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EC number: 947-368-7 | CAS number: -
- 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
Description of key information
Read across from source substance (key studies):
Subacute repeat oral dose toxicity study (OECD 407): NOAEL 10 mg/kg bw/day (Umano 2012)
Combined repeat dose toxicity study with reproductive toxicity screening (OECD 422): NOAEL 30 mg/kg/day; Anon (2011)
Conducted on the substance itself (supportive study):
Combined repeated dose and reproduction / developmental screening (OECD 422): LOAEL 175 mg/kg bw/day; Reliability K1;
Read accross from Source substance (supporting study):
Feng et al. (2012) BPAF study in male rats dosed via oral gavage at 0, 2, 10, 50, or 200 mg/kg/day for 14 days.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 10 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- System:
- other: NOAEL was based on the reduced body weight gain and abnormal estrous cycles in the female rat in the intermediate dose group.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Mode of Action Analysis / Human Relevance Framework
During the treatment period, a dose-dependent decrease in overall mean body weight gain was apparent in all groups of toxicity and recovery phase males and females exposed to BPAF when compared to controls; this decrease in overall weight gain was largely attributable to lower body weight gain and body weight losses. The reduction in body weight performance was evident among the reproductive phase females in the gestation and lactation period and was considered to be an adverse effect. Another finding is the possible endocrine effects as demonstrated by the Leydig cell atrophy and irregular estrous cycles noted in both studies performed on BPAF according to OECD 407 and OECD 422. This effect correlate with the reduced secretory content in prostate and seminal vesicles with no evidence of recovery. Effect on estrous cycles also correlate with the failure in mating and inability to achieve pregnancy
Additional information
In a subacute toxicity study conducted on rats in accordance with OECD 407 under GLP (Umano, 2012), the analogue substance was administered to 30 male and 30 female Sprague-Dawley rats by oral gavage at dose levels of 10, 30 and 100 mg/kg bw/day for up to 28 consecutive days. Although there was no recovery phase, this is not a guideline requirement. The key findings in this study were lower body weight gain at 100 mg/kg/day for males and at 30 and 100 mg/kg/day for females; lower white cell counts in males at 100 mg/kg/day; lower cholesterol levels in both sexes at 100 mg/kg/day; lower cholinesterase and higher bilirubin levels in females at 100 mg/kg/day; longer oestrous cycles in females at 100 mg/kg/day; lower absolute and relative prostate and seminal vesicles weights at 100 mg/kg/day, possibly reflecting the lower body weight; higher adrenal weight in males at 100 mg/kg/day; Leydig cell atrophy at 100 mg/kg/day in 5/10 males; hypertrophy of the adrenal zona fasciculata at 100 mg/kg/day in 8/10 males, 2/10 females; atrophy of mammary glands in 3/10 males at 100 mg/kg/day; decreased haematopoiesis in bone marrow and extramedullary haematopoiesis in spleen at 100 mg/kg/day in 4/10 and 2/10 males, respectively. Many findings were related to endocrine effects, but had not considered that some may have been secondary to the lower body weights. Without having the individual data, it is not possible to comment further. In conclusion, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was 10 mg/kg bw/day due to findings of reduced body weight gain and abnormal estrous cycles in the female rat treated at 30 mg/kg bw/day.
In a combined repeated dose toxicity study with reproductive toxicity screening OECD TG 422 conducted in rats according to GLP, dose levels of 30, 100 and 300 mg/kg bw/day, males were dosed for a total of 6 weeks, with a recovery group maintained for a further 2 weeks. All non-recovery females were mated after 2 weeks dosing, then reared until around Day 4 post partum. Recovery females were not mated, were dosed for a total of 6 weeks followed by 2 weeks recovery. Although mating was not obviously affected, there were no pregnancies at 300 mg/kg bw/day. At 30 and 100 mg/kg bw/day, there were 10/12 and 8/12 females pregnant, respectively, although only 9 and 7 females had live offspring compared with 11 control females. Because of these findings, inter-group comparisons for females were confounded by the different pregnancy statuses of the females. Reproductive findings will be discussed under developmental/ reproductive toxicology. The other key findings were lower body weight gain of both sexes at 100 and 300 mg/kg bw/day; lower haemoglobin, red cell counts and haematocrit in males at 300 mg/kg bw/day; lower cholesterol levels in both sexes at all dose levels; lower albumin levels in males at 100 and 300 mg/kg bw/day; lower epididymides and testis weights at 300 mg/kg bw/day; higher liver and adrenal weights in males at 300 mg/kg bw/day; lower heart weights in females at 30 and 100 mg/kg bw/day possibly reflecting lower body weights; Leydig cell atrophy in males at 100 and 300 mg/kg bw/day, with almost complete regression after 14 days recovery; reduced secretory content in prostate and seminal vesicles with no evidence of recovery; centrilobular hepatocyte enlargement in males at all levels and in females at 100 and 300 mg/kg bw/day, with evidence of recovery.
