Registration Dossier

Administrative data

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.