Dibenzoyl peroxide

Toxicological Summary

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)