Bis(2-chloroethoxy)methane 1,15-dichloro-3,5,8,11,13-penta-oxa pentadecane1-(2-chloroethoxy)-2-(2-chloroethoxymethoxy)ethane

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.76 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):

10

Modified dose descriptor starting point:

NOAEC

Value:

17.63 mg/m³

Explanation for the modification of the dose descriptor starting point:

Due to a lack of experimental data the NOAEC (corr) was derived assuming 100% absorption via the oral and inhalation route.

AF for dose response relationship:

1

Justification:

default

AF for differences in duration of exposure:

2

Justification:

default (extrapolation from sub-chronic to chronic)

AF for interspecies differences (allometric scaling):

1

Justification:

default (inhalation)

AF for other interspecies differences:

1

Justification:

ECETOC approach (TR110))

AF for intraspecies differences:

5

Justification:

default

AF for the quality of the whole database:

1

Justification:

default

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.25 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

DNEL extrapolated from long term DNEL

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.33 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):

300

Modified dose descriptor starting point:

NOAEL

Value:

100 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Due to a lack of experimental data the NOAEC (corr) was derived assuming 100% absorption via the oral (50%) and dermal (100%) route.

AF for dose response relationship:

1

Justification:

default

AF for differences in duration of exposure:

6

Justification:

default (extrapolation from sub-acute to chronic)

AF for interspecies differences (allometric scaling):

4

Justification:

default

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

default (worker)

AF for the quality of the whole database:

1

Justification:

default

AF for remaining uncertainties:

1

Justification:

default

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Conversion of long term systemic inhalation DNEL from mg/m3 to ppm

 

The registered substance, Reaction mass of 1,15-dichloro-3,5,8,11,13-pentaoxapentadecane and 1-chloro-2-[(2-chloroethoxy)methoxy]ethane and 1-chloro-2-{[2-(2-chloroethoxy)ethoxy]methoxy}ethane, is a multi-constituent substance. The DNEL for long term systemic effects via the inhalation route was derived from an OECD422 oral repeated dose study. The DNEL is calculated in mg/m³according to the REACH guidance. This is appropriate in case of exposure to an aerosol.

 

However, a vapour pressure was determined for the multi constituent substance and was found to be10Pa at 20°C and 1050Pa at 90°C (AQURA 2013). This vapour pressure is low at 20°C and moderate at 90°C which means vapours can be formed. For this reason the DNEL in mg/m³needs to be converted to ppm. The only potential exposure to the multi constituent substance is during sampling and if any exposure occurs at all it will be to a vapour.

 

The vapour pressure that was determined does not give an indication which of the constituents is most volatile. To investigate if there are any major differences between the volatility of the constituent the vapour pressure was estimated for the three major constituents.

Several values were estimated using several methods, one or average is then chosen by EPISUITE.

 

Substance	Vapour pressure at 25°C
Multi-constituent: Reaction mass of 1,15-dichloro-3,5,8,11,13-pentaoxapentadecane and 1-chloro-2-[(2-chloroethoxy)methoxy]ethane and 1-chloro-2-{[2-(2-chloroethoxy)ethoxy]methoxy}ethane	Meausured:14.1 Pa Calculated: -
Constituent 1, 40%: bis(2-chloroethoxy)methane	Measured:17.1 Pa Calculated:19.4 Pa
Constituent 2, 25%: 1,15-dichloro-3,5,8,11,13-penta-oxa pentadecane	Measured: - Calculated:0.00647 Pa
Constituent 3, 10%: 2-chloroethoxymethyl-2-chloroethoxyethyl-ether	Measured: - Calculated:1.17 Pa

 

The impurities are similar structures with higher molecular weights. Therefore, it is not expected that the vapour pressures for these substances will be higher than those of the major constituents. An exception is 2-chloroethanol with a vapour pressure of ±700 Pa at 25°C but this substance is present at ca. 0.3% as an impurity of a 2.35 mg/m³DNEL for the multi constituent this is 0.007 mg/m³or 0.002 ppm. 2-chloroethanol has an OEL of 1ppm (3.3 mg/m³) 8h TWA/ 15 min STEL in Germany and this will not be reached. If measurements are performed 2-chloroethanol exposure levels should stay below the OEL.

