Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.76 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
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
44.08 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in workers after long-term inhalation exposure to the test substance was derived via route-to-route extrapolation from the NOAEL identified in both the sub-chronic (90-day) oral repeated dose toxicity study in rats and the extended one-generation study in female rats by oral administration (50 mg/kg bw/day). To convert the oral NOAEL in rats to an inhalation NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38m3/kg bw/8h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3for an 8h exposure period) and under conditions of light activity (wRV: 10 m3for an 8h exposure period); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, inhalatory NOAEC = oral NOAEL*(1/sRVrat 8h)*(ABSoral/ABSinh)*(sRVhuman/wRV) OR 50*(1/0.38)*(50/100)*(6.7/10) = 44.08 mg/m3. Therefore, DNEL = Corrected inhalation NOAEC (44.08 mg/m3)*(1/25{Overall AF}) = 1.76 mg/m3.

AF for dose response relationship:
1
Justification:
Not required as the starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for extrapolation from sub-chronic duration in animals to chronic duration in humans
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when route to route extrapolation has been conducted
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Required studies have been conducted
AF for remaining uncertainties:
1
Justification:
None required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
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:
45.5 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:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
4 550 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in workers after long-term dermal exposure to the test substance was derived via route-to-route extrapolation from the NOAEL identified in both the sub-chronic (90-day) oral repeated dose toxicity study in rats and the extended one-generation study in female rats by oral administration (50 mg/kg bw/day). Therefore, DNEL = 50 mg/kg bw/day*(1/2{modified exposure duration sub chronic to chronic}*4{allometric scaling rat-human}*2.5{interspecies differences}*5{intraspecies differences-worker population}) = 0.5 mg/kg bw/day. This is considered to be the worst-case scenario assuming 100% dermal absorption, however, in accordance with SCCS (2008) data, dermal absorption has been estimated at 1.10% . Therefore, adjustment to the DNEL for bioavailability is considered applicable by the application of the factor 100/1.10 (0.5 mg/kg/day*100/1.10 = 45.5 mg/kg/day).

AF for dose response relationship:
1
Justification:
Not required as the starting point is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Default for extrapolation from sub-chronic duration in animals to chronic duration in humans
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Required studies have been conducted
AF for remaining uncertainties:
1
Justification:
None 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
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The basis for the inhalation and dermal systemic DNELs for worker exposure to the test substance is an oral subchronic repeated dose toxicity study in rats and a one generation reproductive toxicity study in female rats from which the lowest NOAEL of 50 mg/kg bw/day was identified. In the 90-day repeat dose toxicity study, there was no defined NOEL for the stimulatory effect on the thyroid. However, the changes, including increased circulating thyroid hormone levels, increased thyroid weights and associated thyroid pathology, showed dose dependency and the NOAEL could be considered to be >50 mg/kg/day. In the one generation reproductive toxicity study in female rats the only sign of potential toxicity at dose levels up to 50 mg/kg/day was a dose dependent increase in water intake. However, no investigations on thyroid effects were undertaken in this study. Consequently, the NOAEL (No Observed Adverse Effect Level) was considered to be 50 mg/kg bw/day and was used as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length.

For local effects it is considered that the systemic DNEL for inhalation exposure would be protective for this exposure in the absence of specific data. For dermal exposure the combination of acute dermal data and dermal absorption studies indicate no hazard.

General Population - 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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Justification:
Not required as the starting point is a NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Justification:
Not required as the starting point is a NOAEL
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

There is no other consumer use intended for 4-methylbenzylidene camphor other than the cosmetic use. Consequently DNELs for the General Population are not required particularly since the opinion document on 4 -MBC from the Scientific Committee on Consumer Products (SCCP, 2008) concluded that 4 -MBC could be considered safe for use in finished cosmetic products (whole body application) at a concentration of up to 4% based on the margin of safety resulting from assessment of human and rat toxicokinetic data.