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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.9 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):
75
Dose descriptor starting point:
NOAEL
Value:
663 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
818 mg/m³
Explanation for the modification of the dose descriptor starting point:

Conducted using route-to-route extrapolation according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (Version 2.1, November 2012).

Starting Dose Descriptor: Repeated Dose Toxicity: Oral - NOAEL = 663.0 mg/kg bw/d

Correction for differences in respiratory volume (workers): 2.63

Correction for differences in bioavailability: 0.5

Correction for light activity at work: 0.67

Correction for differences between human and experimental exposure conditions (workers): 1.4

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
3.09 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):
300
Dose descriptor starting point:
NOAEL
Value:
663 mg/kg bw/day
Value:
928 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Conducted using route-to-route extrapolation according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (Version 2.1, November 2012).

Starting Dose Descriptor: Repeated Dose Toxicity: Oral - NOAEL = 663.0 mg/kg bw/d

Correction for differences in respiratory volume (workers): 1

Correction for differences in bioavailability: 1

Correction for light activity at work: 1

Correction for differences between human and experimental exposure conditions (workers): 1.4

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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

Relevant endpoint for DNEL derivation: repeated dose toxicity (oral) - NOAEL = 663 mg/kg bw/d

OECD TG 422, 2018 : The study was performed according the requirements of OECD TG 422 guideline under GLP conditions. Following a previously conducted 14-day sighting study, the systemic toxic potential of the test item in rats, including a screen for reproductive/developmental effects and assessment of endocrine disruptor relevant endpoints was conducted by dietary administration for at least six weeks with additional subgroups used to assess reversibility, persistence or delayed effects for 14 days post treatment. Three toxicology treatment groups with a control was conducted, each comprising five or ten male and five female rats which received dietary test item at doses of 0 (Control), 1600, 5200 or 12000 ppm test item. Ten males were treated in the 1600 and 5200 ppm doses for pairing purposes with the reproductive phase females. Recovery phase groups included five males and females treated at 0 ppm (Control) and 12000 ppm. Reproductive phase females, ten per group (10) were treated at doses of 0 (Control), 1600, 5200 or 12000 ppm test item. Toxicity phase males were treated for two weeks before pairing up to necropsy after six weeks. Toxicity phase females were treated for six weeks. Recovery phase males were treated for two weeks before pairing up to necropsy after six weeks followed by a 2-week recovery period. Recovery phase females were treated for six weeks followed by a 2-week recovery period. Reproductive phase females were treated for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation (the treated diet was made available until the morning of necropsy). The offspring received no direct administration of the test item; any exposure was in utero or via the milk. A similarly constituted Control group was assigned to each phase, and received, untreated (no test item) diet, throughout the same relative treatment period. Mean achieved doses for males at 1600, 5200 or 12000 ppm were 93.7, 303 or 663 mg/kg/day, respectively. For females of the toxicity and recovery phase. Dietary administration of test item to CD rats at concentrations up to and including 12000 ppm was generally well tolerated. Test item related histopathological changes were apparent in the kidney and thyroid of males and the liver of both sexes given 12000 ppm. The kidney changes detected in the males (hyaline droplets in tubules) were consistent with species-specific responses of the male rat in response to xenobiotics, and therefore may be of little value as an indicator of hazard to human health. The liver changes (increased bodyweight adjusted liver weights and minimal centrilobular hepatocyte hypertrophy) in both sexes and associated thyroid changes (follicular cell hypertrophy) and lower T4 levels in males are deemed reversible. There were no differences from Control for levels of circulating Triiodothyronine (T3) in adult males or from F1 offspring on Day 13 of age. Based on these considerations, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was concluded to be 12000 ppm (equivalent to 663 mg/kg/day for males and 668 mg/kg/day for females).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.92 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):
150
Dose descriptor starting point:
NOAEL
Value:
663 mg/kg bw/day
Value:
288 mg/m³
Explanation for the modification of the dose descriptor starting point:

Conducted using route-to-route extrapolation according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (Version 2.1, November 2012).

