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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
32.9 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
75
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
2 470 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
5
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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

In the absence of a suitable inhalation toxicity study with repeated exposure, the worker-DNEL long-term for inhalation route - systemic was derived from the NOAEL obtained in the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats (NOAEL 1000 mg SVS/kg bw/d).
A corrected inhalatory NOAEC (NOAECcorr) was calculated using the default respiratory volume for the rat and a correction for the difference between human respiratory rates under standard conditions and under conditions of light activity (under the assumption of no difference in absorption between rat and human). As specified in the toxicokinetic section oral absorption rate was similar to inhalation absorption rate.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
150
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
870 mg/m³
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
DNEL (Derived No Effect Level)
Value:
3.33 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
DNEL (Derived No Effect Level)
Value:
1.67 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Default (DNEL calculator)

AF for dose response relationship:
1
Justification:
Default (DNEL calculator)
AF for differences in duration of exposure:
6
Justification:
Default (DNEL calculator)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator)
AF for other interspecies differences:
2.5
Justification:
Default (DNEL calculator)
AF for intraspecies differences:
10
Justification:
Default (DNEL calculator)
AF for the quality of the whole database:
1
Justification:
Default (DNEL calculator)
AF for remaining uncertainties:
1
Justification:
The approach used for DNEL derivation is conservative. No further assessment factor is required.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

In line with chapter R.7 c (ECHA, 2012) the main toxicokinetic properties of sodium ethylenesulphonate (SVS, CAS-No. 3039-83-6) are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance. Specific toxicokinetics or dermal absorption studies are not available for the substance.


1. Relevant physico-chemical properties of SVS
Molecular weight: 130.1 g/mol
Physical state: liquid (RT)
logPow: -1.01
Water solubility: > 1000 g/L (20 °C)
Vapour pressure: 0.000391 Pa (20 °C)


Absorption
Oral
Based on its low molecular weight of 130 g/mol SVS is likely to be absorbed in the GI tract since small molecular weights below 500 g/mol do favour absorption. This assumption is supported by the results of the key acute oral toxicity study (Hoechst AG (a), 1976) indicating signs of systemic toxicity like semi-prone position and lustreless coat in dose levels of 3750 mg/kg bw (dose level in terms of pure SVS).
Due to the very high water solubility (1000 g/L) SVS will readily dissolve into the gastrointestinal fluids. However, absorption by passive diffusion may be limited by the rate at which the substance partitions out of the gastrointestinal fluid. This is in line with the borderline log Pow value of – 1.01 since absorption by passive diffusion generally requires a moderate log Pow value between -1 and 4.
Inhalation
Due to the very low vapour pressure of SVS and the resulting low volatility, an inhalation exposure of the compounds vapour phase is rather unlikely. In addition, if small amounts of the substance would reach the lungs in its vapour state and/or liquide aerosol the substance would be quantitatively absorbed based on the relevant physico-chemical characteristics outlined above for the oral route (retained within the mucous due to the very high water solubility).
Dermal
With respect to the very high water solubility and the log Pow of -1.01 the dermal uptake of SVS will be low since substances with a water solubility above 10 g/L and a log Pow value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. A limited dermal absorption is supported by the result of an acute dermal toxicity study (Huntingdon Research Centre Ltd. (b), 1993) performed on rats. During the study no mortality and no systemic toxic effects were observed during the study period (24h treatment, 14-day observation) for the highest dose of 500 mg/kg bw (dose level
in terms of pure SVS).


Distribution/Metabolism
In view of the clinical signs observed in the acute toxicity study (Hoechst AG (a), 1976) distribution of SVS in the body cannot be ruled out. However, since SVS revealed a moderate molecular size and a very hydrophilic character a wide distribution and diffusion across the membranes, particularly in fatty tissues, are not expected. Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion. For SVS, no conversion into a metabolite that was more cytotoxic or more genotoxic than the parent substance was noted when comparing in vitro test results with metabolic activation to in vitro test results without metabolic activation system (genetic toxicity tests). Thus, the formation of reactive metabolites is unlikely.


Excretion
The log Pow of -1.01, the high water solubility and the molecular weight below 300 g/mol indicate that SVS has no bioaccumulation potential and that rapid urinary excretion will be the most relevant route of excretion.


Generic absorption rates
Based on the above information and due to the fact that there are no specific toxicokinetic data available it is assumed that oral and inhalation absorption are comparable. Conservatively, it is assumed that dermal absorption is 2-fold lower than oral or inhalation absorption, even though the data suggest a much higher difference between dermal and oral/inhalation absorption.