Potassium cyanate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.96 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

Dose descriptor starting point:

NOAEL

Value:

60 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

74 mg/m³

Explanation for the modification of the dose descriptor starting point:

Using a conservative approach, a worker DNEL (long-term inhalation exposure) is derived.

Relevant dose descriptor (NOAEL): 60 mg/kg bw/day

Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m³

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

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

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

NOAEC_corr = NOAEL_oral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABS_oral/ABS_inh

NOAEC_corr = 60 mg/kg bw/day x (1/0.38 m³/kg bw/day) x (6.7 m³/10 m³) x (7 days/ 5 days) x 0.5 

NOAEC_corr = 74 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:

2

Justification:

The default factor for the differences between sub-chronic and chronic exposure duration is used.

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:

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:

DNEL (Derived No Effect Level)

Value:

8.9 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):

3

DNEL extrapolated from long term DNEL

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:

3.36 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):

100

Dose descriptor starting point:

NOAEL

Value:

60 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

336 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of potassium cyanate especially its high hydrophilicity (log Kow: <0.3 and water solubility: 750 g/L) dermal absorption is considered to be 25% of oral absorption.

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

NOAEL_corr = NOAEL_oral x 7d/5d x ABS_oral/ABS_dermal

NOAEL_corr = 60 mg/kg bw/day x 1.4 x 4

NOAEL_corr = 336 mg/kg bw/day

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:

2

Justification:

The default factor for the differences between sub-chronic and chronic exposure duration is used.

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:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

General

DNEL derivation for the test item is performed under consideration of the recommendations of ECHA (see references below).

 

Workers- Hazard via inhalation route

 

Long term, systemic DNEL

Occupational exposure to potassium cyanate occurs mainly by dermal route and may also occur by inhalation exposure. Therefore, a long-term DNEL for inhalation exposure was calculated for workers.

 

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

An EOGRTS according to OECD TG 443 (2022) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance with OECD guideline and GLP. In this study, the oral NOAEL in rats is 60 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.

 

Relevant dose descriptor (NOAEL): 60 mg/kg bw/day

Standard respiratory volume, human (sRVhuman) for 8 h per person (70 kg): 6.7 m³

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

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

Oral absorption of the rat/ inhalation absorption of humans (ABS oral-rat / ABS inh-human): 1/2 (default)

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEC (inhalation) for workers:

NOAEC_corr = NOAEL_oral x 1/0.38 m³/kg bw/day x 6.7 m³/10m³ x 7d/5d x ABS_oral/ABS_inh

NOAEC_corr = 60 mg/kg bw/day x 0.5 x (1/0.38 m³/kg bw/day) x (6.7 m³/10 m³) x (7 days/ 5 days)

NOAEC_corr = 60 mg/kg bw/day x 0.5 x 2.63 x 0.67 m³ x 1.4

NOAEC_corr = 74 mg/m³

 

Step 3: Use of assessment factors: 25

Intraspecies AF (worker): 5

The default value for the relatively homogenous group "worker" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 1

No allometric scaling is applied for inhalation as the inhalative data is standardized with reference to the respiratory rates. Respiratory rates depend directly on caloric demand, therefore inhalative study results are already extrapolated to humans on the basis of metabolic rate scaling (=allometric scaling).

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The OECD TG 443 toxicity study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1
DNEL Derivation is considered conservative, reflecting reasonable worst-case assumptions. Therefore, no further AF for remaining uncertainties is applied. 

In conclusion, long term systemic inhalation DNEL = 2.96 mg/m³

 

Short term, systemic DNEL

No study for acute inhalation toxicity is available. As the substance is classified for acute oral toxicity, Cat. 4, an acute inhalation toxicity cannot be excluded and an acute inhalation DNEL is derived for precautionary reasons. The acute inhalation DNEL was calculated as 3 times the value of the corresponding long-term DNEL (ECHA CSR R.8, 2012).

