Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.1 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.4 mg/m³
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

Summary of the toxicity of DCBD

Data for DCBD indicate moderate acute toxicity by the oral route (LD50= 222 mg/kg bw) and by the inhalation route (LC50= 2080 mg/m34 h). The most notable sign of acute toxicity following inhalation is pulmonary injury (irritation, respiratory depression, pulmonary oedema and haemorrhage); however effects on the liver and kidney also indicate systemic effects. The substance is regarded to be a skin, eye and respiratory irritant.

Repeated dose toxicity studies are available for the inhalation route; no data are available for other routes of exposure. Findings in a 14-day inhalation study performed in rats at an exposure level of 0.4 mg/L were limited to reduced weight gain and increased relative liver weights with histopathology of unclear significance but possibly representing an adaptive response. In a one-generation reproductive toxicity study, effects in parental rats were apparent at the highest exposure concentration of 50 ppm (271 mg/m3) and consisted of decreased weight gain, reduced food consumption and food efficiency, and degeneration and regeneration of the nasal olfactory epithelium and atrophy of Bowman´s glands, but no histopathological changes in e.g. liver and kidneys. A NOAEC of 5 ppm (25.15 mg/m3) was determined for both local and systemic effects in this study.

A developmental toxicity study was also performed in rats using inhalation exposure. The study identified embryotoxic effects (decreased fetal weight) in the presence of clear maternal toxicity (decreases in maternal body weight, body weight gain and food consumption as well as clinical signs of toxicity during exposure) at the highest concentration tested (50 ppm = 251.5 mg/m3). Therefore the a maternal and offspring LOAEC is 50 ppm, with a NOAEC of 10 ppm (50.30 mg/m3) for maternal toxicity as well as for embryotoxicity.

Local DNEL values [Worker]

Local inhalation DNEL values

A NOAEC of 5 ppm (25.15 mg/m3) was determined for local effects in parental animals in a one-generation reproductive toxicity study (sub-chronic inhalation exposure). The concentration of 25.15 mg/m3 is therefore taken as the point of departure (PoD) for the derivation of local inhalation DNEL values for acute and long term toxicity.

• Short-term local inhalation DNEL

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences (local effects).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

No assessment factor is required to cover exposure duration for the short-term DNEL; the NOAEC is derived from a sub-chronic study .

No additional assessment factor is required for dose-response; the LOAEC in the relevant study was ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 3 is therefore derived.

Applying the overall assessment factor of 3 to the NOAEC of 25.15 mg/m3 results in a short-term local inhalation worker DNEL value of 8.4 mg/m3.

• Long-term local inhalation DNEL

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences (inhalation study, local effects).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

No assessment factor is required to cover exposure duration. Although the NOAEC is derived from a sub-chronic study and the DNEL covers chronic exposure, local effects on the respiratory tract are considered to be related to concentration of the substance rather than the duration of exposure. This is confirmed by the fact that the same LOAEC of 50 ppm (251.5 mg/m3) is found in a subacute range-finding inhalation study, associated with the one generation reproduction toxicity study.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study was ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 3 is therefore derived.

Applying the overall assessment factor of 3 to the NOAEC of 25.15 mg/m3 results in a long-term local inhalation worker DNEL value of 8.4 mg/m3.

Local dermal DNEL values

• Short-term local DNEL

The substance is assumed to be irritating to skin. In the absence of any dose-response data a quantitative dose descriptor is not available and a short-term local dermal DNEL value cannot be calculated.

• Long-term local DNEL

No repeated dose dermal toxicity studies are available. The substance is assumed to be a skin irritant following and local effects following repeated dermal exposure are not predicted. In the absence of any dose-response data a quantitative dose descriptor is not available and a long-term local DNEL value cannot be calculated.

Systemic DNEL values [Worker]

Systemic inhalation DNEL values

• Short-term systemic inhalation DNEL

A NOAEC of 5 ppm (25.15 mg/m3) was determined for systemic effects in parental animals in a one-generation reproductive toxicity study (sub-chronic inhalation exposure; at LOAEC of 50 ppm: decreased weight gain, reduced food consumption and food efficiency). Reproductive toxicity is covered by this NOAEC. The concentration of 25.15 mg/m3 is therefore taken as the point of departure for the derivation of systemic inhalation DNEL values. The rat inhalation NOAEC of 25.15 mg/m3 is corrected for differences in exposure conditions (6 hours/8 hours) and breathing rate (6.7 m3/10 m3) to give a corrected inhalation NOAEC of 12.64 mg/m3.

