Registration Dossier
Registration Dossier
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EC number: 235-166-5 | CAS number: 12108-13-3
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.6 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:
- 15 mg/m³
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- for worker population
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:
- 0.11 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 5.7 mg/kg bw/day
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 2
- Justification:
- monkey to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 5
- Justification:
- worker population
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
Long-term inhalation DNEL worker population
Derivation of the inhalation DNEL for the worker population based on the use of the NOAEC of 30 mg/m3 for the monkey in a subchronic inhalation toxicity study:
NOAECcorrected= 30 mg/m3 x 6/8 x 6.7/10 = 15 mg/m3
Where,
NOAEC = 30 mg/m3
6 hrs of exposure in the study versus 8 hours exposure for the worker
6.7 m3 respiratory volume for avg. person over 8 hours of exposure versus 10 m3 respiratory volume for worker over 8 hrs of exposure.
Interspecies = 2.5
Intraspecies = 5
Sub-chronic to Chronic = 2
Total AF = 25
Inhalation DNEL worker = 15 mg/m3 ÷ 25 = 0.6 mg/m3
Long-term Dermal DNEL worker Population
Derivation of the dermal DNEL for the worker population based on the use of the NOAEC of 30 mg/m3 for the monkey in a subchronic inhalation toxicity study:
NOAEC corrected = 30 mg/m3 x 0.19 m3/kg x 6hrs/8hrs x 2 x 6.7/10= 5.7 mg/kg-day
Where,
The 0.19 m3/kg represents the respiratory rate for the monkey
(Allometric scaling factor of 2 x 0.2 L/min/kg bw = 0.4 L/min-kg bw; (0.4 L/min-kg bw x 0.001 m3/L x 60 min/hr x 8 hrs = 0.19 m3/kg bw) (ECHA Guidance R.8, Tables R.8-2 R.8-3)
The exposure in the study was for 6 hrs/day whereas worker exposure is 8 hrs per day.
An assumption that dermal absorption is 50% of inhalation exposure (hence the factor of 2).
Dose correction for the respiratory volume of an average person for 8 hours (6.7 m3/person) and a worker for 8 hrs (10 m3/person) (ECHA Guidance R.8, Table R.8-2 and Figure R.8-2).
The assessment factors used in the derivation of the DNEL as documented in the CSR are as follows:
Interspecies = 5 (2.5 x 2 (allometic scaling factor for monkey; Table R.8-3 of ECHA’s Guidance R.8))
Intraspecies = 5
Sub-chronic to Chronic = 2
Total AF = 50
The calculated dermal DNEL for the worker is 0.11 mg/kg/day (5.7 mg/kg-day ÷ 50)
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.11 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 5.4 mg/m³
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic
- AF for other interspecies differences:
- 2.5
- Justification:
- other differences
- AF for intraspecies differences:
- 10
- Justification:
- general population
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:
- 0.062 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 100
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 6.2 mg/kg bw/day
- AF for differences in duration of exposure:
- 2
- Justification:
- sub-chronic to chronic
- AF for interspecies differences (allometric scaling):
- 2
- Justification:
- monkey to human
- AF for other interspecies differences:
- 2.5
- Justification:
- remaining differences
- AF for intraspecies differences:
- 10
- Justification:
- general population
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:
- no hazard identified
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
Long-term Inhalation DNEL general population
Derivation of the inhalation DNEL for the general population based on the use of the NOAEC of 30 mg/m3 for the monkey in a subchronic inhalation toxicity study:
NOAECcorrected= 30 mg/m3 x 6hrs/24hrs x 5days/7days = 5.4 mg/m3
Where:
NOAEC = 30 mg/m3
6 hours exposure in study versus 24 hours exposure for general population
5 days of exposure in the study versus 7 days of exposure for the general population
The total AF is 50 based on:
Intraspecies = 10 for general population
Interspecies = 2.5 (allometric factor of 4 is not applied for inhalation dose to inhalation dose)
Sub-chronic to chronic = 2
Total AF = 50
Inhalation DNEL for general population is therefore: 5.4 mg/m3 ÷ 50 = 0.11 mg/m3
Long-term Dermal DNEL general population
Derivation of the dermal DNEL for the general population based on the use of the NOAEC of 30 mg/m3 for the monkey in a subchronic inhalation toxicity study:
NOAELcorrected= 30 mg/m3 x 0.576 m3/kg x 6hrs/24hrs x 5days/7days x 2 = 6.2 mg/kg/day
Where:
NOAEC = 30 mg/m3
Respiratory volume for the monkey for 24 hour exposure (Table R.8-2 of ECHA Guidance) = 0.576 (0.4 L/min-kg bw x 0.001 m3/L x 60 min/hr x 24 hrs)
6 hours exposure in study versus 24 hours exposure for general population
5 days of exposure in the study versus 7 days of exposure for the general population
Factor of 2 to account for 50% absorption through dermal route versus inhalation
The assessment factors used in the derivation of the DNEL as documented in the CSR are as follows:
Interspecies = 5 (2.5 x 2 (allometic scaling factor for monkey; Table R.8-3 of ECHA’s Guidance R.8))
Intraspecies = 10
Sub-chronic to Chronic = 2
Total AF = 100
Dermal DNEL general population = 6.2 mg/kg-day/100 = 0.062 mg/kg/day
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