Dichloroacetic acid

Endpoint summary

Description of key information

Various acute oral toxicity studies with dichloroacetic acid  were available in rats and mice, with LD50 values ranging between 2820 and 5520 mg/kg bw; therefore the substance does not have to be classified for acute oral toxicity. Acute inhalation toxicity testing was waived based on a very low vapor pressure. Finally acute dermal toxicity  was tested in rabbits, resulting in LD50 of 0.51 mL/kg bw, corresponding with 797 mg/kg bw. Classification for acute dermal toxicity is therefore warranted.

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:

key study

Study period:

1941

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Fasting period before study: None of our earlier papers have pointed out that, except in rare cases, all single oral doses are given in this laboratory to animals which have not been fasted overnight. In the few instances where we have made comparisons, the LD50 determined on fasted rats is lower than that on animals not fasted by only some 20 or 30%, a difference on the borderline of statistical significance and not great enough to influence evaluation of practical hazards.

Route of administration:

oral: unspecified

Control animals:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

2 820 mg/kg bw

Conclusions:

The oral LD50 in rats was 2820 mg /kg bw.

Executive summary:

The oral LD50 in rats was 2820 mg /kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 820 mg/kg bw

Quality of whole database:

Reliable; the key study was based on the lowest LD50 value of dichloroacetic acid in a range of 2820 to 5520 mg/kg in rats and mice.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1941

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable publication which meets basic scientific principles.

Principles of method if other than guideline:

no data

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Sex:

not specified

Dose descriptor:

LD50

Effect level:

0.51 mL/kg bw

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Dermal LD50 of dichloroacetic acid in rabbits was 0.51 mL/kg bw.

Executive summary:

Dermal LD50 of dichloroacetic acid in rabbits was 0.51 mL/kg bw. Taking into account a density of 1.563 g/cm3 (mL), corresponding LD50 is 0.797 g/kg bw or 797 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

797 mg/kg bw

Quality of whole database:

Reliable, acceptable publication.

Additional information

The lowest oral LD50 in rats for dichloroacetic acid was 2820 mg /kg bw (Smyth et al., 1951), therefore this study was considered as key study. Although the information on the study was limited, information from supporting studies confirmed that the value was reliable and most conservative. Supportive information was provided by following studies:

- in rats the oral LD50 was 4480 mg/kg bw; in mice the oral LD50 was 5520 mg/kg bw (Woodard et al., 1941).

- in mice the oral LD50 values ranged from 3997 to 4280 mg/kg bw (Young et al., 1982).

Further, following study was disregarded as it was conducted with monochloric acetic acid in non-standard species:

- in male guinea-pigs, the oral LD50 was 0.0798 g/kg bw; in rabbits the oral LD50 was not calculated (Woodard et al., 1941).

Acute inhalation toxicity testing was waived as dichloroacetic acid has a very low vapor pressure of 0.19mbar (19 Pa) at 20°C and is not expected to volatize from drinking water or contaminated environmental media to any appreciable extent. Therefore, inhalation exposure from volatized DCA is negligible. According to Annex VIII of the EC Regulation n° 1907/2006 inhalation testing can be waived. There was an acute inhalation study available, however it was disregarded as it was only preparative and it lasted 8h to derive saturation.

The dermal LD50 of dichloroacetic acid in rabbits was 0.51 mL/kg bw (Smyth et al., 1951). Taking into account a density of 1.563 g/cm3 (mL), the corresponding LD50 is 0.797 g/kg bw or 797 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

Key study

Justification for selection of acute toxicity – dermal endpoint

Key study

Justification for classification or non-classification

Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC) and CLP regulation (EC No. 1272/2008 of 16 December 2008), dichloroacetic acid does not have to be classified and has no obligatory labelling requirement for acute oral toxicity.

For acute dermal toxicity, the test substance is classified with the symbol 'Xn' and risk phrase R21 'HARMFUL IN CONTACT WITH SKIN' according the EU labelling regulations Commision directive 93/21/EEC. According to CLP regulation (No. 1272/2008 of 16 December 2008), Category 3 classification is proposed for acute dermal toxicity with signal word 'DANGER' and hazard statement H311: 'TOXIC IN CONTACT WITH SKIN'.