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Administrative data

Description of key information

Oral: LD50 > 2,000 mg/kg for rat (limit test)
Inhalation: LC50 > 1761 ppm for rat (correspond to 25.5 mg/l; maximum stable vapour concentration achievable)
Dermal: LD50: > 2,000 mg/kg for rat (limit test)

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:
From September 20, 1995 To December, 1995.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP OECD guideline study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7-9 weeks (on receipt)
- Weight at study initiation: Males: 225-250 g, Females: 200-225 g
- Fasting period before study: fasted overnight
- Housing: 5 animal/sex/cage in conditioned room; grill cages 40.5x38.5x18 cm
- Diet: GLP4RF21 (MucedolaS.r.l. Settimo M.se)
- Water : ad libitum
- Acclimation period: at least 5 days before the start of test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 55+/- 10
- Air changes (per hr): 20
- Photoperiod: 12 hrs dark / 12 hrs light (= 7 am - 7 pm)

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.33 ml/kg (density 1.5 g/ml)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality were observed frequently on the first day after administration (at 30 min, 2h, 4h, 6h) and then twice a day/ Body weight was checked twice pre-trial (at randomization and on day 1 to calculate the administration volume) and on days 3, 8 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.
Statistics:
By the method of the Probit, if possible.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animals died.
Clinical signs:
No general clinical signs or behavioral alterations were noted in any animal during the 14-day observation period.
Body weight:
The body weight gain during the observation period was within the normal limits for animals of this species and age.
Gross pathology:
The autoptic examination performed on animals killed at the end of the study did not show any change.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, the test article did not cause apparent sign of toxicity by oral route to rat at the single (limit) dose of 2000 mg/kg bw. Then, the acute oral LD50 of the test material in rats was determined to be greater than 2000 mg/kg bw. The test article is not classified according to CLP Regulation (EC 1272/2008).
Executive summary:

A study was performed with Sprague-Dawley rats to determine the acute oral toxicity of the test material. The study was performed according to the OECD guideline 401.The test substance was administered undiluted by gavage to groups of 5 male and 5 female fasted rats at the single (limit) dose of 2000 mg/kg bw. The animals were observed frequently after dosing. After that the animals were observed daily for clinical signs and twice daily for mortality. The bodyweight of the animals were determined at Day 0, 3, 8 and 14. Necropsy was performed on all animals. No animals died. No general clinical signs or behavioral alterations were noted in any animal during the 14-day observation period. The body weight gain during the observation period was within the normal limits for animals of this species and age. The autoptic examination performed on animals killed at the end of the study did not show any change. Under the test conditions, the acute oral LD50 of test material in rats was determined to be higher than 2000 mg/kg bw, thus the substance is not classified according to CLP Regulation (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Only one study available, of good quality.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 6 June 2001 To 3 July 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP guideline study without deviation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
AlpK:APfSD (Wistar-derived)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Rodent Breeding Unit, Alderley Park, Macclesfield, Cheshire, UK.
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 335 - 357 g +/-9.1 (males); 239-255 g +/- 6.1 (females)
- Housing: 5 per cage per sexe
- Diet (e.g. ): Diet (RM1), supplied by Special Diet Services Limited, Witham, Essex, UK, ad libitum
- Water (e.g. ad libitum): mains water, supplied by an automatic system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 (see also inhalation exposure below for the exposure period)
- Humidity (%): 30 -70 (see also inhalation exposure below for the exposure period)
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12h/ 12h
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The rats were exposed nose-only to the test atmospheres. Animals were restrained in polycarbonate tubes supplied by Battelle, Geneva, Switzerland. These were inserted into a PERSPEX exposure chamber. The chamber was covered with an aluminium cone and stood on an aluminium base.
- Exposure chamber volume: The chamber consisted of sections of PERSPEX tubing (6 mm wall thickness) with an internal diameter of 28 cm and height of 15 cm (approximate volume 9.2 litres).
- System of generating vapour: The test atmosphere was generated using a heated, jacketed glass condenser. The test substance was pumped to the condenser using a Watson Marlow peristaltic pump. A counter current of clean, dry air (dried and filtered using equipment supplied by Atlas-Copco, Sweden) was passed at a nominal flow rate of 20l/minute (at normal temperature and pressure) through the condenser and carried the atmosphere to the exposure chamber (internal volume of 27.6 litres), in order to achieve a minimun of 12 air changes per hour. Since diluting air was not employed, the flow rates through the exposure chambers were the same as that employed in the generation of the test atmosphere. Air flows were monitored continuously and recorded at least 3 times using variable area flowmeters (KDG Flowmeters, Burgess Hill, Sussex, UK)
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity in each chamber were recorded at least 3 times during exposure using a portable, digital temperature and relative humidity monitor; they were within the range of 20.4-21.2 °C and 15-20 % respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: Samples were analysed using gas chromatography.
- Samples taken from breathing zone: yes. Test atmospheres were sampled from a front-facing port of the relevant exposure chamber, using a 5 ml gas-tight syringe equipped with an integral on-off valve and detachable sampling probe.

