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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Report date: 9 April 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test item is not indicated.
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Report date: 9 April 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Purity of the test material is not indicated and the study was performed under occlusive conditions.
Reason / purpose:
reference to same study
Related information:
Composition 1
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive conditions.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO breeding center
- Females nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: 165 - 172 g
- Fasting period before study: yes, during 17 - 20h
- Housing: Cage of dimensions 37.5 x 23.5 x 16 cm (by 2 or 5) with litter of sterilized and dusted sawdust
- Diet: ad libitum, IFFARAT food
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): 8 per hour
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: bandage consisting of a sheet of aluminum foil and strip of adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.23 mL/kg
- Concentration (if solution): prodcut as is
- Constant volume used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
10 (5 males and 5 females)
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (mortality and behaviour) and weighing: Clinical observations were performed on all animals at 1, 2, and 6 hours after dosing and on Days 1, 2, 4, 7 and 14. The body weight was recorded on Days 0, 1, 2, .4, 7 and 14.
- Necropsy of survivors performed: no
Statistics:
Yes, Probit method, Litchfield and Wilcoxon method and Arcsinus method
Preliminary study:
2 groups of 4 animals (2 males and 2 females) received by dermal route the test material at these doses: 1000 and 2000 mg/kg (volume: 0.62 and 1.23 mL/kg, respectively). The test material was applied as such.
The animals were observed and the mortality was recorded after the treatment and during the 14 days after the treatment.
At 1000 and 2000 mg/kg, there was no mortality.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred at the dose level of 2000 mg/kg.
Clinical signs:
There was no clinical sign.
Body weight:
The body weight gain was not affected by the treatment except for the males on Days 7 and 14 (statistical significant decrease).
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities except cutaneous reactions (see below).
Other findings:
Local tolerance:
Day 1: Increase of dermal thickness on application site.
Day 4: Skin lesions on the back of animals.
Day 7: purulent lesions.
Day 14: persistence of skin lesions.

Table 1: Mortality

Administration

Animals

Cumulated mortality

Dose

mg/kg

Volume

mL/kg

Concentration

%

Weight

g

Number

1 hour

2 hours

6 hours

1 day

2 days

4 days

7 days

14

days

%

Control

-

-

M 168

5

0

0

0

0

0

0

0

0

0

F 165

5

0

0

0

0

0

0

0

0

2000

1.23

Product as such

M 172

5

0

0

0

0

0

0

0

0

0

F 171

5

0

0

0

0

0

0

0

0

 

Table 2: Body weight gain

Sex

Dose

mg/kg

 

Mean body weight (g)

 

Day 0

Day 1

Day 2

Day 4

Day 7

Day 14

Males

Control

n

m

s

5

168

5.15

5

153

7.92

5

165

4.27

5

180

5.45

5

210

4.76

5

264

6.60

2000

n

m

s

t

5

172

7.95

0.90

5

157

8.76

0.68

5

161

8.99

1.03

5

172

11.20

- 1.47

5

198

8.57

- 2.78*

5

238

11.48

- 4.45*

Females

Control

n

m

s

5

165

6.38

5

161

8.58

5

166

7.89

5

176

7.23

5

193

6.88

5

217

4.44

2000

n

m

s

t

5

171

7.40

1.37

5

162

7.40

0.20

5

161

6.80

- 1.11

5

171

10.90

- 0.72

5

190

12.84

- 0.58

5

213

9.52

- 0.85

n: number of survivors

m: mean

s: standard deviation

*: significant test t at the threshold of 95%

Interpretation of results:
other: Not classified
Conclusions:
In these test conditions, the acute dermal LD50 value of Trichloroacetyl chloride was found to be higher to 2000 mg/kg.
Executive summary:

The study was performed to assess the acute dermal toxicity of Trichloroacetyl chloride (TCAC) in the rat. The method followed was similar to OECD Guideline 402 and the study was not performed in accordance with GLP.

Ten animals (5 males and 5 females) were exposed to single dermal dose level of 2000 mg/kg. All animals were subjected to observations and determination of body weight. Macroscopic examination was performed after terminal sacrifice. No mortality occurred at the dose level of 2000 mg/kg and there was no clinical sign. Macroscopic examination of the main organs of the animals revealed no apparent abnormalities except cutaneous reactions (Day 7: purulent lesions - Day 14: persistence of skin lesions).

The acute dermal LD50 value of TCAC was higher to 2000 mg/kg.