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the NOEAC has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

No assessment factor is required to cover exposure duration. Extrapolation from a sub-chronic study to short-term exposure represents a conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 3 is therefore appropriate for short-term exposure. Applying the assessment factor of 3 to the corrected inhalation NOAEC of 12.64 mg/m3 results in a short-term systemic inhalation worker DNEL of 4.2 mg/m3.

• Long-term systemic inhalation DNEL

A NOAEC of 5 ppm (25.15 mg/m3) was determined for systemic effects in parental animals in a one-generation reproductive toxicity study (sub-chronic inhalation exposure). Reproductive toxicity is covered by this NOAEC. The concentration of 25.15 mg/m3 is therefore taken as the point of departure (PoD) for the derivation of systemic inhalation DNEL values. The rat inhalation NOAEC of 25.15 mg/m3 is corrected for differences in exposure conditions (6 hours/8 hours) and breathing rate (6.7 m3/10 m3) to give a corrected inhalation NOAEC of 12.64 mg/m3.

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

An assessment factor of 2 is used to cover exposure duration (extrapolation from a sub-chronic study to chronic exposure). It should be noted that systemic effects were limited to decreased weight gain, reduced food consumption and food efficiency without histopathological changes in e.g. liver and kidneys, therefore it is unclear whether the effects observed were primary systemic toxicity or potential secondary responses to e.g. irritation effects after inhalation. Since local effects on the respiratory tract are considered to be related to concentration of the substance rather than the duration of exposure the application of a assessment factor to cover exposure duration can be considered a precautionary and conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 6 is therefore appropriate for long-term exposure. Applying the assessment factor of 6 to the corrected inhalation NOAEC of 12.64 mg/m3 results in a long-term systemic inhalation worker DNEL of 2.1 mg/m3.

Systemic dermal DNEL values

No relevant data are available for dermal exposure. Systemic dermal DNEL values are derived from the corrected inhalation NOAEC of 12.64 mg/m3, with further correction for the relative extent of absorption. In the absence of specific information on the extent of absorption, it is assumed (following REACH guidance) that the extent of absorption following inhalation exposure is twice that following dermal exposure.

• Short-term systemic dermal DNEL

The corrected inhalation NOAEC of 12.64 mg/m3 is equivalent to a dermal NOAEL of 3.6 mg/kg bw/d (assuming 70 kg bodyweight, a breathing rate of 10m3/day and correcting for the relative extent of absorption).

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

No assessment factor is required to cover exposure duration. Extrapolation from a sub-chronic study to short-term exposure represents a conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 3 is therefore appropriate for short-term exposure. Applying the assessment factor of 3 to the extrapolated dermal NOAEL of 3.6 mg/kg bw/d results in a short-term systemic dermal worker DNEL of 1.2 mg/kg bw/d.

• Long-term systemic dermal DNEL

The corrected inhalation NOAEC of 12.64 mg/m3 is equivalent to a dermal NOAEL of 3.6 mg/kg bw/d (assuming 70 kg bodyweight, a breathing rate of 10m3/day and correcting for the relative extent of absorption).

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 3 is used to cover potential intraspecies differences (workers).

An assessment factor of 2 is required to cover exposure duration (extrapolation from a sub-chronic study to chronic exposure).

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 6 is therefore appropriate for long-term exposure. Applying the assessment factor of 6 to the extrapolated dermal NOAEC of 3.6 mg/kg bw/d results in a long-term systemic dermal worker DNEL of 0.6 mg/kg bw/d.

Local DNEL values [General Population]

Local inhalation DNEL values

A NOAEC of 5 ppm (25.15 mg/m3) was determined for local effects in parental animals in a one-generation reproductive toxicity study (sub-chronic exposure). Reproductive toxicity is covered by this NOAEC. The concentration of 25.15 mg/m3 is therefore taken as the point of departure (PoD) for the derivation of local inhalation DNEL values.