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target concentration: 1800 ppm (correspond to 26.07 mg/l; MW=354.1355 g/mol) = maximum stable vapour concentration achievable, as determined in a trial generation.
Achieved concentration: 1761 ppm (correspond to 25.5 mg/l; MW= 354.1355 g/mol)
No. of animals per sex per dose:
5 per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Prior to the start of the study, all rats were examined to ensure that they were physically normal and exhibited normal activity. During exposure, they were observed frequently. At the end of the 4-hour exposure period, each rat was given a detailed clinical examination. The animals were also given detailed clinical observations, (including the finding of "no abnormalities detected') daily during the 14 day observation period.
- Necropsy of survivors performed: yes, all animals were given a gross examination post mortem. This involved an external observation and an internal examination of all thoracic and abdominal viscera.
- Other examinations performed: clinical signs, body weight (d-1, d1, d8, d15)
Statistics:
No statistics were performed.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 761 ppm
Based on:
test mat.
Remarks:
(vapours)
Exp. duration:
4 h
Remarks on result:
other: correspond to 25.5 mg/l (maximum stable vapour concentration achievable)
Mortality:
There were no deaths in animals exposed to 1761 ppm during the exposure or observation periods.
Clinical signs:
other: Observations during exposure: Abnormalities generally associated with restraint (wet fur and chromodacryorrhoea) were seen in some animals exposed to 1761 ppm. All animals had stains around the snout. Observations immediately after exposure: All animals h
Body weight:
All animals had gained weight by day 8 of the study and this trend continued until day 15.
Gross pathology:
There were no macroscopic changes seen post mortem.
Other findings:
None. There was no evidence of respiratory irritation or toxicity.
Interpretation of results:
GHS criteria not met
Remarks:
CLP criteria
Conclusions:
Under the experimental conditions of this test, no deaths occurred at a vapour concentration of 1761 ppm (25.5 mg/l; maximum stable vapour concentration achievable) and there was no evidence of respiratory irritation or toxicity.
Executive summary:

One group of five male and five female Alpk:APfSD (Wistar-derived) rats were exposed nose-only for a single four-hour period to a vapour of dodecafluoro, deca-1,9 -diene at a target concentration of 1800 ppm (which was the maximum stable vapour concentration achievable). Test atmospheres were analysed to determine the vapour concentration of the test substance. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and bodyweights were recorded throughout the study and at the end of the scheduled period, the animals were killed and given a gross examination post mortem. At an exposure concentration of 1761 ppm all animals had gained weight by day 8 and the trend continued throughout the study. There were no clinical changes indicative of toxicity, no macroscopic changes and no deaths. Nose-only exposure for 4 hours to Dodecafluoro, deca-1,9-diene at a vapour concentration of 1761 ppm caused no deaths. Under the test conditions, the acute inhalation LC50 of test material in rats was determined to be higher than 1761 ppm (correspond to 25.5 mg/l, vapours), thus the test substance does not require classification according to CLP Regulation (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
> 25 500 mg/m³
Quality of whole database:
Only one study available, of good quality.

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:
From September 21, 1995 To December, 1995.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP OECD 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
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A.
- Age at study initiation: 7-9 weeks (on receipt)
- Weight at study initiation: Males: 225-250 g, Females: 200-225 g
- Fasting period before study: fasted overnight
- Housing: 5 animal/sex/cage in conditioned room ; grill cages 40.5x38.5x18 cm
- Diet: GLP4RF21 (MucedolaS.r.l. Settimo M.se)
- Water : ad libitum
- Acclimation period: at least 5 days before the start of test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 55+/- 10
- Air changes (per hr): 20
- Photoperiod: 12 hrs dark / 12 hrs light (= 7am - 7 pm)

Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: no specific indication in report but reference methods cited state 10% of body surface
- Type of wrap if used: No specific indication in report, but reference methods cited state semi-occlusive

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

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 per sexe per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality were observed frequently on the first day after administration and then twice a day/ Body weight was checked twice pre-trial (at randomization and on day 1 to calculate the administration volume) and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.
Statistics:
By the method of the Probit, if possible.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died.
Clinical signs:
No general or local clinical signs or behavioral alterations were observed in any animal during the observation period.
Body weight:
The body weight gain during the observation period was within the normal limits for animals of this species and strain.
Gross pathology:
The autoptic examination performed on animals killed at the end of the study did not show any change.
Other findings:
None.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this test, the test article did not cause apparent sign of toxicity by dermal route to rat at the single (limit) dose of 2000 mg/kg bw. Then, the acute dermal LD50 of the test material in rats was determined to be greater than 2000 mg/kg bw. The test article is not classified according to CLP Regulation (EC 1272/2008).
Executive summary:

A study was performed with Sprague-Dawley rats to determine the acute dermal toxicity of the test material. The study was performed according to the OECD guideline 403.The test substance was administered uniformly by gentle inunction onto the cleared dorsal area of the trunk of the animals to groups of 5 male and 5 female fasted rats at the single (limit) dose of 2000 mg/kg bw for 24 hours. The animals were observed frequently on the first day after administration and then twice a day. The bodyweight of the animals were determined at Day 0, 8 and 15. Necropsy was performed on all animals. No animals died. No general or local clinical signs or behavioral alterations were observed in any animal during the observation period. The body weight gain during the observation period was within the normal limits for animals of this species and age. The autoptic examination performed on animals killed at the end of the study did not show any change. Under the test conditions, the acute dermal LD50 of test material in rats was determined to be higher than 2000 mg/kg bw, therefore the substance is not classified according to CLP Regulation (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 2 000 mg/kg bw
Quality of whole database:
Only one study available, of good quality.

Additional information

Acute Toxicity assessment:

For each acute end point, one reliable study is available.

Acute oral toxicity:

A study was performed with Sprague-Dawley rats to determine the acute oral toxicity of the test material. The study was performed according to the OECD guideline 401.The test substance was administered undiluted by gavage to groups of 5 male and 5 female fasted rats at the single (limit) dose of 2000 mg/kg bw. The animals were observed frequently after dosing. After that the animals were observed daily for clinical signs and twice daily for mortality. The bodyweight of the animals were determined at Day 0, 3, 8 and 14. Necropsy was performed on all animals. No animals died. No general clinical signs or behavioral alterations were noted in any animal during the 14-day observation period. The body weight gain during the observation period was within the normal limits for animals of this species and age. The autoptic examination performed on animals killed at the end of the study did not show any change. Under the test conditions, the acute oral LD50 of test material in rats was determined to be higher than 2000 mg/kg bw, thus the substance does not require classification according to CLP Regulation (EC 1272/2008).

Acute inhalation toxicity:

One group of five male and five female Alpk:APfSD (Wistar-derived) rats were exposed nose-only for a single four-hour period to a vapour of the test substance at a target concentration of 1800 ppm (which was the maximum stable vapour concentration achievable). Test atmospheres were analysed to determine the vapour concentration of the test substance. Following exposure, the animals were retained without treatment for 14 days. Clinical observations and bodyweights were recorded throughout the study and at the end of the scheduled period, the animals were killed and given a gross examination post mortem. At an exposure concentration of 1761 ppm all animals had gained weight by day 8 and the trend continued throughout the study. There were no clinical changes indicative of toxicity, no macroscopic changes and no deaths. Nose-only exposure for 4 hours to the test substance at a vapour concentration of 1761 ppm caused no deaths. Under the test conditions, the acute inhalation LC50 of test material in rats was determined to be higher than 1761 ppm (which corresponds to 25.5 mg/l) thus the substance does not require classification according to CLP Regulation (EC 1272/2008).

Acute dermal toxicity:

A study was performed with Sprague-Dawley rats to determine the acute dermal toxicity of the test material. The study was performed according to the OECD guideline 403.The test substance was administered uniformly by gentle inunction onto the cleared dorsal area of the trunk of the animals to groups of 5 male and 5 female fasted rats at the single (limit) dose of 2000 mg/kg bw. The animals were observed frequently on the first day after administration and then twice a day. The bodyweight of the animals were determined at Day 0, 8 and 15. Necropsy was performed on all animals. No animals died. No general or local clinical signs or behavioral alterations were observed in any animal during the observation period. The body weight gain during the observation period was within the normal limits for animals of this species and age. The autoptic examination performed on animals killed at the end of the study did not show any change. Under the test conditions, the acute dermal LD50 of test material in rats was determined to be higher than 2000 mg/kg bw, thus the substance does not require classification according to CLP Regulation (EC 1272/2008).


Justification for selection of acute toxicity – oral endpoint
Study performed according to OECD TG 401 and EC method B.1.

Justification for selection of acute toxicity – inhalation endpoint
Study performed according to OECD TG 403 and EC method B.2.

Justification for selection of acute toxicity – dermal endpoint
Study performed according to OECD TG 402 and EC method B.3.

Justification for classification or non-classification

The test material appears to have no acute toxicity in in vivo studies with rat. Therefore, 1,6-Divinylperfluorohexane does not require classification for acute toxicity according to the criteria of the CLP regulation No. 1272/2008.