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Administrative data

Description of key information

According to the CLP Regulation EC 1272/2008 Annex VI the substance is classified as Harmful, Xn R22 for acute oral toxicity or Acute Toxicity 4 (H302). A number of literature studies are reported from publicly available sources which support this classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Data from Literature without sufficient experimental details.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
No guideline or method is referenced.
GLP compliance:
not specified
Test type:
other: Acute method but no additional data presented
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
No additional data presented
Route of administration:
other: No data presented
Vehicle:
not specified
Details on oral exposure:
No additional data presented
Doses:
No additional data presented
No. of animals per sex per dose:
No additional data presented
Control animals:
not specified
Details on study design:
No additional data presented
Statistics:
No additional data presented
Preliminary study:
No information on any preliminary study reported
Sex:
male
Dose descriptor:
LD50
Effect level:
800 mg/kg bw
Remarks on result:
other: Rat
Sex:
male
Dose descriptor:
LD50
Effect level:
400 mg/kg bw
Remarks on result:
other: This test was conducted on mice
Mortality:
No additional data presented
Clinical signs:
other: No additional data presented
Gross pathology:
No additional data presented
Other findings:
No additional data presented

None

Interpretation of results:
other: harmful
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 for 2-chloropropionic acid in male rats is reported as 800 mg/kg. In mice the LD50 is reported as 400 mg/kg/bw. This would result in a harmful classification under the EU system with the risk phrase R22, Harmful if swallowed and Acute Toxicity Category 4 under CLP.
Executive summary:

The Toxnet website ( http://toxnet.nlm.nih.gov/ ) entry for 2 -chloropropionic acid contains a number of references to the American Conference of Governmental Industrial Hygienists(ACGIH). This is a professional association of industrial hygienists and practitioners of related professions.

With regard to acute toxicity, the LD50 in male rats is reported to be 800 mg/kg bw and in male mice is reported to be 400 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
400 mg/kg bw
Quality of whole database:
The data available is based in available literature sources and covers a wide range of values; the lowest value quoted has been taken as the ‘endpoint’ value. The data set is considered sufficient for the determination of classification.

Additional information

The substance is classified in Annex I to 67/548/EEC as Harmful (Xn), Harmful if swallowed (R22); Corrosive (C), R35 (Causes severe burns) and in Annex VI (Table 3.1) of CLP-Regulation (EC) No 1272/2008 as Acute Toxicity 4, (H302: Harmful if swallowed); Skin Corr. 1A (H314: Causes severe skin burns and eye damage).

Annex VII of Regulation (EC) No 1907/2006 in section 8.5 states the study/ies do(es) not generally need to be conducted if : - the substance is classified as corrosive to the skin. This is reiterated in section R.7.4.2 of the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.7a : Endpoint specific guidance.

Although this endpoint is not required for a substance classified as corrosive to skin, a number of acute oral toxicity studies are publicly available which are reported here.

Fourteen LD50 values are reported - these are summarised in the table below:-

LD50 

Substance 

IUCLID 5 Endpoint 

 Species

 1671 mg/kg  Sodium 2 -chloropropionate 001   Mouse
 800 mg/kg and 400 mg/kg 2 -Chloropropionic acid  002  Rat (800 mg/kg), Mouse (400 mg/kg)
 635 mg/kg  2 -Chloropropionic acid   003  Rat
 500 mg/kg  2 -Chloropropionic acid 003   Rat
800 mg/kg   2 -Chloropropionic acid  003   Rat
 890 mg/kg  Sodium 2 -chloropropionate  003   Rat
 2150 mg/kg  Sodium 2 -chloropropionate  003   Rat
   980 mg/kg  Sodium 2 -chloropropionate    004  Mouse
  1670 mg/kg  Sodium 2 -chloropropionate    004   Mouse
 400 mg/kg  Other test substance  004   Mouse
 980 mg/kg  2-Chloropropionic acid  004   Mouse
 500 mg/kg  2 -Chloropropionic acid  005  Rat
 535 mg/kg and 800 mg/kg  2 -Chloropropionic acid  006  Not specified

The IUCLID 4 dataset for 2-chloropropionic acid contains ten reported LD50 values. In four cases these relate to the sodium salt of 2-chloropropionic acid. GLP is quoted as "yes" in only one case. In the remainder of cases GLP is either "no" (three cases) or no information available. In all but one case the LD50 values reported are between 400 and 1670 mg/kg bw which would result in a harmful classification with the R22 risk phrase, Harmful if swallowed and under CLP [Regulation (EC) No 1272/2008 this

would result in an Acute Toxicity Category 4. One value is reported as 2150 mg/kg bw which would render the substace non classified for acute toxicity effects. However, this value is reported to be on the sodium salt. The substance is classified in Annex I of Directive 67/548/EEC as Harmful, Xn, with Risk Phrases R22 (Harmful if swallowed) and Acute Toxicity Category 4 under CLP with the Hazard Statement H302 (Harmful if swallowed).

One publication ( Journal of Pharmacology and Experimental Therapeutics, 1982, 222 (2), 501-508 - Comparison of the Metabolic and Toxic Effects of 2-Chloropropionate and Dichloroacetate) reports the LD50 (in mice) to be 15.4 mmol/kg bw (equivalent to 1671 mg/kg bw).

Given the endpoint values reported it is concluded that the LD50 for 2 -chloropropionic acid lies in the range 400 - 2000 mg/kg.

Justification for classification or non-classification

The substance is currently classified in Annex I of Directive 67/548/EEC as :-

Harmful, Xn       R22,       Harmful if swallowed

and in Annex VI (Table 3.1) of CLP-Regulation (EC) No 1272/2008 as :-

Acute Toxicity Category 4, with Hazard Statement H302 (Harmful if swallowed)

From the available data only one value is reported which is outside the range 200 -2000 mg/kg. Therefore, it is concluded that the classification of the substance for acute oral toxicity is :-

Harmful, Xn       R22, Harmful if swallowed.

Acute Toxicity Category 4 with Hazard Statement, H302 (Harmful if swallowed).