Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.162 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
600
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.05 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
300
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

No acute effects have been observed following exposure to S191820 and therefore no acute DNELs are required.

The only long-term test conducted on S191820 is a 28-day repeated dose oral toxicity study.  Dose levels used in this study were 1000, 150 and 15 mg/kg/bw/day.

No toxicologically significant effects were seen in males at any dose and hence the NOEL for males was determined to be 1000 mg/kg/bw/day.  However, toxicologically significant tubular basophilia/degeneration observed in relation to treatment was observed in female rats dosed at 1000 mg/kg/day and 150 mg/kg/day.  The presence of the effect in females only suggests sex differences in toxicological response which may be the result of differences in metabolism of S191820 between the sexes or other physiological factors.  Within the confines of the study the toxicological importance of these changes were considered minimal given that there was no effect on kidney weight nor any other evidence of renal dysfunction.  However, they cannot be discounted for DNEL derivation, as they may represent an early indication of target organ toxicity especially since nephropathology is sometimes a consequence of repeated administration of coloured test materials and may indicate a continuing cellular response to the persistent accumulation of test material and/or its’ metabolite(s).  Thus it is possible that following longer-term exposure (e.g. a 90-day study) more serious effects may be observed.  As a result it has been concluded that the female NOEL from the oral 28-day study is the only dose descriptor applicable for DNEL derivation for systemic exposure.  This is because it is the only dose value at which it can be assumed no adverse toxicity will occur.  Dose descriptors for long-term dermal and inhalation exposure have been extrapolated from this oral endpoint.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.081 mg/m³
DNEL related information
Overall assessment factor (AF):
1 200
Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.025 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
600
Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.025 mg/kg bw/day
DNEL related information
Overall assessment factor (AF):
600
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Discussion as for workers.