• Short-term local inhalation DNEL

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences (local effects).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

No assessment factor is required to cover exposure duration; the NOAEC is derived from a sub-chronic study.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study was ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 5 is therefore derived.

Applying the overall assessment factor of 5 to the NOAEC of 25.15 mg/m3 results in a short-term local inhalation general population DNEL value of 5.0 mg/m3.

• Long-term local inhalation DNEL

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences (local effects).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

No assessment factor is required to cover exposure duration. Although the NOAEC is derived from a sub-chronic study and the DNEL covers chronic exposure, local effects on the respiratory tract are considered to be related to concentration of the substance rather than the duration of exposure. This is confirmed by the fact that the same LOAEC of 50 ppm (251.5 mg/m3) is found in a subacute range-finding inhalation study, associated with the one generation reproduction toxicity study.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study was ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 5 is therefore derived.

Applying the overall assessment factor of 5 to the NOAEC of 25.15 mg/m3 results in a long-term local inhalation general population DNEL value of 5.0 mg/m3.

Local dermal DNEL values

• Short-term local DNEL

The substance was assumed to be irritating to skin irritant following a single exposure. In the absence of any dose-response data a quantitative dose descriptor is not available and a short-term local dermal DNEL value cannot be calculated.

• Long-term local DNEL

No repeated dose dermal toxicity studies are available. The substance is assumed to be a skin irritant following a single exposure and local effects following repeated dermal exposure are not predicted. In the absence of any dose-response data a quantitative dose descriptor is not available and a long-term local DNEL value cannot be calculated.

Systemic DNEL values [General Population]

Systemic inhalation DNEL values

• Short-term systemic inhalation DNEL

A NOAEC of 5 ppm (25.15 mg/m3) was determined for systemic effects in parental animals in a one-generation reproductive toxicity study (sub-chronic inhalation exposure; at LOAEC of 50 ppm: decreased weight gain, reduced food consumption and food efficiency). The concentration of 25.15 mg/m3 is therefore taken as the point of departure for the derivation of systemic inhalation DNEL values. The rat inhalation NOAEC of 25.15 mg/m3 is corrected for differences in exposure conditions (6 hours/24 hours) to give a corrected inhalation NOAEC of 6.29 mg/m3.

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

No assessment factor is required to cover exposure duration. Extrapolation from a sub-chronic study to short-term exposure represents a conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 5 is therefore appropriate for short-term exposure. Applying the assessment factor of 5 to the corrected inhalation NOAEC of 6.29 mg/m3 results in a long-term systemic inhalation general population DNEL of 1.3 mg/m3.

• Long-term systemic inhalation DNEL

A NOAEC of 5 ppm (25.15 mg/m3) was determined for systemic effects in parental animals in a one-generation reproductive toxicity study (sub-chronic exposure). The concentration of 25.15 mg/m3 is therefore taken as the point of departure for the derivation of systemic inhalation DNEL values. The rat inhalation NOAEC of 25.15 mg/m3 is corrected for differences in exposure conditions (6 hours/24 hours) to give a corrected inhalation NOAEC of 6.29 mg/m3.

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

An assessment factor of 2 is used to cover exposure duration (extrapolation from a sub-chronic study to chronic exposure).

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 10 is therefore appropriate for long-term exposure. Applying the assessment factor of 6 to the corrected inhalation NOAEC of 6.29 mg/m3 results in a long-term systemic inhalation general population DNEL of 0.6 mg/m3.

Systemic dermal DNEL values

No relevant data are available for dermal exposure. Systemic dermal DNEL values are derived from the corrected inhalation NOAEC of 6.29 mg/m3, with further correction for the relative extent of absorption. In the absence of specific information on the extent of absorption, it is assumed (following REACH guidance) that the extent of absorption following inhalation exposure is twice that following dermal exposure. It should be noted that systemic effects were limited to decreased weight gain, reduced food consumption and food efficiency without histopathological changes in e.g. liver and kidneys, therefore it is unclear whether the effects observed were primary systemic toxicity or potential secondary responses to e.g. irritation effects after inhalation. Therefore the derivation of an oral or dermal DNEL based on these data represents a precautionary and conservative approach.

