Under which legislation was the information requested (Regulation 793/93 or Directive 67/548/EEC): Regulation 793/93
|
|
- Jared Shields
- 5 years ago
- Views:
Transcription
1 1 (16) Conclusion of substance evaluation for transitional dossiers Summary conclusion of evaluation of a substance according to transitional measures described in Article 135(2), 136 (1) or 136(2) and 48 of the REACH Regulation. Substance concerned: 1. Chemical name: 4-tert-butylphenol 2. EC No: CAS No: Member State reviewing the transitional dossier: Norway Under which legislation was the information requested (Regulation 793/93 or Directive 67/548/EEC): Regulation 793/93 The specific decision, reference or regulation number, which relates to this testing request: Commission Regulation (EC) No 506/2007/ and Com. Reg. (EC) No 466/2008 Date of submission by Member State: September 2013 Registration number (if available): 9d8bb7ca-18a5-44ef-e f67d249/DISS-9d8bb7ca-18a5-44ef-e f67d249_DISS-9d8bb7ca-18a5-44ef-e f67d249.html
2 2 CONCLUSION OF TRANSITIONAL SUBSTANCE EVALUATION Need for harmonised classification and labelling Need for identification as SVHC (authorisation) Need for a restrictions proposal Need for other Community-wide measures Such as: substance evaluation process/dossier evaluation Need for action at national level or voluntary action by industry Such as: update of registrations No follow-up action at EU level required Tick relevant box(es) x x
3 3 SHORT JUSTIFICATION FOR CONCLUSION 1) Commission Regulation No 466/2008 required local exposure information on the release from two processing sites (5 and 6) into wastewater treatment plants and aquatic compartment (freshwater and marine) from industry. It is recognised that the exposure information in the EU risk assessment report is no longer relevant since production and use volumes have changed significantly since REACH entered into force. Several companies have submitted registrations dossier for 4-tert-butylphenol in 2010 and ) Commission Regulation No (EC) No 506/2007 requires an endocrine effects study with fish ( draft OECD ext. ELS test). Background In vitro data for ptbp and structurally related chemicals: Para-tert-butylphenol (ptbp) has been identified as a potential endocrine disruptor based on the chemicals ability to interact with and activate the estrogen receptor (ER) in vitro in several organisms and bioassays. These in vitro studies include recombinant cell reporter systems (yeast and bacterial estrogen screens) which express the human estrogen receptor, estrogen dependable MCF7 cancer cells, receptor-binding assays with purified liver homogenates containing ERs and induction of the estrogenic biomarker vitellogenin (VTG) in primary liver cells from fish. Estrogen receptor-binding studies The results from receptor-binding studies show that ptbp, and a range of alkylphenols and other industrial chemicals, are able to bind to the human, rat and fish ERs. The studies with human ERs report that ptbp binds to the ER with times lower affinity than the natural ligand 17β-estradiol (E2) (Olsen et al., 2005). The binding affinity of ptbp to the human ER were 20 times lower than the more hydrophobic alkylphenol 4-tert-octylphenol (ptop) and 500 times
4 4 lower than Bisphenol A (BPA). The binding affinity of ptbp to the human ERs resemble that of the rat ER, where binding affinity of ptbp were times lower than E2, 15 times lower than ptop and 30 times lower than BPA (Blair et al., 2000). Interestingly, ptbp displayed similar binding affinity as the structurally related alkylphenol 4-tert-pentylphenol, ptpp. Studies with rainbow trout liver homogenates demonstrate that ptbp binds to the ER with about times lower binding affinity than E2, and fairly similar binding affinity as ptpp, ptop and BPA (Olsen et al., 2005; Tollefsen and Nilsen, 2008). The available in vitro receptor-binding studies clearly suggest that ptbp binds to the human, rat and fish ER with binding affinities that are comparable to well-characterised endocrine disruptors such as ptpp, ptop and BPA. Activation of the estrogen receptor ptbp has been demonstrated to activate the human and fish ERs. Studies with the yeast estrogen screen, which is stably transfected with the human ER, report that ptbp activate the human ER at approximately 1.4 million times lower potency than E2, 10 times lower potency than ptpp, 1000 times lower potency than ptop and 1500 lower potency than BPA (Routledge and Sumpter, 1997; Sohoni and Sumpter, 1998). Other studies using the estrogen dependent MCF7 cancer cell line, which also express the human ER, confirm that ptbp has a relative low estrogenic potency (0.3-5 million times lower than E2), similar potency as ptpp, about times lower potency than ptop and BPA (Olsen et al., 2005; Soto et al., 1995). Interestingly, induction of the estrogenic biomarker VTG in rainbow trout liver cells (hepatocytes) show that ptbp exhibit a higher relative potency than that reported in bioassays with the human ERs, with a potency times lower than E2, similar potency as ptpp and within one order of magnitude lower potency than ptop and BPA (Olsen et al., 2005; Tollefsen et al., 2008). An interspecies comparison confirms that ptbp display a higher relative ER binding affinity and estrogenic potency in fish than human-derived from in vitro bioassays (Olsen et al., 2005). Structure activity relationship (SAR) studies with a range of alkylphenols with different chain lengths, number of alkylated substituents and substituent position show that ptbp are among the most estrogenic alkylphenols in rainbow trout when tested in vitro
5 5 (Tollefsen et al., 2008). In vivo data and read across to structurally related chemicals No fish in vivo data has to date been provided for ptbp in open literature, so read-across to closely related alkylphenols was conducted. A full life-cycle (2 generation) study with Japanese medaka (Oryzias latipes) exposed to ptpp demonstrated that low µg/l concentrations of ptpp led to abnormal sexual differentiation (LOEC=224 µg/l) and VTG induction (LOEC=51 µg/l) in the F1 generation (Seki et al., 2003). Reports of in vivo endocrine modulating and disrupting effects of ptpp also in common carp (Cyprinus carpio) and fathead minnow (Pimephales promelas) at low µg/l concentrations strengthened the concern that moderately sized parasubstituted alkylphenols such as ptpp and ptbp are likely to cause endocrine disruption in fish (Gimeno et al., 1996; Gimeno et al., 1997; Hagino et al., 2001; Panter et al., 2006; Panter et al., 2002). Studies with other well-characterised estrogenic compounds such as BPA and ptop (see RAR for BPA and ptop) have previously led to proposal for low NOECs for reproductive effects in fish at 16 and 12 µg/l, respectively. ptop is currently identified as an SVHC and included in the candidate list due to endocrine disrupting properties ( see. The requirement for a long term study in fish The in vitro estrogenic properties of ptbp, which were found to be fairly similar to ptpp, ptop and BPA in fish, and read across to in vivo data introduced the requirement for a regulatoryinitiated investigation of potential endocrine disrupting effects in in vivo. A protocol for performing a Partial Life Cycle Test with the Fathead Minnow was therefore developed. The test was conducted as a two tiered approach based on an initial test optimisation and range finding test (pilot study) followed by a full study design (final study). Pilot study: A Partial Life Cycle Test with the Fathead Minnow (Pimephales promelas) A 128-day non GLP pilot study with ptbp to determine test concentrations for the full study and evaluate the suitability of endocrine endpoints to be used in a partial life cycle test with fathead minnow has been performed with ptbp at nominal concentrations of 1, 30, 100 and 500 µg/l. Traditional endpoints of fish early life-stage studies, including effects of the test substance on time to hatch, hatching success, stage specific survival and growth were monitored. Endocrine
