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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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:
10.8 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:
658 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
812.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by inhalation. For details on calculations please refer to discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
1
Justification:
Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.1 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:
658 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 842.4 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal route. For details on calculations please refer to discussion.

AF for dose response relationship:
1
Justification:
The dose response relationship is considered unremarkable, therefore no additional factor is used.
AF for differences in duration of exposure:
6
Justification:
The default extrapolation factor for exposure duration is used: subacute (starting point) to chronic (end point).
AF for interspecies differences (allometric scaling):
4
Justification:
The default allometric scaling factor for the differences between rats and humans is used.
AF for other interspecies differences:
2.5
Justification:
Recommended AF for other interspecies differences.
AF for intraspecies differences:
5
Justification:
The default value for the relatively homogenous group "worker" is used.
AF for the quality of the whole database:
1
Justification:
The quality of the whole data base is considered to be sufficient and uncritical.
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factors are required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test substance is performed under consideration of the recommendations of ECHA. In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1, and are thus not shown in the calculations presented below.

The repeated dose oral toxicity study was performed with a commercial formulation containing 46.2% (w/w) of the REACH registration substance. The water content of the actual test item was 57.6% (w/w). For the substance subject to REACH registration a water content of 3.8% (w/w) was analytically determined (please refer IUCLID section 1.2). DNELs were derived on the effect level determined for the commercial formulation which was not correced for the higher water content in comparison to the REACH registration substance. This has been done since in the risk assessment the commercial formulation was used for exposure assessment (instead of the adaptation to the REACH registration substance with a lower water content).

.

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

The DNEL long term, systemic (inhalation) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The 28-day repeated dose oral toxicity study is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 658 mg/kg bw/day.

 

Step 2: Modification into a correct starting point:

Using a conservative approach, a worker DNEL (long term inhalation exposure) is derived considering a two times higher absorption via inhalation (100 %) than oral (50 %) absorption.

 

Relevant dose descriptor (NOAEL): 658 mg/kg bw/day

Standard respiratory volume of the rat (sRVrat) for 8 hours: 0.38 m³/kg bw/d

Oral absorption of the rat / inhalation absorption of humans (ABSoral-rat 50 % / ABSinh-human 100 %): 0.5

Standard respiratory volume of humans (sRVhuman) for 8 hours: 6.7 m³

Worker respiratory volume (wRV) for 8 hours with light physical activity: 10 m³

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

Corrected inhalatory NOAEC for workers

= 658 mg/kg bw/day * 0.5 * (1 / 0.38 m³/kg bw/day) * (6.7 m³/10 m³) * (7/5)

= 812.1 mg/m³

 

Step 3: Use of assessment factors: 75

Interspecies: Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation. 

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 6

Remaining uncertainties AF: 1

 

In conclusion, long term systemic inhalation DNEL, workers = 10.8 mg/m3

 

Short term systemic inhalation DNEL, worker

No data for the classification and labelling of the test substance for acute systemic toxicity (inhalation) is available. The substance is not classified for acute oral or dermal toxicity, therefore no adverse result for inhalation toxicity is expected (in accordance with "Guidance on information requirements and chemical safety assessment", chapter R8). Thus, no DNEL is required.

 

Short and long term local inhalation DNEL, worker

No data on local toxicity after inhalation is available. As studies on skin and eye irritation showed adverse effects the occurrence of local effects on the respiratory system, respectively the mucosal membrane, can’t be excluded. Based on the classification for eye irritation Cat. 2 a low hazard is identified.Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore appropriate RMMs are carried into execution.

 

 

 

Workers – Hazard via dermal route

Long term systemic dermal DNEL, worker

The DNEL long term, systemic (dermal) is derived by route-to route extrapolation from the repeated dose oral toxicity study.

 

Step 1: Selection of the relevant dose descriptor (starting point):

The 28-day repeated dose toxicity study is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance to OECD guideline and GLP. In this study, the oral NOAEL is 658 mg/kg bw/day.

 

Step 2: Modification of the starting point:

The logPow of the test substance was determined to be 2.99. Therefore the dermal uptake is considered to be 50 % of the oral uptake in the worst case.

 

Factor for dermal NOAEL= 100 % oral / 50 % dermal= 2

Frequency of exposure in study: 7 days/week

Frequency of worker exposure: 5 days/week

 

oral NOAEL 658 mg/kg bw/day * 2 * (7/5) = 1842.4 mg/kg bw/day dermal NOAEL

 

Step 3: Use of assessment factors: 300

Interspecies AF, allometric scaling (rat to human): 4

Interspecies AF, remaining differences: 2.5

Intraspecies AF (worker): 5

Exposure duration AF: 6

Remaining uncertainties AF: 1

 

In conclusion, long term systemic dermal DNEL, workers = 6.1 mg/kg bw/day

 

Short term systemic dermal DNEL, worker

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, no DNEL is required.

 

Short term and long term local dermal DNEL, worker

The test material is classified for skin irritation toxicity cat. 2, according to Regulation (EC) No 1272/2008 (CLP). Thus, a qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore gloves and further appropriate RMMs are carried into execution.

 

 

Worker – Hazard for the eyes

For exposure to the eyes a low hazard was identified, as the test substance is classified for eye irritation Cat.2 according to Regulation (EC) No 1272/2008 (CLP). A qualitative risk assessment is conducted (in accordance with "Guidance on information requirements and chemical safety assessment", Part E). Therefore goggles and further appropriate RMMs are carried into execution.

 

References

(not included as endpoint study record)

- ECHA (2012). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2.1. November 2012.

- ECHA (2017). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. June 2017.

- ECHA (2012) Practical Guide 15: How to undertake a qualitative human health assessment and document it in a chemical safety report, November 2012.

- ECHA (2016). Guidance on information requirements and chemical safety assessment. Part E: Risk Characterisation, Version 3.0, May 2016.

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
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