kidney weight and reduced body weight gain and food intake at the highest dose. Using a correction for molecular weight, this results in a NOAEL of 41 x (610/ 478) = 52 mg/kg bw/day for ZBEC.

 

Data on reproductive and developmental toxicity are not available for ZBEC. Regarding reproductive toxicity, a reliable 2-generation diet study with rats is available for its structural analogue ZDMC. In this study, no adverse effects on fertility were noted at the highest tested dose, resulting in a NOAEL of 25 mg/kg bw/day. Signs of parental toxicity, manifested as reduced body weight and food consumption, were observed in the high-dose group, resulting in a NOAELparental of 10 mg/kg bw/day. Using a correction for molecular weight, this results in NOAELreproductive = 25 x(610/306) = 50 mg/kg bw/day and NOAELparental = 10 x(610/306) = 20 mg/kg bw/day.

 

Regarding developmental toxicity, data are available on a structural analogue of ZBEC, ZDEC (zinc bis(diethyldithiocarbamate)). In the study with rats administered ZDEC in olive oil by gavage at dose levels up to 250 mg/kg bw/day during gestation days 7-15, no adverse effects on development were found up to the highest dose. Signs of severe maternal toxicity were noted at the same dose level while at 125 mg/kg bw/day only slight diarrhea was noted in some animals. Therefore a dose level of 125 mg/kg bw/day was chosen as a NOAEL for parental toxicity. Applying the correction for molecular weight, this results in NOAELdevelopment of 250 x (610/366) = 417 mg/kg bw/day and NOAELmaternal  = 125 x (610/366) = 208 mg/kg bw/day.

 

Based on these data, no DNELs need to be derived for reproductive and developmental toxicity for ZBEC, as the substance is not toxic to fertility and development and established NOAELs for these effects are higher than the NOAELs for systemic toxicity.

 

DNELs for systemic toxicity for ZBEC shall be derived in two ways, using the two lowest NOAELs of 52 mg/kg bw/day, obtained in a 17-week oral toxicity study with ZDBC, and 20 mg/kg bw/day obtained in a two-generation study with ZDMC,using the scientifically based assessment factors as reported by ECETOC (2003).The lowest of these DNELs shall be considered critical and will be taken forward for risk assessment. As NOAEL for parental toxicity observed in a developmental study with ZDEC is significantly higher, and the same assessment factors shall be applied for reproductive and developmental toxicity studies, they will not lead to a critical DNEL. Therefore no DNEL calculation using this NOAEL as a point of departure has been performed.

DNEL calculation, using as a starting point a NOAEL of 52 mg/kg bw/day (corrected for molecular weight), established in a 17-week diet study with rats with a structural analogue ZDBC

 

For workers:

 DNELchronic for systemic effects by inhalation exposure:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 52 mg/kg bw/day

Based on an oral 17-weeks study with ZDBC (increased liver and kidney weight; decreased body weight and food uptake), corrected for molecular weight

Step 2) Modification of starting point

0.5

 

1

 

 

 

0.38 m3/kg bw

 

 

 

6.7 m3/10 m3

Proportion oral absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is required

Intraspecies

3

The default assessment factor for workers, as proposed in the ECETOC Guidance

Exposure duration

2

Correction from subchronic to chronic exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

52 x (0.5 / 1) x (6.7/10) / (0.38 x 1 x 3 x 2 x 1 x 1) = 8 mg/m3

 

DNELchronic for systemic effects by dermal exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 52 mg/kg bw/day

Based on an oral 17-weeks study with ZDBC (increased liver and kidney weight; decreased body weight and food uptake), corrected for molecular weight

Step 2) Modification of starting point

0.6

 

0.001

 

 

Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Value obtained inin vitroskin penetration study with ZDMC

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

3

The default assessment factor for workers, as proposed by ECETOC

Exposure duration

2

 Correction from subchronic to chronic exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

= 52 x (0.6 / 0.001) / (4 x 3 x 2 x 1 x 1) = 1293 mg/kg bw/day

DNEL calculation, using as a starting point a NOAEL of 20 mg/kg bw/day (corrected for molecular weight), established in a 2-generation diet study with rats with a structural analogue ZDMC

 

For workers:

 

DNELchronic for systemic effects by inhalation exposure:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 20 mg/kg bw/day

Based on an oral 2-generation reproductive study with ZDMC (reduced body weight and food consumption in parental animals), corrected for molecular weight

Step 2) Modification of starting point

0.6

 1

 

 

 

0.38 m3/kg bw

 

 

 

6.7 m3/10 m3

Percentage oral absorption of ZDMC

 

Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance (R.8.4.2)

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is required

Intraspecies

3

The default assessment factor for workers, as proposed in the ECETOC Guidance

Exposure duration

1

No correction for exposure duration is required, as the data are obtained from a 2-generation study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

20 x (0.6 / 1) x (6.7/10) / (0.38 x 1 x 3 x 1 x 1 x 1) =7 mg/m3

 

DNELchornic for systemic effects by dermal exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 20 mg/kg bw/day

Based on an oral 2-generation reproductive study with ZDMC (reduced body weight and food consumption in parental animals), corrected for molecular weight

Step 2) Modification of starting point

0.6

 

 0.001

 

 

Percentage oral absorption of ZDMC

 

 Value obtained inin vitroskin penetration study with ZDMC

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

3

The default assessment factor for workers, as proposed by ECETOC

Exposure duration

1

 No correction for exposure duration is required, as the data are obtained from a 2-generation study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

= 20 x (0.6 / 0.001) / (4 x 3 x 1 x 1 x 1) =1000 mg/kg bw/day

Choice of the critical DNELs

 

As can be seen from the results above, the DNEL values calculated based on the results of the studies with two structural analogues of ZBEC, ZDBC and ZDMC, are essentially in the same order of magnitude and in general very close, if not identical. However, the use of a NOAEL of 20 mg/kg bw/day (corrected for molecular weight) established in a two-generation oral toxicity study with ZDMC as a point of departure for DNEL derivation leads to slightly lower DNELs in comparison with the ones obtained based on a NOAEL of 52 mg/kg bw/day (corrected for molecular weight) established in a 17-week oral toxicity study with ZDBC. Consequently, using a precautionary principle, the former DNELs shall be considered critical and will be taken forward to risk characterization.


References

 

ECETOC, Technical Report No. 86. Derviation of Assessment Factors for Human Health Risk Assessment, February 2003. ISSN-0773-6347-86.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
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:
600 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
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:
1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
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

This information will be updated later based on ECHA decision number CCH-D-2114382075-49-01.

According to the REACH guidance on information requirements and chemical safety assessment a leading DN(M) EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible. In the present case, DNELs have been derived according to the ECETOC guidance, using the assessment factors as proposed by ECETOC (ECETOC, Technical Report No. 86, 2003). In case no substance specific data were available, read-across from an appropriate read-across candidate was used. In this situation, a correction for molecular weight was used since it was assumed that the toxicity is exerted by the number of molecules rather than by the amount of substance expressed in weight. No assessment factor was used to correct for uncertainties that may occur when read-across is used. The reason is that the read-across substances used appear to have higher toxic potential than ZBEC. This becomes clear in the read-across justification available in the current dossier.

Kinetics

No toxicokinetic data on ZBEC are available. The approach used for the different routes of exposure for DNEL derivation is described below.

Oral absorption

No long-term substance-specific data on ZBEC which could be used for DNEL derivation are available. Therefore the information on its long-term toxicity has been derived by read-across from its three structural analogues, zinc dibutyldithiocarbamate, (ZDBC), zinc bis(diethyldithiocarbamate) (ZDEC) and zinc bis(dimethyldithiocarbamate) (ZDMC). A default value of 50% for oral absorption, recommended by Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment was used in case of route-to-route extrapolation if DNELs were calculated based on the data on ZDBC or ZDEC, as no substance-specific data on oral absorption are available for these substances. For ZDMC, 60% oral absorption was determined in the GLP-compliant study with rats. Therefore this value for used to determined the internal dose of ZDMC in DNEL derivation when the ZDMC-specific data were used. The use of default value of 50% for oral absorption in case of route-to-route extrapolation if the data from ZDBC or ZDEC are used represents a worst-case approach, as it represents lower internal dose.  

Inhalation absorption

As no data are available on inhalation absorption, the default value of 100%, as set in Chapter R.8 of REACH Guidance on information requirements and chemical safety assessment, will be used for DNEL derivation in case of oral-to-respiratory route extrapolation.

