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EC number: 500-537-5 | CAS number: 161075-00-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- concentration-driven
Effects on fertility
Description of key information
Existing data on the substance and on the analogue H GALDEN were evaluated in a Weight of Evidence approach. The data support the low concern for effects on the reproduction and fertility for the fluoropolyether GALDEN LMW.
Effect on fertility: via oral route
- Endpoint conclusion:
- no study available
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- All the studies used for read across and weight of evidence procedures were carried out under GLP conditions.
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Information from the subacute repeated-dose toxicity study by oral route conducted on GALDEN LMW and from the subchronic and subacute repeated-dose inhalation toxicity studies, as well as on the embryo-fetal developmental inhalation toxicity study conducted on the analogue substance H GALDEN, support the low concern for effects on the reproduction and fertility for the fluoropolyether GALDEN LMW.
According to the testing strategy for reproductive toxicity from ECHA “Endpoint specific guidance – R.7A, section R.7.6” the observation of no adverse effects on the reproductive organs in a repeated-dose toxicity study, may justify a lower priority for further testing for effects on fertility.
In the sub-chronic OECD 413 toxicity study by inhalation administration to CD rats conducted on H-Galden, relative weights, dimensions and appearance of testes, ovaries, epididymides and uterus with cervix were determined.
The relative weights of these organs did not show any substance related effect and the macroscopic examinations revealed no changes attributable to treatment with H-Galden. Epididymides, ovaries, testes and uterus with cervix were subsequently examined microscopically for the control and high dose groups. There were no findings in these organs.
In the sub-acute toxicity study on Galden LMW, after oral administration, there was no effect on relative weights, dimensions and appearance of testes or ovaries.
Galden LMW and H-Galden have similar chemical structure and common characteristic which are typical of compound having C-F bounds. However the presence of –OCF2H as terminal groups in H-Galden, gives to the product slight more reactivity than those observed for Galden LMW, characterized by neutral, non-functional terminal groups –OCF3. In the available repeated dose inhalation toxicity studies conducted with the analogue H-GALDEN, limited effects were observed, except at very high concentrations, indicating a low toxicity potential.
The Weight of Evidence assessed several in vivo reproductive and repeated toxicity studies. Individually, these studies may have deficiencies. However, taking account of the reliability and relevance and consistency of findings, collectively these studies could provide an adequate level of information leading to an appropriate classification decision and risk assessment.
On the basis of the overall above considerations, available data support a low concern for Galden LMW regarding effects on reproduction and developmental toxicity.
Effects on developmental toxicity
Description of key information
Based on the experimental developmental toxicity study conducted on an analogue substance, GALDEN LMW is not expected to impair embryo-fetal development.
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 October 2001 to 01 October 2002
- 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 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Remarks:
- Crl:CD rats
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: livestock farming
- Age at study initiation: 10-11 weeks
- Weight at study initiation: about 224-340 g
- Fasting period before study: no. Animals had no access to food during the 6-hour inhalation exposures.
- Housing: 5 animals /cage
- Diet (e.g. ad libitum): pellet diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 3-4 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 °C (measured)
- Humidity (%): 46-66 % (measured)
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour cicle (6.00 a.m.- 6.00 p.m.)
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- air
- Details on exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body exposure chambers
- Method of holding animals in test chamber: Animals were placed into individual compartment of the exposure chamber. A separate exposure chamber was used for each group. The Control animals were exposed using an identical exposure chamber to that used for the test groups.
- Source and rate of air: about 60 - 100 l/minute
- Method of conditioning air: Air supplied to the vapour generators and secondary dilution vessels was filtered to remove any residual particulate and was dried.
- System of generating vapour: The chamber atmospheres were produced by metering the liquid test substance into glass vapour generators through which dried and heated air was passed at a group dependent flow rate ranging from 60 to 100 l/minute. For all exposed groups, the vapour/air mixture produced in the vapour generators was passed into the base of a secondary dilution vessel. A further supply of clean and dry air was supplied to Groups 2 and 3. The air supply to Group 4 was provided solely by the vapour generation system.
- Temperature, humidity, pressure in air chamber: The mean temperatures in chambers ranged between 22.5 °C +-0.85 (Group 1 Chamber) and 24.0 °C +- 0.91 (Group 4 Chamber). The mean relative humidity (RH) in chambers ranged between 38% +- 3.5 (Group 4 Chamber) and 47% +- 5.8 (Group 1 Chamber).
