Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.8 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):
12.5
Modified dose descriptor starting point:
NOAEC
DNEL value:
35.3 mg/m³
Explanation for the modification of the dose descriptor starting point:
DNEL calculated from route-to-route extrapolation from 90-day oral toxicity study on NH4SCN resulting to a NOAEL of 20 mg/kg bw/day. The corrected inhalation NOAEC for workers is NOAEL * 1.76 mg/m3 = 35.3 mg/m3. ADME data indicate rapid and almost complete absorption following oral exposure. As worst case, absorption via inhalation is also considered 100%, and thus being similar to oral absorption no additional factor 2 is needed for extrapolation from oral to inhalation. Besides, exposure via inhalation is not expected. The vapour pressure is extremely low (< 0.015 Pa based evaporation of ammonia rather than SCN at temperatures > 70°C) and thus does not present any potential for inhalation exposure due to volatilization of the salt. Furthermore thiocyanates are very hygroscopic (see granulometry). Inhalable particles are not available and will also not be formed during handling and use of the substance. Finally high peak inhalation exposures do not occur during the manufacturing or use of thiocyanates.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Default assessment factor for sub-chronic to chronic is 2, but in this case it can be considered that the mechanism of concern is inhibition of thyroid, and further prolongation of exposures beyond 90 days is not supposed to affect the threshold effect on thyroid.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
Remaining uncertainties to cover additional variation in thyroid sensitivity between species. (Although available data indicates that human are less sensitive than rodents justifying a possible AF of 1)
AF for intraspecies differences:
5
Justification:
ECHA default value. ECETOC concept for combined inter-/intra-species for workers is an AF 3. However, to compensate for possible additional variation in thiocyanate background levels (due to smoking habits, food sources) this factor is increased from 3 to 5.
AF for the quality of the whole database:
1
Justification:
Database contains valid studies. For the key endpoint (effects on thyroid) much is known on effects in human.
AF for remaining uncertainties:
1
Justification:
Database contains information of mechanism of toxicity and human based information, indicating that human are less sensitive than rodents.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 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):
50
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
DNEL calculated from route-to-route extrapolation from 90-day oral toxicity on NH4SCN resulting to a NOAEL of 20 mg/kg bw/day. Assuming 10% dermal absorption compared to 100% oral absorption (see toxicokinetics for justification), this results to a derived dermal NOAEL of 200 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Default assessment factor for sub-chronic to chronic is 2, but in this case it can be considered that the mechanism of concern is inhibition of thyroid, and further prolongation of exposures beyond 90 days is not supposed to affect the threshold effect on thyroid.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Remaining uncertainties to cover additional variation in thyroid sensitivity between species. (Although available data indicates that human are less sensitive than rodents justifying a possible AF of 1)
AF for intraspecies differences:
5
Justification:
ECHA default value. ECETOC concept for combined inter-/intra-species for workers is an AF 3. However, to compensate for possible additional variation in thiocyanate background levels (due to smoking habits, food sources) this factor is increased from 3 to 5.
AF for the quality of the whole database:
1
Justification:
Database contains valid studies. For the key endpoint (effects on thyroid) much is known on effects in human.
AF for remaining uncertainties:
1
Justification:
Database contains valid and complete studies including information of mechanism of toxicity and human based information.
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

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.7 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
17.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
DNEL calculated from route-to-route extrapolation from 90-day oral toxicity study on NH4SCN resulting to a NOAEL of 20 mg/kg bw/day. The corrected 24 hr inhalation NOAEC for general population is NOAEL * 1/1.15 mg/m3 = 17.4 mg/m3. ADME data indicate rapid and almost complete absorption following oral exposure. As worst case, absorption via inhalation is also considered 100%, and thus being similar to oral absorption no additional factor 2 is needed for extrapolation from oral to inhalation. Besides, exposure via inhalation is not expected. The vapour pressure is extremely low (< 1.33 x 10-8 Pa) and thus does not present any potential for inhalation exposure due to volatilization of the salt. Furthermore thiocyanates are very hygroscopic (see granulometry). Inhalable particles are not available and will also not be formed during handling and use of the substance.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
1
Justification:
Default assessment factor for sub-chronic to chronic is 2, but in this case it can be considered that the mechanism of concern is inhibition of thyroid, and further prolongation of exposures beyond 90 days is not supposed to affect the threshold effect on thyroid.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
Remaining uncertainties to cover additional variation in thyroid sensitivity between species. (Although available data indicates that human are less sensitive than rodents justifying a possible AF of 1)
AF for intraspecies differences:
10
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, However, to compensate for possible additional variation in thiocyanate background levels (due to smoking habits, food sources) this factor is increased from 5 to 10.
AF for the quality of the whole database:
1
Justification:
Database contains valid studies. For the key endpoint (effects on thyroid) much is known on effects in human.
AF for remaining uncertainties:
1
Justification:
Database contains valid and complete studies including information of mechanism of toxicity and human based information.
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:
2 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
DNEL calculated from route-to-route extrapolation from 90-day oral toxicity on NH4SCN resulting to a NOAEL of 20 mg/kg bw/day. Assuming 10% dermal absorption compared to 100% oral absorption (see toxicokinetics for justification), this results to a derived dermal NOAEL of 200 mg/kg bw/day
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Default assessment factor for sub-chronic to chronic is 2, but in this case it can be considered that the mechanism of concern is inhibition of thyroid, and further prolongation of exposures beyond 90 days is not supposed to affect the threshold effect on thyroid.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Remaining uncertainties to cover additional variation in thyroid sensitivity between species. (Although available data indicates that human are less sensitive than rodents justifying a possible AF of 1)
AF for intraspecies differences:
10
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, However, to compensate for possible additional variation in thiocyanate background levels (due to smoking habits, food sources) this factor is increased from 5 to 10.
AF for the quality of the whole database:
1
Justification:
Database contains valid studies. For the key endpoint (effects on thyroid) much is known on effects in human.
AF for remaining uncertainties:
1
Justification:
Database contains valid and complete studies including information of mechanism of toxicity and human based information.
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:
0.2 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
Modified dose descriptor starting point:
NOAEL
DNEL value:
20 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
DNEL calculated from route-to-route extrapolation from 90-day oral toxicity on NH4SCN resulting to a NOAEL of 20 mg/kg bw/day. No route-to-route extrapolation is needed.
AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Default assessment factor for sub-chronic to chronic is 2, but in this case it can be considered that the mechanism of concern is inhibition of thyroid, and further prolongation of exposures beyond 90 days is not supposed to affect the threshold effect on thyroid.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for allometric scaling from rat to human.
AF for other interspecies differences:
2.5
Justification:
Remaining uncertainties to cover additional variation in thyroid sensitivity between species. (Although available data indicates that human are less sensitive than rodents justifying a possible AF of 1)
AF for intraspecies differences:
10
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, However, to compensate for possible additional variation in thiocyanate background levels (due to smoking habits, food sources) this factor is increased from 5 to 10.
AF for the quality of the whole database:
1
Justification:
Database contains valid studies. For the key endpoint (effects on thyroid) much is known on effects in human.
AF for remaining uncertainties:
1
Justification:
Database contains valid and complete studies including information of mechanism of toxicity and human based information.
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

Thiocyanates are only applied in professional or industrial setting applying adequate PPE.

No consumer uses are identified. However, in order to be able to evaluate possible secondary exposures via environment, additionally long-term systemic DNELs for general population have been derived. It should be considered however, that the possible exposures levels from indirect uses are not relevant compared to the natural background of thiocyanates in biological systems.