Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 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
Value:
8 mg/m³
Explanation for the modification of the dose descriptor starting point:
the systemic toxicity of ziram is mediated by CS2 which is formed by abiotic hydrolysis, independent of route
AF for dose response relationship:
1
Justification:
not necesssary, NOAEL is starting point
AF for differences in duration of exposure:
1
Justification:
not necessary, chronic NOAEL is starting point
AF for interspecies differences (allometric scaling):
1
Justification:
Not necessary for inhalation route
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default for workers
AF for the quality of the whole database:
1
Justification:
The database is complete
AF for remaining uncertainties:
1
Justification:
All endpoints covered, no uncertainties
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 mg/m³
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Most sensitive endpoint:
irritation (respiratory tract)
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.64 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 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):
17.5
Modified dose descriptor starting point:
NOAEL
Value:
21.1
Explanation for the modification of the dose descriptor starting point:
The systemic toxicity of ziram is mediated by CS2 which is formed by abiotic hydrolysis, independent of route
AF for dose response relationship:
1
Justification:
not necesssary, NOAEL is starting point
AF for differences in duration of exposure:
1
Justification:
not necessary, chronic NOAEL is starting point
AF for interspecies differences (allometric scaling):
1.4
Justification:
default for dog-to-human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
1
Justification:
The database is complete
AF for remaining uncertainties:
1
Justification:
All endpoints covered, no uncertainties
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
sensitisation (skin)
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Separate short-term DNELs are not proposed since only long-term scenarios apply to worker exposure. The long-term DNELs are sufficiently protective to cover any acute exposure.

No quantitative dose-response data are available for local effects on skin and respiratory tract. The most sensitive local endpoint is skin sensitisation.

The long-term dermal DNEL for systemic effects is based on the one-year feeding study in dogs (NOAEL = 1.6 mg/kg bw/day). The NOAEL was corrected with the assumed dermal absorption value of 0.1%, whereas the oral absorption of ziram is 60%.

The long-term inhalation DNEL for systemic effects is based on the one-year feeding study in dogs (NOAEL = 1.6 mg/kg bw/day). The starting point was first converted into an oral NAEL for humans by applying allometric scaling (1.4). The NAEL (1.14 mg/kg bw/day) is converted into a NAEC using 10 m³ breathing volume per 8-h shift under light physical activity and 70 kg bw. The NAEC is then 8.0 mg/m³. Assessment factors of 2.5 and 5 are then applied for inter-species and intra-species variability, respectively, giving a long-term DNEL of 0.64 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The general population is not exposed to ziram from its identified uses. For dietary exposure to ziram from its pesticide uses, an ADI of 0.01 mg/kg bw/day was set by the European Commission.