Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.55 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
Modified dose descriptor starting point:
NOAEC
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:
9.29 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
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
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

1. Relevant Toxicology Data, exposure pattern and route

Repeat dose toxicity test is not available for this substance, but a 28-day repeat dose toxicity test was available for an analogous substance EC 224-235-5 and suitable for read across. In this study, the oral repeat dose toxicity of EC224-235-5 was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407. Treatment-related deaths occurred at 500 mg/kg/day in both sexes. All of these animals had reddened adrenal and pituitary glands and yellow contents in the stomach. Microscopic examinations found edema and inflammation of the stomach in all 500 mg/kg/day group females and thickened mucosa in the nonglandular portion of the stomach in one male. In the 250 mg/kg/day group, one male also had edema and inflammation of the stomach. Clinical signs were toxicologically significant at 250 mg/kg/day and 500 mg/kg/day dose levels. The occurrence of soft stools, diarrhea, mucoid diarrhea, and a decrease in the general condition of the animals was greater than in the controls and lower dose. Significant decreases in body weight gain occurred only in the 500 mg/kg/day group males and females. Food consumption showed a slightly decrease in the 500 mg/kg/day groups although only the food consumption for females was significantly different from the controls. These findings are primary orsecondary effects dueto the local irritation via the experimental route of administration Treatment-related increases in mean absolute and relative adrenal gland weights occurred at the 250 and 500 mg/kg/day dose levels. However, no test article-related histopathological lesions were observed in the adrenal glands to account for the increases. Based on these findings, the No Adverse Effect Level NOAEL was determined to be 125 mg/kg/day. 

 

2. Mode of action

No non-threshold mode of action is associated with this substance; in particular, the test substance has no genotoxic potential.

 

3. Correction of dose descriptor

NOAELoralis converted into a NOAELcorrectedin accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose [concentration] - response for human health, ECHA, May 2008.

NOAELoral= 125 mg/kg/d

NOAELcorrected= 1250 mg/kg/d for dermal exposure, dermal absorption of 10% was justified (see Toxicokinetic Statement).

NOAELcorrected= NOAELrat-oral÷ 0.38 m3/kg*(ABSrat-oral÷ ABShuman-inhalation) * 6.7 ÷ 10.3 (sRV human 8h/wRV 8h) = 214.0 mg/m3for inhalation exposure.

Purity of the test material is 89.2%, and it was taken into account when calculating DNEL.

 

4. Application of assessment factors

Dermal route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 1 for remaining difference due to lack of dermal biotransformation potential (QSAR analysis using OECD tool box), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Inhalation route: The following assessment factors were chosen: interspecies difference (1), intraspecies difference (5 for workers), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.61 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEC
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:
4.65 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
240
Modified dose descriptor starting point:
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
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:
0.19 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
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:
medium hazard (no threshold derived)

Additional information - General Population

1. Relevant Toxicology Data, exposure pattern and route

Descriptor: Repeat dose toxicity test is not available for this substance, but a 28-day repeat dose toxicity test was available for an analogous substance EC 224-235-5 and suitable for read across. In this study the oral repeat dose toxicity of EC 224-235-5 was evaluated in rats at levels up to 500 mg/kg/day according to OECD 407. Treatment-related deaths occurred at 500 mg/kg/day in both sexes. All of these animals had reddened adrenal and pituitary glands and yellow contents in the stomach. Microscopic examinations found edema and inflammation of the stomach in all 500 mg/kg/day group females and thickened mucosa in the nonglandular portion of the stomach in one male. In the 250 mg/kg/day group, one male also had edema and inflammation of the stomach. Clinical signs were toxicologically significant at 250 mg/kg/day and 500 mg/kg/day dose levels. The occurrence of soft stools, diarrhea, mucoid diarrhea, and a decrease in the general condition of the animals was greater than in the controls and lower dose. Significant decreases in body weight gain occurred only in the 500 mg/kg/day group males and females. Food consumption showed a slightly decrease in the 500 mg/kg/day groups although only the food consumption for females was significantly different from the controls. These findings are primary orsecondary effects dueto the local irritation via the experimental route of administration Treatment-related increases in mean absolute and relative adrenal gland weights occurred at the 250 and 500 mg/kg/day dose levels. However, no test article-related histopathological lesions were observed in the adrenal glands to account for the increases. Based on these findings, the No Adverse Effect Level NOAEL was determined to be 125 mg/kg/day. 

 

 

2. Mode of action

No non-threshold mode of action is associated with this substance, in particular, the test substance has no genotoxic potential.

 

3. Correction of dose descriptor

NOAELoralis converted into a NOAELcorrectedin accordance to Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterization of dose [concentration] - response for human health, ECHA, May 2008.

NOAELoral= 125 mg/kg/d

NOAELcorrected= 1250 mg/kg/d for dermal exposure, dermal absorption of 10% was justified (see Toxicokinetic Statement).

NOAELcorrected= NOAELrat-oral÷ 1.15 m3/kg*(ABSrat-oral÷ ABShuman-inhalation) =108.7 mg/m3for inhalation exposure.

Purity of the test material is 89.2%, and it was taken into accounts when calculating DNEL.

 

4. Application of assessment factors

Dermal route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 1 for remaining difference), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Inhalation route: The following assessment factors were chosen: interspecies difference (1), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).

Oral route: The following assessment factors were chosen: interspecies difference (4 for allometric scale, 2.5 for remaining difference), intraspecies difference (10 for general population), duration extrapolation (6 for subacute to chronic exposure duration), and quality of the data (1 for a reliable study).