6 6 mediated endpoints were evaluated including gonadosomatic index (GSI), sex ratio, observation of secondary sex characteristics, measurement of VTG and histopathology of gonads and gonadal ducts. The protocol was based upon the experimental design presented in ANNEX E, Partial Life Cycle Test (or Extended Early Life-Stage Test) of the OECD Detailed Review Paper on Fish Screening Assays for the Detection of Endocrine Active Substances (OECD, 2004). The study also incorporated procedures in the OECD Guideline for Testing of Chemicals, 210: Fish Early- Life Stage Toxicity Test (OECD, 1992) and ASTM Standard E Standard Guide for Conducting Early Life Stage Toxicity Tests with Fish (ASTM, 1998). The main findings of the pilot study were as follows (nominal concentrations in brackets): 1. Water concentrations: measured water concentrations were (2, 25, 82, 413 µg/l), thus deviated more than 20% from the nominal concentrations (1, 30, 100, 500 µg/l). Suggestions to use the measured, rather than nominal have been proposed and both have consequently been presented for clarity. 2. Hatching success: No effects were observed in the hatching success in any group, but a significant delay in hatching for the 82 µg/l (nominal: 100 µg/l) and 413 µg/l (nominal: 500 µg/l) group was observed according to the Jonkheere-Terpstra trend test (p<0.05). Although the biological significance of these findings was questioned, a need for improved sampling design was proposed to properly assess this effect. 3. Survival of Larvae and Juvenile fish: No significant differences in survival of fish at any fish stage observed. 4. Sex ratio: A significant reduction in male fish and fish displaying male gonads was observed at the 413 µg/l (nominal: 500 µg/l) treatment group according to the Jonkheere- Terpstra trend test (p<0.05). The findings were based on gross internal sex and on external sex determination. 5. Growth: No significant changes in length and weight of females were observed. A
7 7 treatment-related effect on fish length and weight were observed for males at the concentration of 413 µg/l (nominal: 500 µg/l) according to the Jonkheere-Terpstra trend test (p<0.05). No significant differences were identified in males of any treatment group when compared to the control according to the Dunnett s test (p<0.05) 6. Gonadosomatic index (GSI): No significant changes in GSI of either males or females were observed. 7. Vitellogenin (VTG): No significant changes in plasma VTG in males were observed, apparently due to high inter-replicate variations. An apparent treatment-related increase in female plasma concentrations of VTG in the 413 µg/l (nominal: 500 µg/l) group was suggested, although this was not identified to be significant according to either the Jonkheere-Terpstra trend test (p<0.05) nor the Dunnett s test (p<0.05). Large intra and inter-replicate variation was clearly evident in both males and female groups, leading to concern that an apparent trend in reduction of VTG in females at the 2 µg/l (nominal: 1 µg/l) and 25 µg/l (nominal: 30 µg/l) may have been treatment related. No explanation for a non-endocrine mechanism causing this lowconcentration effect could be provided, and thus leading to this observation remained unclear. 8. Onset of male sex characteristics: A treatment related effect on fish displaying at least one male secondary sex characteristic was observed in the 413 µg/l (nominal: 500 µg/l) group. It was not possible to discriminate whether the observed effect were due to a delay in maturation or lack of ability to develop male secondary sexual characteristics, however. 9. Pigmentation on dorsal fin or nose/lip: Pigmentation on the dorsal fin or nose/lip of fish in the treatment groups was not significantly different from the control. However, the fish in the 413 µg/l (nominal: 500µg/l) treatment group displayed an apparent, although non-significant, treatment-related effect. 10. Presence of fatpad and fatpad Score: A treatment-related reduction in the proportion of male fish with a fatpad and in fatpad scores was identified in the 413 µg/l (nominal: 500 µg/l) treatment group according to the Jonkheere-Terpstra trend test (p<0.05). The male fish in the 82
8 8 µg/l (nominal: 100µg/l) treatment also displayed an apparent, although non-significant, treatment-related effect. 11. Presence of Tubercles, Tubercle Count and Tubercle Score: Presence of tubercles (counts and score) of fish in the treatment groups were not significantly different from the control. However, the fish in the 413 µg/l (nominal: 500µg/l) treatment displayed an apparent, although not significant, treatment-related effect. 12. Histopathology: All of the males (12 out of 12) evaluated in the 413 µg/l (nominal: 500 µg/l) treatment group exhibited feminization of gonadal ducts (minimal to moderate). Presence of testicular oocytes (minimal to mild) was observed in 5 out of 12 samples evaluated at the same treatment group. The presence of intravascular fluid in female ovaries, which was considered indicative of increased VTG production, was observed at 82 µg/l (nominal: 100 µg/l) and 413 µg/l (nominal: 500µg/L). The effect occurring at 82 µg/l was not considered statistically significant. Summary assessment of pilot study: It is concluded that the induction of VTG in females, changes in male sex ratio, feminization of male gonads and presence of testicular oocytes (intersex) are clear indicators of endocrine disruption. Observations such as delayed onset of male sex charateristics, pigmentation of fin or nose/lip, reduction in fatpads and/or fatpad scores, and reduction in tubercles, tubercle count and score, and presence of intravascular fluid in female gonads were all considered to provide supportive evidence for an ED mode of action. Delayed hatching, presence of intravascular fluid in female gonads and the presence of fatpads and fadpad score in male fish were identified as being the most sensitive endpoints determined and suggest a NOEC of 25 µg/l (nominal: 30 µg/l) and a LOEC of 82 µg/l (nominal: 100 µg/l). A negative trend in VTG production in females was indicated at even lower concentrations, although an endocrine mechanism to explain the observations could not be provided. It was concluded that the limited test design of the PILOT study could not secure sufficient statistical power to conclude on all of the endpoints tested nor comply fully with test criteria proposed for a full fish test (E ; OECD, 1992, 2004), thus required a full test adopting to a revised and improved test design.
9 9 Full study: A Partial Life Cycle Test with the Fathead Minnow (Pimephales promelas) A GLP study was performed with ptbp at 10, 30, 100 and 300 µg/l for 128 days to determine if exposure of fathead minnows to ptbp during their early development would result in changes typically associated with exposure of fish to estrogenic chemicals. The study was conducted according to the procedure Para-Tertiary Butyl Phenol (PTBP): A Partial Life Cycle Test with the Fathead Minnow (Pimephales promelas) (Krueger et al, 2008). The exposure period included a five-day hatching period followed by up to 123 days of post-hatch development of larvae and juvenile fish. Survival, body weights and lengths, and observations of abnormal behavior as well as endocrine-mediated endpoints including time to hatch, hatching success, observations of secondary sex characteristics, measurement of plasma VTG, measurement of GSI and histopathology of gonads were recorded and results are summarised below. A study summary is available in the disseminated data of the registration dossier: The main findings of the full study were as follows: 1. Water concentrations: The mean measured concentrations in the 10, 30, 100 and 300 µg/l treatment groups were 96, 90, 83 and 85% of nominal concentrations, respectively. Although some single measurements in the 100 and 300 µg/l groups were slightly lower than 80% of nominal, measured concentrations in these groups remained within ±20% of the initial measured concentrations. 2. Hatching Success and Time to Hatch: No effects were observed on hatching success at any of the concentrations tested over the five-day hatching period. A significant delay in the mean time to 50% hatch was observed at the highest concentration (300 µg/l) according to both the Jonkheere-Terpstra trend test (p 0.05) and the Dunnett s test (p 0.05).