- Air flow rate: 100 litre/minute
- Air change rate: not reported
- Method of particle size determination: not relevant
- Treatment of exhaust air: not reported
TEST ATMOSPHERE
- Brief description of analytical method used: Gas Chromatograph was used to measure the concentration of H GALDEN in the test atmospheres within the four inhalation chambers.
- Samples taken from breathing zone: yes. Chamber atmosphere was sampled in sequence from each of the four exposure chambers and from one point within each chamber. Air from each chamber was continually drawn through a transfer line, which was therefore equilibrated with the mean concentration from each chamber. Every seven minutes, air from the transfer lines was swiched to the injection loop pf the gas chromatograph for automated analysis and data logging. When not being sampled, these transfer lines were pumped to waste.
VEHICLE (if applicable)
- Justification for use and choice of vehicle: air
- Composition of vehicle: air
- Type and concentration of dispersant aid (if powder): not relevant
- Concentration of test material in vehicle: 1004, 3367, 10006 ppm
- Lot/batch no. of vehicle (if required): not relevant
- Purity of vehicle: not relevant - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The samples of chamber atmosphere were injected into a gas chromatograph, which was calibrated using vapour standards prepared in gas sampling bags.
Vapour samples were collected using an automated system fitted with electrically controlled valves, which were manipulated using Chamber Environment Monitoring System (CEMS-2) software.
The test atmosphere was drawn directly from the inhalation chamber through the sample line to the gas-sampling valve located on the GC. Initially, the gas-sampliong valve of the GC was set to the "load" position and the valve was automatically switched to the "inject position" after 60 seconds. Simultaneously, the GC activates the start of the run sequence.
Chromatographic conditions:
Analytical column: DB-1, 5 micrometer film thickness, 30 m x 0.53 mm i.d.
Carrier gas: Helium (2.1 ml/minute)
Split ratio 1:25
Oxidant: Air ( 330 ml/minute)
Fuel: Hydrogen (33 ml/minute)
Injection volume: 500 microliter via an automated gas valve
Injection temperature: 200 °C
Detector temperature: 200 °C
Range: 1000
Gas sample valve: Off at 2.5 minute
Retention time H GALDEN: approximately 0.6-2.3 minutes (analysis for major peak at 0.9 minutes)
- Details on mating procedure:
- Time-mated females were supplied from the livestock farming. Females arrived to the Laboratory on Days 2 or 3 of gestation.
The females were mated by identified males. - Duration of treatment / exposure:
- 6 hours
- Frequency of treatment:
- 6 hours/day for 14 consecutive days
- Duration of test:
- 3-4 days of acclimatisation + 14 days of exposure period (Gestation days 6 to 19)
- Dose / conc.:
- 0 ppm (analytical)
- Dose / conc.:
- 1 004 ppm (analytical)
- Remarks:
- Target: 1000 ppm
- Dose / conc.:
- 3 367 ppm (analytical)
- Remarks:
- Target: 3300 ppm
- Dose / conc.:
- 10 006 ppm (analytical)
- Remarks:
- Target: 10000 ppm
- No. of animals per sex per dose:
- 25 mated females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The dose levels were selected in consultation with the sponsor, based on the results of a 14 day repeated dose preliminary toxicity study.
- Rationale for animal assignment: Animals were allocated to groups randomly on arrival. A review of the mating details provided by the supplier confirmed that no females allocated to the same group had been mated with the same male. - Maternal examinations:
- DETAILED CLINICAL OBSERVATIONS: Yes
Dated and signed records of appearence, change and disappearence of clinical signs were maintened for individual animals.
Individual animal were observed at least once daily for any signs of behavioural changes, reaction to treatment or ill health. In addition, detailed observations were made daily, on the days of exposure, as follows:
- Pre exposure observations
- During exposure
- As each animal was returned to its home cage
- As late as possible in the working day.
During the daily exposure, obvious signs were recorded as a group response, where all visible animals appeared to be responding similarly to the test substance. Due to the type of exposure system used the ability to observe individual animals during the exposures was severely restricted.
Throughout the study, checks were made early in the working day and again in the afternoon to look for dead or moribund animals.
BODY WEIGHT: Yes
The weight of each rat was recorded on day of arrival and on Days 6-20 after mating.
During the period of exposures, the bodyweights were recorded before exposure on the day.
Group mean values and SD were calculated for Days 4 and 6 to 20 of gestation for females with live young at Day 20. Weight changes were also calculated and plotted graphically with respect to Day 6 of gestation.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
The quantity of food comsumed by each cage of rats was recorded from the periods:
Days 2-5, 6-9, 10-13, 14-17 and 18-19 after mating.
Group mean values were calculated for days 2-5, 6-9, 10-13, 14-17 and 18-19 of pregnancy.
WATER CONSUMPTION: Yes
The quantity of water comsumed by each cage of rats was recorded on a daily basis, commencing from Day 2.
Group mean values were calculated for days 2-19 of pregnancy.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: the reproductive tract, complete with ovaries.
Each animal was first examined macroscopically for evidence of disease or adverse reaction to treatment and specimens of tissues considered to be abnormal were retained. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes (assessed in each ovary before removal)
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number and distribution of fetuses in each uterine horn. - Fetal examinations:
- Each fetus was weighed, sexed and examined for any macroscopic external abnormalities. Individual placental weights and placental abnormalities were recorded.
The neck and the thoracic and abdonimal cavities of approximately half of the fetus of each litter were dissected and examined. fetal abnormalities were recorded and the fetus eviscerated prior to fixation in Industrial Methylated Spirit. After fixation, the fetuses were processed, stained with Alizarin and Red and skeletal development and abnormalities assessed.
The remained fetuses in each litter were placed in Bouin's fixative, subjected to free-hand serial sectioning and examined for visceral abnormalities.
The numbers of affected fetuses and the litters in which an observation occurred were reported for each group.
Data processing for fetuses at skeletal or visceral examination following free-hand serial sectioning was performed as following:
Structural changes are presented as major abnormalities, minor abnormalities and variants, classified according to severity and incidence as:
- Major abnormalities: rare and/or probably lethal changes e.g folded retina.
- Minor abnormalities: minor differences from "normal" that are detected relatively frequently either by skeletal examination or following free-hand serial sectioning e.g. cervical rib, variation in eye size.
- Variants: alternative structure occurring regurarly in the Control population e.g. incomplete ossification of 5th and 6th sternebrae. - Statistics:
- Data relating to food and water consumption were analysed on a cage basis. For all other parameters the analysis were performed using the individual animal as the experimental unit. Bodyweight data were analysed using weight gains.
A sequence of statistical analysis was used for bodyweight, food and water consumption and litter/fetal data.
Details on the sequence of statistical analysis are reported in the section "Any other information on materials and method". - Indices:
- LITTER RESPONSE
Litter data group mean values and SD (where appropriate) were calculated for number of corpora lutea, implantations, resorptions (early, late and total) and live youngs (male, female and total) at Day 20 of gestation. The group mean sex ratio (percentage of males) was also calculated.
Pre-natal losses were considered separately for the pre- and post- implantation phases.
- Pre-implanation loss:
Pre-implanation loss was calculated from the formula: [ (Number of corpora lutea - Number of implantations) / Number of corpora lutea ] x 100
- Post-implanation loss:
Post-implanation loss was calculated from the formula: [ (Number of implanations - Number of live fetus) / Number of implanations ] x 100
Group values were calculated using litter mean values. The number of implantations was substituted for the corpora lutea copunt in calculating pre-implantation loss where the number of implantations exceeded the corpora lutea count.
GROUP MEAN FETAL, LITTER AND PLACENTAL WEIGHTS
Group mean fetal and placental weights and SD were calculated for each group as:
(Total individual litter mean fetal or placental weights) / (Number of litters )
Mean fetal weights and SD were also calculated for each sex.
Group mean litter weights and SD were calculated for each group as:
(Total individual litter weights) / (Number of litters ) - Historical control data:
- not applied
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no adverse signs seen during the course of the study.
- Mortality:
- no mortality observed
- Description (incidence):
- There were no unscheduled deaths.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Group mean bodyweight gain of High dose females was transiently lower than the concurrent control group following the start of treatment.
Differences in bodyweight gain were -29.4% at day 9; -20.0% at day 10; -14.7% at day 11; -12.5% at day 12; -11.4% at day 13; -12.0% at day 14.
Although these difference were statistically significant, from mid-pregnancy the rate of bodyweight gain in the High dose group exceeded that of the Controls such that, by termination, overall bodyweight change was similar in these two groups.
