Hexafluoropropene, oxidized, oligomers, reduced, fluorinated

Endpoint summary

Description of key information

An oral toxicity study conducted according to OECD guideline No. 401 , a dermal toxicity study conducted according to OECD guideline No. 402 and an inhalation toxicity study conducted according to OECD guideline No. 403 are reported.
All the three studies were conducted under GLP. The reliability of the studies according to Klimish score is K1.
Basing on experimental results, according to REGULATION (EC) No 1272/2008, the substance does not meet the classification criteria for human health for acute toxicity.

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:

25 March 1992 to 9 April 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes (incl. QA statement)

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: livestock farming
- Age at study initiation: about 7-9 weeks
- Weight at study initiation: males: 225-250 g, females: 200-225 g
- Fasting period before study: 16 hours. Feed was returned to rats three hours after the administration of the test article.
- Housing: 5 animals/sex/cage in air-conditioned rooms. Grill cages. Cage size (cm):40.5 x 38.5 x 18
- Diet (e.g. ad libitum): Certificated pelleted diet, supplied with vitamins and trace elements. Available ad libitum
- Water (e.g. ad libitum): from municipal water main system, filtered and disrtibuted ad libitum.
- Acclimation period: at least 5 days before the strat of the test. Animals were observed daily to ascertain their fitness for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +-2
- Humidity (%): 55 % +- 10
- Air changes (per hr): about 20 hour filtered on HEPA 99.97%.
- Photoperiod (hrs dark / hrs light): 12 hour cicle (7 a.m.-7 p.m.)

IN-LIFE DATES: From: 25-MAR-1992 To: 9-APR-1992

Route of administration:

oral: gavage

Vehicle:

other: 0.5% methylcellulose 400 cps water solution, containing 0.4% Polysorbate 80.

Details on oral exposure:

VEHICLE: no details

MAXIMUM DOSE VOLUME APPLIED: 20 ml/kg

Doses:

2000 mg/kg
5000 mg/kg

No. of animals per sex per dose:

10 (5 males + 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Observation of clinical signs and mortality were performed after 30 minutes, 2, 4 and 6 hours on the first day after the administration and then twice a day up to the termination of the observastion period.
Body weight was detected twice pre-trial (at randomization and on day 1 just before treatment) and on days 3, 8 and 14.
On day 1 the animals were weighted after a 16-hour fasting.
Volume of administration was based on day 1 body weight.

- Necropsy of survivors performed: yes.

- Other examinations performed: clinical signs, body weight, gross pathology at post mortem examination.

Statistics:

Calculation of LD 50 was not possible.

Preliminary study:

not relevant

Sex:

male/female

Dose descriptor:

LD0

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No animals died during the observation period.

Clinical signs:

other: Only piloerection was observed in some treated animals starting from 30 minutes and lasting up to 6 hours. Recovery of all animals was achieved within day 2 of the study.

Gross pathology:

The autoptic examination performed on animals killed at the end of the study did not show any change.

Other findings:

none

CLINICAL SIGNS FREQUENCY (Cumulative)

 

Table a

No. Rats treated:5 males + 5 females
Dose: 2000 mg/kg
Clinical signs	Number of rats affected	Signs observed (time)
		from	to
Piloerection	4	30 minutes	4 hours
Recovery	4	6 hours

 

Table b

No. Rats treated:5 males + 5 females
Dose: 5000 mg/kg
Clinical signs	Number of rats affected	Signs observed (time)
		from	to
Piloerection	4	30 minutes	6 hours
Recovery	4	day  2

 

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental consitions applied in this study, GALDEN LMW showed an LD50 higher than 5000 mg/kg when administered by oral route to rats. Only transient piloerection was noted in some treated animals.

Executive summary:

The purpose of the study was to evaluate the acute toxicity of the test article GALDEN LMW and to determine the LD 50, its statistical limits and slope, if possible.

The test method was in accordance with OECD guideline 401 (Paris, 1981) and subsequent revisions.

The test article was suspended in 0.5% Methylcellulose 400 cps water solution plus 0.4% Polysorbate 80.

The animals were weighed twice before the trial (at randomization and on day 1 just before treatment) and on day 3, 8 and 14. They were clinically observed for 14 days following administration and killed at the end of the study by excision of the femoral arteries after i.p. overdosage injection of 5% sodium pentobarbital.

A throughout autoptic examination was performed on animals killed at the end of the observation period.

No deaths occurred as consequence of GALDEN LMW oral administration at the dosages applied in this study.

Only piloerection was observed in some animals treated with both dose levels starting from 30 minutes and lasting up to 6 hours.

Recovery of all animals was achieved within 24 hours from treatment.

The body weight gain appeared normal.

At the gross pathology examination no drug-related changes were seen.

In conclusion the test test article GALDEN LMW when administered by oral route to rats under the experimental conditions applied in this study, showed an LD50 higher than 5000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

No adverse effects at the highest dose in existing standards.

