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EC number: 288-003-5 | CAS number: 85631-54-5
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The study is a scientific publication and well documented. The read across hypothesis is based on the assumption that due to its characteristic as ester, after ingestion in mammalians the ester bound of the target chemical will be subject to metabolic cleavage into its corresponding alcohols and the acrylic acid. Thus FTAC (target) and its associated alcohols (perfluoro-alkylethanol) n:2 FTOH mixture are considered to form not only a group of structurally related analogues, but are also closely related based on metabolic pathway considerations. For details see section 13 of this IUCLID document.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- publication
- Title:
- Evaluation of the reproductive and developmental toxicity of a fluoroalkylethanol mixture
- Author:
- Mylchreest, E., Ladics, G.S., Munley, S.M., Buck, R.C., and Stadler, J.C.
- Year:
- 2 005
- Bibliographic source:
- Drug Chem. Toxicol. 28 (2005): 159-175
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- fluoroalkylethanol mixture
- IUPAC Name:
- fluoroalkylethanol mixture
- Reference substance name:
- 65530-60-1
- EC Number:
- 613-814-1
- Cas Number:
- 65530-60-1
- IUPAC Name:
- 65530-60-1
- Test material form:
- other: medium tan waxy solid
- Details on test material:
- - The fluoroalkylethanol [also known as fluorotelomer alcohol, F(CF2CF2)nCH2CH20H, n = 3 to 6] mixture (CAS no. 65530-60-1) as commercially produced was supplied as a pale to medium tan waxy solid by DuPont Chemical Solutions Enterprise (Deepwater, NJ, USA).
- The purity of the test substance was 95%.
- The test substance contained 2% residual fluoroalkylethyl iodide [F(CF2CF2)nCH2CH2I, n =3 to 6], which is the chemical precursor to the fluorotelomer alcohol.
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- Nulliparous, time-mated females were received from Charles River Breeding Laboratories. The rats were 63 days old upon receipt and were at
either GD 1, 2, or 3. Body weights recorded on the day that evidence of copulation was observed (GD 0) were provided by the vendor and ranged from 226 to 260 g. The rats were housed individually in wire-mesh cages throughout the developmental toxicity study. Animal rooms were maintained on a timer-controlled, 12-hour light/12hour dark cycle (fluorescent light). Environmental conditions of the rooms were targeted to be within a temperature range of 22 ± 3°C and a relative humidity range of 50 ± 20%. Tap water and PMI Nutrition International, Inc., Certified Rodent LabDiet 5002 were available ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% aqueous methylcellulose
- Details on exposure:
- Formulated suspensions of the test substance in 0.5% aqueous methylcellulose were prepared daily and were administered at a volume of 10 mL/kg throughout the study.
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- Nulliparous, time-mated females were received from Charles River Breeding Laboratories. The rats were 63 days old upon receipt and were at
either GD 1, 2, or 3. Rats were assigned to lots according to their gestation day and then randomized within their respective lots on the basis of GD 0 body weights. They were assigned either to the control or to an experimental group by random sampling from a ranked list, so that means and standard deviations were similar across dose groups. - Duration of treatment / exposure:
- treatment on gestation days 6 to 20.
- Frequency of treatment:
- daily treatment on gestation days 6 to 20.
- Duration of test:
- gestation days 4 to 21.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
50, 200 and 500 mg/kg bw/d
Basis:
nominal conc.
- No. of animals per sex per dose:
- 22 mated and pregnant females/group
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- Body weights were recorded daily during the intubation period (GD 6-20) and on the day of sacrifice (GD 21). Clinical signs were recorded daily in the morning for each animal on study. Afternoon clinical observations were recorded during the intubation period (GD 6-20).
- Ovaries and uterine content:
- All dams were sacrificed on GD 21 and examined grossly for external and internal alterations. The gravid uteri were removed and weighed to permit calculation of the final maternal body weight adjusted for the weight of the uterine contents. The fetuses were removed from each uterus and individually identified.
- Fetal examinations:
- Each fetus was weighed, sexed, and examined for external alterations.
- Approximately half of the fetuses were subjected to fresh visceral (Staples, 1974) and fixed head (Barrow and Taylor, 1969) examinations.
- All fetuses were examined for skeletal alterations.
- Stages of renal papillary development were determined as described by Woo and Hoar (1972) - Statistics:
- Sequential trend tests were applied until no dose response was detected (Selwyn, 1995). Continuous data (maternal body weight, weight change, and feed consumption) were analyzed using a linear contrast of means from analysis of variance (ANOVA) (Snedecor and Cochran, 1967). For litter count data and fetal alteration data, Jonckheere's test was applied in a sequential fashion (Jonckheere, 1954).
Where litter effects (pup/fetal weight, sex ratio) must be considered, a linear contrast of least square means from ANCOVA was sequentially applied; litter size and sex ratio were considered covariates for pup/fetal weight analyses, and litter size was considered a covariate for sex ratio analysis (Dempster et al., 1984).
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: reduced body weigth were observed at the 500 mg/kg/bw/d group
Details on maternal toxic effects:
Reduced body weigth and increased perineal fur staining were observed at the 500 mg/kg/bw/d group.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes. Remark: increased fetal skeletal alterations (variations but no malformations) were observed at 500 mg/kg/d
Details on embryotoxic / teratogenic effects:
Increased fetal skeletal alterations (variations but no malformations) were observed at 500 mg/kg/d
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Exposure of pregnant rats to the test substance at levels of 0, 50, 200, or 500 mg/kg/day did not produce any test substance-related mortality neither in maternal rats nor in the pups.