In these test conditions, TCAC is not classified according to the UN GHS and CLP criteria.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:

Name of the test material in the report: Chlorure de trichloracetyle

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO breeding center
- Females nulliparous and non-pregnant: no data
- Age at study initiation: no data
- Weight at study initiation: 160 - 200 g
- Fasting period before study: yes, during 17 - 20h
- Housing: Cage of dimensions 37.5 x 23.5 x 16 cm (by 2 or 5) with litter of sterilized and dusted sawdust
- Diet: ad libitum, IFFARAT food
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): 8 per hour
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 10 - 18 mL/kg
- Justification for choice of vehicle: no data
- Lot/batch no.: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 18 mL/kg

DOSAGE PREPARATION: The test material is dissolved in the vehicle.

Doses:
1000, 1200, 1500, 1600 and 1800 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on all animals at 1, 2, and 6 hours after dosing and on Days 1, 2, 4, 7 and 14. The body weight was recorded on Days 0, 1, 2, .4, 7 and 14.
- Necropsy of survivors performed: no
Statistics:
Yes, Probit method, Litchfield and Wilcoxon method and Arcsinus method

Results and discussion

Preliminary study:
3 groups of 4 animals (2 males and 2 females) received by oral route the test material at these doses: 1000, 2500 and 5000 mg/kg after a fasting period of 18 hours.
The test material is dissolved in arachis oil at a concentration of 25%.
The animals was observed and the mortality was recorded after the treatment and during the 14 days after the treatment.
At 2500 and 5000 mg/kg, all animals died on Day 0. And at 1000 mg/kg, 1 animal died on Day 1.

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 643 mg/kg bw
Based on:
test mat.
95% CL:
> 1 552 - < 1 740
Mortality:
At 1000 and 1200 mg/kg, there was no mortality. 
At 1500 mg/kg, one female died and the autopsy revealed hemorrhagic lesions onto lungs and stomach.
At 1600 mg/kg, 4 females died between Day 1 and 2 and one male at Day 12. At the autopsy, animals presented hemorrhagic lesions onto lungs and stomach. For the male died at Day 12, the autopsy revealed  that the stomach was joint to the peritoneum, kidney were granular and  hemorrhagic aspect, thymic involution.
At 1800 mg/kg, 8 animals died. Autopsies revealed hemorrhagic stomach, lungs and thymus.
Clinical signs:
At 1000, 1200 mg/kg and 1500 mg/kg, 1 to 6 hours after treatment animals presented prostation, apathy, and had a reduce spontaneous activity. At  day 1, all the animals exposed at doses of 1000 and 12000 mg/kg presented no abnormalities, but apathy and prostation persisted until day 3 at dose of 1500 mk/kg. 
At 1600 mg/kg, surviving animals presented prostation, apathy, reduce spontaneous  activity, and piloerection until day 4. Prostation and apathy persisted for one male until day 12.
At 1800 mg/kg, surviving animals presented prostation, apathy, reduce spontaneous  activity, and piloerection until day 3.
Body weight:
Statistical significant decrease in body weight was observed at 1000, 1200 and 1500 mg/kg for males, and at doses of 1200 et 1500 mg/kg for females.

Any other information on results incl. tables

Table 1: Cumulated mortality

Administration

Animals

Cumulated mortality

Dose

mg/kg

Volume

mL/kg

Concentration

%

Weight

g

Number

1 hour

2 hours

6 hours

1 day

2 days

4 days

7 days

14 days

%

Control

18

Arachis oil

M 156

5

0

0

0

0

0

0

0

0

0

F 150

5

0

0

0

0

0

0

0

0

1000

10

10

M 155

5

0

0

0

0

0

0

0

0

0

F 155

5

0

0

0

0

0

0

0

0

1200

12

10

M 152

5

0

0

0

0

0

0

0

0

0

F 150

5

0

0

0

0

0

0

0

0

1500

15

10

M 156

5

0

0

0

0

0

0

0

0

10

F 151

5

0

0

0

0

0

0

0

0

1600

16

10

M 176

5

0

0

0

0

0

0

0

1

50

F 168

5

0

0

0

3

4

4

4

4

1800

18

10

M 155

5

0

0

0

2

3

4

4

4

80

F 148

5

0

0

0

3

4

4

4

4

LD50 according to:

-      Probit: 1643 mg/kg (1566 – 1723 mg/kg)