 

Based on these estimations it can be shown that the vapour pressure for multiconstituent andbis(2-chloroethoxy)methane are in the same range. Bis(2-chloroethoxy)methane is the most volatile constituent with the highest concentration in the multi constituent and therefore that potential exposure would be to this constituent. This substance has a long term systemic DNEL of 1.76 mg/m³this is 0.24 ppm, and a short term acute systemic DNEL of 6.25 mg/m3 this is 0.87 ppm

The risk assessment will be based on this DNEL since it is most relevant for inhalation exposure.

 

Annex 1

 

EPISUITE outputMPBPWIN v1.43

 

C(COCOCCCl)Cl

Experimental Database Structure Match:

 Name    : BIS(2-CHLOROETHOXY)METHANE

 CAS Num : 000111-91-1

 Exp MP (deg C): -32

 Exp BP (deg C): 218

 Exp VP (mm Hg): 1.32E-01 (extrapolated)

        (Pa  ): 1.76E+001

 Exp VP (deg C): 25

 Exp VP ref   : PERRY,RH & GREEN,D (1984)

 

SMILES : C(COCOCCCL)CL

CHEM  :

MOL FOR: C5 H10 CL2 O2

MOL WT : 173.04

------------------------ SUMMARY MPBPWIN v1.43 --------------------

 

 

Boiling Point: 214.16 deg C (Adapted Stein and Brown Method)

 

Melting Point: -22.75 deg C (Adapted Joback Method)

Melting Point:  11.39 deg C (Gold and Ogle Method)

Mean Melt Pt :  -5.68 deg C (Joback; Gold,Ogle Methods)

 Selected MP:  -5.68 deg C (Mean Value)

 

Vapor Pressure Estimations (25 deg C):

 (Using BP: 218.00 deg C (exp database))

 (MP not used for liquids)

   VP: 0.156 mm Hg (Antoine Method)

     : 20.7 Pa (Antoine Method)

   VP: 0.135 mm Hg (Modified Grain Method)

     : 18 Pa (Modified Grain Method)

   VP: 0.226 mm Hg (Mackay Method)

     : 30.1 Pa (Mackay Method)

 Selected VP: 0.145 mm Hg (Mean of Antoine & Grain methods)

            : 19.4 Pa (Mean of Antoine & Grain methods)

   

-------+-----+--------------------+----------+---------

 TYPE | NUM | BOIL DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 5 | -CH2-            |  24.22 | 121.10

 Group | 2 | -O- (nonring)    |  25.16 |  50.32

 Group | 2 | -Cl (primary)    |  62.63 | 125.26

  *  |    | Equation Constant |         | 198.18

=============+====================+==========+=========

RESULT-uncorr| BOILING POINT in deg Kelvin | 494.86

RESULT- corr | BOILING POINT in deg Kelvin | 487.32

            | BOILING POINT in deg C      | 214.16

-------------------------------------------------------

 

-------+-----+--------------------+----------+---------

 TYPE | NUM | MELT DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 5 | -CH2-            |  11.27 |  56.35

 Group | 2 | -O- (nonring)    |  22.23 |  44.46

 Group | 2 | -Cl (primary)    |  13.55 |  27.10

  *  |    | Equation Constant |         | 122.50

=============+====================+==========+=========

  RESULT   | MELTING POINT in deg Kelvin | 250.41

            | MELTING POINT in deg C      | -22.75

-------------------------------------------------------

 

C(COCOCCOCCOCOCCCl)Cl

Experimental Database Structure Match: no data

 

SMILES : C(COCOCCOCCOCOCCCL)CL

CHEM  :

MOL FOR: C10 H20 CL2 O5

MOL WT : 291.17

------------------------ SUMMARY MPBPWIN v1.43 --------------------

  

Boiling Point: 340.69 deg C (Adapted Stein and Brown Method)

 

Melting Point: 100.29 deg C (Adapted Joback Method)

Melting Point:  85.27 deg C (Gold and Ogle Method)

Mean Melt Pt :  92.78 deg C (Joback; Gold,Ogle Methods)

 Selected MP:  92.78 deg C (Mean Value)

 

Vapor Pressure Estimations (25 deg C):

 (Using BP: 340.69 deg C (estimated))

 (Using MP: 92.78 deg C (estimated))

   VP: 2.54E-005 mm Hg (Antoine Method)

     : 0.00339 Pa (Antoine Method)