10 10 3. Survival of Larvae and Juvenile Fish: A significant reduction in the survival of fish at the 300 µg/l concentration was observed at day 33. The overall high survival rates (>90%) for all groups were proposed to be an indicator of good health and findings proposed to be of low biological relevance. There were no apparent effects on fish survival from day 33 to test termination in any treatment group. 4. Sex Ratio: No significant changes in sex ratio were identified at the concentrations tested. 5. Growth: Treatment-related effects on growth (weight and length) in both males and females were observed in the 30, 100 and 300 µg/l treatment groups according to both the Jonkheere- Terpstra trend test (p 0.05) and the Dunnett s test (p 0.05). No significant change in the condition index of the fish was observed in either males or females. The lack of consistency between the growth parameters (e.g. weight and length) and condition index was proposed caused by a general treatment-related delay in fish development at concentrations higher than 10µg/L. 6. Gonadosomatic Index (GSI): There were no statistically significant differences in the GSI of females or males between the negative control and any of the treatment groups. 7. Vitellogenin (VTG): A treatment-related increase in female plasma VTG concentrations was identified in the 300 µg/l treatment group according to both the Jonkheere-Terpstra trend test (p 0.05) and the Dunnett s test (p 0.05). No statistically significant differences were observed in male plasma VTG concentrations. 8. Male Secondary Sex Characteristics: A treatment-related effect on fish displaying at least one male secondary sex characteristic was observed in the 30, 100 and 300 µg/l treatment groups according to the Jonkheere-Terpstra trend test (p 0.05). Only the 300 µg/l treatment group was significantly different from the control according to the Dunnett s test (p 0.05). 9. Pigmentation on dorsal fin or nose/lip: A treatment-related decrease in the proportion of males with a pigmented spot on the dorsal fin or nose/lip was observed in the
11 11 30, 100 and 300 µg/l treatment groups according to the Jonkheere-Terpstra trend test (p 0.05). Only the 30 µg/l treatment group was significantly different from the control when assessing pigmentation on the dorsal fin, whereas the 300 µg/l treatment group was significant different from control when assessing pigmentation on the nose/lip according to a Dunnett s test (p 0.05). 10. Presence of fatpad and fatpad Score: A treatment-related decrease in the proportion of males with a fatpad was observed in the 30, 100 and 300 µg/l treatment groups according to the Jonkheere-Terpstra trend test (p 0.05). No significant differences was observed between the control and any treatment group according to a Dunnett s test (p 0.05), however. 11. Presence of Tubercles, Tubercle Count and Tubercle Score: A treatment-related decrease in the proportion of males with tubercles, tubercules count and tubercle score were observed in the 30, 100 and 300 µg/l treatment groups. No significant difference was observed between the control and any treatment group according to the Dunnett s test (p 0.05), however. 12. Frequency distribution of male secondary sex characteristics: A treatment-related change in the frequency distribution of the various combinations of secondary sex characteristics was observed in the 30, 100 and 300 µg/l treatment groups according to the Fisher s Exact test. 13. Histopathology: Almost all of the males evaluated in the 300 µg/l treatment group (42 of 45) exhibited feminization of gonadal ducts (minimal to mild) according to a Fisher s Exact test. Presence of testicular oocytes (intersex) in one out of 45 male samples was also recorded. Summary assessment of full study: It is concluded that the induction of VTG in females, complete feminization of male gonads are clear indicators of endocrine disruption. Observations such as delayed onset of male sex characteristics, pigmentation of fin or nose/lip, reduction in fatpads and/or fatpad scores, and reduction in tubercles, tubercle count and score, were all considered to provide supportive evidence for an ED mode of action. It was noted by the contract laboratory that these endpoints showed treatment-related effects that potentially could be related to small delays in development,
12 12 where the overall effect on the fish population level was uncertain. Taking all available information into account, the most sensitive endpoints were reduced growth, reduction in secondary male sex characteristics, and the delay in the time to hatch. Overall statistical LOEC and NOEC values were 30 µg/l and 10 µg/l, respectively. Clearly defined estrogenic effects were clearly present in the 300 µg/l treatment group as evidenced by feminization of gonadal ducts of male fish and elevated levels of plasma VTG in females. Overall conclusion As identification of an endocrine disruptor should be based on a weight-of-evidence (WoE) approach providing causal relationship between an endocrine mode of Action (MoA) and adverse effects (Kortenkamp et al., 2011; Munn and Goumenou, 2013), demonstration of an estrogenic MoA and in vivo effects at the OECD conceptual framework (CF) for ED testing level 4 or 5 (OECD, 2012) is considered essential. A combination of available in vitro and in vivo data from literature on ptbp and compounds with structural or mechanistic (e.g. estrogenic compounds) similarities and data from the pilot and full fish studies have been used to support a WoE approach. The present data clearly demonstrates that ptbp bind and activate human, rat and fish ERs and in this respect display an endocrine MoA. The data from the two fish studies with ptbp shares a resemblance with previously reported studies with ptpp in various fish species by causing adverse effects such as changing male sex ratios (pilot study: 413 µg/l (nominal: 500 µg/l)), feminization of male gonads (Pilot study: 413 µg/l (nominal: 500 µg/l), Full study: 300 µg/l) and causing variable levels of intersex (pilot study: 413 µg/l (nominal: 500 µg/l), Full study: 300 µg/l). A range of endpoints such as delayed onset of male sex characteristics, pigmentation of fin or nose/lip, reduction in fatpads and/or fatpad scores, and reduction in tubercles, tubercle count and score, were considered to provide supportive evidence for an ED MoA in male fish, although the role of other factors such as treatment-related delay of fish development may not be completely disregarded. Clear estrogenic effects consistent with identifying ptbp as an endocrine disruptor was observed at 300 µg/l in the full study, leading to an NOEC for endocrine disruption of 100 µg/l and a LOEC of 300 µg/l. Based on the available fish studies and endpoints of ptbp reported herein, an overall NOEC of 10 µg/l and a LOEC of 30 µg/l on basis of data from the full study is justified.
13 13 It is considered that the current information is sufficient to classify/identify ptbp as an endocrine disruptor, although low-concentration effects observed in the fish studies such as changes in secondary male characteristics and delay in fish development may warrant additional studies to determine if they are mediated by an endocrine MoA. SUMMARY OF INFORMATION REVIEWED Include a brief overview of the new information reviewed in the transitional dossier. Information A pilot study based on Annex E of OECD "Detailed Review Paper on Fish Screening Assays for the Detection of Endocrine Active Substances A partial life cycle test with fathead minnow (Pimephales promelas) Date study was conducted Reason for information request Determine test concentrations and evaluate endocrine endpoints for the full study partial life cycle test Wildlife International, Ltd Concern on endocrine disruption Comments Results from the pilot study will be used in designing a partial life cycle test with fathead minnow (Pimephales promelas) Used to revise PNECaquatic, sediment and soil and update the risk assessment SUPPORTING DOCUMENTS AVAILABLE List documents available to support the conclusion of the substance evaluation e.g. risk assessment addendum or update, Annex XV dossier.
