Thionyl dichloride

Endpoint summary

Description of key information

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
As outlined in the endpoint summary of IUCLID chapter 7.5, repeated dose toxicity, comprehensive data are available in animals and humans to evaluate the repeated dose toxicity of both hydrolysis products (e.g. HCl: OECD SIDS assessment published in 2002, SO2 and HCl: German Federal Institute for Occupational Safety and Health (BauA), TRGS900). Potential systemic effects are not seen in studies with HCl and SO2. 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).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
As outlined in the endpoint summary of IUCLID chapter 7.5, repeated dose toxicity, comprehensive data are available in animals and humans to evaluate the repeated dose toxicity of both hydrolysis products (e.g. HCl: OECD SIDS assessment published in 2002, SO2 and HCl: German Federal Institute for Occupational Safety and Health (BauA), TRGS900). Potential systemic effects are not seen in studies with HCl and SO2. 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).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
As outlined in the endpoint summary of IUCLID chapter 7.5, repeated dose toxicity, comprehensive data are available in animals and humans to evaluate the repeated dose toxicity of both hydrolysis products (e.g. HCl: OECD SIDS assessment published in 2002, SO2 and HCl: German Federal Institute for Occupational Safety and Health (BauA), TRGS900). Potential systemic effects are not seen in studies with HCl and SO2. 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).

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
Local effects: Thionyl dichloride and both hydrolysis products are considered to be corrosive; thionyl dichloride is labeled with R35 (causes severe burns).

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
As outlined in the endpoint summary of IUCLID chapter 7.5, repeated dose toxicity, comprehensive data are available in animals and humans to evaluate the repeated dose toxicity of both hydrolysis products (e.g. HCl: OECD SIDS assessment published in 2002, SO2 and HCl: German Federal Institute for Occupational Safety and Health (BauA), TRGS900). Potential systemic effects are not seen in studies with HCl and SO2. 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).

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water). Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.
Local effects: Thionyl dichloride and both hydrolysis products are considered to be corrosive; thionyl dichloride is labeled with R35 (causes severe burns).

Additional information

As outlined in the IUCLID chapter 7.1. toxicokinetics, thionyl dichloride undergoes immediate disintegration upon contact with water, as cleavage products sulfur dioxide and hydrogen cloride are formed. Rapid, spontaneous, violent and exothermic hydrolysis in water is described in different reviews on physico-chemical properties and in toxicological evaluations.

Ullmann’s Encyclopedia of Industrial Chemistry, 2012 (Ref), indicates: “Thionyl chloride is hydrolyzed rapidly and completely by water in an exothermic reaction (∆H = -136 kJ/mol) with excess water. SOCl2 reacts vigorously and completely [with water] with formation of HCl and SO2. It fumes in moist air due to HCl formation”.

ACGIH (2010) evaluated the toxicity of thionyl dichloride and defined a TLV “There are limited toxicological data available for thionylcloride; however, its vapors have long been recognized as highly irritating to skin, eyes, and mucous membranes due to the formation of sulfur dioxide and chloride in reaction with water. Thus, the TLV is derived from the TLVs of those irritant gases. “

Thionyl dichloride is also evaluated by the EU and labeled according to DSD and GHS with R35 and Skin. Corr. 1A, respectively (ESIS). In a Classification and Labelling Justification prepared by Austria the physic-chemical properties are described as follows: “violent decomposition in water to hydrochloric, sulfurous, and sulfuric acid (1 ppm produces a total irritant gas concentration of 3 ppm); when exposed to moist air it produces fumes,…” (C&L 1997).

In a recent experimental study the kinetics of the hydrolysis of thionyl dichloride in the gas phase was investigated by Johnson et al, 2003. The atmospheric fate of SOCl2 has been investigated in a sealed mixing chamber by simulating the effects of varied temperature and humidity. It was determined that humidity plays an important role, as water reacts rapidly with the parent compound, forming HCl(g) and SO2(g) in a nearly stoichiometric ratio of 2:1. The rate constant for hydrolysis at 297 K was determined to be kh = (6.3+3.5) x E10-21 cm³/molecules, resulting in a tropospheric lifetime due to hydrolysis on the order of only a few minutes for this volatile inorganic species. Derived from the decay constants, half-lives for thionyl dichloride of1.4 minutes (74% relative humidity) to 5.9 minutes (28% relative humidity) are calculated at 20°C.