   VP: 4.85E-005 mm Hg (Modified Grain Method)

     : 0.00647 Pa (Modified Grain Method)

   VP: 9.2E-005 mm Hg (Mackay Method)

     : 0.0123 Pa (Mackay Method)

 Selected VP: 4.85E-005 mm Hg (Modified Grain Method)

            : 0.00647 Pa (Modified Grain Method)

 Subcooled liquid VP: 0.000219 mm Hg (25 deg C, Mod-Grain method)

                    : 0.0292 Pa (25 deg C, Mod-Grain method)

 

-------+-----+--------------------+----------+---------

 TYPE | NUM | BOIL DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 10 | -CH2-            |  24.22 | 242.20

 Group | 5 | -O- (nonring)    |  25.16 | 125.80

 Group | 2 | -Cl (primary)    |  62.63 | 125.26

  *  |    | Equation Constant |         | 198.18

=============+====================+==========+=========

RESULT-uncorr| BOILING POINT in deg Kelvin | 691.44

RESULT- corr | BOILING POINT in deg Kelvin | 613.85

            | BOILING POINT in deg C      | 340.69

-------------------------------------------------------

 

-------+-----+--------------------+----------+---------

 TYPE | NUM | MELT DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 10 | -CH2-            |  11.27 | 112.70

 Group | 5 | -O- (nonring)    |  22.23 | 111.15

 Group | 2 | -Cl (primary)    |  13.55 |  27.10

  *  |    | Equation Constant |         | 122.50

=============+====================+==========+=========

  RESULT   | MELTING POINT in deg Kelvin | 373.45

            | MELTING POINT in deg C      | 100.29

-------------------------------------------------------

Experimental Database Structure Match: no data

 CAS 117994-78-2

SMILES : C(CL)COCCOCOCCCL

CHEM  :

MOL FOR: C7 H14 CL2 O3

MOL WT : 217.09

------------------------ SUMMARY MPBPWIN v1.43 --------------------

 

 

Boiling Point: 268.51 deg C (Adapted Stein and Brown Method)

 

Melting Point:  22.02 deg C (Adapted Joback Method)

Melting Point:  43.12 deg C (Gold and Ogle Method)

Mean Melt Pt :  32.57 deg C (Joback; Gold,Ogle Methods)

 Selected MP:  32.57 deg C (Mean Value)

 

Vapor Pressure Estimations (25 deg C):

 (Using BP: 268.51 deg C (estimated))

 (Using MP: 32.57 deg C (estimated))

   VP: 0.0084 mm Hg (Antoine Method)

     : 1.12 Pa (Antoine Method)

   VP: 0.00874 mm Hg (Modified Grain Method)

     : 1.17 Pa (Modified Grain Method)

   VP: 0.0156 mm Hg (Mackay Method)

     : 2.08 Pa (Mackay Method)

 Selected VP: 0.00874 mm Hg (Modified Grain Method)

            : 1.17 Pa (Modified Grain Method)

 Subcooled liquid VP: 0.0102 mm Hg (25 deg C, Mod-Grain method)

                    : 1.36 Pa (25 deg C, Mod-Grain method)

 

-------+-----+--------------------+----------+---------

 TYPE | NUM | BOIL DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 7 | -CH2-            |  24.22 | 169.54

 Group | 3 | -O- (nonring)    |  25.16 |  75.48

 Group | 2 | -Cl (primary)    |  62.63 | 125.26

  *  |    | Equation Constant |         | 198.18

=============+====================+==========+=========

RESULT-uncorr| BOILING POINT in deg Kelvin | 568.46

RESULT- corr | BOILING POINT in deg Kelvin | 541.67

            | BOILING POINT in deg C      | 268.51

-------------------------------------------------------

 

-------+-----+--------------------+----------+---------

 TYPE | NUM | MELT DESCRIPTION | COEFF  | VALUE 

-------+-----+--------------------+----------+---------

 Group | 7 | -CH2-            |  11.27 |  78.89

 Group | 3 | -O- (nonring)    |  22.23 |  66.69

 Group | 2 | -Cl (primary)    |  13.55 |  27.10

  *  |    | Equation Constant |         | 122.50

=============+====================+==========+=========

  RESULT   | MELTING POINT in deg Kelvin | 295.18

            | MELTING POINT in deg C      |  22.02

-------------------------------------------------------

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified