Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.75 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Additional information - workers

The REACH Technical Guidance Document R.8 contains default assessment factors which should be applied to a modified dose descriptor in order to obtain a DNEL. These factors are multiplicative and can lead to a human chronic NAEL that is 100 or 200 fold lower than the equivalent rat subchronic NOAEL. However other guidance is available from ECETOC (2003), which supports smaller assessment factors to account for inter- and intra- species differences; leading to a human chronic NAEL that is only 24 to 40 -fold lower than an equivalent rat sub\chronic NOAEL.

 

The ECETOC technical report includes scientific justification for the magnitude of these assessment factors, including:

 

  • Although “residual” interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability.

 

  • Following analysis of the inherent variability in human toxicokinetic and toxicodynamic parameters, a difference of 3 (close to the 90th percentile) was considered appropriate to account for variability present in worker groups while a value of 5 (equivalent to the 95th percentile) was appropriate for the general population.

 

Section R.8.4.3.3 of the REACH Technical Guidance Document recognizes that the overall assessment factor applied to an experimental NOAEL when developing a DNEL is multiplicative in nature, and that “Care should be taken to avoid double counting several aspects when multiplying the individual factors.” Based on the information presented in ECETOC (2003) and summarized above, use of the standard defaults for inter- and intra- species variability contained in REACH Technical Guidance Document appears to result in “double counting”, and if used inappropriately, would lead to a large, conservative overall assessment factor.

 

In order to retain the scientific credibility in its DNEL setting process, we will adopt the assessment factors proposed by ECETOC (2003) when developing DNELs.

 

Inhalation – Worker (Long term effects – Local)

The only effect CAS#98072-31-2 is anticipated to exhibit in repeated exposure is local irritation in the respiratory system; demonstrated by CAS#68526-82-9.

 

Dose descriptor

 

A rat inhalation NOAEC of 100 mg/m3 will be used to derive the DNEL long term effects-local inhalation.

 

Modification of dose descriptor

Correct the NOAEC to adjust for differences in duration in the animal study (6 h) and the

worker (8 h) and light work following the TGD Figure R.8-2:

 

100 mg/m3 x [6 h / 8 h] x [6.7 m3 / 10 m3] x [5d / 5d] = 50.25 mg/m3

 

It is assumed that DCPD is similarly and efficiently (100%) absorbed after inhalation by rats and humans.

 

Assessment factors

Uncertainty AF Justification

Interspecies differences

1

default for inhalation route

Intraspecies differences

3

default AF for workers

Duration of exposure

1

irritation expected regardless of exposure duration

Dose-response

1

default

Overall

3

 

 

DNELlong term local inhal = 50.25 mg/m3 / 3

= 16.75 mg/m3

Risk management measures and other occupational controls are designed to limit local irritation effects will also protect against long term local respiratory tract effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.57 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
5
Dose descriptor:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The REACH Technical Guidance Document R.8 contains default assessment factors which should be applied to a modified dose descriptor in order to obtain a DNEL. These factors are multiplicative and can lead to a human chronic NAEL that is 100 or 200 fold lower than the equivalent rat subchronic NOAEL. However other guidance is available from ECETOC (2003), which supports smaller assessment factors to account for inter- and intra- species differences; leading to a human chronic NAEL that is only 24 to 40 -fold lower than an equivalent rat sub\chronic NOAEL.

 

The ECETOC technical report includes scientific justification for the magnitude of these assessment factors, including:

 

  • Although “residual” interspecies variability may remain following allometric scaling, this is largely accounted for in the default assessment factor proposed for intraspecies variability.

 

  • Following analysis of the inherent variability in human toxicokinetic and toxicodynamic parameters, a difference of 3 (close to the 90th percentile) was considered appropriate to account for variability present in worker groups while a value of 5 (equivalent to the 95th percentile) was appropriate for the general population.

 

Section R.8.4.3.3 of the REACH Technical Guidance Document recognizes that the overall assessment factor applied to an experimental NOAEL when developing a DNEL is multiplicative in nature, and that “Care should be taken to avoid double counting several aspects when multiplying the individual factors.” Based on the information presented in ECETOC (2003) and summarized above, use of the standard defaults for inter- and intra- species variability contained in REACH Technical Guidance Document appears to result in “double counting”, and if used inappropriately, would lead to a large, conservative overall assessment factor.

 

In order to retain the scientific credibility in its DNEL setting process, we will adopt the assessment factors proposed by ECETOC (2003) when developing DNELs.

 

Inhalation – General Population (Long term effects – Local)

The only effect CAS#98072-31-2 is anticipated to exhibit in repeated exposure is local irritation in the respiratory system; demonstrated by CAS#68526-82-9.

 

Dose descriptor

 

A rat inhalation NOAEC of 100 mg/m3 will be used to derive the DNEL systemic effects-local inhalation.

 

Modification of dose descriptor

Correct the NOAEC to adjust for differences in duration in the animal study (6 h) and the population (24 h) and light work following the TGD Figure R.8-2:

 

100 mg/m3 x [6 h / 24 h] x [5d / 7/] = 17.85 mg/m3

 

It is assumed that DCPD is similarly and efficiently (100%) absorbed after inhalation by rats and humans.

 

Assessment factors

Uncertainty AF Justification

Interspecies differences

1

default for inhalation route

Intraspecies differences

5

default AF for population

Duration of exposure

1

irritation expected regardless of exposure duration

Dose-response

1

default

Overall

5

 

 

DNEL long term local nhal = 17.85 mg/m3 / 5

= 3.57 mg/m3

Risk management measures and other occupational controls are designed to limit local irritation effects will also protect against long term local respiratory tract effects.