Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
284 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2.5
Modified dose descriptor starting point:
NOAEL
DNEL value:
710 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The oral route of exposure is considered to be a conservative route of exposure as compared to dermal.
AF for differences in duration of exposure:
1
Justification:
Chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL).
AF for other interspecies differences:
2.5
AF for intraspecies differences:
1
Justification:
AF’s = 1 for Intraspecies differences workers. Normally this AF = 5 but this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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

The long-term DNEL’s are based on the NOEL for the 2 year oral study in Fischer 344 rats. Body weight information is not available but chronic body weight for the male Fischer 344 rats has been estimated by the USEPA as 380 grams. The males consumed 40 grams of Allantoin during the 106 week study period. This equates to a NOEL of 142 mg/kg bw/d.

DNEL dermal long term workers:

Oral NOAEL 142 mg x 20% worst case measured skin absorption = 142 x 5 = 710 mg/kg bw d

 

AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL) x 2.5 (Remaining interspecies differences) x 1 (Intraspecies differences workers. Normally 5 but again this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight) x 1 (chronic study) x 1 (DR reliability) x 1 (Quality of the database) = 2.5

 

DNEL Dermal long term workers = 710/2.5 = 284 mg/kg bw d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
284 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
2.5
Modified dose descriptor starting point:
NOAEL
DNEL value:
710 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic 2 yr study
AF for interspecies differences (allometric scaling):
1
Justification:
AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL).
AF for other interspecies differences:
2.5
AF for intraspecies differences:
1
Justification:
AF’s = 1 for Intraspecies differences workers. Normally this AF = 5 but this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
56.8 mg/kg bw/day
Most sensitive endpoint:
carcinogenicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
2.5
Modified dose descriptor starting point:
NOAEL
DNEL value:
142 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic 2 yr study
AF for interspecies differences (allometric scaling):
1
Justification:
AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL).
AF for other interspecies differences:
2.5
AF for intraspecies differences:
1
Justification:
AF’s = 1 for Intraspecies differences workers. Normally this AF = 5 but this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The long-term DNEL’s are based on the NOEL for the 2 year oral study in Fischer 344 rats. Body weight information is not available but chronic body weight for the male Fischer 344 rats has been estimated by the USEPA as 380 grams. The males consumed 40 grams of Allantoin during the 106 week study period. This equates to a NOEL of 142 mg/kg bw d.

 

DNEL dermal long term general population:

 

Oral NOAEL 142 mg/kg bw d x 20% worst case measured skin absorption = 142 x 5 = 710 mg/kg bw d

 

AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL) x 2.5 (Remaining interspecies differences) x 1 (Intraspecies differences general population. Normally 10 but again this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight) x 1 (chronic study) x 1 (DR reliability) x 1 (Quality of the database) = 2.5

 

DNEL Dermal long term general population = 710/2.5 = 284 mg/kg bw d

 

 

DNEL Oral long term general population:

 

Oral NOAEL 142 mg/kg bw d

 

AF’s = 1 (Allometric scaling. Normally 4 for rat to human but this is an endogenous compound in both species and the reference toxicity value is a NOEL not a NOAEL) x 2.5 (Remaining interspecies differences) x 1 (Intraspecies differences general population. Normally 10 but again this is an endogenous compound which is considered safe at single oral doses of 10 grams in both healthy and unhealthy patients and has been used safely in skin preparations for many years at concentrations of up to 2% by weight) x 1 (chronic study) x 1 (DR reliability) x 1 (Quality of the database) = 2.5

 

DNEL oral long term general population = 142/2.5 = 56.8 mg/kg bw d