-      Litchfield & Wilcoxon: 1643 mg/kg (1552 – 1740 mg/kg)

-      Arcsinus: 1647 mg/kg (1577 – 1721 mg/kg)

Table 2: Body weight gain

a) Males

Sex

Dose

mg/kg

 

Mean body weight (g)

 

Day 0

Day 1

Day 2

Day 4

Day 7

Day 14

Males

Control

n

m

s

5

156

3.11

5

174

2.88

5

178

2.51

5

194

4.09

5

217

3.42

5

259

10.09

1000

n

m

s

t

5

155

5.94

- 0.40

5

150

7.06

- 6.81*

5

164

5.77

- 4.69*

5

179

8.47

- 3.71*

5

203

6.76

- 4.13*

5

258

13.39

- 0.21

1200

n

m

s

t

5

152

6.86

- 1.13

5

145

6.46

- 9.16*

5

153

7.69

- 6.85*

5

169

7.09

- 6.99*

5

191

6.80

- 7.57*

5

251

10.94

- 1.29

1500

n

m

s

t

5

156

2.86

0.21

5

149

4.60

- 10.04*

5

153

6.40

- 7.80*

5

171

3.96

- 9.04*

5

193

4.56

- 9.65*

5

255

17.21

- 0.79

1600

n

m

s

t

5

176

/

/

5

157

 

 

5

157

 

 

5

170

 

 

5

161

 

 

4

250

 

 

1800

n

m

s

t

5

155

/

/

3

139

 

 

2

137

 

 

1

163

 

 

1

184

 

 

1

250

 

 

b) Females

Sex

Dose

mg/kg

 

Mean body weight (g)

 

Day 0

Day 1

Day 2

Day 4

Day 7

Day 14

Females

Control

n

m

s

5

150

3.77

5

166

2.49

5

169

2.19

5

181

1.87

5

187

1.14

5

221

6.23

1000

n

m

s

t

5

155

4.72

1.63

5

155

5.22

- 5.49*

5

164

7.09

- 1.75

5

177

4.22

- 2.13

5

187

5.10

- 0.17

5

215

8.00

0.57

1200

n

m

s

t

5

150

6.50

0.00

5

137

3.63

- 14.72*

5

147

10.42

- 4.71*

5

164

6.40

- 5.70*

5

178

6.12

- 3.37*

5

205

6.11

- 1.79

1500

n

m

s

t

5

151

6.46

0.18

5

141

7.16

- 7.19*

4

149

17.39

- 2.71*

4

163

17.52

- 2.39*

4

181

15.46

- 0.98

4

212

21.28

- 1.52

1600

n

m

s

t

5

168

/

/

2

148

 

 

1

147

 

 

1

181

 

 

1

194

 

 

1

215

 

 

1800

n

m

s

t

5

148

/

/

2

137

 

 

1

153

 

 

1

168

 

 

1

185

 

 

1

212

 

 

n: number of survivors

m: mean

s: standard deviation

*: significant test t at the threshold of 95%

/: no information on this sigle in the report

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In these test conditions, the acute oral LD50 value of Trichloroacetyl chloride was 1643 mg/kg according to Probit method or Litchfield and Wilcoxon method.
Executive summary:

The study was performed to assess the acute oral toxicity of Trichloroacetyl chloride (TCAC) in the rat. The method followed was similar to the OECD Guideline 401 and the study was not performed in accordance with GLP.

TCAC was administered to five Sprague-Dawley rats of each sex. The animals were exposed to single oral dose levels of 1000, 1200, 1500, 1600 and 1800 mg/kg. All animals were subjected to observations and determination of body weight. Macroscopic examination was performed on the day of death. At 1800 mg/kg, 8 animals died. Autopsies revealed hemorrhagic stomach, lungs and thymus. At 1600 mg/kg, 4 females died between Day 1 and 2 and one male at Day 12. At the autopsy, animals presented hemorrhagic lesions onto lungs and stomach. For the male died at Day 12, the autopsy revealed that the stomach was joint to the peritoneum, kidney were granular and hemorrhagic aspect, thymic involution. At 1500 mg/kg, one female died and the autopsy revealed hemorrhagic lesions onto lungs and stomach. At 1000 and 1200 mg/kg, there is no mortality.

The acute oral LD50 value of TCAC was 1643 mg/kg according to Probit method or Litchfield and Wilcoxon method.

In these test conditions, TCAC is classified harmful if swallowed according to the UN GHS and CLP criteria.