Based on the available information on the physicochemical properties of thionyl dichloride it is considered appropriate by the registrant to follow other thionyl dichloride evaluations and to conclude that due to spontaneous and exothermic hydrolysis thionly dichloride undergoes immediate disintegration. The data of the hydrolysis products, HCl and SO2, should be considered as appropriate and sufficient to characterize the toxicity of thionyl dichloride for endpoints where no data on the instable parent compound are available.

Subsequent to a draft decision on a compliance check of the dossier by ECHA submitted to the registrant on 11 June 2013 the registrant decided to initiate a guideline hydrolysis study in order to confirm rapid and quantitative hydrolysis of thionyl dichloride in a guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH”.

The test was performed according to the OECD Guidelines for Testing of Chemicals, Section 1 – Physical-Chemical Properties, OECD TG 111 (2004). As the hydrolysis was known to occur rapidly, hydrolysis behavior of the test item in aqueous solutions was investigated in a Tier 1 test at room temperature instead of 50 °C, at pH 4, pH 7 and pH 9. The hydrolysis behavior was monitored by ion chromatography analysis with conductivity detection. Chloride, Sulfite and Sulfate as the only by Ion Chromatography hydrolysis detectable products were identified by comparison with the retention time of the calibration substances. The concentrations of the formed Chloride in the hydrolysis test solutions were determined by external calibration method and correspond to the theoretical values assuming a complete degradation of the test item (recovery 99.1 to 102.4 %). Sulfite and Sulfate were quantified accordingly. Recoveries were in the range of 80 to 95 %. Losses of Sulfur might be explained by the evaporation of gaseous Sulfur Dioxide. For further details on this study see study endpoint summary in IUCLID chapter 5.1.2.: hydrolysis.

Due to the observed immediately and complete degradation (100 %) of the test item between sample preparation time and injection time by ion chromatography, the half-life time at 23 °C (room temperature) was calculated to by < 2 minutes at all pH (4, 7 and 9).

Overall, based on available reviews and handbooks, an experimental hydrolysis study in the gas phase and a recent guideline hydrolysis study according to OECD TG 111 “Hydrolysis as a Function of pH” it can be concluded that thionyl dichloride undergoes violent decomposition in aqueous milieu and decomposes quantitatively to HCl (CAS n° 7647-01-0) and SO2 (CAS n° 7446-09-5) with half-lives between 1.4 minutes and 5.9 minutes in the gas phase and < 2 minutes in water. SOCl2 is classified as R14 (Reacts violently with water).

Since SOCl2 reacts vigorously and completely with water within minutes with formation of HCl and SO2 these hydrolysis products are considered relevant for the potential toxicity of thionyl dichloride.

Local effects: Thionyl dichloride and both hydrolysis products are considered to be corrosive; thionyl dichloride is labeled with R35 (causes severe burns).

Potential systemic effects: Based on a weight of evidence taking into account thionyl dichloride hydrolysis data 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.

The following data are available for the hydrolysis products:

HCl:

For repeated dose toxicity, 13 inhalation and 7 oral dose studies have been reported in the OECD SIDS assessment published in 2002. The following conclusion was drawn in the SIAR summary conclusion:

“For repeated dose toxicity, local irritation effects were observed in the groups of 10 ppm and above in a 90-day inhalation study in compliance with FDA-GLP. The NOAEL for systemic toxicity has been determined to be 20 ppm for rats and mice.

…

For carcinogenicity, no pre-neoplastic or neoplastic nasal lesions were observed in a 128-week inhalation study with SD male rats at 10 ppm hydrogen chloride gas. No evidence of treatment related carcinogenicity was observed either in other animal studies performed by inhalation, oral or dermal administration. In humans, no association between hydrogen chloride exposure and tumor incidence was observed.

…

Because protons and chloride ions are normal constituents in the body fluid of animal species, low concentrations of hydrogen chloride gas/mist or solution do not seem to cause adverse effects to animals.”

All available data on HCl were evaluated in comprehensive evaluations by the German “Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area” the expert concluded: “Hydrogen chloride at the pH value of biological systems dissociates completely into protons and chloride ions. Provided the MAK value is observed, the amount of chloride ions taken up from 30 mg (assuming 10 m3 respiratory volume, 100 % retention) is equivalent to 1/200 of the daily intake of chloride ions from 6 g (Jungermann and Möhler 1984). In analogy to the estimation for formic acid (MAK value 5 ml/m3) it can be concluded that 2 ml hydrogen chlroide/m3 does not lead to a marked change of the blood pH.” (MAK 2004).

SO2:

All available data on SO2 were evaluated in comprehensive evaluations by the German “Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area” (Schwefeldioxid [MAK Value Documentation in German language, 1974, 1981, 1998, 2000, 2013]).

