natgillin/translations-raw huggingface dataset:
Procedures for calibrating and ensuring the equivalence of devices and the balancing of treatment groups in testing procedures;
De asemenea, se furnizează toate informațiile care nu au fost obținute în timpul studiului, dar care sunt utile pentru interpretarea rezultatelor (de exemplu, asemănări cu efectele oricăror substanțe cunoscute cu efecte neurotoxice).
Short justification explaining any decisions involving professional judgment;
Interpretarea rezultatelor
Detailed description of all behavioural/functional, neuropathological and morphometric findings by sex and dose group, including both increases and decreases from controls;
Un studiu extins de toxicitate pentru reproducere efectuat pe o generație va furniza informații privind efectele expunerii repetate la o substanță chimică în toate etapele ciclului de reproducere, după caz.
Brain weight;
În special, studiul furnizează informații cu privire la sistemul reproducător și la dezvoltarea, creșterea, supraviețuirea și parametrii funcționali ai puilor până la PND 90.
Any diagnoses derived from neurological signs and lesions, including naturally-occurring diseases or conditions;
Interpretarea rezultatelor studiului trebuie să ia în considerare toate informațiile disponibile cu privire la substanța chimică, inclusiv proprietățile fizico-chimice, TK și toxicodinamice, informațiile relevante disponibile cu privire la analogi structurali, precum și rezultatele studiilor de toxicitate efectuate anterior cu substanța de testat (de exemplu, toxicitate acută, toxicitate după aplicare repetată, studii mecaniciste și studii de evaluare în cazul în care există diferențe calitative și cantitative semnificative la nivelul speciei referitoare la proprietățile metabolice in vivo/in vitro).
Images of exemplar findings;
Rezultatele autopsiei macroscopice și cu privire la greutatea organelor trebuie să fie evaluate în corelație cu observațiile din alte studii cu doze repetate, atunci când acest lucru este fezabil.
Low-power images to assess homology of sections used for morphometry;
Scăderile la nivelul dezvoltării puilor ar putea fi considerate în relație cu o influență a substanței chimice de testat asupra compoziției laptelui (29).
Statistical treatment of results, including statistical models used to analyse the data, and the results, regardless of whether they were significant or not;
Cohorta 2 (neurotoxicitatea pentru dezvoltare)
Relationship of any other toxic effects to a conclusion about the neurotoxic potential of the test chemical, by sex and dose group;
Rezultatele neuropatologice și neurocomportamentale trebuie interpretate în contextul tuturor constatărilor, prin intermediul abordării axate pe forța probantă a dovezilor cu expertiză.
Impact of any toxicokinetic information on the conclusions;
Evaluarea neurotoxicității pentru dezvoltare, inclusiv studii epidemiologice umane sau rapoarte de caz și studii experimentale pe animale (de exemplu, datele toxicocinetice, informații de structură-activitate, date de la alte studii de toxicitate), trebuie să fie cuprinsă în caracterizare.
Data supporting the reliability and sensitivity of the test method (i.e.positive and historical control data);
Pentru orientări privind interpretarea rezultatelor de neurotoxicitate pentru dezvoltare, a se vedea metoda de testare B.53 (35) și Tyl et al., 2008 (31).
Relationships, if any, between neuropathological and functional effects;
Cohorta 3 (imunotoxicitatea pentru dezvoltare)
NOAEL or benchmark dose for dams and offspring, by sex and dose group;
Suprimarea sau consolidarea funcției imunitare, astfel cum au fost evaluate cu ajutorul TDAR (răspunsul anticorpilor dependent de celulele T), trebuie evaluate în contextul tuturor observațiilor realizate.
Discussion of the overall interpretation of the data based on the results, including a conclusion of whether or not the chemical caused developmental neurotoxicity and the NOAEL;
Semnificația rezultatului testului TDAR poate fi susținută de alte efecte asupra indicatorilor imunologici (de exemplu, celularitatea măduvei osoase, greutatea și histopatologia țesuturilor limfoide, distribuția subsetului de limfocite).