14 14 Title Author Date Comments Risk assessment on p-tert butylphenol Norway 2008 TIMETABLE FOR FOLLOW-UP ACTIONS (IF NECESSARY) Indicate a preliminary timetable, if available, for any follow-up actions proposed. A formal commitment to prepare an Annex XV dossier is made via the Registry of Intentions. Follow-up action Date for completion Who to complete action? Registrants to update their CSR to reflect the conclusion of this evaluation -Norway concludes with an overall NOEC of 10 µg/l and a PNEC of 1 µg/l. Propose ptbp for CoRAP (substance evaluation) June 2014 Registrants References: Blair, R.M., Fang, H., Branham, W.S., Hass, B.S., Dial, S.L., Moland, C.L., Tong, W., Shi, L., Perkins, R., Sheehan, D.M., The estrogen receptor relative binding affinities of 188 natural and xenochemicals: structural diversity of ligands. Toxicol Sci 54, E , A.S., Standard Guide for Conducting Early Life-stage Toxicity Testswith Fish. American Society for Testing and Materials. European Union Risk Assessment Report, 4,4'-ISOPROPYLIDENEDIPHENOL (BISPHENOL- A); CAS No: ; Complete risk assessment in one document, (February 2010) A European Union Risk Assessment Report, P-TERT-BUTYLPHENOL CAS No: , RISK ASSESSMENT, Final report 2008
15 15 Environment Agency UK: Environmental Risk Evaluation Report: 4-tert-octylphenol Gimeno, S., Gerritsen, A., Bowmer, T., Komen, H., Feminization of male carp. Nature 384, Gimeno, S., Komen, H., Venderbosch, P.W.M., Bowmer, T., Disruption of sexual differentiation in genetic male common carp (Cyprinus carpio) exposed to an alkylphenol during different life stages. Environ. Sci. Technol. 31, Hagino, S., Kagoshima, M., Ashida, S., Effects of ethinylestradiol, diethylstilbestrol, 4-t pentylphenol, 17β-estradiol, methyltestosterone and flutamide on sex reversal in S-rR strain medaka (Oryzias latipes). Environmental Sciences 8, Henry O. Krueger et al 2008: FINAL REPORT PARA-TERTIARY BUTYL PHENOL (PTBP): A Partial Life Cycle Test with the Fathead Minnow (Pimephales promelas) Kortenkamp, A., Martin, O., Faust, M., Evans, R., McKinlay, R., Orton, F., Rosivatz, E., State of the art assessment of endocrine disrupters final report. Munn, S., Goumenou, M., Key scientific issues relevant to the identification and characterisation of endocrine disrupting substances. Report of the Endocrine Disrupters Expert Advisory Group (ED EAG), p. 34. OECD, OECD Guidelines for Testing of Chemicals 210: Fish, Early-life Stage Toxicity Test., OECD Guideline for testing of chemicals. Organization for Economic Cooperation and Development, Paris, France. OECD, Detailed review paper on fish screening assays for the detection of endocrine active substances. Organization for Economic Cooperation and Development, Paris, France. OECD, Draft Guidance Document on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption, OECD Guideline for testing of chemicals. Organization for Economic Cooperation and Development, Paris, France., p. 44. Olsen, C.M., Meussen-Elholm, E.T., Hongslo, J.K., Stenersen, J., Tollefsen, K.E., Estrogenic effects of environmental chemicals: an interspecies comparison. Comp Biochem Physiol C Toxicol Pharmacol 141, Panter, G.H., Hutchinson, T.H., Hurd, K.S., Bamforth, J., Stanley, R.D., Duffell, S., Hargreaves, A., Gimeno, S., Tyler, C.R., Development of chronic tests for endocrine active
16 16 chemicals. Part 1. An extended fish early-life stage test for oestrogenic active chemicals in the fathead minnow (Pimephales promelas). Aquat Toxicol 77, Panter, G.H., Hutchinson, T.H., Lange, R., Lye, C.M., Sumpter, J.P., Zerulla, M., Tyler, C.R., Utility of a juvenile fathead minnow screening assay for detecting (anti-)estrogenic substances. Environ Toxicol Chem 21, Routledge, E.J., Sumpter, J.P., Structural features of alkylphenolic chemicals associated with estrogenic activity. J. Biol. Chem. 272, Seki, M., Yokota, H., Matsubara, H., Maeda, M., Tadokoro, H., Kobayashi, K., Fish full life-cycle testing for the weak estrogen 4-tert-pentylphenol on medaka (Oryzias latipes). Environ. Toxicol. Chem. 22, Sohoni, P., Sumpter, J.P., Several environmental oestrogens are also anti-androgens. J Endocrinol 158, Soto, A.M., Sonnenschein, C., Chung, K.L., Fernandez, M.F., Olea, N., Serrano, F.O., The E-SCREEN assay as a tool to identify estrogens: An update on estrogenic environmental pollutants. Environ. Health Perspect. 103, Tollefsen, K.E., Eikvar, S., Finne, E.F., Fogelberg, O., Gregersen, I.K., Estrogenicity of alkylphenols and alkylated non-phenolics in a rainbow trout (Oncorhynchus mykiss) primary hepatocyte culture. Ecotoxicol Environ Saf 71, Tollefsen, K.E., Nilsen, A.J., Binding of alkylphenols and alkylated non-phenolics to rainbow trout (Oncorhynchus mykiss) hepatic estrogen receptors. Ecotoxicol Environ Saf 69,
Annex XV report PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57
Annex XV report PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57 Substance Name(s): Reaction products of 1,3,4-thiadiazolidine-2,5-dithione,
4-Heptylphenol, branched and linear (4- HPbl) 1 EC No._ - CAS No: -
HAZARD ASSESSMENT OUTCOME DOCUMENT for 4-Heptylphenol, branched and linear (4- HPbl) 1 EC No._ - CAS No: - Member State(s): Austria Dated: September 2016 Disclaimer: The information and views set out in
AGREEMENT OF THE MEMBER STATE COMMITTEE ON THE IDENTIFICATION OF 4,4'-ISOPROPYLIDENEDIPHENOL (BISPHENOL A) AS A SUBSTANCE OF VERY HIGH CONCERN
AGREEMENT OF THE MEMBER STATE COMMITTEE ON THE IDENTIFICATION OF 4,4'-ISOPROPYLIDENEDIPHENOL (BISPHENOL A) AS A SUBSTANCE OF VERY HIGH CONCERN According to Articles 57 and 59 of Regulation (EC) 1907/2006
Annex XV report PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57
Annex XV report PROPOSAL FOR IDENTIFICATION OF A SUBSTANCE OF VERY HIGH CONCERN ON THE BASIS OF THE CRITERIA SET OUT IN REACH ARTICLE 57 Substance Name(s): 4-tert-butylphenol EC Number(s): 202-679-0 CAS
The presence and effect of endocrine disruptors on reproductive organs of fish in a reservoir used for aquiculture
Environmental Toxicology 139 The presence and effect of endocrine disruptors on reproductive organs of fish in a reservoir used for aquiculture L. S. Shore 1 & M. Gophen 2 1 Kimron Veterinary Institute,
Availability of R eceptor B inding A ssay for Screening of E ndocrine D isrupting C hemicals
Session II. Endocrine Disrupting Effects and Test Methods with medaka : Part I Availability of R eceptor B inding A ssay for Screening of E ndocrine D isrupting C hemicals Makoto Nakai Chemicals Assessment
Phase-3 OECD 21-day Fish Screening Assay Validation Report Additional Test Substance Studies
Report of Eight 21-day Fish Endocrine Screening Assays With Additional Test Substances for Phase-3 of the OECD Validation Program: Studies with Octylphenol in the Fathead Minnow (Pimephales promelas) and
Potential Health Effects of Alkylphenols in Japan
Endocrine Disruptors Potential Health Effects of Alkylphenols in Japan JMAJ 46(3): 108 114, 2003 Fujio KAYAMA*, Hyogo HORIGUCHI* and Akihiko HAMAMATSU** *Division of Environmental Immunology and Toxicology,
Causes and consequences of feminisation of male fish in English rivers
Causes and consequences of feminisation of male fish in English rivers Science Report SC030285/SR The Environment Agency is the leading public body protecting and improving the environment in England and
Setting the scene: Is mixtures risk assessment necessary and feasible?