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:

6 December 1995 to 26 December 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

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

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

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: livestock farming
- Age at study initiation: about 8 weeks
- Weight at study initiation: males: 320-337 g, females: 216-246 g
- Fasting period before study: not reported
- Housing: 5 rat of same sex/cage. Cage size: 35cm x 53 cm x 25 cm, suspended on a movable rack.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the day of exposure

ENVIRONMENTAL CONDITIONS
- Temperature (°C): within the limit of 12°C - 22°C
- Humidity (%): betwen 36% and 53%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour cicle (8 a.m.-8 p.m.)

IN-LIFE DATES: From: To: not reported

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of atmosphere generation: The test atmosphere was generated by vaporising GALDEN LMW in a stream of air flowing through a heated coppel coil (vaporiser) immersed in a water bath. The test substance was delivered to the vaporiser at a constant flow rate from a stainless steel reservoir by a metering pump. The air supplied to the vaporiser was dried, filtered and oil free.

- Exposure apparatus: The test atmosphere entered through a port at the top of the chamber and passed out through a port in the base of the chamber.
- Exposure chamber volume: approximately 70 litres

- Description of exposure chambers: The whole-body exposure chambers used for the exposures were of square section and were fitted with pyramidal tops. The chambers were made of acrylic polymer. Each chamber was divided by wire mesh partitions to provide 10 separate animal compartements. Each chamber was positioned inside a large cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.
The rats to be exposed were placed into separate compartments of the exposure chambers.

- Temperature in air chamber: 24 °C +- 0.6 (Test group), 23 °C +- 0.4 (Control group);
- Oxygen concentration in air chamber: 20% +- 0.2 (Test group), 20% +- 0.1 (Control group);

TEST ATMOSPHERE
- Brief description of analytical method used: Analysis was carried out by gas chromatography and standardised by using preparations of the test substance vapour in gas bags. (Pye Unicam PU4550 Gas Chromatograph fitted with gas injection valve; Detector: Flame Ionisation)
- Samples taken from breathing zone: Yes. Six air samples were taken from the chamber during the exposure. The air samples, obtained using a polypropylene syringe, were directed straight to the Gas Chromatograph.

VEHICLE
- Composition of vehicle (if applicable): air.
- Concentration of test material in vehicle (if applicable): 9.47 % (v/v) +- 0.623
- Lot/batch no. (if required): n.a.
- Purity: n.a.

PROCEDURE
The test material was pumped from the reservoir, mixed with a supply of clean dried air and passed through the vapour generator. The flow rate of test material was 14ml/minute and the air supply pressure was adjusted to give a flow rate of 14 litres per minute through the generator.
The pump and air supplies were switched on and the exposure time for 4 hours, following a 12-minute equilibration period (12 minutes is the theoretical time required for the concentration of vapour in the chamber to reach 90% of its final value under the conditions of exposure employed).
The control group was treated similarly but exposed to clean air only for 4 hours. The control rats were returned to the holding room at the end of the exposure procedure.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

9.47 % (v/v) +- 0.623 (target concentration : 10% v/v)

No. of animals per sex per dose:

10 (5 males + 5 females)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs.
All rats were weighed daily from the day of delivery to the testing laboratory until the end of the observation period.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, lung weights, gross pathology.

Preliminary study:

Not performed.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 94 700 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: analytical mean value

Remarks:

ppm (v/v)

Mortality:

There were no deaths in the group of rats exposed to the test material.

Clinical signs:

other: There were no clinical signs during the exposure or following exposure to the test material.

Body weight:

There were no effect on the rate of bodyweight gain for rats exposed to the test material.

Gross pathology:

There were no macroscopic abnormalities in test and control rats.

Other findings:

The lung weight to bodyweight ratio was within normal limit for all rats.

Food and water consumption was not affected by exposure to the test material.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 (4-hour) of GALDEN LMW to rats was in excess of 9.47% (v/v) in air.
Based on MW range 350-500 this is equivalent to 1355-1936 mg/L.

Executive summary:

The objective of this study was to establish the acute inhalation toxicity of Galden LMW to rats.

The study design was in compliance with the OECD guideline Method No. 403 and EEC guideline Method B2.

One group of five male and five female Sprague Dawley CD rats was exposed to an atmosphere containing 9.47% (v/v) of GALDEN LMW. Exposure was continuous for 4 hours using a whole body exposure system. An additional group of 5 males and 5 females acted as controls and were exposed to air only for 4 hours.

Animals were observed during the exposure period and for 14 days post exposure. Group food and water consumption were measured daily throughout. Each animal was subjected to post mortem examination.

There were no deaths following exposure to GALDEN LMW.

No clinical signs were observed during and after exposure.

Bodyweight gain for the rats exposed to GALDEN LMW was similar to that of the control rats.

Food and water consumption were no affected following exposure to GALDEN LMW.

Lung weight to bodyweight ratios for the rats exposed to GALDEN LMW were within normal limits.

There were no macroscopic abnormalities in rats exposed to GALDEN LMW.