Evidence of maternal and developmental toxicity was detected at 500 mg/kg/day (Table 1). At 500 mg/kg/ day, there were reductions in mean absolute and adjusted final body weights (about 5 %) and weight gain (about 15 %) (calculated for the entire intubation period: GD 6 through 21). The reduced weight gains were most pronounced during the first week of intubation. There were also increased occurrences of perineal fur staining at 500 mg/kg/day; 9 of 22 animals from this level were affected at some point during the study.
With regard to developmental toxicity, there were increased incidences of fetal skeletal alterations (delayed skull and pelvic bone ossification and wavy ribs) accompanied by a slight decrease in mean fetal weight (about 3%). At 200 and 500 mg/kg/day, there were some instances in the data where effects occurred that were considered test substance-related.
At 200 mg/kg/day, maternal weight gains were reduced early in the treatment period; however, the magnitude of the reductions was small and transient, because the reduced gains had no appreciable impact on final body weight. Similarly, feed consumption was reduced at the beginning of treatment at both the 200 and 500 mg/kg/day doses. These reductions were not considered adverse because they were transient and had no appreciable impact on overall feed consumption.
Mean fetal weight was slightly reduced at 200 and 500 mg/kg/day; however, the magnitude of the reduction was minimal (3% lower than for controls) and thus was not considered adverse. The significant increase in the incidence of retarded skull bone ossification at 200 mg/kg/day was not considered test substance-related because it was within the relevant historical control range, and the statistical significance appeared to be the result of a relatively low value for the concurrent control group. There were no test substance-related effects observed at 50 mg/kg/day.
Table 1: Summary of maternal toxicity and reproductive outcome
|
Dose (mg/kg bw/d) |
|||
|
0 |
50 |
200 |
500 |
Maternal Toxicity endpointsa |
|
|
|
|
Clinical observation |
— |
— |
— |
Increased perineal staining |
Absolute final body weight |
416.8 (27.86)b |
415.9 (23.54) |
407.5 (28.74) |
399.4 (28.51)* |
Net final body weightC |
319.0 (19.75) |
315.3 (17.44) |
310.9 (21.05) |
303.4 (18.99)* |
Dosing period weight gain |
156.7 (22.42) |
151.4 (15.78) |
143.2 (21.08)* |
133.1 (27.54)* |
Net dosing period weight gainC |
58.9 (14.88) |
50.8 (12.39) |
46.6 (15.74)* |
37.1 (18.48)* |
Dosing period food consumption |
26.6 (4.71) |
25.9 (2.67) |
24.9 (2.13) |
25.4 (1.91) |
|
|
|
|
|
Reproductive outcome and litter data |
|
|
|
|
No. mated |
22 |
22 |
22 |
22 |
No. pregnant |
22 |
22 |
22 |
22 |
|
|
|
|
|
Means per litter |
|
|
|
|
Corpra lutea |
16.7 (1.93) |
16.6 (2.32) |
16.6 (3.02) |
15.8 (1.77) |
Implantations |
14.2 (1.31) |
14.8 (1.82) |
14.2 (2.29) |
14.4 (1.81) |
Resorptions (combined) |
0.4 (0.58) |
0.4 (0.59) |
0.2 (0.39) |
0.4 (0.91) |
- Early resorptions |
0.4 (0.58) |
0.3 (0.57) |
0.2 (0.39) |
0.4 (0.91) |
- Late resorptions |
0 |
0.1 (0.29) |
0 |
0 |
Dead fetuses |
0 |
0 |
0 |
0 |
Live fetuses |
13.9 (1.49) |
14.4 (1.71) |
14.0 (2.44) |
14.0(2.24) |
Sex ration (% males) |
45 |
45 |
49 |
46 |
Fetal weight (g) |
5.53 (0.30) |
5.52 (0.26) |
5.36 (0.20) |
5.38 (0.44)* |
a: AII weights are in grams (body weight and weight gain) or grams/day (food consumption).
b: Mean (standard deviation)
C: Products of conception excluded from maternal body weight
*:Statistically significant trend (p < 0.05) by linear contrast of means from ANOVA.
**:Statistically significant trend (p < 0.05) by linear contrast least square means from ANCOVA (litter size and sex ratio covariates).
Applicant's summary and conclusion
- Executive summary:
In order to evaluate the pre-natal developmental toxicity of the mixed fluorotelomer alcohol, groups of time-mated Sprague-Dawley female rats were administered the test substance by oral gavage in 0.5% methylcellulose as vehicle at daily dosages of 0, 50, 200, or 500 mg/kg/d on gestation days 6-20. In the developmental toxicity study, reduced maternal body weight parameters, increased perianal fur staining and increased fetal skeletal alterations (variations but no malformations) were observed at 500 mg/kg/d. There was no maternal or developmental toxicity at 50 or 200 mg/kg/d. Minimal fetal weight reduction in the 500 mg/kg/d group were considered secondary to maternal toxicity. Thus, the no-observed-adverse effect level (NOAEL) for maternal and developmental toxicity was considered to be 200 mg/kg/d.
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