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Description of key information

Oral (OECD 423), female rat: LD50 >300 and <2000 mg/kg bw

Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw

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:
12 Feb - 04 Mar 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Japanese test guidelines (2000)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10-11 weeks
- Weight at study initiation: 220-255 g
- Fasting period before study: food was withheld overnight (for a maximum of 20 h) prior to dosing until 3-4 h after administration of the test substance
- Housing: group housing of 3 animals per sex and cage in labelled Macrolon cages (type IV, height 18 cm) containing purified sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands)
- Diet: standard pelleted laboratory animal diet (Altromin VRF 1, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: From 2004-02-12 To 2004-03-04
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DOSE VOLUME APPLIED:
2000 mg/kg bw: 1.3 mL/kg bw
300 mg/kg bw: 0.19 mL/kg bw
dose volume calculated as dose level according to specific gravity

CLASS METHOD (if applicable)
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg bw. The absence or presence of mortality of aminals dosed at one step determined the next step, based on the procedure defined in the test guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
Doses:
2000 mg/kg bw
300 mg/kg bw
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on Day 1 (prior to the administration) and on Days 8 and 15. A careful clinical examination was made several times on the day of dosing. Thereafter, animals were observed for clinical signs once daily until the end of the 14-day observation period.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 experimental
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off according to OECD 423
Mortality:
Step 1 – 2000 mg/kg bw: 2/3 females died (both 4 h after tratment)
Step 2 – 300 mg/kg bw: 0/3 females died
Step 3 – 300 mg/kg bw: 0/3 females died
Clinical signs:
other: 2000 mg/kg bw: Lethargy, hunched posture, uncoordinated movements, slow breathing, shallow respiration, piloerection, hypothermia and/or ptosis (all females). The surviving animal had recovered from the symptoms on day 5. 300 mg/kg bw: Hunched posture on
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Table 1. Clinical signs and mortality

Step

Dose
[mg/kg bw]

Toxicological results*

1

2000

2/3/3

2

300

0/3/3

3

300

0/3/3

 * first number = number of dead animals

 second number = number of animals with clinical signs

 third number = number of animals used

         
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Acute Tox. 4., H302
DSD: Xn, R22
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
18 Feb - 03 Mar 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: JMAFF Japanese Test Guidelines (2000)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: males: 314-378 g, females: 233-256 g
- Fasting period before study: food was withheld overnight (for a maximum of 20 h) prior to dosing until 3-4 h after administration of the test substance
- Housing: individual housing in labelled Macrolon cages (type III, height 15 cm) containing purified sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren, The Netherlands)
- Diet: standard pelleted laboratory animal diet (Altromin VRF 1, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before start of treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 +/- 3.0
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: From 2004-02-12 To 2004-03-04
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm²
- % coverage: approx. 10%
- Type of wrap if used: The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with an aluminium foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing: the skin was cleaned of residual test substance using water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (1.3 mL/kg bw, based on specific gravity)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
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 and weighing:
Mortality/Viability: twice daily
Body weights: days 1 (pre-administration), 8 and 15
Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter until day 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured.
Clinical signs:
other: Chromodacryorrhea, flat and/or hunched posture were noted among all animals between days 1 and 3. In addition, scales were seen on the treated skin area of two females during the observation period.
Gross pathology:
No toxicologically relevant abnormalities were found at macroscopic post-mortem examination of the animals.
Pelvic dilation of the kidneys found in one animal is commonly noted among rats of this age and strain and was therefore not considered of toxicological relevance.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral route:

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl 2-chloropropenoic acid ester (CAS 96383-55-0) was tested for its acute oral toxicity in a study according to OECD 423 and in compliance with GLP in female Wistar rats (van Otterdijk, 2004). The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg bw. 2/3 animals died within 4 h after treatment. Lethargy, hunched posture, uncoordinated movements, slow breathing, shallow respiration, piloerection, hypothermia and/or ptosis were observed in all animals. The surviving animal had recovered from the symptoms on day 5. In a second step 3 animals were treated with a dose of 300 mg/kg bw. No mortality was observed. Thus, a third step was performed dosing further 3 animals with 300 mg/kg bw. Again no mortality was observed. Clinical findings included hunched posture on days 1 and/or 2 in all animals of the 300 mg/kg bw dose group. A slightly low body weight gain was noted for one female at 300 mg/kg bw between days 8 and 15. The body weight gain shown by the other surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. In conclusion, an experimental LD50 of >300 and <2000 mg/kg bw was observed for acute oral toxicity. The LD50 cut-off according to OECD 423 guideline is 1000 mg/kg bw.

Dermal route:

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl 2-chloropropenoic acid ester (CAS 96383-55-0) was tested for its acute dermal toxicity in a study according to OECD 402 and in compliance with GLP in male and female Wistar rats (van Otterdijk, 2004). 5 animals per sex were dermally exposed to 2000 mg/kg bw (1.3 mL/kg bw) test substance for 24 h under occlusive conditions. After 24 h the skin was washed with water. No mortality occurred during the study. Chromodacryorrhea, flat and/or hunched posture were noted among all animals between days 1 and 3. In addition, scales were seen on the treated skin area of two females during the observation period. The changes noted in body weight gain in males and in females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No toxicologically relevant abnormalities were found at macroscopic post-mortem examination of the animals. Pelvic dilation of the kidneys found in one animal is commonly noted among rats of this age and strain and was therefore not considered of toxicological relevance. In conclusion, an experimental LD50 of >2000 mg/kg bw was deduced for acute dermal toxicity.

Justification for selection of acute toxicity – oral endpoint

The reliable GLP compliant OECD Guideline study was chosen.

Justification for selection of acute toxicity – dermal endpoint

The reliable GLP compliant OECD Guideline study was chosen.

Justification for classification or non-classification

Oral:

Based on available data on acute oral toxicity, of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl 2-chloropropenoic acid ester meets the criteria for classification as Acute Oral Cat. 4, H302 according to Regulation (EC) 1272/2008 and as Xn, R22 according to Directive 67/548/EEC.

Inhalation:

There is no data available on acute inhalation toxicity.

Dermal:

No mortality occurred up to the dose level of 2000 mg of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl 2-chloropropenoic acid ester/kg bw and therefore, the data is conclusive but not sufficient for classification according to Regulation (EC) 1272/2008 and according to Directive 67/548/EEC.