Sulfur dioxide is readily soluble in water and is converted on the moist mucosa to sulfurous acid (H2SO3). In a further oxidation step sulfurous acid is metabolized to sulfuric acid. Excess sulfate is excreted via urine. According to the German “Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area” (1998) theoretical calculations on the sulfate concentrations demonstrate that no toxicologically relevant increase in the sulfate concentration in the humans can be assumed inhaling SO2 in the occupational setting and, consequently, a developmental or reproductive effect is not anticipated. In their calculation the panel considered quantitative conversion of sulfur dioxyde to sulfate. Exposure level was calculated based on air concentrations of 1.3 mg/m3 over an entire 8 hours shift (=10 m3 air), a volume of distribution of 4.5 l and no increase in urinary sulfate excretion was also considered as worst case assumptions. Based on these assumptions the sulfate concentration in the blood might increase by approx. 3 mg/l. Based on the normal sulfate concentration in blood (8.4 – 19.5 mg/l) and a daily excretion rate of ca. 750 mg sulfate/l urine the authors conclude that no significant increase in sulfate is assumed in humans. These calculations were confirmed by experimental studies in mice and rabbits where no reproductive toxicity was observed even at doses where slight maternal toxicity was observed. There are also well conducted and reported human epidemiologic studies available that do not indicate any systemic effect (e.g. MAK 1998, Peacock and Spence 1967). Overall, the only toxicologically relevant effect reported is local irritation, due to the corrosive properties of SO2. The available data are also recently evaluated by a nominated expert group and an official German occupational exposure limit value (published in the TRGS 900) of 2.5 mg/m3 was defined in 2011 based on the comprehensive data in animals and humans ( Federal Institute for Occupational Safety and Health (BauA), TRGS900 2011, http://www.baua.de/de/Themen-von-A-Z/Gefahrstoffe/TRGS/Arbeitsplatzgrenzwerte.html).

In a reliable subacute exposure of rats (4 weeks, 2 hours/day, 5 days/week) to 5 ppm (= 13.3 mg/m³) sulfur dioxide by nose-only exposure was without any effect on body or lung weights, histopathology of lung and nose tissue (examination by light microscopy), or particle clearance (Wolff et al 1989). Since the derived DNEL for thionyl dichloride will be 1 mg/m3, far below 13. mg/m3, the data on SO2 support the risk assessment on thionyl dichloride.

Overall, thionyl dichloride and both hydrolysis products are considered to be corrosive; thionyl dichloride is labeled with R35 (causes severe burns). Potential systemic effects are not seen in studies with HCl and SO2. In the aqueous milieu of mammalian bodies the sulfur dioxide will form an equilibrium with the sulfite ion, which is further oxidized to sulfate by sulfite oxidase, which is abundantly available in mitochondria of liver, kidney and heart of eukaryotes. Endogenously occurring inorganic sulfate plays important roles in physiology, a sufficient supply with sulfate is even required for normal fetal development, excess sulfate will be excreted. Hydrogen chloride will dissociate in an aqueous milieu, as well, the resulting chloride ion also plays an important role in physiology, is abundantly available in the body anyway, and has not to be regarded as toxicologically relevant. As the mammalian physiology is maintained at well buffered conditions, no pH-related effects due to the formation of hydronium ions have to be expected, either. In conclusion, the systemic toxicity of both coumpounds is low at human relevant exposure.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: nose

Repeated dose toxicity: dermal - systemic effects (target organ) other: skin

Justification for classification or non-classification

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. No repeated dose toxicityx studies are available for SOCl2. However for the hydrolysis products of SOCl2 (HCl and SO2), repeated dose studies are available. For repeated dose toxicity, local irritation effects were observed (nose, lung). The systemic toxicity of both coumpounds is low.

Hydrogen chloride will rapidly dissociate and its effects are thought to be a result of pH change (local deposition of H+) rather than effects of hydrogen chloride/hydrochloric acid. Chloride is a normal constituent of the blood and the excess is expected to be excreted into the urine.

SO2 is readily soluble in water and is converted on the moist mucosa to sulfurous acid (H2SO3). In a further oxidation step sulfurous acid is metabolized to sulfuric acid. Excess sulfate is excreted via urine.

Chloride and the conversion products of SO2 are normal body constituents. The data for repeated dose toxicity of HCl and SO2 are sufficient for the assessment of the toxicity (repeated dose) of SOCl2.

The data are conclusive and no classification for repeated dose toxicity is warrented.