Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
80.4 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
5
Modified dose descriptor starting point:
NOAEC
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:
6.25 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
12
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified. The long-term DNEL concerning reprotoxic (developmental) effects also covers possible acute toxic effects.

Long-term inhalatory systemic DNEL based on NOEL (developmental, oral) in rabbits:
- 75 mg/kg bw/d

- NOAEL(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.3 (p. 68).
corrected NOAEL(inhal.)     = NOEL(oral, rabbit) x 1/sRVrabbitxABS(oral-rabbit)/ABS(inh-human)
                                              x sRVhuman/wRV

                                            = 75 mg/kg bw/d x 1/0.125 m3/kg/d x 100%/100% x 6.7 m3/10 m3
                                            = 402 mg/m3
with sRV: standard respiratory volume;ABS: Absorption; wRV: worker respiratory volume and
respiratory volume (rabbit): 94 L/kg bw/6 hours (according to Snipes, M.B.; long-term Retention and Clearance of Particles inhaled by mammalian Species; Crit. Rev. Toxicol. 20, 175-211, cited by the Federal Institute for occupational Safety and Health, 1998) and 125 L/kg/8 hours, respectively

- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 5(intraspecies worker)
=> =80.4 mg/m3

 

Long-term dermal systemic DNEL based on NOEL (developmental, oral) in rabbits:
- NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOEL(oral, rabbit) x Absorption(oral-rabbit)/Absorption(dermal-human)
                                                  = 75 mg/kg bw/d x 100%/100%
                                                  = 75 mg/kg bw/d
- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 12 (2.4(interspecies rabbit-human) x 5(intraspecies worker))
=> =6.25 mg/kg bw/d

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.9 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
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:
3.13 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
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:
3.13 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
24
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

According to RIP 3.2.2, Chapter R8, R8.1.2.5, p. 16 no acute DNELs were derived since no acute toxicity hazard has been identified. The long-term DNEL concerning reprotoxic (developmental) effects also covers possible acute toxic effects.

Long-term oral systemic DNEL based on NOEL (developmental) in rabbits: 75 mg/kg bw/d
applying assessment factor 24 (2.4(interspecies rabbit-human) x 10 (intraspecies general population))
=> =3.13 mg/kg bw/d

Long-term inhalatory systemic DNEL based on NOEL (developmental, oral) in rabbits:
- 75 mg/kg bw/d

- NOAEL(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.3 (p. 68).
corrected NOAEL(inhal.)     = NOEL(oral, rabbit) x 1/sRVrabbitxABS(oral-rabbit)/ABS(inh-human)
                                              x sRVhuman/wRV

                                            = 75 mg/kg bw/d x 1/0.376 m3/kg/d x 100%/100%
                                            = 199.5 mg/m3
with sRV: standard respiratory volume;ABS: Absorption and
respiratory volume (rabbit): 94 L/kg bw/6 hours (according to Snipes, M.B.; long-term Retention and Clearance of Particles inhaled by mammalian Species; Crit. Rev. Toxicol. 20, 175-211, cited by the Federal Institute for occupational Safety and Health, 1998) and 376 L/kg/24 hours, respectively

- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 10(intraspecies)
=> =19.9 mg/m3

 

Long-term dermal systemic DNEL based on NOEL (developmental, oral) in rabbits:
- NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)         = NOEL(oral, rabbit) x Absorption(oral-rabbit)/Absorption(dermal-human)
                                                  = 75 mg/kg bw/d x 100%/100%
                                                  = 75 mg/kg bw/d
- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 24 (2.4(interspecies rabbit-human) x 10(intraspecies))
=> =3.13 mg/kg bw/d