Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
46.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
Value:
230.65 mg/m³
Explanation for the modification of the dose descriptor starting point:
In a repeated dose inhalation toxicity study in rats that were exposed 6 hours/day 5 days/week over 2 years the NOAEC(rat) is 75 ppm for systemic effects in liver and kidneys as well as local effects at the respiratory tract (Aiso 2005)
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
the DNEL is derived from a long term toxicity study
AF for interspecies differences (allometric scaling):
1
Justification:
this allometric scaling factor is already included in the extrapolation NOAEC (rat) to NOAEC (human)
AF for other interspecies differences:
1
Justification:
due to the complete database covering a wide variety of animals species
AF for intraspecies differences:
5
Justification:
worker, as adviced in ECHA Guidance document R8
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are of high or at least of a very good quality because they are mostly performed according to or equivalent to the current guidelines.
AF for remaining uncertainties:
1
Justification:
In an evaluation by ECETOC 2003 and 2010 it is considered that routine application of the factor 2.5 as default factor is scientifically unjustified. In addition, the complete database covers wide variety of animals species
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
300 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: EU ILV

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.4 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):
7
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no long term dermal study available. Therefore the long term dog study was taken into account because it was demonstrated that the dog is more susceptible to p-dichlorobenzene than rodent. Furthermore, under the assumption that dermal absorption is in the same range as oral absorption the oral NOAEL is considered as NOAEL (dermal, long term). This procedure is in line with ECHA guidance Document R8
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
the DNEL is derived from a long term study
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog versus human
AF for other interspecies differences:
1
Justification:
Due to the complete dtabase covering a wie variety of species
AF for intraspecies differences:
5
Justification:
worker, as adviced By ECHA guidance document R8
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are of high or at least of a very good quality because they are mostly performed according to or equivalent to the current guidelines.
AF for remaining uncertainties:
1
Justification:
In an evaluation by ECETOC 2003 and 2010 it is considered that routine application of the factor 2.5 as default factor is scientifically unjustified. In addition, the complete database covers wide variety of animals species
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Calculated DNELs: worker

 ENDPOINT  CALCULATED DNEL

    DNEL SHORT TERM

 Inhalation worker  50 ppm
 Dermal worker

7 mg/kg bw/d

   DNEL REPEATED DOSE TOXICOLOGY
 Oral worker  1.4 mg/kg bw/d
 Inhalation worker  7.5 ppm
 
Dermal worker

1.4 mg/kg bw/d 

       DNEL REPRODUCTIVE TOXICOLOGY: DEVELOPMENTAL TOXICOLOGY
 Oral worker 12.5 mg/kg bw/d

Inhalation worker
  51 ppm
  Dermal worker  12.5 mg/kg bw/d

DNEL for Fertility and Developmental Toxicity

p-Dichlorobenzene does not affect fertility or dervelopment in the absence of general toxicity. Therefore, the DNEL long term covers reproductive toxicity and no seperate DNELS were calculated.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.2 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
81.96 mg/m³
Explanation for the modification of the dose descriptor starting point:
In a repeated dose inhalation toxicity study in rats that were exposed 6 hours/day 5 days/week over 2 years. The NOAEC(rat) is 75 ppm for systemic effects in liver and kidneys as well as local effects at the respiratory tract (Aiso 2005). For the general public the exposure period is 24h/day and 7 days per week. 75 ppm= 459 mg/m³/6h= 114.75 mg/m³/24h [ 1 ppm=6.12 mg/m³]. 114.75 mg/m³/24h /5 d * 5/7= 81.96 mg/m³/24h/7d
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
the DNEL is derived from a long term study
AF for interspecies differences (allometric scaling):
1
Justification:
this allometric scaling factor is already included in the extrapolation NOAEC (rat) to NOAEC (human)
AF for other interspecies differences:
1
Justification:
due tothe complete database covering a wide variety of animal species
AF for intraspecies differences:
10
Justification:
general public, as adviced By ECHA Guidance Document R8
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are of high or at least of a very good quality because they are mostly performed according to or equivalent to the current guidelines.
AF for remaining uncertainties:
1
Justification:
In an evaluation by ECETOC 2003 and 2010 it is considered that routine application of the factor 2.5 as default factor is scientifically unjustified. In addition, the complete database covers wide variety of animals species
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
300 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
1 690 mg/m³
Explanation for the modification of the dose descriptor starting point:
A DNEL (short term) should be derived if any acute toxicity hazard has been identified and there is a potential for high peak exposure. High peak exposures are usually for the inhalation route. This takes into consideration local and systemic toxicity. For 1,4-dichlorobenzene a LC50 (rat) greater than 5070 mg/m³ and a LOAEC of 5070 mg/m³ is available (Signs during exposure: closing of eyes, wetness around the mouth, fluid discharge from the mouth, exaggerated respiratory movements; signs during observation period: increased respiration rate, wet fur around snout and jaws, yellow staining around the urogenital region, piloerection and brown staining of snout and jaws; the signs persisted for up to 4 hours following exposure but all rats were normal in appearance and behaviour by day 1 of observation period)(Hardy 1987) LOAEC (acute toxicty: 5070 mg/m³/4h. 5070 :3 = 1690 mg/m³/4 h
AF for intraspecies differences:
10
Justification:
general public; as adviced by ECHA guidance

