Oxybenzone

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

27.7 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):

25

Modified dose descriptor starting point:

NOAEC

Value:

693 mg/m³

Explanation for the modification of the dose descriptor starting point:

using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 393 mg/kg/day / 0.38 m^3/kg * 6.7/10 = 693 mg/m^3 is used.

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

2

Justification:

default value for subchronic data

AF for interspecies differences (allometric scaling):

1

Justification:

not required due to route-to-route extrapolation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker, a default AF of 5 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

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:

39 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

Modified dose descriptor starting point:

NOAEL

Value:

3 930 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

using bioavailability of 100% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 3930 mg/kg bw/day

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

2

Justification:

default value for subchronic data

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor rat-human

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker, a default AF of 5 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Oxybenzone was investigated by NTP (National Toxicology Program, US) for subchronic toxicity towards rats and mice by using oral and dermal exposure. Systemic effects were seen in rats and a NOAEL oral of 393 mg/kg bw/d (females) and 429 mg/kg bw/d males) respectively was derived. The NOAEL found with mice was more than a magnitude higher (7579 mg/kg bw/d females and 5981 mg/kg bw/d males) but also showed liver and kidneys being the target organ. Also the dermal route was investigated for both species and the NOAEL was set to 200 mg/kg bw/d as systemic availability by dermal route was limited and hardly any effects were seen at the high dose of 200 mg/kg bw/d and also no local effects were observed in the subchronic dermal studies. A 27-day subacute study on rats by oral exposure resulted in a higher NOAEL but was limited in parameters observed.

Thus, for DNEL derivation the results from the subchronic studies in rats (female) are used following a conservative worst-case approach.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.8 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):

50

Modified dose descriptor starting point:

NOAEC

Value:

342 mg/m³

Explanation for the modification of the dose descriptor starting point:

using bioavailability of 100% for the oral and 100% for the inhalation route and assuming that rat oral and inhalation absorptions are equal to human oral and inhalation absorption, a NOAEC corr of 393 mg/kg/day / 1.15 m^3/kg = 342 mg/m^3 is used.

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

2

Justification:

default value for subchronic data

AF for interspecies differences (allometric scaling):

1

Justification:

not required due to route-to-route extrapolation

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

for general population, a default AF of 10 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

20 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):

200

Modified dose descriptor starting point:

NOAEL

Value:

3 930 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

using bioavailability of 100% for the oral and 10% for the dermal route and assuming that rat oral and dermal absorptions are equal to human oral and dermal absorption, thus the corrected dermal NOAEL is 3930 mg/kg bw/day

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

2

Justification:

default value for subchronic data

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor rat-human

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

for general population, a default AF of 10 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

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

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):

200

Modified dose descriptor starting point:

NOAEL

Value:

393 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

NOAEL for oral exposure used, no route to route extrapolation applied

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

2

Justification:

default value for subchronic data

AF for interspecies differences (allometric scaling):

4

Justification:

allometric scaling factor rat-human

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

10

Justification:

for general population, a default AF of 10 is to be used

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Oxybenzone was investigated by NTP (National Toxicology Program, US) for subchronic toxicity towards rats and mice by using oral and dermal exposure. Systemic effects were seen in rats and a NOAEL oral of 393 mg/kg bw/d (females) and 429 mg/kg bw/d males) respectively was derived. The NOAEL found with mice was more than a magnitude higher (7579 mg/kg bw/d females and 5981 mg/kg bw/d males) but also showed liver and kidneys being the target organ. Also the dermal route was investigated for both species and the NOAEL was set to 200 mg/kg bw/d as systemic availability by dermal route was limited and hardly any effects were seen at the high dose of 200 mg/kg bw/d and also no local effects were observed in the subchronic dermal studies. A 27 -day subacute study on rats by oral exposure resulted in a higher NOAEL but was limited in parameters observed.

A NOAEL of 200 mg/kg body weight was identified in the developmental study. Given the next highest dose in the study was 1000 mg/kg body weight the use of the NOAEL from the 90 day rat oral study (393 mg/kg body weight) for development of the DNELs is still considered appropriate as it lies between the two doses.