3 rd SETAC Special Science Symposium Setting the scene: Is mixtures risk assessment necessary and feasible? Andreas Kortenkamp The School of Pharmacy, University of London 2-3 February 2011, Brussels The
European Food Safety Authority (EFSA)
TECHNICAL REPORT APPROVED: 06 April 2017 doi:10.2903/sp.efsa.2017.en-1210 Outcome of the preliminary pesticides peer review meeting on the assessment of endocrine disrupting properties in mammalian toxicology
Endocrine disruptors s approach Department of Product Policy and Chemical Substances (DG ENV, BELGIUM)
1 Endocrine disruptors s approach Department of Product Policy and Chemical Substances (DG ENV, BELGIUM) Martine RÖHL 19 February 2014 Kick-off event ChildProtect Life Project 2 EU Context 3 EU Context
Risk Management Option Analysis Conclusion Document
Risk Management Option Analysis Conclusion Document Substance Name: Octamethylcyclotetrasiloxane (D4) EC Number: 209-136-7 CAS Number: 556-67-2 Substance Name: Decamethylcyclopentasiloxane (D5) EC Number:
Assessment and regulation of endocrine disrupters under European chemical legislations Susy Brescia Chemicals Regulation Directorate (CRD) HSE
Health and and Safety Executive Assessment and regulation of endocrine disrupters under European chemical legislations Susy Brescia Chemicals Regulation Directorate (CRD) HSE EDs and the current EU legislative
COMMISSION IMPLEMENTING DECISION. of
EUROPEAN COMMISSION Brussels, 4.7.2017 C(2017) 4462 final COMMISSION IMPLEMENTING DECISION of 4.7.2017 on the identification of bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), benzyl butyl
ES/RP 531 Fundamentals of Environmental Toxicology Fall September 24, 2003 Lecture 8: In-Vivo Studies Showing Endocrine System Toxicity
September 24, 2003 Lecture 8: In-Vivo Studies Showing Endocrine System Toxicity I. ase of the Less than Manly Alligators A. One of the most publicized cases of endocrine disruption at possibly the population
The influence of a surfactant, linear alkylbenzene sulfonate, on the estrogenic response to a mixture of (xeno)estrogens in vitro and in vivo.
Submission of a Short Communication to Aquatic Toxicology The influence of a surfactant, linear alkylbenzene sulfonate, on the estrogenic response to a mixture of (xeno)estrogens in vitro and in vivo.
4-hydroxybenzoic acid
SUBSTANCE EVALUATION CONCLUSION DOCUMENT as required by REACH Article 48 for 4-hydroxybenzoic acid EC No 202-804-9 CAS No 99-96-7 Evaluating Member State(s): Czech Republic Dated: 26 th May 2016 Evaluating
Risk Management Option Analysis Conclusion Document
Risk Management Option Analysis Conclusion Document Substance Name: tributyl O-acetylcitrate (ATBC) EC Number: 201-067-0 CAS Number: 77-90-7 Authority: France Date: August 2016 Version 2.1 October 2015
of the French Agency for Food, Environmental and Occupational Health & Safety
The Director General Maisons-Alfort, 27 March 2012 of the French Agency for Food, Environmental and Occupational Health & Safety regarding a request for scientific and technical support for the revising
OECD GUIDELINE FOR THE TESTING OF CHEMICALS. Fish Short Term Reproduction Assay. Replaced
OECD/OCDE 229 Adopted: 7 September 2009 OECD GUIDELINE FOR THE TESTING OF CHEMICALS INTRODUCTION Fish Short Term Reproduction Assay 1. The need to develop and validate a fish assay capable of detecting
Testing of estrogenic and androgenic reference compounds using 2 versions of the yeast-based YES and YAS assay
Testing of estrogenic and androgenic reference compounds using 2 versions of the yeast-based YES and YAS assay Markus Kamber Xenometrix AG Gewerbestr. 25 CH - 4123 Allschwil Switzerland Poster No. 12-C
Justification for the selection of a candidate CoRAP substance
Justification for the selection of a candidate CoRAP substance Substance Name (Public Name): Diethyl phthalate Chemical Group: EC Number: 201-550-6 CAS Number: 84-66-2 Submitted by: Germany/Portugal Published:
Comments CLH proposal Cadmium hydroxide
1 Comments CLH proposal Cadmium hydroxide GENERAL COMMENTS: The International Cadmium association (ICdA) welcomes the opportunity to provide its contribution to the public consultation on the proposed
Justification for the selection of a candidate CoRAP substance
Justification for the selection of a candidate CoRAP substance Substance Name (Public Name): Chemical Group: N,N-dicyclohexylbenzothiazole-2-sulphenamide Benzothiazole EC Number: 225-625-8 CAS Number:
DRAFT COMMISSION DELEGATED REGULATION (EU) /... of XXX
EUROPEAN COMMISSION Brussels, XXX C(2016) 3752 projet DRAFT COMMISSION DELEGATED REGULATION (EU) /... of XXX setting out scientific criteria for the determination of endocrine-disrupting properties pursuant
Contribution to the European Commission s Public Consultation on. 15 January 2015
Contribution to the European Commission s Public Consultation on Defining criteria for identifying Endocrine Disruptors in the context of the implementation of the Plant Protection Product Regulation and
Effects of TBCO on the Reproductive Capacity of 2 Generations of Japanese Medaka (Oryzias latipes)
Effects of on the Reproductive Capacity of 2 Generations of Japanese Medaka (Oryzias latipes) Br Br Br Br Steve Wiseman University of Saskatchewan Multigenerational Effects Pesticides Vinclozolin (anti-androgen)
TECHNICAL REPORT. European Food Safety Authority 2. European Food Safety Authority (EFSA), Parma, Italy
supporting publication 2014:EN-680 TECHNICAL REPORT Outcome of the consultation with Member States, the applicant and on the pesticide risk assessment of for the active substance difenoconazole 1 European
An investigation of the incidence of intersex fish in Seine-Maritime and Sussex regions
Endocrine disruptors Dossier An investigation of the incidence of intersex fish in Seine-Maritime and Sussex regions C. Minier 1 *, G. Caltot 1, F. Leboulanger 1 and E.M. Hill 2 1 LEMA, UPRES-EA 3222,
Effects of Pharmaceuticals in the Canadian Environment
Effects of Pharmaceuticals in the Canadian Environment Joanne Parrott, Science and Technology Branch, Environment Canada, 867 Lakeshore Road, Burlington, Ontario L7R 4A6 Why Worry about Pharmaceuticals?