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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):
14
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There is no long term dermal study available. Therefore the long term dog study was taken into account because it was demonstrated that the dog is more susceptible to p-dichlorobenzene than rodent. Furthermore, under the assumption that dermal absorption is in the same range as oral absorption the oral NOAEL is considered as NOAEL (dermal, long term). This procedure is in line with ECHA guidance Document R8
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
the DNEL is derived from along term study
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog versus human
AF for other interspecies differences:
1
Justification:
due to the complete databalse covering a wide variety of animal species
AF for intraspecies differences:
10
Justification:
general public: as adviced by ECHA Guidance document R8
AF for the quality of the whole database:
1
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are of high or at least of a very good quality because they are mostly performed according to or equivalent to the current guidelines.
AF for remaining uncertainties:
1
Justification:
In an evaluation by ECETOC 2003 and 2010 it is considered that routine application of the factor 2.5 as default factor is scientifically unjustified. In addition, the complete database covers wide variety of animals species
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 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

Local effects

Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
0.7 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):
10
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation necessary. There is a reliable long term dog study available which resuted in a NOAEL of 10 mg /kg bw/day after an application of one year. With the result in this study it is shown that the dog is as susceptible to the treatment with p-dichlorobenzene as rondent
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
the DNEL is derived from a long term study
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog versus human
AF for other interspecies differences:
1
Justification:
due to the complete database covering a wide variety of animal speci
AF for intraspecies differences:
10
Justification:
general public: as adviced by ECHA guidance document R8
Justification:
There is information available to cover all relevant toxicological endpoints. The available studies are of high or at least of a very good quality because they are mostly performed according to or equivalent to the current guidelines.
Justification:
In an evaluation by ECETOC 2003 and 2010 it is considered that routine application of the factor 2.5 as default factor is scientifically unjustified. In addition, the complete database covers wide variety of animals species
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Calculated DNELS: general population

 ENDPOINT  CALCULATED DNEL
    DNEL SHORT TERM
 Inhalation general population  50 ppm
 dermal general population

3.5 mg/kg bw    

 oral general population  3.5 mg/kg bw
    DNEL REPEATED DOSE TOXICOLOGY
 Dermal general population  0.7 mg/kg bw/d
 Oral general population

0.7 mg/kg bw/d    

 Inhalation general population  1.3 ppm
    DNEL REPRODUCTIVE TOXICOLOGY: DEVELOPMENTAL TOXICOLOGY   
 Oral general population 6.25 mg/kg bw/d
 Inhalation general population
 
8.5 ppm 
 Dermal general population  6.25 mg/kg bw/d

DNEL for Fertility and Developmental Toxicity

p-Dichlorobenzene does not affect fertility or dervelopment in the absence of general toxicity. Therefore, the DNEL long term covers reproductive toxicity and no seperate DNELS were calculated.