Reaction mass of chlorodifluoroacetic acid and trifluoroacetic acid

Endpoint summary

Description of key information

- The reaction mass of CDFA/TFA is considered fatal by the oral route based on the available data on chlorodifluoroacetic acid.
- The reaction mass of CDFA/TFA being highly corrosive no studies on acute dermal and inhalation toxicity were performed and no classification is required.

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:

supporting study

Study period:

from 03 jan 1990 to 23 aug 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, OECD 401 compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo (69592 L'Arbresle, France)
- Age at study initiation: 5 to 7 weeks old
- Weight at study initiation: 127 to 173 g
- Housing: 5 par sex and per group, in polycarbonte cages, type MI (365x225x180 mm)
- Diet (e.g. ad libitum): ad libitum, rat-mice pellets (U.A.R, formule A.04 - U.A.R Villemoison, 91360 Epinay/Orge, France)
- Water (e.g. ad libitum): softened and filtered water (0.6µm), ad libitum
- Acclimation period: 10 days before

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: not indicated

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 0.066 mL/kg

Doses:

0, 26, 56, 75 and 101 mg/kg

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: the day before treatment, just before administration, Day 8 and Day 15, or just after death.
Clinical signs and mortality: 1/4 hour, 1 hour, 2 hours and 4 hours after gavage, then daily up to day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Clinical signs: breathing, piloerection, central nervous system, tremor, salivation . . .

In a preliminary test, the product was tested at the following doses: 62.7, 125.5, 250.9 and 500.3 mg/kg. There was 100% of mortality at 125.5, 250.9 and 500.3 mg/kg and 75% at 62.7 mg/kg.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 26 - < 56.6 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Lethality was caused by local corrosive effects.

Mortality:

10% at 26 mg/kg, 80% at 56.6 mg/kg, 90% at 75 mg/kg and 100% at 101 mg/kg.

Clinical signs:

other: At 26 mg/kg: no clinical signs observed. At 56.6 mg/kg: roaring breathing, piloerection, ataxia. Nomore clinical signs after 7 or 8 days in the survivals. there 3/5 deaths in males and 5/5 deaths in females. At 75 mg/kg: ataxia in all animals, with roarin

Gross pathology:

Oesophagus perforation, stomach ulcer (at the highest dose), congestive areas in lungs.

Interpretation of results:

Toxicity Category II

Conclusions:

Chlorodifluoroacetic acid is fatal if swallowed according to CLP 1272/2008.

Executive summary:

In a GLP study, Chlorodifluoroacetic acid was tested to evaluate the acute toxicity following a single oral adminitration at doses from 0, 26, 56.6, 75 and 101 mg/kg bw undiluted.

There were 0, 10 80, 90 and 100% of mortality respectivley so the LD50 by oral route is between 26 and 56.1 mg/kg bw.

Macroscopic examination observation showed that mortality is related to strong corrosivity of CDFA and thus to local effects instead of actual systemic effects.

In these conditions, Chlorodifluoroacetic acid is considered fatal by ingestion according to CLP 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

26 mg/kg bw

Quality of whole database:

Key study rated Klimisch 1.

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:

supporting study

Study period:

from 14 dec 1989 to 18 apr 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, OECD 402 compliant

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo (69592 L'Arbresle, France)
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 200 to 242 g
- Housing: individual in polycarbonte cages, typeFI (305x180x184 mm)
- Diet (e.g. ad libitum): ad libitum, rat-mice pellets (U.A.R, formule A.04 - U.A.R Villemoison, 91360 Epinay/Orge, France)
- Water (e.g. ad libitum): softened and filtered water (0.6µm), ad libitum
- Acclimation period: 6 days before

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 10 minimum
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: from 02 jan 1990 to 09 jan 1990

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back or flanks
- % coverage: 10%
- Type of wrap if used: semiocclusive gauze dressing under an elastic bandage (Creplux / Moliner)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
1.31 ml/mg

Duration of exposure:

24 hours

Doses:

2004 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1/4 hour after application, then 1, 2 and 4 hours and daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, necropsy

Sex:

male/female

Dose descriptor:

LD50

Based on:

test mat.

Remarks on result:

other: No LD 50 could be determined because product is corrosive

Mortality:

Animals were sacrified on day 2, for human reason because Chlorodifluoroacetic acid was corrosive.

Clinical signs:

other: None

Other findings:

Total necrosis of tissues including skin and muscles.

Interpretation of results:

other: LD50 not determined becaude of corrosivity

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The LD50 of Chlorodifluoroacetic acid could not be determined because of its corrosivity.

Executive summary:

In a GLP study, Chlorodifluoroacetic acid was tested to evaluate the acute toxicity following a single cutaneous adminitration at doses 0 and 2004 mg/kg bw undiluted.

Total necrosis of tissues including skin and muscles was observed at the treatment site.

In these conditions, the LD50 of Chlorodifluoroacetic acid could not be determined because of its corrosivity.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

It is the only available study selected as key study.

Additional information

Acute oral toxicity:

No data is available on the reaction mass of chlorodifluoroacetic acid and trifluoroacetic acid as a waiving of this study was done based on the substance corrosivity.

Data are available only on chlorodifluoroacetic acid and the LD50 was between 26 to 56.6 mg/kg (OECD 401). Necropsy showed that the toxic effects are related to the corrosivity of CDFA and thus are actually local effects rather than systemic effects.

However, in a worst case approach, and because the reaction mass CDFA/TFA is mainly composed of CDFA, the result on the CDFA was retained, and the reaction mass is considered as fatal by ingestion, according to the CLP 1272/2008 and toxic by ingestion according to the 67/548/EC directive.

 

Acute inhalation toxicity:

No data are available on the reaction mass of chlorodifluoroacetic acid and trifluoroacetic acid as a waiving of this study was done based on the substance corrosivity.

The only available study is trifluoroacetic acid alone which is at percentage inferior to 15% in the reaction mass of CDFA/TFA and cannot be used for the reaction mass classification. This study evidenced a NOAEC of 300 mg/m3 for irritation of the upper respiratory tract and no LC 50 was determined.

Based on these results no classification for acute inhalation toxicity is required.

 

Acute dermal toxicity:

No data are available on the reaction mass of chlorodifluoroacetic acid and trifluoroacetic acid as a waiving of this study was done based on the substance corrosivity.

An experimental study was available on chlorodifluoroacetic acid, but no LD50 was determined due to high corrosivity of the substance.

Based on these results, no LD50 for the reaction mass was determined and no classification for acute dermal toxicity is required. 

Justification for classification or non-classification

Based on available results on each component of the reaction mass, the classification of the reaction mass is Fatal by ingestion (Acute oral toxicity category 2 H300) according to the CLP 1272/2000 criteria.