Prediction of mixture effects?
Swedish Society of Toxicology Is mixtures risk assessment necessary and what are obstacles to making progress? Andreas Kortenkamp Institue for the Environment, Brunel University London 23 March 2012, Stockholm,
Justification for the selection of a candidate CoRAP substance UPDATE
Justification for the selection of a candidate CoRAP substance UPDATE Substance Name (Public Name): Chemical Group: Tetrapropylenebenzene Branched alkylbenzenes EC Number: 246-772-4 CAS Number: 25265-78-5
Histopathological Effects on Testis of Adult Male Carp, Cyprinus carpio carpio, Following Exposure to Graded Concentrations of Water-Borne Bisphenol A
Tropical Journal of Pharmaceutical Research January 2016; 15 (1): 73-80 ISSN: 1596-5996 (print); 1596-9827 (electronic) Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001
Justification for the selection of a substance for CoRAP inclusion
Justification for the selection of a substance for CoRAP inclusion Substance Name (Public Name): Chemical Group: Aluminium chloride inorganic mono constituent substance EC Number: 231-208-1 CAS Number:
10/18/2016. Endocrine Disruption and the Environment. Endocrine Policy Forum US EPA S LEGISLATIVE MANDATES (1996)
Endocrine Disruption and the Environment Ellen Mihaich, Ph.D., DABT PCPC Environmental Safety Workshop October 25, 2016 1 Endocrine Policy Forum Consortium of List 1 test order recipients and other interested/involved
Official Journal of the European Union. (Non-legislative acts) REGULATIONS
21.2.2015 L 50/1 II (Non-legislative acts) REGULATIONS COMMISSION REGULATION (EU) 2015/282 of 20 February 2015 amending Annexes VIII, IX and X to Regulation (EC) No 1907/2006 of the European Parliament
4. General test considerations
1 1 1 1 1 1 1 1 0 1 0 1. General test considerations.1 Concentration setting Test concentration setting is an important part of the study design. Effective choice of concentrations ensures a successful
First Phase of Impact Assessment on Endocrine Disruptors:
First Phase of Impact Assessment on Endocrine Disruptors: How to screen which chemicals would fall under different options for criteria to identify endocrine disruptors EU Conference on Endocrine Disruptors,
Evaluation & Reporting of Data: How to provide a (robust) study summary
Evaluation & Reporting of Data: How to provide a (robust) study summary Webinar on Information requirements 30 November 2009 Evaluation of all available information Step 1: Evaluation of the data quality
Observations: UN Global List Pilot Project versus Published GHS Classifications
Observations: UN Global List Pilot Project versus Published GHS Classifications Darlene Susa-Anderson March 28, 2017 1 Published GHS Classifications Australia 4803 Canada 1253 China 2903 EU 4623 Indonesia
59) Gray,M.A. and Metcalfe,C.D.(1997)Induction of testis-ova in Japanese medaka (Oryzias latipes)exposed to p-nonylphenol. Environmental Toxicology
References 1) Japan Environment Agency (1998) Strategic Programs on Environmental Endocrine Disruptors 98 - SPEED 98. 2) Soto,A.M.,Justicia,H.,Wray,J.W. and Sonnenschein,C.(1991)P-Nonyl-phenol: An estrogenic
COMMISSION REGULATION (EU)
11.3.2011 Official Journal of the European Union L 64/15 COMMISSION REGULATION (EU) No 234/2011 of 10 March 2011 implementing Regulation (EC) No 1331/2008 of the European Parliament and of the Council
Stakeholders consultations on Info Cards and Brief Profiles
Stakeholders consultations on Info Cards and Brief Profiles Workshop on Substance Brief Profiles 06 November 2014 Janne Kilpinen Tiago Pedrosa Contents 1 st Written Consultation Overview Main topics, main
1,1 - iminodipropan-2-ol
Possibility for MSCA Logo] SUBSTANCE EVALUATION CONCLUSION DOCUMENT as required by REACH Article 48 for 1,1 - iminodipropan-2-ol EC No 203-820-9 CAS No 110-97-4 Evaluating Member State(s): Czech Republic
Survey results - Analysis of higher tier studies submitted without testing proposals
Survey results - Analysis of higher tier studies submitted without testing proposals Submission of higher tier studies on vertebrate animals for REACH registration without a regulatory decision on testing
European Food Safety Authority (EFSA)
TECHNICAL REPORT APPROVED: 03/05/2017 doi:10.2903/sp.efsa.2017.en-1223 Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for L-ascorbic acid in light
RISK MANAGEMENT OPTION ANALYSIS CONCLUSION DOCUMENT
RISK MANAGEMENT OPTION ANALYSIS CONCLUSION DOCUMENT for Substance name: 2,4,6-trimethyl-2,4,6-tris(3,3,3- trifluoropropyl)cyclotrisiloxane, F-D3 EC number: 219-154-7 CAS number: 2374-14-3 Member State(s):
EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL
EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL Directorate C - Scientific Opinions C2 - Management of scientific committees ; scientific co-operation and networks SCIENTIFIC COMMITTEE
Endocrine Disruptors
Endocrine Disruptors Dr. Bettina Hrdina-Zödl Institute for Plant Protection Products, Department of Toxicology Antragstellerkonferenz Vienna, 27.03.2014 www.ages.at Österreichische Agentur für Gesundheit
Kazunori Fujii. National Research Institute of Fisheries and Environment of Inland Sea, Fisheries Research Agency
The Effects of Endocrine Disruptors on Fish Maturation and Reproduction - A Focus on Projects Underway at the Ministry of Agriculture, Forestry, and Fisheries - Kazunori Fujii National Research Institute
Practical guidance for applicants on the submission of applications on food additives, food enzymes and food flavourings
Version 2 Updated on 29/11/2011 Practical guidance for applicants on the submission of applications on food additives, food enzymes and food flavourings Valid as of: 11 September 2011 Disclaimer: This
ECPA position paper on the criteria for the determination of endocrine disrupting properties under Regulation
POSITION PAPER 09/06/2016 PP/14/PD/23734 ECPA position paper on the criteria for the determination of endocrine disrupting properties under Regulation The European Commission is currently developing new
Report on the Test Results of Endocrine Disrupting Effects of Nonylphenol on Fish (Draft)
Report on the Test Results of Endocrine Disrupting Effects of Nonylphenol on Fish (Draft) 1. Background In its SPPED (Strategic Programs on Environmental Endocrine Disrupters) 98 1) published in May, 1998,
FÜR RISIKOBEWERTUNG BUNDESINSTITUT
BUNDESINSTITUT FÜR RISIKOBEWERTUNG Legal and Practical Aspects of the Cut-off Criteria for Reproductive Toxic and Endocrine Disrupting Effects for Approval and Classification of Pesticides in Europe Roland
Roadmap of SVHC identification and implementation of REACH risk management measures 1
