Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.76 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
375
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.84 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
1 500
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The substance is of low acute toxicity following oral administration and dermal application, with no mortality or signs of systemic toxicity observed at the limit dose of 2000 mg/kg bw in both studies. No signs of skin irritation were observed following dermal application in rabbits while only very minimal and transient irritation (redness of the conjunctiva of degree 1 at the one hour reading) was observed follwoing instillation into the eye, with or without washing the eye after instillation. No sensitisation potential was demonstrated in a fully compliant Local Lymph Node Assay, up to and including a 50 % concentration in acetone/olive oil (4:1 v/v).

Negative results were obtained for two endpoints of in-vitro genotoxicity i.e. gene mutation in bacterial cells and clastogenicity in mammalian (CHO) cells and on this basis the substance is considered not to possess any genotoxic potential.

 

In a fully compliant repeated-dose 28-day dietary study in rats, inclusive of evaluation of neurotoxicity endpoints (i.e. functional observation battery and motor activity assessment), the registered substance did not evoke any systemic toxicity as evidenced by the lack of any effects on body weights and/or food consumption, clinical signs, haematological and clinical chemistry parameters, organ weight and histopathology, as well as abnormalities at FOB and motor activity assessment. The NOAEL of the study was set at 15 ppm, the highest dose level tested, which corresponds to mean achieved intakes higher than the limit dose of 1000 mg/kg bw/day for repeat-dose studies (i.e. 1176 mg/kg bw/day in males and 1247 mg/kg bw/day in females). This endpoint has been chosen as the starting point for DNEL calculations. Although reproductive toxicity studies are waived on the basis of lack of human exposure through the manufacturing process and use of the photographic paper in line with the column 2 adaptation specified in point 8.7.1, Annex VIII of Regulation 1907/2006, an additional assessment factor of 5 has been used for quality of the data base as a highly precautionary measure.

Based on the physical-chemical properties of the substance (i.e. molecular weight >500, log Pow >4) a default dermal absorption value of 10 % is considered appropriate for the derivation of the long-term dermal DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.68 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
750
Modified dose descriptor starting point:
NOAEC
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.92 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3 000
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
exposure based waiving
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.39 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
3 000
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The same toxicological endpoint chosen for setting the DNELs for workers was chosen for setting the DNELs for the general population. The increased assessment factor for interspecies sensitivity is considered adequately protective.