Sodium chloroacetate:USES；TOXICITY DATA

Sodium chloroacetate is a white to off-white crystalline powder with  pungent smell,the melting Point is: 170 °C (338 °F). Decomposes slowly at 150 °C  by localized heating.Sodium chloroacetate is stable at normal temperatures and  pressures. Incompatible with oxidizing agents, reducing  agents.

USES

Sodium chloroacetate is used as a contact herbicide and a  component in other herbicides, an intermediate in the  production of carboxymethyl-cellulose, and other synthetic  organic chemicals.(2,3)

ANIMAL TOXICITY DATA  

Acute Toxicity  

1. Lethality Data  Species Route LD50 mg/kg Rat Oral 76-580(2,3,9) Rat Dermal >2000 mg/kg(2,3) Mouse Oral 165-339(2,3,9) Golden Hamster Oral 245(2,3) Guinea Pig Oral 80-115(2,3,9) Rabbit Oral 156(2,3,9) In one study systemic effects to Sprague-Dawley rats (M/F,  numbers per group not indicated) given single doses of sodium  chloroacetate at 94, 282, or 470 mg/kg bw demonstrated  increased sodium concentration in urine, increased potassium  concentration in plasma, and reduced glutathione level in the  liver at the highest dose; 2/3 of males died within 24 hours of  treatment in the middle and high dose groups. 

2. Eye Irritation  A 25% aqueous solution of sodium chloroacetate was mildly  irritating to eyes in rabbits. (2) 

3. Skin Absorption  Sodium chloroacetate has not been shown to be absorbed in  toxicologically significant quantities through the skin.(2,3,10) 

4. Skin Irritation Sodium chloroacetate was shown to be a non- to moderate skin  irritant but not corrosive to the skin. (3,4,15)

5. Skin Sensitization  Not indicated to be a sensitizer. (2,3) 6. Acute Inhalation Toxicity  No cases of “acute intoxication from MCA (sodium salt)” have been located in the literature. (10)

Subchronic Toxicity  

Sprague-Dawley rats were given repeated oral doses (by  gavage) for 90 days at 0, 15, 30, 60, or 120 mg/kg/day (10  animals/dose). In the highest dose group, 80 % of males and  30% of females died. In both sexes of the 60 mg/kg/day group  there were significant increases in liver and kidney weights. In  all dose groups there were changes to hematological parameters,  and numerous clinical chemistry parameters (increases in urea  nitrogen, creatinine, calcium and phosphate, increases in ALT  and AST in serum). In males of the 60 mg/kg/day dose group  there was a significant increase in chronic nephropathy and  spleen pigmentation as well as a dose-dependent increase in  vacuolated hepatocytes. The LOAEL is concluded to be 15  mg/kg/day.(2,3,11) 

Chronic Toxicity/Carcinogenicity  

There was no evidence of carcinogenic activity in F344N rats or  B6C3F mice at 15 or 30 mg/kg, or 50 or 100 mg/kg respectively  in an NTP study using the parent compound monochloroacetic  acid (MCA (CAS 79-11-8). Neither structurally similar MCA  or sodium chloroacetate are considered likely potential human  carcinogens. (10,12,13) 

Reproductive/Developmental Toxicity  

Rats (strain not indicated) were dosed by gavage with 17-140  mg/kg bw (0, 17, 35, 70, or 140 mg/kg sodium chloroacetate)  on gestation days 6-15. The maternal NOEL was 17 mg/kg/day  and the maternal NOAEL was 70 mg/kg/day (mean adjusted  percentage bodyweight gain). Cardiovascular malformations,  and other soft tissue malformations were seen at the high-dose  group with no effects seen at other dose levels. (2) 

Genotoxicity/Mutagenicity  

Ames (TA 1535, 1537, 1538, 98, 100) bacterial test: was  negative (+/- S9); HPRT/V79 CHL test was negative (+/-S9);  Mice (Swiss strain) micronucleus test was negative.(2,5,10,14)

Metabolism/Pharmacokinetics  

After absorption, monochloroacetic acid (parent compound  CAS 79-11-8) is converted to thiodiacetic acid and glycolic acid  and is accumulated in the liver and kidneys of rats.(10,15) Metabolism of sodium monochloroacetate is expected to have a  similar pharmacokinetic profile.