Roadmap of SVHC identification and implementation of REACH risk management measures 1 Authorities to focus on substances of potential concern Roadmap for SVHC identification and implementation of REACH
COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL
EUROPEAN COMMISSION Brussels, 15.6.2016 COM(2016) 350 final COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT AND THE COUNCIL on endocrine disruptors and the draft Commission acts setting out
Developmental neurotoxicity & REACH
Developmental neurotoxicity & REACH Hannele Huuskonen DNT WS 2016 REACH Article 1 The purpose of this Regulation is to ensure a high level of protection of human health and the environment, including the
4,4'-Isopropylidenediphenol (Bisphenol A) Additional information on REACH registration dossier
4,4'-Isopropylidenediphenol (Bisphenol A) EC Number: 201-245-8 CAS Number: 80-05-7 IUPAC Name: 2,2-bis(4-hydroxyphenyl)propane Additional information on REACH registration dossier The information compiled
Justification Document for the Selection of a CoRAP Substance
Justification Document for the Selection of a CoRAP Substance Group Name: Iron complexes with N,N'-1,2- ethanediylbis{n-[(2- hydroxyphenyl)methyl]glycine} derivatives EC Numbers: 938-828-8, 283-041-9,
Draft Agreed by Biosimilar Working Party (BMWP) October Adoption by CHMP for release for consultation 17 November 2011
1 2 3 17 November 2011 EMA/CHMP/BMWP/671292/2010 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 7 Guideline on non-clinical and clinical development of similar biological medicinal products
The 3 rd International Medaka Symposium, 2003
The 3 rd International Medaka Symposium, 2003 Development of Test Methods with Medaka to Detect Endocrine Disrupting Chemicals February 27 and 28, 2003 Okazaki Conference Center, Okazaki, Japan Organized
COMMENTS AND RESPONSE TO COMMENTS ON CLH: PROPOSAL AND JUSTIFICATION. Last data extracted on 10/12/2012
COMMENTS AND RESPONSE TO COMMENTS ON CLH: PROPOSAL AND JUSTIFICATION Comments provided during public consultation are made available in this table as submitted by the webform. Please note that the comments
EFFECTS OF EXPOSURE TO LOW LEVELS OF WATER-BORNE 17b-ESTRADIOL ON NEST HOLDING ABILITY AND SPERM QUALITY IN FATHEAD MINNOWS
EFFECTS OF EXPOSURE TO LOW LEVELS OF WATER-BORNE 17b-ESTRADIOL ON NEST HOLDING ABILITY AND SPERM QUALITY IN FATHEAD MINNOWS ABSTRACT Heiko L. Schoenfuss University of Minnesota Dalma Martinovic University
Foundations of Mixture Toxicology and Their Regulatory Implications
BfR - Mehrfachrueckstaende von Pestiziden in Lebensmitteln Foundations of Mixture Toxicology and Their Regulatory Implications Andreas Kortenkamp Institute for the Environment, Brunel University London
EUROPEAN COMMISSION HEALTH AND FOOD SAFETY DIRECTORATE-GENERAL. PHARMACEUTICAL COMMITTEE 21 October 2015
EUROPEAN COMMISSION HEALTH AND FOOD SAFETY DIRECTORATE-GENERAL Health systems and products Medicinal products authorisations, European Medicines Agency PHARM 689 PHARMACEUTICAL COMMITTEE 21 October 2015
A Testing Strategy for the Identification of mammalian Endocrine Disruptors with particular focus on steroids
A Testing Strategy for the Identification of mammalian Endocrine Disruptors with particular focus on steroids Tzutzuy Ramirez, Robert Landsiedel, Susanne Kolle, Hennicke Kamp, Bennard van Ravenzwaay EUSAAT
Title: Scientific principles for the identification of endocrine disrupting chemicals a consensus statement
Title: Scientific principles for the identification of endocrine disrupting chemicals a consensus statement Outcome of an international expert meeting organized by the German Federal Institute for Risk
ANNEX XV REPORT AN ASSESSMENT OF WHETHER THE USE OF MUSK XYLENE IN ARTICLES SHOULD BE RESTRICTED IN ACCORDANCE WITH ARTICLE 69(2) OF REACH
ANNEX XV REPORT AN ASSESSMENT OF WHETHER THE USE OF MUSK XYLENE IN ARTICLES SHOULD BE RESTRICTED IN ACCORDANCE WITH ARTICLE 69(2) OF REACH SUBSTANCE NAME(S): musk xylene IUPAC Name(s): 5-tert-butyl-2,4,6-trinitro-m-xylene
BIOTIC LIGAND MODELS (BLMS) FOR ASSESSING BIOAVAILABILITY OF SELECTED METALS IN FRESHWATERS: CURRENT VALIDATION BOUNDARIES AND ON-GOING INITIATIVES
BIOTIC LIGAND MODELS (BLMS) FOR ASSESSING BIOAVAILABILITY OF SELECTED METALS IN FRESHWATERS: CURRENT VALIDATION BOUNDARIES AND ON-GOING INITIATIVES Biotic Ligand Models (BLMs) for predicting the chronic
Bisphenol A Incorporated into Eggs from Parent Fish Persists for Several Days
Journal of Health Science, 54(2) 235 239 (2008) 235 Bisphenol A Incorporated into Eggs from Parent Fish Persists for Several Days Yuji Takao,,a Mayumi Oishi, a Masaki Nagae, a Shinya Kohra, a and Koji
Specific aspects for PNEC derivation for metals. P. Van Sprang, F. Verdonck, M. Vangheluwe
Specific aspects for PNEC derivation for metals P. Van Sprang, F. Verdonck, M. Vangheluwe 1 2 Outline PNEC derivation Uncertainty management 3 PNEC DERIVATION 4 Effects assessment general framework PNEC
SCIENTIFIC COMMITTEE ON TOXICITY, ECOTOXICITY AND THE ENVIRONMENT (CSTEE)
EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL Directorate C Public Health and Risk Assessment C7 Risk assessment Brussels, C7/VR/csteeop/Cr/100903 D(03) SCIENTIFIC COMMITTEE ON TOXICITY,
DOSE SELECTION FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS *)
DOSE SELECTION FOR CARCINOGENICITY STUDIES OF PHARMACEUTICALS *) Guideline Title Dose Selection for Carcinogenicity Studies of Pharmaceuticals *) Legislative basis Directive 75/318/EEC as amended Date
COMMISSION OF THE EUROPEAN COMMUNITIES COMMISSION STAFF WORKING DOCUMENT. Accompanying document to the
EN EN EN COMMISSION OF THE EUROPEAN COMMUNITIES Brussels, 28.5.2009 SEC(2009) 710 COMMISSION STAFF WORKING DOCUMENT Accompanying document to the Draft Commission Decision amending, for the purpose of adaptation
In vitro study of the effects of cadmium on the activation of the estrogen response element using the YES screen
In vitro study of the effects of cadmium on the activation of the estrogen response element using the YES screen Xavier Denier, Jérome Couteau, Magalie Baudrimont, Elisabeth M. Hill, Jeanette Rotchell,
Challenges in environmental risk assessment (ERA) for birds and mammals and link to endocrine disruption (ED) Katharina Ott, BASF SE, Crop Protection
Challenges in environmental risk assessment (ERA) for birds and mammals and link to endocrine disruption (ED) Katharina Ott, BASF SE, Crop Protection Charles River Symposium, Den Bosch, 3rd October 2017
Nickel : one of the strongest documented metal
Overview on Regulatory Issues with relevance for nickel International Nickel Study Group Environment and Economic Committee Meeting Lisbon April 12, 2011 Nickel : one of the strongest documented metal