Starting Dose Descriptor: Repeated Dose Toxicity: Oral - NOAEL = 663.0 mg/kg bw/d

Correction for differences in respiratory volume (general population): 0.87

Correction for differences in bioavailability: 0.5

Correction for differences between human and experimental exposure conditions (experimental population): 1

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
1.11 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):
600
Dose descriptor starting point:
NOAEL
Value:
663 mg/kg bw/day
Value:
663 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Conducted using route-to-route extrapolation according to ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.8 (Version 2.1, November 2012).

Starting Dose Descriptor: Repeated Dose Toxicity: Oral - NOAEL = 663.0 mg/kg bw/d

Correction for differences in respiratory volume (general population): 1

Correction for differences in bioavailability: 1

Correction for differences between human and experimental exposure conditions (general population): 1

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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:
1.11 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):
600
Dose descriptor starting point:
NOAEL
Value:
663 mg/kg bw/day
Value:
663 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting Dose Descriptor: Repeated Dose Toxicity: Oral - NOAEL = 663.0 mg/kg bw/d

No modification of the starting dose descriptor is required.

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
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

Relevant endpoint for DNEL derivation: repeated dose toxicity (oral) - NOAEL = 663 mg/kg bw/d

OECD TG 422, 2018 : The study was performed according the requirements of OECD TG 422 guideline under GLP conditions. Following a previously conducted 14-day sighting study, the systemic toxic potential of the test item in rats, including a screen for reproductive/developmental effects and assessment of endocrine disruptor relevant endpoints was conducted by dietary administration for at least six weeks with additional subgroups used to assess reversibility, persistence or delayed effects for 14 days post treatment. Three toxicology treatment groups with a control was conducted, each comprising five or ten male and five female rats which received dietary test item at doses of 0 (Control), 1600, 5200 or 12000 ppm test item. Ten males were treated in the 1600 and 5200 ppm doses for pairing purposes with the reproductive phase females. Recovery phase groups included five males and females treated at 0 ppm (Control) and 12000 ppm. Reproductive phase females, ten per group (10) were treated at doses of 0 (Control), 1600, 5200 or 12000 ppm test item. Toxicity phase males were treated for two weeks before pairing up to necropsy after six weeks. Toxicity phase females were treated for six weeks. Recovery phase males were treated for two weeks before pairing up to necropsy after six weeks followed by a 2-week recovery period. Recovery phase females were treated for six weeks followed by a 2-week recovery period. Reproductive phase females were treated for two weeks before pairing, throughout pairing, gestation and until Day 13 of lactation (the treated diet was made available until the morning of necropsy). The offspring received no direct administration of the test item; any exposure was in utero or via the milk. A similarly constituted Control group was assigned to each phase, and received, untreated (no test item) diet, throughout the same relative treatment period. Mean achieved doses for males at 1600, 5200 or 12000 ppm were 93.7, 303 or 663 mg/kg/day, respectively. For females of the toxicity and recovery phase. Dietary administration of test item to CD rats at concentrations up to and including 12000 ppm was generally well tolerated. Test item related histopathological changes were apparent in the kidney and thyroid of males and the liver of both sexes given 12000 ppm. The kidney changes detected in the males (hyaline droplets in tubules) were consistent with species-specific responses of the male rat in response to xenobiotics, and therefore may be of little value as an indicator of hazard to human health. The liver changes (increased bodyweight adjusted liver weights and minimal centrilobular hepatocyte hypertrophy) in both sexes and associated thyroid changes (follicular cell hypertrophy) and lower T4 levels in males are deemed reversible. There were no differences from Control for levels of circulating Triiodothyronine (T3) in adult males or from F1 offspring on Day 13 of age. Based on these considerations, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was concluded to be 12000 ppm (equivalent to 663 mg/kg/day for males and 668 mg/kg/day for females).