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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on revialbe OEL for the hydrolysis products HCl and SO2 including a plausibility check with available data for thionyl dichloride.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Based on revialbe OEL for the hydrolysis products HCl and SO2 including a plausibility check with available data for thionyl dichloride.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

Thionyl dichloride (CAS 7719-09-7)_ Derivation of DNELs

Introduction:

SOCl2 (thionyl dichloride) is a colorless, refractive liquid with a suffocating odor. The boiling point 76 °C at 100 kPa and the vapor pressure is 12.9 kPa at 20°C.

Vapours of thionyl chloride are highly irritating to skin, eyes and mucous membranes due to the formation of sulphur dioxide and hydrogen chloride in reaction with water (ACGIH threshold limit values, 2001). SOCl2 is classified as C; R35 Causes severe burns.

Thionyl dichloride (SOCl2): The LC50 for acute inhalation toxicity is (LC50 = 2.7 mg/l air (exposure 4 h) and LC50 = 5.4 mg/l air (exposure 1 h), Pauluhn 1986). The LD50 for acute oral toxicity 324 mg/kg bw (male and female rats; Pauluhn 1988).

Thionyl dichloride is rapidly hydrolyzed in moist air and water according the following equation:

SOCl2 + H20 -> 2 HCl (g) and SO2 (g)

There are sufficient data on thionyl dichloride and the hydrolysis products, to conclude that thionyl dichloride and both hydrolysis products are considered to be corrosive; thionyl dichloride is labeled with R35 (causes severe burns).

There are no repeated dose toxicity studies available for thionyl dichloride. Since SOCl2 reacts vigorously and completely with water within a very short time frame (< 2 minutes) with formation of HCl and SO2 the parent compound is systemically not available and the hydrolysis products are considered relevant for the toxicological evaluation. Taking into account thionyl dichloride hydrolysis data experimental data on the hydrolysis products and theoretical assumptions of potential systemic concentrations of the hydrolysis products HCl and SO2 after exposure above the derived worker DNEL, no toxicologically relevant absorption of thionyl dichloride or the hydrolysis products HCl or SO2 can be assumed at the derived local DNEL and, consequently, no toxicologically relevant systemic effect is anticipated at this exposure level and the local DNEL is consideered to protect both, against local effects and potential systemic effects.

Derivation of DNELS (workers):

Local effect at the respiratory tract related to the corrosivity of thionyl dichloride is the leading health effect. The NOAEC for the local effects by that also covers the NOAEL for potential systemic toxicity. Thus, the DNEL for local effects after inhalation exposure controls also the systemic effects and no systemic DNEL is derived. This procedure is in agreement with the below discussed OEL values for the hydrolysis products of thionyl dichloride which take into account the comprehensive database on local and systemic toxicity and conclude that local effects are the leading health effects.

Thionyl dichloride (SOCl2) undergoes hydrolysis in aqueous media and in contact with moist air, resulting in two equivalents HCl and one equivalent SO2 as main products. The latter can further react with water under formation of H2SO3. Since hydrolysis occurs rapidly, exposure occurs mainly to the hydrolysis products. Therefore data on these hydrolysis products are of high relevance for the toxicological potential of thionyl dichloride including the derivation of respective DNELs.

Official occupational exposure limits are available for HCl in Europe (RL 2000/39/EG) and e.g. Germany (TRGS 900) and for SO2 in Germany (TRGS 900). In line with Guidance Document R.8, Appendix 8-13) derivation of DNELs based on available community/national occupational exposure limits is an agreed way forward. Therefore this information is included in the DNEL derivation of thionyl dichloride.

Hydrogen chloride (HCl):

The EU IOELV for hydrogen chloride is 5 ppm (8 mg/m3) with a STEL of 10 ppm (15 mg/m3). The German OEL is 2 ppm (3 mg/m3) with a STEL of 4 ppm (6 mg/m3). Both values are based on long term rat inhalation studies and the available human evidence was also taken into consideration especially in the German OEL.

Sulphur dioxide (SO2):

The German OEL is 1 ppm (2.5 mg/m3). The OEL is based on a long term rat inhalation study as well as a short term inhalation studies in human volunteers that specifically examined inhalation parameters as most sensitive endpoints. The STEL is identical with the TWA.

Estimate for a DNEL for thionyl dichloride based on OELs for HCL and SO2:

A DNEL for thionyl dichloride derived from the available OEL from the hydrolysis products had to take into consideration the molar ratio of the parent compound and the hydrolysis products.

The molar ratio in case of 1 mol SOCl2 (thionyl dichloride) is 1mol SO2 and 2 mol HCl. This means, the reaction of one molecule of thionyl dichloride with one molecule of water produces two molecules of hydrogen chloride and one of sulphur dioxide; thus 1 ppm of SOCl2 yields a total irritant gas concentration equivalent to 3 ppm. Using the lowest of the mentioned OEL as starting point the OELs for HCL (3 mg/m3) and SO2 (2.5 mg/m3) would lead to limit values of 1.5 mg/m³ SOCl2 based on the HCl formation and 2.5 mg/m³ SOCl2 based on the SO2 formation .

As a pragmatic and precautionary approach it is proposed to define a DNEL long term for thionyl dichloride of 1 mg/m³. This is clearly below the respective OELs from the hydrolysis product and by that also covers the remaining uncertainties from the use of a read across in that context.

For the OEL for HCl there is a factor of 2 between short term and long term value, whereas for SO2 the short term and long term values are the same. Therefore a DNEL acute for thionyl dichloride of 1 mg/m³ is derived as a precautionary approach.