Dermal absorption

Regarding dermal absorption, an available in vitro study on structural analogue ZDMC indicated 0.1% dermal absorption. As ZBEC is a larger molecule than ZDMC, it is expected that its dermal absorption will not exceed this value. Based on this, the dermal absorption percentage used fore the DNEL derivation is set to 0.1% for ZBEC.

 Acute toxicity

ZBEC is not classified for acute toxicity and therefore derivation of a DNELacute is not necessary.

ZBEC is not irritating to the skin, eyes and respiratory tract and not sensitising. Therefore, no DNELs are derived for these endpoints.

Long-term toxicity

Regarding repeated dose toxicity studies, a 17-week diet study with rats is available for a structural analogue of ZBEC, ZDBC (zinc bis(dibutyldithiocarbamate)). A NOAEL of 41 mg/kg bw/day (males) and 47 mg/kg bw/day (females) was established in this study based on increased relative liver and kidney weight and reduced body weight gain and food intake at the highest dose. Using a correction for molecular weight, this results in a NOAEL of 41 x (610/ 478) = 52 mg/kg bw/day for ZBEC.

 

Data on reproductive and developmental toxicity are not available for ZBEC. Regarding reproductive toxicity, a reliable 2-generation diet study with rats is available for its structural analogue ZDMC. In this study, no adverse effects on fertility were noted at the highest tested dose, resulting in a NOAEL of 25 mg/kg bw/day. Signs of parental toxicity, manifested as reduced body weight and food consumption, were observed in the high-dose group, resulting in a NOAELparental of 10 mg/kg bw/day. Using a correction for molecular weight, this results in NOAELreproductive = 25 x(610/306) = 50 mg/kg bw/day and NOAELparental = 10 x(610/306) = 20 mg/kg bw/day.

 

Regarding developmental toxicity, data are available on a structural analogue of ZBEC, ZDEC (zinc bis(diethyldithiocarbamate)). In the study with rats administered ZDEC in olive oil by gavage at dose levels up to 250 mg/kg bw/day during gestation days 7-15, no adverse effects on development were found up to the highest dose. Signs of severe maternal toxicity were noted at the same dose level while at 125 mg/kg bw/day only slight diarrhea was noted in some animals. Therefore a dose level of 125 mg/kg bw/day was chosen as a NOAEL for parental toxicity. Applying the correction for molecular weight, this results in NOAELdevelopment of 250 x (610/366) = 417 mg/kg bw/day and NOAELmaternal  = 125 x (610/366) = 208 mg/kg bw/day.

 

Based on these data, no DNELs need to be derived for reproductive and developmental toxicity for ZBEC, as the substance is not toxic to fertility and development and established NOAELs for these effects are higher than the NOAELs for systemic toxicity.

 

DNELs for systemic toxicity for ZBEC shall be derived in two ways, using the two lowest NOAELs of 52 mg/kg bw/day, obtained in a 17-week oral toxicity study with ZDBC, and 20 mg/kg bw/day obtained in a two-generation study with ZDMC,using the scientifically based assessment factors as reported by ECETOC (2003).The lowest of these DNELs shall be considered critical and will be taken forward for risk assessment. As NOAEL for parental toxicity observed in a developmental study with ZDEC is significantly higher, and the same assessment factors shall be applied for reproductive and developmental toxicity studies, they will not lead to a critical DNEL. Therefore no DNEL calculation using this NOAEL as a point of departure has been performed.

 

DNEL calculation, using as a starting point aNOAEL of 52 mg/kg bw/day (corrected for molecular weight), established in a 17-week diet study with rats with a structural analogue ZDBC

For general population:

 

DNELchronic for systemic effects by inhalation exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 52 mg/kg bw/day

Based on an oral 17-weeks study with ZDBC (increased liver and kidney weight; decreased body weight and food uptake), corrected for molecular weight

Step 2) Modification of starting point

0.5

 

 1

 

 

 

 1.15 m3/kg bw

 

 

Proportion oral absorption (default value, as proposed in the REACH guidance (R.8.4.2)

Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is required

Intraspecies

5

The default assessment factor for general population, as proposed in the ECETOC Guidance

Exposure duration

2

Correction from subchronic to chronic exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

52 x (0.5 / 1) / (1.15 x 1 x 5 x 2 x 1 x 1) = 2 mg/m3

 