Based on the 2 studies conducted on the analogue substance, the key findings were lower weight gain in males at ≥100 mg/kg/day and in females at ≥ 30 mg/kg/day; lower cholesterol levels in both sexes at ≥100 mg/kg/day and possibly at 30 mg/kg/day; lower epididymides and testis weights at 300 mg/kg/day; higher liver and adrenal weights in males at 300 mg/kg/day, with possible increase in adrenal weights at 100 mg/kg/day; Leydig cell atrophy at ≥100 mg/kg/day with regression during recovery period; reduced secretory content in prostate and seminal vesicles with no evidence of recovery at ≥100 mg/kg/day; centrilobular hepatocyte enlargement in males at ≥30 mg/kg/day and in females at ≥100 mg/kg/day, with evidence of recovery.
The key value for chemical safety assessment used was NOAEL = 10 mg/kg bw/day (Umano, 2012).
The registered substance was tested for reproduction/developmental toxicity screening study with rats (OECD 422), range of tested doses (175, 375, 750 mg/kg bw/day).Because the effects observed in the study conducted on the registered substance so closely match the effects reported in similar studies with substance in the BPA family, the observed toxicity was the result of the BPAF present in the registered substance. Since no NOAEL was determinde in the study of the registered substance, the studies conducted on the analogue substance were taken as key studies for the risk assessment of this endpoint.
In another repeated dose toxicity study (Feng 2012), the substance was administered to 30 Sprague-Dawley male rats by gavage at dose levels of 2, 10, 50 and 100 mg/kg bw/day along with a vehicle control group for 14 days. Key finding included, decreased total serum cholesterol at dose of 50 and 200 mg/kg/day, Reduced serum testosterone and increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were observed in rats in the higher dose groups. Dose related accumulation of the testate in the testes, decline in genes and protein involved in cholesterol biosynthesis, transport and steroid biosynthesis. Similarly, the testicular mRNA levels of inhibin B, estrogen receptor (ER) and luteinizing hormone receptor (LHR) also decreased in rats given a dosage of 200 mg/kg/d. The NOEAL for male Sprague-Dawley rats was < 10 mg/kg/bw.
In an uterotrophic and Hershberger repeated dose test (Yamasaki 2003), the test item was administered to rats via subcutaneous injections and oral garage at dose levels of 8, 40 and 100 mg/kg bw/day and 50, 200 and 600 mg/kg bw/day respectively. Test item related effects were noted in both female and male individuals in their respective tests at the tested concentrations, significant reduction in weight increase and significant increase glans penis weight observed in the 200 and 600 mg/kg bw/day male treatment groups. Mortality of two individuals was also observed in the male Hershberger test at the highest dose group. There was also significant increase in relative uterus weight in the 8 and 40 mg/kg bw/day dose groups. The NOAEL for male and female rats was < 8 mg/kg bw/day based on histopathology results, where a significant increase in organ weight (uterus) was observed in female individuals, there is an implication that the test item has estrogen agonistic properties.
Justification for classification or non-classification
The analogous source substance meets the criteria for classification as STOT-RE Category 2 in accordance with Regulation (EC) No 1272/2008 (CLP). This classification is based on the following:
- Lower absolute and relative prostate and seminal vesicle weights at 100 mg/kg bw/day (Umano et al., 2012)
- Higher adrenal weights in males at 100 mg/kg bw/day (Umano et al., 2012)
- Leydig cell atrophy at 100 mg/kg bw/day (Umano et al., 2012)
- Lower epididymide & testes weights at 300 mg/kg bw/day (OECD 422, Anon., 2011)
- Higher liver & adrenal weights in males at 300 mg/kg bw/day (OECD 422, Anon., 2011)
- Leydig cell atrophy at 100 mg/kg bw/day (OECD 422, Anon., 2011)
- Reduced secretory content of prostate and seminal vesicle at 100 mg/kg bw/day (OECD 422, Anon., 2011)
Based on an analogue approach to related degradation products BPAF (the source substance), one may conclude the target substance is also having the same toxicological profile for Repeated dose toxicity, meeting the criteria to classify STOT RE cat.2, in accordance with Regulation (EC) No 1272/2008 (CLP).
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