There were no effects on bodyweight change in the Low and Intermediate dose goups. - Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Following the start of treatment group mean food consumption was slightly yet statistically significantly lower than the controls in High dose females. This effect tended to correlate with the effect on bodyweight. There were no effects on group mean food consumption in the Low or Intermediate dose groups.
Food consumption amongst the High dose animals reflected the pattern of bodyweight change. These changes are considered to be very slight and not to reflect any adverse effect of treatment. - Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Group mean water consumption of High dose was marginally greater than the Control during the majority of the treatment period (from Day 10), but since the overall difference was less than 5%, this is considered to be of no toxicological significance.
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- There were no macroscopic changes detected at post mortem examination of the females on Day 20 of pregnancy.
- Pre- and post-implantation loss:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects on the number of implantations or subsequent litter size. Implantation losses were low and there was no evidence of the selective loss of either sex, as evidenced by a similar sex ratio in all groups.
- Total litter losses by resorption:
- no effects observed
- Dead fetuses:
- no effects observed
- Description (incidence and severity):
- All females had live fetuses at Day 20.
The number of fetuses per litter is reported in the table below. - Other effects:
- no effects observed
- Description (incidence and severity):
- placental weights were unaffected by treatment.
- Details on maternal toxic effects:
- Maternal toxic effects: no effects
Details on maternal toxic effects:
Amongst females exposed to 10006 ppm, there was a transient slightly lower bodyweight gain following the start of treatment when compared to the controls. (Differences in bodyweight gain were -29.4% at day 9; -20.0% at day 10; -14.7% at day 11; -12.5% at day 12; -11.4% at day 13; -12.0% at day 14). Athough these difference were statistically significant, bodyweight gain of these treated females exceeded the one of the controls from mid-pregnancy such that, by termination, overall bodyweight gain in the High dose group and the Control were similar.
Food consumption amongst the High dose animals reflected the pattern of bodyweight change. These changes are considered to be very slight and not to reflect any adverse effect of treatment.
There were no maternal effects upon animals exposed to 1004 or 3267 ppm. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 10 006 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Key result
- Dose descriptor:
- NOEC
- Effect level:
- 3 267 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Key result
- Abnormalities:
- no effects observed
- Fetal body weight changes:
- no effects observed
- Description (incidence and severity):
- Fetal weights were unaffected by treatment.
- Reduction in number of live offspring:
- no effects observed
- Changes in sex ratio:
- no effects observed
- Changes in litter size and weights:
- no effects observed
- Description (incidence and severity):
- There were no treatment-related effects on the number of implantations or subsequent litter size.
Litter weights were unaffected by treatment. - External malformations:
- no effects observed
- Description (incidence and severity):
- There were no gross macroscopic changes detected at external examination of fetuses from females killed on Day 20 of pregnancy.
- Skeletal malformations:
- no effects observed
- Description (incidence and severity):
- The incidence of major abnormalities, skeletal abnormalities and skeletal variants were low and showed no relationship to the treatment.
- Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There was an increased incidence of displaced testis in the highest dosage group, but given the isolated nature of this findings the involvement of H GALDEN in its development is considered unlikely.
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects: no effects
Details on embryotoxic / teratogenic effects:
There were no effects of maternal exposure on litter parameters (survival and growth) or on the pattern of abnormalities amongst the fetuses at Day 20 post-coitum. A slightly higher incidence amongst the High dose group, of displaced testis (Incidence of displaced testes, High dose group = 5.91 %, Control group = 1.79 %) was considered to be unrelated to treatment due to the isolated nature of the findings, and the lack of any other related changes. - Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 10 006 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No substance-related adverse effects were observed at the highest tested dose.
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Key result
- Abnormalities:
- effects observed, non-treatment-related
- Localisation:
- visceral/soft tissue: male reproductive system
- Description (incidence and severity):
- A slightly higher incidence amongst the High dose group, of displaced testis (Incidence of displaced testes, High dose group = 5.91 %, Control group = 1.79 %) was considered to be unrelated to treatment due to the isolated nature of the findings, and the lack of any other related changes.
- Key result
- Developmental effects observed:
- no
- Conclusions:
- No treatment related effects were noted both in adult females and in fetuses. The no-observed-effect concentration (NOAEC) for maternal exposure to H GALDEN and embryo-fetal development in rats is 10006 ppm.