• Short-term systemic dermal DNEL

The corrected inhalation NOAEC of 6.29 mg/m3 is equivalent to a dermal NOAEL of 4.2 mg/kg bw/d (assuming 60 kg bodyweight, a breathing rate of 20m3/day and correcting for the relative extent of absorption).

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

No assessment factor is required to cover exposure duration. Extrapolation from a sub-chronic study to short-term exposure represents a conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 5 is therefore appropriate for short-term exposure. Applying the assessment factor of 5 to the extrapolated dermal NOAEL of 4.2mg/kg bw/d results in a short-term systemic dermal general population DNEL of 0.8 mg/kg bw/d.

• Long-term systemic dermal DNEL

The corrected inhalation NOAEC of 6.29 mg/m3 is equivalent to a dermal NOAEL of 4.2 mg/kg bw/day (assuming 60 kg bodyweight, a breathing rate of 20m3/day and correcting for the relative extent of absorption).

The use of assessment factors is considered according to ECETOC guidance:

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

An assessment factor of 2 is required to cover exposure duration (extrapolation from a sub-chronic study to chronic exposure).

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 10 is therefore appropriate for long-term exposure. Applying the assessment factor of 10 to the extrapolated dermal NOAEC of 4.2 mg/kg bw/d results in a long-term systemic dermal general population DNEL of 0.4 mg/kg bw/d.

Systemic oral DNEL values

No relevant data are available for oral exposure. Systemic oral DNEL values are derived from the corrected inhalation NOAEC of 6.29 mg/m3 . In the absence of specific information on the extent of absorption, it is assumed that the extent of absorption following inhalation exposure is the same as following oral exposure. It should be noted that systemic effects were limited to decreased weight gain, reduced food consumption and food efficiency without histopathological changes in e.g. liver and kidneys, therefore it is unclear whether the effects observed were primary systemic toxicity or potentiall secondary responses to e.g. irritartion effects after inhalation. Therefore the derivation of an oral or dermal DNEL based on these data represents a precautionary and conservative approach.

• Short-term systemic oral DNEL

The corrected inhalation NOAEC of 6.29 mg/m3 is equivalent to an oral NOAEL of 2.1 mg/kg bw/d (assuming 60 kg bodyweight, a breathing rate of 20m3/day and assuming that the relative extent of absorption is the same after inhalation and oral exposure).

The use of assessment factors is considered according to ECETOC guidance.

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

No assessment factor is required to cover exposure duration. Extrapolation from a sub-chronic study to short-term exposure represents a conservative approach.

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 5 is therefore appropriate for short-term exposure. Applying the assessment factor of 5 to the extrapolated oral NOAEL of 2.1 mg/kg bw/d results in a short-term systemic oral general population DNEL of 0.4 mg/kg bw/d.

• Long-term systemic oral DNEL

The corrected inhalation NOAEC of 6.29 mg/m3 is equivalent to an oral NOAEL of 2.1 mg/kg bw/day (assuming 60 kg bodyweight, a breathing rate of 20m3/day and assuming that the relative extent of absorption is the same after inhalation and oral exposure).

The use of assessment factors is considered according to ECETOC guidance.

No assessment factor is required for interspecies differences; the endpoint has been corrected to reflect differences in rat and human breathing rate (allometric factors).

An assessment factor of 5 is used to cover potential intraspecies differences (general population).

An assessment factor of 2 is required to cover exposure duration (extrapolation from a sub-chronic study to chronic exposure).

No additional assessment factor is required for dose-response; the LOAEC in the relevant study is ten times the NOAEC, therefore the use of the NOAEC as the PoD represents a conservative approach.

No additional assessment factor is required for database quality: the toxicological database is considered to be adequate.

An overall assessment factor of 10 is therefore appropriate for long-term exposure. Applying the assessment factor of 10 to the extrapolated oral NOAEL of 2.1 mg/kg bw/d results in a long-term systemic oral general population DNEL of 0.2 mg/kg bw/d.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/m³
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.8 mg/kg bw/day
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.2 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.4 mg/kg bw/day
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

see discussion worker