Short term, systemic inhalation DNEL: 3 x 2.96 = 8.9 mg/m³

 

Acute/long term DNEL for local effects

Potassium cyanate causes eye irritation and may also lead to irritation in the mucous membrane of the respiratory tract. Therefore, a qualitative assessment is conducted.

 

Appropriate qualitative risk managements measures should be implemented to avoid exposure. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016).

 

Worker- Hazard via dermal route 

 

Long term, systemic DNEL

Occupational exposure to potassium cyanate occurs mainly by dermal route and may also occur by inhalation exposure. Therefore, a long-term DNEL for dermal exposure was calculated for workers.

 

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

An EOGRTS according to OECD TG 443 (2022) is selected for DNEL derivation as it is the relevant repeated dose study performed in accordance with OECD guideline and GLP. In this study, the oral NOAEL in rats is 51 mg/kg bw/day.

 

Step 2: Modification of the starting point:

Using a conservative approach, a worker DNEL (long-term dermal exposure) is derived. Based on the physico-chemical properties of potassium cyanate especially its high hydrophilicity (log Kow: <0.3 and water solubility: 750 g/L) dermal absorption is considered to be 25% of oral absorption.

 

Correction for difference between human and experimental exposure conditions: 7 d rat/5 d worker

Corrected NOAEL (dermal) for workers:

NOAEL_corr = NOAEL_oral x 7d/5d x ABS_oral/ABS_dermal

NOAEL_corr = 60 mg/kg bw/day x 1.4 x 4

NOAEL_corr = 336 mg/kg bw/day

 

Step 3: Use of assessment factors: 100

Intraspecies AF (worker): 5

The default value for the relatively homogenous group "worker" is used.

Interspecies AF, remaining differences: 2.5

The recommended AF for other interspecies differences is applied.

Allometric scaling AF: 4

The default allometric scaling factor for the differences between rats and humans is applied.

Dose response relationship AF: 1

The dose response relationship is considered unremarkable, therefore no additional factor is used.

Exposure duration AF: 2

Extrapolation from subchronic to chronic exposure.

Whole database AF: 1

The OECD 443 study was conducted according to regulatory standards and was adequately reported. On this basis the quality of the database is not considered to contribute uncertainty and it is therefore not necessary to apply an additional factor.

AF for remaining uncertainties: 1

DNEL Derivation is considered conservative, reflecting reasonable worst-case assumptions. Therefore, no further AF for remaining uncertainties is applied.

In conclusion, long term systemic dermal DNEL = 3.36 mg/kg bw/day

 

Short term, systemic DNEL

Potassium cyanate is not classified for acute dermal toxicity according to Regulation (EC) 1272/2008 (CLP). Therefore, no hazard assessment was conducted and no DNEL was derived.

 

Acute/long term DNEL for local effects

Potassium cyanate is not classified for skin irritation and skin sensitisation according to Regulation (EC) No 1272/2008 (CLP) based on the available experimental data. Therefore, no hazard assessment was conducted. 

 

Workers- Hazard for the eyes

Potassium cyanate is classified for eye irritation, Cat. 2 according to Regulation (EC) No 1272/2008 (CLP), based on the results of the eye irritation studies available. The substance is assigned to the low hazard band in accordance with ECHA Guidance on information requirements and chemical safety assessment Part E: Risk Characterisation (2016) and a qualitative risk assessment was conducted.

 

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.

- ECHA (2014). Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance, Guidance on Toxicokinetics.

- 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.

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

General

 

General population is not intended to be exposed to Potassium cyanate via inhalation or dermal route. Therefore, no DNEL (long-term, inhalation and dermal exposure) is derived for general population. As Potassium cyanate has no bioaccumulation potential no risk assessment for secondary poisoning is required for the general population.

 

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 ECHA-2010-G-19-EN.

- ECHA (2011) Guidance on information requirements and chemical safety assessment. Part B: Hazard assessment. Version 2 ECHA-11-G-16-EN