HUMAN USE AND EXPERIENCE  

There are a number of case studies of the parent compound,  monochloroacetic acid (MCA), involving corrosion of skin and  eyes and fatalities related to skin absorption of toxicologically  significant amounts of MCA and a health-based target  concentration of 0.1 mg/L was calculated for MCA in drinking  water(10) although Health Canada and Environment Canada have  categorized MCA as not entering the environment at levels that  may be hazardous to human health. (16) There are, however, no  similar data or epidemiological reports for sodium  chloroacetate.(2–4)

REFERENCES

 (1) International Programme on Chemical Safety (IPCS). ICSC  1449 - Sodium Chloroacetate  http://www.inchem.org/documents/icsc/icsc/eics1449.htm  (accessed Jan 20, 2016).

(2) OECD. OCED SIDS Program: Sodium Chloroacetate;  Organization for Economic Cooperation and Development  (OECD), UNEP Publications. Available at:  http://www.inchem.org/documents/sids/sids/3926623.pdf, 1994. 

(3) IUCLID. Sodium Chloroacetate; 1995. 

(4) Franklin Research Center. Monohaloacetic Acids. Contract  No. 210-79-0091; Franklin Research Center: Silver Spring, MD,  1980.

 (5) German Chemical Society. Monochloracetic Acid CAS-No.  79-11-8, Sodium Monochloroacetate CAS-No. 3926-62-3. BUA  Report 127; GDch-Advisory Committee on Existing Chemicals  of Environmental Relevance: Germany, 1993. 

(6) CHEMINFO. Sodium chloroacetate  http://ccinfoweb2.ccohs.ca/cheminfo/records/5049E.html  (accessed Jan 20, 2016). 

(7) Regulatory Affairs Government of Canada; Transport  Canada; Transport Dangerous Goods. Guide 151  http://wwwapps.tc.gc.ca/saf-sec-sur/3/erg  gmu/erg/guidepage.aspx/guide151/id1817/mnid1973 (accessed  Jan 20, 2016). 

(8) U.S. Department of Transportation. 49 CFR 172.101 - Purpose and use of hazardous materials table.  https://www.law.cornell.edu/cfr/text/49/172.101 (accessed Jan  20, 2016).

 (9) RTECS. RTECS Number AG1400000- Acetic acid, chloro- , sodium salt  http://ccinfoweb2.ccohs.ca/rtecs/records/AG1400000.html  (accessed Jan 20, 2016). 

(10) Health Canada Government of Canada. Guidelines for  Canadian Drinking Water Quality http://www.hc-sc.gc.ca/ewhsemt/pubs/water-eau/sum_guide-res_recom/index-eng.php  (accessed Jan 20, 2016). 

(11) Daniel, F. B.; Robinson, M.; Stober, J. A.; Page, N. P.;  Olson, G. R. Ninety-Day Toxicity Study of Sodium  Monochloracetate in Sprague-Dawley Rats. Toxicology 1991,  67, 171–185.

 (12) ECHA. Registration Dossier- Sodium Chloroacetate;  European Chemical Agency (ECHA). Available at:  http://echa.europa.eu/registration-dossier/-/registereddossier/14347, 2015.

 (13) National Toxicology Program. Chemical Properties of  CAS Registry Number: 79-11-8  http://tools.niehs.nih.gov/cebs3/ntpviews/index.cfm?action=test article.properties&cas_number=79-11-8 (accessed Jan 20,  2016). 

(14) Federal Institute for Consumer Health Protection and  Veterinary Medicine. ZEBET Registry of Cytotoxicity Data;  German Centre for the Documentation and Validation of  Alternative Methods., 2005; pp. 101–112. 

(15) Dartsch, P. C.; Wolburg, H.; Makdessi, S. A.; Schiek, D.;  Sweidan, H.; Kimmel, R.; Schmahl, F. W. Sodium  Monochloroacetate Causes Cytotoxic Effects, an Increased  Lactate and Pyruvate Level and Induces Ultra Structural and  Cytoskeletal Alterations in Cultured Kidney and Liver  Epithelial Cells. Hum. Exp. Toxicol. 2000, 19, 138–148. 

(16) Environment Canada Government of Canada. Substances  on the DSL http://www.ec.gc.ca/lcpecepa/eng/subs_list/DSL/DSLsearch.cfm (accessed Jan 20,  2016).

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