Cohort 3 parameters:
Efectele stabilite de TDAR ar putea fi mai puțin semnificative în cazul altor fenomene toxice observate la concentrații de expunere mai mici.
Serum IgM antibody titres (sensitisation to SRBC or KLH), or splenic IgM PFC units (sensitisation to SRBC);
Documentul de orientare nr. 43 al OCDE ar trebui să fie consultat pentru ajutor în interpretarea rezultatelor privind reproducerea și neurotoxicitatea (26).
Performance of the TDAR method should be confirmed as part of the optimisation process by laboratory setting up the assay for the first time, and periodically (e.g. yearly) by all laboratories;
Whitby (2006), A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment, Critical Reviews in Toxicology, 36, 69-98.
Discussion of the overall interpretation of the data based on the results, including a conclusion of whether or not the chemical caused developmental immunotoxicity and the NOAEL;
Forsythe (1999), Phytoestrogen Content of Purified Open and Closed Formula Laboratory Animal Diets, Lab.
Discussion of results
Sci., 49, 530-536.
Conclusions, including NOAEL values for parental and offspring effects
Moser, V.C., I. Walls and T. Zoetis (2005), Direct Dosing of Preweaning Rodents in Toxicity Testing and Research: Deliberations of an ILSI RSI Expert Working Group, International Journal of Toxicology, 24, 87-94.
All information not obtained during the study, but useful for the interpretation of the results (e.g. similarities of effects to any known neurotoxicants), should also be provided.
Goodman (1999), Stimulating Research to Improve the Scientific Basis of Risk Assessment, Toxicological Sciences, 49, 1-4.
Interpretation of Results
Palmer (1995), Detection of Effects on Male Reproduction — a Literature Survey, Journal of the American College of Toxicologists, 14, 293-327.
An Extended One-Generation Reproductive Toxicity Study will provide information on the effects of repeated exposure to a chemical during all phases of the reproductive cycle, as necessary.
Mangelsdorf, I., J. Buschmann and B. Orthen (2003), Some Aspects Relating to the Evaluation of the Effects of Chemicals on Male Fertility, Regulatory Toxicology and Pharmacology, 37, 356-369.
In particular, the study provides information on the reproductive system, and on development, growth, survival, and functional endpoints of offspring up to PND 90.
Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats — overview of the studies, Journal of Toxicological Sciences, 25, 1-21.
Interpretation of the results of the study should take into account all available information on the chemical, including physico-chemical, TK and toxicodynamic properties, available relevant information on structural analogues, and results of previously-conducted toxicity studies with the test chemical (e.g. acute toxicity, toxicity after repeated application, mechanistic studies and studies assessing if there are substantial qualitative and quantitative species differences in in vivo/in vitro metabolic properties).
, Evaluation of Testicular Toxicology: A Synopsis and Discussion of the Recommendations Proposed by the Society of Toxicologic Pathology, Birth Defects Research, Part B, 68, 408-415.
Gross necropsy and organ weight results should be assessed in context with observations made in other repeat-dose studies, when feasible.
Cooper (2007), The Rodent Estrous Cycle: Characterization of Vaginal Cytology and its Utility in Toxicological Studies, Birth Defects Research, Part B, 80 (2), 84-97.
Decreases in offspring growth might be considered in relationship to an influence of the test chemical on milk composition (29).
, Cycles and Seasons, in C.R.
Cohort 2 (Developmental neurotoxicity)
I. Germ Cells and Fertilization, Cambridge, New York.
Neurobehavioral and neuropathology results should be interpreted in the context of all findings, using a weight-of-evidence approach with expert judgment.
Reynolds (1999), Interpreting the Toxicologic Significance of Alterations in Anogenital Distance: Potential for Confounding Effects of Progeny Body Weights, Reproductive Toxicology, 13:
The evaluation of developmental neurotoxicity, including human epidemiological studies or case reports, and experimental animal studies (e.g. toxicokinetic data, structure-activity information, data from other toxicity studies) should be included in this characterisation.
Weiner (1977), Preputial Separation as an External Sign of Pubertal Development in the Male Rat, Biological Reproduction, 17, 298-303.
