Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
39 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
494 mg/m³
Explanation for the modification of the dose descriptor starting point:
oral absorption of 100% and inhalation absorption of 100% are assumed
AF for dose response relationship:
1
Justification:
Not needed, the PoD is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Not needed, the PoD is from a chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not needed
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor
AF for the quality of the whole database:
1
Justification:
Not needed, complete data base including reprotoxicity and carcinogenicity studies
AF for remaining uncertainties:
1
Justification:
Not needed, a conservative NOAEL was used to derive the DNEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
13.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
87.5
Dose descriptor starting point:
NOAEL
Value:
833 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 166 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Based on the available data, the dermal absorption is not expected to be significantly different between mouse and human.
AF for dose response relationship:
1
Justification:
Not needed, the PoD is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Not needed, the PoD is from a chronic study
AF for interspecies differences (allometric scaling):
7
Justification:
Default AF for mice
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
5
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed, complete data base including reprotoxicity and carcinogenicity studies
AF for remaining uncertainties:
1
Justification:
Not needed, a conservative NOAEL was used to derive the DNEL
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
34 µg/cm²
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
5
Dose descriptor:
other: NOAEL
AF for dose response relationship:
1
Justification:
Not needed
AF for differences in duration of exposure:
1
Justification:
Defaut AF for a chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Not needed for skin irritation
AF for other interspecies differences:
1
Justification:
Not needed for skin irritation
AF for intraspecies differences:
5
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed
AF for remaining uncertainties:
1
Justification:
Not needed
Acute/short term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

In numerous countries an 8-h OEL was established at 5 mg/m3for benzoyl peroxide:

Substance

Dibenzoyl peroxide

CAS No.

94-36-0

Limit value - Eight hours

Limit value - Short term

 

ppm

mg/m³

ppm

mg/m³

Australia

 

5

 

 

Austria

 

5 inhalable aerosol

 

10 inhalable aerosol

Belgium

 

5

 

 

Canada - Ontario

 

5

 

 

Canada - Québec

 

5

 

 

Denmark

 

5

 

10

Finland

 

5

 

10 (1)

France

 

5

 

 

Germany (AGS)

 

5 inhalable aerosol

 

5 inhalable aerosol (1)

Germany (DFG)

 

5 inhalable aerosol

 

5 inhalable aerosol

Hungary

 

5

 

5

Ireland

 

5

 

 

New Zealand

 

5

 

 

People's Republic of China

 

5

 

 

Singapore

 

5

 

 

South Korea

 

5

 

 

Spain

 

5

 

 

Switzerland

 

5 inhalable aerosol

 

5 inhalable aerosol

USA - NIOSH

 

5

 

 

USA - OSHA

 

5

 

 

United Kingdom

 

5

 

 

 

Remarks

Finland

(1) 15 minutes average value

Germany (AGS)

(1) 15 minutes average value

Spain

sen

 

The MAK Value Documentation (1992) concluded that the currently available toxicological data for dibenzoyl peroxide support the establishment of a MAK value of 5 mg/m3 (Peak Limitation Category 1). However, how was derived the 5 mg/m3value was not clearly explained.Therefore, DNELs are derived according REACH guidance R8.

Studies in animals and man have shown benzoyl peroxide to be a dermal irritant and possibly a contact sensitizer. Benzoyl peroxide has been used for a number of years at concentrations of up to 10% in OTC products for acne without any apparent significant systemic toxicity. Topically applied benzoyl peroxide penetrates unchanged through the stratum corneum or follicular openings of excised human skin and is converted metabolically to benzoic acid within the skin (Nacht, S.et al, 1981). A study in rhesus monkeys in vivo showed that this benzoic acid is systemically absorbed as benzoate and rapidly excreted in the urine in an unchanged form, without being conjugated to hippuric acid, as would be predicted to occur following oral administration. From these data, it can be estimated that the dermal absorption of benzoyl peroxide as benzoic acid didn’t exceed 50%. Benzoic acid is listed as GRAS substance for food and the World Health Organization has established an acceptable daily intake of benzoic acid of 5 mg/kg.Given the rapidity of the hydrolysis reaction of benzoyl peroxide to benzoic acid, and the readily absorption of benzoic acid, the oral absorption of benzoyl peroxide can be considered to be 100%.

Chronic toxicity studies are available for both the oral and dermal routes of administration. Based on the weight of evidence and considering the limited toxicological effects reported in subacute (Park, 2002; Jia et al., 2011) and chronic (Sharratt et al., 1964) oral toxicity studies, and supported by the low repeated dose toxicity of the BPO metabolite, benzoic acid (IPCS, 2000), the NOAEL of ca. 200 mg/kg bw/day in rats derived from the 120 weeks dietary administration of benzoyl peroxide in rats (Sharratt et al., 1964) can be considered as a conservative NOAEL. There were no findings indicative of systemic toxicity resulting from daily topical exposure of rats and mice to benzoyl peroxide gels at dose level of 100 and 833 mg/kg bw/d for 104 consecutive weeks, respectively. Skin irritation was observed at a dose level as low as 0.3 mg/cm²/day (1.67%) in rats but not at 0.17 mg/cm² (1%) in mice (CHPA, 2000, 2001).

Dibenzoyl Peroxide is in the form of a wet white powder (25% of water) and its calculated vapor pressure is very low (0.009 Pa).Therefore, an inhalation exposure under the normal conditions of use will be limited. As no repeated dose toxicity study is available by inhalation exposure, the inhalation DNEL is derived by route-to-route extrapolation considering a default pulmonary absorption of 100%.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 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):
100
Dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Not needed, the PoD is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Not needed, the PoD is based on a chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF
AF for other interspecies differences:
2.5
Justification:
Default AF
AF for intraspecies differences:
10
Justification:
Default AF
AF for the quality of the whole database:
1
Justification:
Not needed, complete data base including reprotoxicity and carcinogenicity studies
AF for remaining uncertainties:
1
Justification:
Not needed, a conservative NOAEL was used to derive the DNEL
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population