DNELchronic for systemic effects by dermal exposure:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 52 mg/kg bw/day

Based on an oral 17-weeks study with ZDBC (increased liver and kidney weight; decreased body weight and food uptake), corrected for molecular weight

Step 2) Modification of starting point

0.6

 

 0.001

 

Proportion oral absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 Value obtained inin vitroskin penetration study with ZDMC

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

Exposure duration

2

Correction from subchronic to chronic exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

= 52 x (0.5 / 0.001) / (4 x 5 x 2 x 1 x 1) = 650 mg/kg bw/day

 

DNELchronic for systemic effects by oral exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 52 mg/kg bw/day

Based on an oral 17-weeks study with ZDBC (increased liver and kidney weight; decreased body weight and food uptake), corrected for molecular weight

Step 2) Modification of starting point

1

 

No modification of the starting point is required

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

Exposure duration

2

Correction from subchronic to chronic exposure duration

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

52/ (4 x 5 x 2 x 1 x 1) = 1 mg/kg bw/day

DNEL calculation, using as a starting point a NOAEL of 20 mg/kg bw/day (corrected for molecular weight), established in a 2-generation diet study with rats with a structural analogue ZDMC

For general population:

 

DNELchronic for systemic effects by inhalation exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 20 mg/kg bw/day

Based on an oral 2-generation reproductive study with ZDMC (reduced body weight and food consumption in parental animals), corrected for molecular weight

Step 2) Modification of starting point

0.6

 1

 

 

 

 1.15 m3/kg bw

 

 

Percentage oral absorption of ZDMC

Proportion inhalation absorption (default value, as proposed in the REACH guidance (R.8.4.2)

 

Standard respiratory volume of a rat, corrected for 24 h exposure, as proposed in the REACH Guidance (R.8.4.2)

Step 3) Assessment factors

 

 

Interspecies

1

No allometric scaling is required

Intraspecies

5

The default assessment factor for general population, as proposed in the ECETOC Guidance

Exposure duration

1

No correction for exposure duration is required, as the data are obtained from a 2-generation study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

20 x (0.6 / 1) / (1.15 x 1 x 5 x 1 x 1 x 1) =2 mg/m3

 

DNELchronic for systemic effects by dermal exposure:

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 20 mg/kg bw/day

Based on an oral 2-generation reproductive study with ZDMC (reduced body weight and food consumption in parental animals), corrected for molecular weight

Step 2) Modification of starting point

0.6

 0.001

 

Percentage oral absorption of ZDMC

 

 Value obtained inin vitroskin penetration study with ZDMC

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

Exposure duration

1

No correction for exposure duration is required, as the data are obtained from a 2-generation study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

= 20 x (0.5 / 0.001) / (4 x 5 x 1 x 1 x 1) x = 600 mg/kg bw/day

 

DNELchronic for systemic effects by oral exposure:

 

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 20 mg/kg bw/day

Based on an oral 2-generation reproductive study with ZDMC (reduced body weight and food consumption in parental animals), corrected for molecular weight

Step 2) Modification of starting point

1

 

No modification of the starting point is required

Step 3) Assessment factors

 

 

Interspecies

4

Allometric scaling factor for rat

Intraspecies

5

The default assessment factor for general population, as proposed by ECETOC

Exposure duration

1

No correction for exposure duration is required, as the data are obtained from a 2-generation study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

20 / (4 x 5 x 1 x 1 x 1) =1 mg/kg bw/day

  

Choice of the critical DNELs

 

As can be seen from the results above, the DNEL values calculated based on the results of the studies with two structural analogues of ZBEC, ZDBC and ZDMC, are essentially in the same order of magnitude and in general very close, if not identical. However, the use of a NOAEL of 20 mg/kg bw/day (corrected for molecular weight) established in a two-generation oral toxicity study with ZDMC as a point of departure for DNEL derivation leads to slightly lower DNELs in comparison with the ones obtained based on a NOAEL of 52 mg/kg bw/day (corrected for molecular weight) established in a 17-week oral toxicity study with ZDBC. Consequently, using a precautionary principle, the former DNELs shall be considered critical and will be taken forward to risk characterization.


References

 

ECETOC, Technical Report No. 86. Derviation of Assessment Factors for Human Health Risk Assessment, February 2003. ISSN-0773-6347-86.