Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
30
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:
1.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
120
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

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 dermal systemic DNEL based on NOAEC (14 d, inhalation) in rats:
- derived systemic NOAEL: 132.6 mg/kg bw/d (for calculation details please refer to Endpoint summary“Reproductive toxicity”)

- NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
corrected NOAEL(dermal)   = NOAEL(systemic, rat) x Absorption(inhal-rat)/Absorption(dermal-human)

                                            = 132.6 mg/kg bw/d x 100%/100%
                                            = 132.6 mg/kg bw/d
- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 120 (4(interspecies rat-human) x 5(intraspecies worker) x 6(subacute-chronic))
=> =1.1 mg/kg bw/d

 

Long-term inhalatory DNEL based on NOAEL (14 d, inhalation) in rats:
- NOAEC(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4, Figure 8-2 (p. 27).

corrected NAEC(inhalation)    = NOAEC(inhal., rat) x 6(h/d)/8(h/d) x 6.7 m3/10 m3
                                               = 187 mg/m3x 6(h/d)/8(h/d) x 6.7 m3/10 m3
                                               = 94.0 mg/m3
- DNEL(inhalation) derived from corrected NOAEC(inhalation) applying the assessment factor 30 (5(intraspecies) x 6(subacute-chronic))
=>=
3.1 mg/m3

The 14 days inhalation study in rats was chosen for the long-term DNEL derivation for workers since the rat is the commonly accepted and best investigated species for repeated dose toxicity studies. Furthermore, it can be assumed that workers are trained in handling chemicals and according to general occupational health regulations an exposure of pregnant workers to Ethylene glycol dimethyl ether at the production site is excluded. Ethylene glycol dimethyl ether is labeled as reprotoxic and teratogenic.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
DNEL related information
Overall assessment factor (AF):
10
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:
0.23 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:
0.23 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 NOAEC (14d, inhalation teratognicity study) in rabbits: 5.6 mg/kg bw/d
(for calculation details please refer to Endpoint summary“Reproductive toxicity”)
applying assessment factor 24 (2.4(interspecies rabbit-human) x 10 (intraspecies general population))
=> =0.23 mg/kg bw/d

Long-term dermal systemic DNEL based on NOAEC (14 d, inhalation teratogenicity study) in rabbits:
- derived systemic NOAEL: 5.6 mg/kg bw/d (for calculation details please refer to Endpoint summary“Reproductive toxicity”)

- NOAEL(dermal) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8-2, Example B.5 (p. 69).
-corrected NOAEL(dermal) 

= NOAEL(systemic, rabbit) x Absorption(inhal-rabbit)/Absorption(dermal-human)

= 5.6 mg/kg bw/d x 100%/100%

= 5.6 mg/kg bw/d

- DNEL(dermal) derived from corrected NOAEL(dermal) applying the assessment factor 24 (2.4(interspecies rabbit-human) x 10(intraspecies general population))
=> =0.23 mg/kg bw/d

Long-term inhalatory DNEL based on NOAEC (14 d, inhalation teratogenicity study) in rabbits:
- NOAEC(inhalation) derived according to “Guidance on information requirements and chemical safety assessment”, Chapter R8.4, Figure 8-2 (p. 27).

corrected NAEC(inhalation) = NOAEC(inhal., rabbit) x 6(h/d)/24(h/d)
            = 60 mg/m3x 6(h/d)/24(h/d)
            = 15.0 mg/m3
- DNEL(inhalation) derived from corrected NOAEC(inhalation) applying the assessment factor 10(intraspecies)
=>= 1.5 mg/m3