Registration Dossier
Registration Dossier
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EC number: 701-394-3 | CAS number: 1782069-81-1
Toxicological Summary
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.
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