Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 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):
5
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
125 mg/m³
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated exposure by inhalation. A conservative approach is used assuming a two times higher absorption via the inhalation route (end route) as compared to the oral route (starting route).

In a first step the oral NOAEL was transferred to humans with a factor of 1.4 for allometric scaling from dogs. For worker a NOEC long-term, inhalation was calculated assuming 70 kg per person, 8h light activity (10 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

In a first step the oral NOAEL was transferred to humans with a factor of 1.4 for allometric scaling from dogs. For worker a NOEC long-term, inhalation was calculated assuming 70 kg per person, 8h light activity (10 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

 

NOEC (Worker)inhalation = 50 mg/kg bw/day * 1/1.4 *70 kg * 1/10 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) =125 mg/m³

 

NOEC (Worker)inhalation = 50 mg/kg bw/day * 1/1.4 *70 kg * 1/10 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) =125 mg/m³

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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
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:
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:
28.57 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):
7
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
There are no relevant experimental data on repeated dermal exposure. Based on the physical chemical properties of the substance (inorganic ionic substance, with high water solubility) a dermal absorption rate of 25 % through skin was deduced.
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:
1
Justification:
No time extrapolation factor is needed since a chronic toxicity study is available.
AF for interspecies differences (allometric scaling):
1.4
Justification:
The default allometric scaling factor for the differences between dogs and humans is used.
AF for other interspecies differences:
1
Justification:
There is no evidence for species differences in the general mode of action or kinetics.
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:
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

General

DNEL derivation for the substance sodium cyanate 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.

 

 

Workers – Hazard via inhalation route

 

Long term systemic inhalation DNEL, worker

Calculation of dose descriptor

 

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

For risk characterisation a inhalation NOAEC was derived by route to route extrapolation.

The oral NOAEL of 50 mg/kg bw/day, obtained from chronic repeated dose toxicity testing in dogs by Cerami, A (1973), was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

 

Step 2: Modification into a correct starting point:

In a first step the oral NOAEL was transferred to humans with a factor of 1.4 for allometric scaling from dogs. For worker a NOEC long-term, inhalation was calculated assuming 70 kg per person, 8h light activity (10 m³ breathing volume), 50 % absorption via oral routes and 100 % absorption via inhalatory routes.

 

NOEC (Worker)inhalation = 50 mg/kg bw/day * 1/1.4 *70 kg * 1/10 m³ * 50%Abs, (oral) / 100 % Abs, (inhal) =125 mg/m³

 

Step 3: Use of assessment factors: 5

Interspecies: no allometric scaling factor is applied because an oral-to-inhalation route extrapolation is performed.

Interspecies AF, remaining differences: 1

Intraspecies AF (worker): 5

 

In conclusion the long term systemic inhalation DNEL workers was calculated to be 25 mg/m³ bw/day.

 

Short term acute inhalation DNEL, worker

 

The test material is not classified and labelled for acute dermal toxicity, according to Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

 

Local effects

No data on respiratory irritation is available. As the substance is not classified as skin and eye irritating also no adverse effects on respiratory system is expected. Based on the physical parameters a peak exposure is not expected. The substance is solid with an expected very low vapour pressure. In addition no particles below 10 µm were found in the granolometry test. Thus, no DNEL is required.

 

Workers – Hazard via dermal route

 

Long term systemic dermal DNEL, worker

Calculation of dose descriptor

 

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

For risk characterisation a dermal NOAEL was derived by route to route extrapolation.

The oral NOAEL of 50 mg/kg bw/day, obtained from chronic repeated dose oral toxicity testing in dogs by Cerami, A (1973), was considered as key value for the chemical safety assessment and therefore, most relevant starting point.

 

Step 2: Modification into a correct starting point:

Based on the physical chemical properties of the substance (inorganic ionic substance, with high water solubility) a dermal absorption rate of 25 % through skin was deduced.

In conclusion, dermal NOAEL = oral NOAEL x [ABS oral dog /ABS dermal human] = 50 mg/kg bw/day x (100/25) = 200 mg/kg bw/d.

 

Step 3: Use of assessment factors: 7

Interspecies AF, allometric scaling (dog to human): 1.4

Interspecies AF, remaining differences: 1

Intraspecies AF (worker): 5

Exposure duration AF (chronic exposure period): 1

 

In conclusion the long term systemic dermal DNEL workers were calculated to be 28.57 mg/kg bw/day.

 

Acute short term dermal DNEL, worker

The test material is not classified and labelled for acute dermal toxicity, according to Directive 67/548/EEC (DSD) and Regulation (EC) No 1272/2008 (CLP). Thus, in accordance with “Guidance on information requirements and chemical safety assessment chapter R8: Characterisation of dose (concentration)- response for human health” no DNEL is required.

 

Local effects

Worker local DNEL for dermal route does not need to be derived as no dermal and eye irritation and no skin sensitisation (leading to C&L) has been identified (in accordance with "Guidance on information requirements and chemical safety assessment, chapter R8: Characterisation of dose (concentration)- response for human health").

 

Worker – Hazard for the eyes

According to the EU (GHS) criteria for classification and labelling requirements for dangerous substances and preparations the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

 

 

References

(not included as endpoint study record)

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19 –EN.

 

- ECHA (2010). Guidance on information requirements and chemical safety assessment.Chapter R.7.12: Endpoint specific guidance: Guidance on Toxicokinetics. May 2008

 

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

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

No exposure is intended for the general population. Thus, no DNELS were derived.