- Executive summary:
Under the conditions of the reported study H GALDEN was administered to pregnant female CD rats by inhalation, during the organogenesis phase of the pregnancy.
Three groups, each of 25 time-mated female rats, were exposed to an aerosol of H GALDEN, 6 hours a day, from days 6-19 after mating using a whole body exposure system. A fourth group, also of 25 females, acted as a control and was exposed to air only. The target dose of H GALDEN were 1000, 3300 and 10000 ppm.
During the study clinical signs, bodyweight, food and water consumption were recorded. On day 20 of pregnancy the animals were killed, examined macroscopically, and the uterus excised for examination of litter parameters and subsequent fetal examination.
The exposure chamber mean analysed concentration over the duration of the study were 0 (Control), 1004, 3267, and 10006 ppm.
There were no treatment related clinical observations and no deaths amongst adult females.
Bodyweight gain and food consumption of the High dose females was slightly lower than that of the control during the first few days of treatment. Bodyweight gain recovered thereafter such that, overall, the gain was similar to the controls. These changes are very slight and considered not to reflect an adverse effect.
No treatment related effects were noted.
No treatment related macroscopic changes were noted.
There were no obvious effects on treatment on the in-utero parameters investigated.
There were considered no treatment related findings at detailed visceral and skeletal examination.
It was concluded that the maternal no-observable-effect concentration (NOAEC) for maternal exposure to H GALDEN and embryo-fetal development in rats is 10006 ppm.
- Endpoint:
- developmental toxicity
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH: see document attached
- Reason / purpose for cross-reference:
- read-across source
- GLP compliance:
- yes
- Limit test:
- no
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 10 006 ppm (analytical)
- Based on:
- test mat.
- Basis for effect level:
- body weight and weight gain
- Key result
- Abnormalities:
- no effects observed
- Key result
- Dose descriptor:
- NOAEC
- Effect level:
- 10 006 ppm (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No substance-related adverse effects were observed at the highest tested dose.
- Key result
- Abnormalities:
- effects observed, non-treatment-related
- Key result
- Developmental effects observed:
- no
- Conclusions:
- No treatment related effects were noted both in adult females and in fetuses in the study conducted with the analogue substance. The no-observable-effect concentration (NOAEC) for maternal exposure to H GALDEN and embryo-fetal development in rats is 10006 ppm.
Based on the analogue approach, GALDEN LMW is not expected to impair embryo-fetal development and the NOAEC of 10006 ppm can be considered a worst case for assessment. - Executive summary:
The read-across approach with the analogue substance H-GALDEN was applied in order to assess the potential effects on embryo-fetal survival and development of GALDEN LMW following exposure by inhalation.
GALDEN LMW and H GALDEN have similar chemical structure and common characteristic which are typical of compound having C-F bounds. However the presence of –OCF2H as terminal groups in H-GALDEN, gives to the product slight more reactivity and more polarity than those observed for GALDEN, characterised by neutral, non functional terminal groups –OCF3.
The available experimental data show that GALDEN LMW and H GALDEN have the same profile regarding physico-chemical reactivity, skin and eye irritation and skin sensitization.
Under the reported study H GALDEN was administered to pregnant female CD rats by inhalation, during the organogenesis phase of the pregnancy.
Three groups, each of 25 time-mated female rats, were exposed to an aerosol of H GALDEN, 6 hours a day, from days 6-19 after mating using a whole body exposure system. A fourth group, also of 25 females, acted as a control and was exposed to air only. The target dose of H GALDEN were 1000, 3300 and 10000 ppm.
During the study clinical signs, bodyweight, food and water consumption were recorded. On day 20 of pregnancy the animals were killed, examined macroscopically, and the uterus excised for examination of litter parameters and subsequent fetal examination.
The exposure chamber mean analysed concentration over the duration of the study were 0 (Control), 1004, 3267, and 10006 ppm.
There were no treatment related clinical observations and no deaths amongst adult females.
Bodyweight gain and food consumption of the High dose females was slightly lower than that of the control during the first few days of treatment. Bodyweight gain recovered thereafter such that, overall, the gain was similar to the controls. These changes are very slight and considered not to reflect an adverse effect.
No treatment related effects were noted.
No treatment related macroscopic changes were noted.
There were no obvious effects on treatment on the in-utero parameters investigated.
There were considered no treatment related findings at detailed visceral and skeletal examination.