In conclusion the acute inhalation LC50 (4-hour) of GALDEN LMW to rats was in excess of 9.47% (v/v) in air (corresponding to 1355 - 1936 mg/L).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

1 610 mg/m³ air

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:

07 April 2006 to 03 May 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

OECD Guideline-conform study conducted under GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1992)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(1987)

GLP compliance:

yes (incl. QA statement)

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: livestock farming
- Age at study initiation: males: 8 weeks, females: 12 weeks
- Weight at study initiation: Males: 230-247 g; Females: 190-204 g
- Fasting period before study: not reported
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. During treatment and observation in Makrolon type-3 cages with standard softwood bedding.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light cycle

IN-LIFE DATES: From: To: not reported

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
One days before the treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only animals without injury or irritation on the skin were used in the test.
On test day1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.2 ml/Kg bw (corrisponding to 2000 mg/Kg bw)
- Concentration (if solution): n.a. The test material was applied unchanged.
- Constant volume or concentration used: yes
- For solids, paste formed: n.a.

VEHICLE
- Amount(s) applied (volume or weight with unit): n.a.
- Concentration (if solution): n.a.
- Lot/batch no. (if required): n.a.
- Purity: n.a.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 (5 males + 5 females)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Viability was checked daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weight was recorded on test day 1 (prior to administration), 8 and 15. Animals were examined for clinical signs daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Animals were examined for local signs once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, local signs, body weight, macroscopic examinations at necropsy.

Statistics:

no statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic or local signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

None.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of GALDEN LMW after single dermal administration to rats of both sexes, observed over a period of 14 days, is greater than 2000 mg/kg body weight.

Executive summary:

The purpose of this study was to assess the acute dermal toxicity of GALDEN LMW when administered to rats by a single semi-occlusive dermal application, followed by an observation period of 14 days.

Five male and five female HanRcc:WIST (SPF) rats were treated with GALDEN LMW at 2000mg/kg by dermal application. The test item was applied undiluted as delivered from the sponsor at a volume dosage 1.2 mL/kg. The application period was 24 hours. The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recordered. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2 -15. Local signs were recorded once daily from test day 2 to 15. Mortality/viability was recordered at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2 -15. Body weights were recordered on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. No clinical signs were observed during the course of the study. The body weights of the animals was within the range commonly recordered for this strain and age. No macroscopic findings were observed at necropsy. In conclusion the median lethal dose of GALDEN LMW after single dermal administration to rats of both sexes, observed over a period of 14 days is LD50 (rat) greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is OECD-guideline conform and conducted under GLP.

Additional information

Under the oral toxicity study, two groups of ten rats each (five males and five females) were dosed at 2000 mg/kg bw and 5000 mg/kg bw of GALDEN LMW respectively. The animals were weighed twice before the trial and on day 3, 8 and 14. They were clinically observed for 14 days following administration. A thorough autoptic examination was performed on animals killed at the end of the observation period.

No deaths occurred as consequence of GALDEN LMW oral administration at the dosages applied in this study. The body weight gain appeared normal. At the gross pathology examination no drug-related changes were seen. Only transient piloerection was noted in some treated animals.

In conclusion the median lethal dose of GALDEN LMW, when administered by oral route to rats under the experimental conditions of the study, is higher than 5000 mg/kg bw.

Under the dermal toxicity study, a group of five male and five female rats was treated with GALDEN LMW at 2000mg/kg by dermal application. The test item was applied undiluted at a volume dosage 1.2 mL/kg. The application period was 24 hours.

Animals were clinically observed for 14 days following administration and mortality, viability and clinical signs were recordered. At the end of the observation period all animals were necropsied and examined macroscopically.

No deaths occurred during the study. No clinical signs were observed during the course of the study. The body weights of the animals was within the range commonly recordered for this strain and age. No macroscopic findings were observed at necropsy.

In conclusion the median lethal dose of GALDEN LMW after single dermal administration to rats of both sexes is greater than 2000 mg/kg body weight.

 

Under the toxicity study by inhalation, a group of five male and five female rats was exposed to an atmosphere containing 1610 mg/L of GALDEN LMW. Exposure was continuous for 4 hours using a whole body exposure system. An additional group of five males and five females was exposed to air only for 4 hours as control.

Animals were observed during the exposure period and for 14 days post exposure. Each animal was subjected to post mortem examination.

There were no deaths following exposure to GALDEN LMW. Bodyweight gain for the rats exposed to GALDEN LMW was similar to that of the control rats. Food and water consumption were no affected following exposure to GALDEN LMW. There were no macroscopic abnormalities in rats exposed to GALDEN LMW. Lung weight to bodyweight ratios for the rats exposed to GALDEN LMW were within normal limits.

In conclusion the acute inhalation LC50 (4 -hour) of GALDEN LMW to rats is in excess of 1610 mg/L in air.

Justification for classification or non-classification

Basing on experimental results, according to REGULATION (EC) No 1272/2008 and GHS criteria, GALDEN LMW does not meet the classification criteria for the hazard classes Acute Toxicity and STOT-SE (Specific Target Organ Toxicity Single Exposure) by oral, dermal and inhalation exposure routes.