Effects of Primary Exposure to Environmental and Natural Estrogens on Vitellogenin Production in Carp (Cyprinus carpio) Hepatocytes
TOXICOLOGICAL SCIENCES 67, 75 80 (2002) Copyright 2002 by the Society of Toxicology Effects of Primary Exposure to Environmental and Natural Estrogens on Vitellogenin Production in Carp (Cyprinus carpio)
Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for cyflumetofen in light of confirmatory data
TECHNICAL REPORT APPROVED: 11 February 2016 PUBLISHED: 25 February 2016 Outcome of the consultation with Member States, the applicant and EFSA on the pesticide risk assessment for cyflumetofen in light
Environmental Risk Assessment Summary Ganciclovir / Valganciclovir
Environmental Risk Assessment Summary Ganciclovir / Valganciclovir Introduction The publication of environmental risk assessment summaries is part of Roche s engagement on developing a better understanding
ECHA Committee for Risk Assessment: Evaluation of the Classification and Labelling of Glyphosate
ECHA Committee for Risk Assessment: Evaluation of the Classification and Labelling of Glyphosate Tim Bowmer, Committee Chairman Ari Karjalainen, Dossier Manager for Glyphosate 10 May 2017 1 Established
ASSESSING ENDOCRINE DISRUPTING SUBSTANCES
FEDERAL INSTITUTE FOR RISK ASSESSMENT ASSESSING ENDOCRINE DISRUPTING SUBSTANCES Handling of risk assessment under different regulations Andreas Hensel How EDs may act - sexual hormones as an example Hypothalamus
Chemicals and Health & Safety at work, a European perspective. Tony Musu, European Trade Union Institute Kemiens Dag 16 Copenhagen, 23 November 2016
Chemicals and Health & Safety at work, a European perspective Tony Musu, European Trade Union Institute Kemiens Dag 16 Copenhagen, 23 November 2016 Overview Good and bad side of chemicals Main EU legislations
THE SHEEPSHEAD MINNOW AS AN IN VIVO MODEL FOR ENDOCRINE DISRUPTION IN MARINE TELEOSTS: A PARTIAL LIFE-CYCLE TEST WITH 17 -ETHYNYLESTRADIOL
Environmental Toxicology and Chemistry, Vol. 2, No. 9, pp. 1968 1978, 21 21 SETAC Printed in the USA 73-7268/1 $9.. THE SHEEPSHEAD MINNOW AS AN IN VIVO MODEL FOR EOCRINE DISRUPTION IN MARINE TELEOSTS:
EFSA Statement regarding the EU assessment of glyphosate and the socalled
EFSA Statement regarding the EU assessment of glyphosate and the socalled Monsanto papers Background On 29 May 2017, EFSA received a request from the European Commission to produce a statement concerning
Genotoxicity Testing Strategies: application of the EFSA SC opinion to different legal frameworks in the food and feed area
Genotoxicity Testing Strategies: application of the EFSA SC opinion to different legal frameworks in the food and feed area Juan Manuel Parra Morte. Pesticides Unit. EFSA. 19th Annual Conference of the
Shin ichiro Kawai 1,, Makito Kobayashi 2, and Hideo Kaneko 3. Pure Appl. Chem., Vol. 75, Nos , pp , 2003.
Pure Appl. Chem., Vol. 75, Nos. 11 12, pp. 2335 2341, 2003. 2003 IUPAC Topic 4.11 Effects of endocrine active substances in wildlife species: Genetic, biochemical, and physiological factors in variable
The ABC's of EDCs: Endocrine Disrupting Chemicals in the Environment
The ABC's of EDCs: Endocrine Disrupting Chemicals in the Environment David Quanrud Water Resources Research Center 2007 Water Conference Phoenix, Arizona June 5, 2007 What is an endocrine disrupting compound?
Estrogen receptor expression and vitellogenin synthesis induced in hepatocytes of male frogs Rana chensinensis exposed to bisphenol A
2011 Jun. 32(3): 317 322 CN 53-1040/Q ISSN 0254-5853 Zoological Research DOI 10.3724/SP.J.1141.2011.03317 A, *,,,, (, 710062) A(bisphenol A, BPA) (estrogen receptor, ER) (vitellogenin, VTG), (Rana chensinensis)
Identification of specific plastics which do not release estrogenic activity causing chemicals
Identification of specific plastics which do not release estrogenic activity causing chemicals Thousand Oaks High School AP Research STEM Introduction » Chemicals which cause Estrogenic Activity (EA) were
Morphological sex reversal upon short-term exposure to endocrine modulators in juvenile fathead minnow (Pimephales promelas)
Toxicology Letters 131 (2002) 51 63 www.elsevier.com/locate/toxlet Morphological sex reversal upon short-term exposure to endocrine modulators in juvenile fathead minnow (Pimephales promelas) Melanie Zerulla
Feedback from the Member States questionnaire
Annex 6 Feedback from the Member States questionnaire Reinhilde A.R. Schoonjans Special meeting of the EFSA Advisory Forum on GMO risk assessment in Europe 13 November 2007, Brussels Topics 1. Highlights
COMMISSION REGULATION (EU) / of XXX
EUROPEAN COMMISSION Brussels, XXX SANTE/11992/2017 Rev. 0 [ ](2017) XXX draft COMMISSION REGULATION (EU) / of XXX amending Annex II to Regulation (EC) No 1107/2009 by setting out scientific criteria for
Reproductive toxicity classification under CLP (Regulation (EC) no 1272/2008 on Classification, Labelling and Packaging of chemicals)
Reproductive toxicity classification under CLP (Regulation (EC) no 1272/2008 on Classification, Labelling and Packaging of chemicals) A satellite workshop to the 45th Annual Meeting of the European Teratology
Effects of 17a-ethinylestradiol in a fathead minnow(pimephales promelas) gonadal recrudescence assay
Ecotoxicology and Environmental Safety 57 (2004) 330 345 Effects of 17a-ethinylestradiol in a fathead minnow(pimephales promelas) gonadal recrudescence assay S. Pawlowski, a, R. van Aerle, b C.R. Tyler,
Substance Evaluation Conclusion document EC No SUBSTANCE EVALUATION CONCLUSION DOCUMENT. as required by REACH Article 48.
SUBSTANCE EVALUATION CONCLUSION DOCUMENT as required by REACH Article 48 for Butanone oxime EC No 202-496-6 CAS No 96-29-7 Evaluating Member State(s): Germany Dated: 18 March 2014 Evaluating Member State
gonad phosvitin levels in relation to the seasonal reproductive cycles of female brown trout
Wild Plasma gonadotropin, estradiol, and vitellogenin and gonad phosvitin levels in relation to the seasonal reproductive cycles of female brown trout L. W. CRIM, D. R. IDLER Marine Sciences Research Laboratory,
Action plan for improving the peer review process. European Food Safety Authority (EFSA)
TECHNICAL REPORT APPROVED: 29 November 2017 doi:10.2903/sp.efsa.2017.en-1349 Action plan for improving the peer review process European Food Safety Authority (EFSA) Abstract This document reflects on the
Webinar: use of alternative methods to animal testing in your REACH registration
Webinar: use of alternative methods to animal testing in your REACH registration Using alternative methods to meet your information requirements 22 September 2016 Kimmo Louekari Evaluation Unit European