It was concluded that the maternal no-observable-effect concentration (NOAEC) for maternal exposure to H GALDEN and embryo-fetal development in rats is 10006 ppm.
Based on the analogue approach GALDEN LMW is expected to have the same toxicological profile as H GALDEN, therefore it is not expected to impair embryo-fetal developmental and the NOAEC of 10006 ppm for effects on embryo-fetal developmental and maternal toxicity can be considered as a worst case.
Moreover it should be underlined that, because of the greater reactivity of H GALDEN, the reported read across represents a worst case approach and it allows to be on the safe side in regard to the potential effects of GALDEN LMW on embryo-fetal development.
Referenceopen allclose all
Implantations and litter size
concentration (analytical) | 0 | 1004 ppm | 3267 ppm | 10006 ppm | |
number of females |
|
25 | 25 | 25 | 25 |
Corpora lutea |
mean SD |
15.9 2.6 |
16.2 1.7 |
15.1 2.3 |
15.0 1.7 |
Implantations number |
mean SD |
14.4 1.8 |
14.7 1.6 |
13.8 2.9 |
14.2 1.8 |
Resorptions Total Early Late |
mean mean mean |
0.8 0.8 0.0 |
1.0 1.0 0.0 |
0.6 0.6 0.0 |
0.7 0.7 0.0 |
Live young Total |
mean SD |
13.6 1.9 |
13.6 2.1 |
13.2 3.1 |
13.5 1.9 |
Male |
mean SD |
7.2 2.2 |
7.2 2.4 |
6.4 2.2 |
6.5 2.4 |
Female |
mean SD |
6.4 2.4 |
6.4 2.1 |
6.8 2.6 |
7.0 2.2 |
Sex ratio (% males/litter) |
|
53.5 |
52.7 |
49.0 |
47.7 |
Pre-implantation loss (%) |
|
9.4 |
9.2 |
8.9 |
5.7 |
Post-implantation loss (%) |
|
5.6 |
7.01 |
5.3 |
4.8 |
SD: standard deviation
no statistical differences (p>0.05)
Litter data
concentration (analytical) |
0 |
1004 ppm |
3267 ppm |
10006 ppm |
# of litters |
25 |
25 |
25 |
25 |
# of live fetuses |
339 |
341 |
329 |
337 |
mean litter weight (g) SD |
50.81 7.72 |
51.28 8.60 |
49.57 11.19 |
51.11 7.38 |
mean fetal weight (g) (M+F) SD |
3.75 0.23 |
3.75 0.21 |
3.78 0.23 |
3.79 0.16 |
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Quality of whole database:
- All the studies were conducted under GLP.
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
The read-across approach with the analogue substance H-GALDEN was applied in order to assess the potential effects on embryo-fetal survival and development of GALDEN LMW following exposure by inhalation.
GALDEN LMW and H GALDEN have a similar chemical structure and common characteristics which are typical of compound having C-F bounds. However the presence of –OCF2H as terminal groups in H-GALDEN, gives to the product slight more reactivity than those observed for GALDEN LMW, characterized by neutral, non functional terminal groups –OCF3.
The selected key-study for this endpoint is OECD 414 Guideline-conform, the experimental procedure permits to assess the effects of the test substance on implantation, resorptions, foetal growth, morphological variations and malformations.
No treatment related effects were observed and the NOAEL of 10006 ppm for effects on embryo-fetal developmental and maternal toxicity was derived.
The conclusion of the study is consistent with the results of the two supporting sighting studies, in which H GALDEN was administered to pregnant females up to the maximum concentration of 20000 ppm for 5 and 14 days respectively. At the end of both studies, foetus were examined macroscopically and no signs of embryotoxic and/or teratogenic effects were observed. The only possible effect was a decrease in mean fetal weight (decrease of 10.16%, statistically significant) observed at the highest concentration (19589 ppm) in the 14-day repeated dose toxicity study.
In conclusion, GALDEN LMW is not expected to impair embryo-fetal development. Moreover, it should be underlined that because of the greater reactivity of H GALDEN, the reported read-across represents a worst case approach and a conservative assessment of the potential hazardous effects of GALDEN LMW.
Justification for classification or non-classification
According to Regulation (EC) 1272/2008 GALDEN LMW does not meet the classification criteria for the hazard class “Reproductive toxicity”.
Additional information
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