Taking all this together, the DNEL of 1 mg/m³ for SOCl2 (thionyl dichloride) is regarded to be reliable and sufficient to cover the inhalation hazard for workers.

As a plausibility check this derived DNEL (acute and long term) for thionyl dichloride is compared to a DNEL derivation based on the available data on thionyl dichloride.

An important input for the DNEL derivation comes from on an acute inhalation toxicity study, which was conducted similar to OECD test guideline 403 (non- GLP; Pauluhn, 1986) and that defined a NOAEC for toxicity after acute exposure. 5 Wistar rats per sex per dose were exposed to vapors of thionyl dichloride in a nose/head only inhalation system for 4 h. The doses applied were analytically verified and amounted 5, 63, 403, 1326, 1596, 2544, 2832, 7986 and 9318 mg/m³. Mortality was observed at 1326 mg/m³ and above for males and at 2544 mg/m³ and above for females. The calculated combined LC50 value for males and females is 2717 mg/m³ air. The predominant clinical signs were signs of respiratory irritation/corrosion and comprised piloerection, reduced motility, laboured breathing, dyspnea, breathing noises, necrosis in snout and rhinarium, bloody and suppurative eye lids, bleached incisors, stained fur coat and corneal opacity at doses of 1596 to 9318 mg/m³; piloerection, laboured breathing, reduced motility, hyperemia of rhinarium, serous discharge from nose, bleeding of the nose and necrosis of rhinarium at 1326 mg/m³; hyperemia of rhinarium, serous discharge from nose, moderately laboured breathing at 403 mg/m³ and slight hyperemia of rhinarium and piloerection at 63 mg/m³. No signs of toxicity were observed in low dose animals exposed to 5 mg/m³. At necropsy, deceased animals showed necrotic changes in the area of the nose and snout and extremities with a yellowish-greenish discoloration. Serous fluids were found in lungs and thorax and lungs were distended and showed liver-like changes. The livers appeared pale, with lobular pattern and the gastrointestinal tracts were reddened and filled with reddish mucus and bleached incisors, which appeared white.

Based on the overall effects observed at 63 mg/m³ and above, a LOAEC value of 63 mg/m³ and consequently a NOAEC value of 5 mg/m³ were derived from this study.

This NOAEC from acute exposure will be used as a starting point to estimate a DNEL and to check whether the DNEL derived from the hydrolysis products is plausible.

Extrapolation factors:

Duration of exposure: 1 (rationale: because corrosion as leading toxic effect is mainly driven by the exposure concentration than the exposure duration, therefore time scaling is not appropriate).

Intraspecies differences (worker): 5 (ECHA default)

Interspecies differences: 1 (rationale: allometric scaling not necessary for direct reactivity (local corrosivity) at the port of entry. The mode of action for direct corrosive activity at the port of entry is well known. Therefore the additional default factor of 2.5 according to the ECHA Guidance Chapter R.8.4.3.1 (local effects) for uncertainties in interspecies comparison ( “there could be significant quantitative differences in deposition, airflow patterns, clearance rates and protective mechanisms between humans and animals and when there is no data to inform on this uncertainty, it is prudent to assume that humans would be more sensitive than animals to effects on the respiratory tract”. ) needs not to be applied in this case.

Using the factors as shown above would lead to an estimated overall DNEL (acute/short term exposure – local – inhalation - worker) of :

5 mg/m³ : 5 = 1 mg/m³

It needs to be mentioned, that in the study that led to the NOAEC the dose group spacing was very large with a NOAEC: exposure to 5 mg/m³ that caused no signs of toxicity and the next higher concentration revealing irritating effects to the respiratory tract (LOAEC) that was about a factor of more than 12 higher (63 mg/m³). Thus, it is not unrealistic, that the “true” NAEC is >5 mg/m³ and < 63 mg/m³. Therefore the irritation threshold might be higher than the experimentally derived NOAEC and by that the DNEL estimation includes an element of caution, even if there are remaining uncertainties due to the overall limited database and the selection of the extrapolation factors.

Derivation of DNELS (general population):

Since exposure for the general public is not given and administration via the oral route is not relevant for workers, oral DNELs are not derived. Furthermore, thionyl dichloride is classified as corrosive, and consequently allocated to the “high hazard” band. Hence, personal protective equipment will be worn during handling of the substance and dermal DNELs are superfluous.

Conclusion:

The DNEL of 1 mg/m³ for SOCl2 (thionyl dichloride) is regarded to be reliable and sufficient to cover the inhalation hazard for workers.

The DNEL is derived based on the available OELs from the hydrolysis products. From the available acute toxicity data for SOCl2 a DNEL of 1 mg/m³ is plausible.

As the leading health effect is corrosion, the NOAEC local also covers the NOAEL systemic Therefore in adherence to the local DNEL no systemic effects are expected. Thus, the DNEL for local effects after inhalation exposure controls also the systemic effects and no systemic DNEL is derived.

References:

SO2:

TRGS 900

http://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/TRGS/pdf/900/900-schwefeldioxid.pdf?__blob=publicationFile&v=2

MAK 2013:

http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb744609d0055/pdf

MAK 2000:

http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb744609d0030/pdf

MAK 1998:

http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb744609d0026/pdf

HCl

MAK 2004

http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb764701d0038/pdf

EU 1994:

http://ec.europa.eu/social/BlobServlet?docId=3844&langId=en

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

Exposure for the general public is not given.

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