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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
1.792 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Linearised approach and high-to-low dose risk extrapolation to a risk of 4E-03 (German traffic light model).
Overall assessment factor (AF):
62.5
Dose descriptor starting point:
LOAEC
DNEL value:
29.12 mg/m³
Modified dose descriptor starting point:
T25
DNEL value:
112 mg/m³
Explanation for the modification of the dose descriptor starting point:

Calculation of the T25:

 

Study output:

 

 

Control group

(C)

Treated

(T)

Dose (ppm)

0

25

Dose (mg/m3)

0

99.12

# Animals

50

50

# Tumors

1

12

% Tumors

2

24

 

Calculation of net tumor incidence:

 

Net tumor incidence (%)   = % Tum.(T) - % Tum.(C) / [ 100% - % Tum.(C) ]

                                          = 22.45%

 

Correction for standard lifespan:

 

- Study duration: 105 wks

- Standard lifespan: 104 wks

 

Corrected dose = 99.12 * 105 / 104 = 100.07 mg/m3

 

Calculation of T25:

 

T25   = corrected dose * 25% tumor incidence / net tumor incidence

          = 111.45 mg/m3

 

Modifications of the dose descriptor:

      

- Differences in inhalation absorption: no correction

- Route-to-route extrapolation: no correction

- Correction factor for workers (light activity) = 6.7 m3/ 10 m3= 0.67      

- Correction factor for exposure conditions = (6h/8h) * (52wk/48wk)* (75y/40y) = 1.5

with:

8h daily exposure for workers vs. 6h testing conditions

48 wk/year exposure for workers vs. 52wk/year testing conditions

75y human lifetime vs. 40y operational exposure

Modified dose descriptor:

 

T25 = 112.00 mg/m3

Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
38 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 250
Dose descriptor starting point:
other: LC50
DNEL value:
28 350 mg/m³
Modified dose descriptor starting point:
other: LC50
DNEL value:
47 863 mg/m³
Explanation for the modification of the dose descriptor starting point:

The LC50 value (28350 mg/m3) from the acute inhalation study with rats by Zeller and Klimish (1979) was selected for the point of departure. To obtain the corrected LC50 value, the following aspects were taken into consideration:

  • exposure duration: using the modified Haber’s law formula: Cn*t=k with n=3 (as specified in Appendix R8-8)
  • worker light activity (10 m3/person/8h work instead of normal activity 6.7 m3/person/8h).
AF for dose response relationship:
100
Justification:
LC50 to NOAEL extrapolation according to appendix R8-8, box 5
AF for interspecies differences (allometric scaling):
1
Justification:
Starting point is an inhalation study.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences not related to allometry.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences in workers.
AF for the quality of the whole database:
1
Justification:
Default value relevant for data-rich dossier.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
75.6 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Closed systems are used for the production and industrial use of 1,1-dichloroethene. Therefore dermal exposure of workers to 1,1-dichloroethene is unlikely. A dermal DNEL was nevertheless derived to provide a guidance value in case such figure would be necessary in some particular (currently not considered) cases.

No chronic dermal exposure studies are available allowing the direct calculation of a DNEL. Therefore a route-to-route extrapolation was performed based on the key value (NOAELoral 9 mg/kg bw/d) from a chronic oral study (Quast et al. 1983, 24h/day, exposure 7 days/week, 24 months treatment period).

In order to introduce a sufficient degree of conservatism in the approach the following assumptions were made:

  • ABSoral = ABSdermal
  • ABSrat = ABShuman

 

However, because the very high volatility of the substance, a conservative assumption was made that 50% of the applied substance would not be available for absorption due to evaporation leading to a NOAELdermal of 18 mg/kg bw / d. This assumption is supported by the data of Dilling (1977) and by the observation made by Fasano et al. (2008) which mention that the evaporation of the substance significantly hindered the in vitro dermal absorption experiments.

 

The corrected NOAEL of 18.9 mg/kg was obtained by considering the e exposure regime (24h/day, 7days/week versus 8h/day, 5 days/week).

Corrected NOAEL = 18 mg/kg bw * (24h / 8h) * (7d / 5d) = 75.6 mg/kg bw/d

AF for dose response relationship:
1
Justification:
Default value for using an NOAEL as the starting point.
AF for differences in duration of exposure:
1
Justification:
Default factor for NOAEL obtained from a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for interspecies differences between rat and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences not related to allometry.
AF for intraspecies differences:
5
Justification:
Default factor for intraspecies differences in workers.
AF for the quality of the whole database:
1
Justification:
Default value relevant for data-rich dossier.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DMEL (Derived Minimum Effect Level)
Value:
0.032 mg/m³
Most sensitive endpoint:
carcinogenicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
other: Linearised approach and high-to-low dose risk extrapolation to a risk of 4E-04 (German traffic light model).
Overall assessment factor (AF):
625
Dose descriptor starting point:
LOAEC
DNEL value:
29.12 mg/m³
Modified dose descriptor starting point:
T25
DNEL value:
112 mg/m³
Explanation for the modification of the dose descriptor starting point:

Calculation of the T25:

See derivation of the workers inhalation systemic DMEL.

T25   = corrected dose * 25% tumor incidence / net tumor incidence

           = 111.45 mg/m3

 

Modifications of the dose descriptor:

      

- Differences in inhalation absorption: no correction

- Route-to-route extrapolation: no correction

- Difference in respiratory volume: no correction

- Correction factor for exposure conditions = (6h/24h) * (5d/7d) = 0.179

with:

24h daily exposure for the general population vs. 6h testing conditions

7d/wk exposure for the general population vs. 5d/wk testing conditions

Modified dose descriptor:

 

T25 = 19.90 mg/m3

Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.09 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):
100
Dose descriptor starting point:
NOAEL
DNEL value:
9 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
9 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation was performed starting from the key value (NOAEL oral 9 mg/kg) from the chronic oral study by Quast et al. 1983.

No modification of the dose descriptor required.

AF for dose response relationship:
1
Justification:
Default value for using an NOAEL as the starting point.
AF for differences in duration of exposure:
1
Justification:
Default factor for NOAEL obtained from a chronic study.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor for interspecies differences between rat and humans.
AF for other interspecies differences:
2.5
Justification:
Default factor for other interspecies differences not related to allometry.
AF for intraspecies differences:
10
Justification:
Default factor for intraspecies differences in the general population.
AF for the quality of the whole database:
1
Justification:
Default value relevant for data-rich dossier.
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties.
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population