For guidance on the interpretation of developmental neurotoxicity results, refer to test method B.53 (35) and Tyl et al., 2008 (31).
, Use of SRBC Antibody Responses for Immunotoxicity Testing, Methods, 41, 9-19.
Cohort 3 (Developmental immunotoxicity)
Herzyk (2004), Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation, Toxicology, 197, 23-35.
Suppression or enhancement of immune function as assessed by TDAR (T-cell dependent antibody response), should be evaluated in the context of all observations made.
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott and J. Laskey (1989), A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat, Fundamental and Applied Toxicology, 12, 92-108.
Significance of the outcome of TDAR may be supported by other effects on immunologically-related indicators (e.g. bone marrow cellularity, weight and histopathology of lymphoid tissues, lymphocyte subset distribution).
Killian (1978), Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats, Journal of Reproduction and Fertility,54, 103-107.
Effects established by TDAR may be less meaningful in case of other toxicities observed at lower exposure concentrations.
Suarez (1991), The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration in the Rat.
OECD Guidance Document 43 should be consulted for aid in the interpretation of reproduction and neurotoxicity results (26).
Reproductive Toxicology,5, 39-44.
Whitby (2006), “A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment”, Critical Reviews in Toxicology, 36, 69-98.
Wise (1996), Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report, Reproductive Toxicology, 10, 237-244.
Forsythe (1999), “Phytoestrogen Content of Purified Open and Closed Formula Laboratory Animal Diets”, Lab.
Russell and S. Schrader (1992), Methods for Assessing Rat Sperm Motility, Reproductive Toxicology, 6, 267-273.
Sci., 49, 530- 536.
Suarez (1992), Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration, Journal of Andrology, 13, 409-421.
Moser, V.C., I. Walls and T. Zoetis (2005), “Direct Dosing of Preweaning Rodents in Toxicity Testing and Research: Deliberations of an ILSI RSI Expert Working Group”, International Journal of Toxicology, 24, 87-94.
Perreault (1991), Rat Sperm Motility Analysis: Methodologic Considerations, Reproductive Toxicology, 5, 449-458.
Goodman (1999), “Stimulating Research to Improve the Scientific Basis of Risk Assessment”, Toxicological Sciences, 49, 1-4.
Perreault (1993), Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer, Methods in Toxicology, Part A, Academic, Orlando, Florida. pp.
Palmer (1995), “Detection of Effects on Male Reproduction — a Literature Survey”, Journal of the American College of Toxicologists, 14, 293-327.
319-333.
Mangelsdorf, I., J. Buschmann and B. Orthen (2003), “Some Aspects Relating to the Evaluation of the Effects of Chemicals on Male Fertility”, Regulatory Toxicology and Pharmacology, 37, 356-369.
Suarez (1992), Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants, Reproductive Toxicology, 6, 491-505.
“Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats — overview of the studies”, Journal of Toxicological Sciences, 25, 1-21.
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No.
, “Evaluation of Testicular Toxicology: A Synopsis and Discussion of the Recommendations Proposed by the Society of Toxicologic Pathology”, Birth Defects Research, Part B, 68, 408-415.
43, ENV/JM/MONO(2008)16, OECD, Paris.
Cooper (2007), “The Rodent Estrous Cycle: Characterization of Vaginal Cytology and its Utility in Toxicological Studies”, Birth Defects Research, Part B, 80 (2), 84-97.
Working, P.K., M. Hurtt (1987), Computerized Videomicrographic Analysis of Rat Sperm Motility, Journal of Andrology, 8, 330-337.
I. Germ Cells and Fertilization, Cambridge, New York.
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, and R. Duffard (2006), Detection of 2,4-dichlorophenoxyacetic Acid in Rat Milk of Dams Exposed During Lactation and Milk Analysis of their Major Components, Food Chemicals Toxicology, 44, 8-16.
Reynolds (1999), “Interpreting the Toxicologic Significance of Alterations in Anogenital Distance: Potential for Confounding Effects of Progeny Body Weights”, Reproductive Toxicology, 13:
Forsythe (2007), Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but not in CD Sprague Dawley Rats, Environmental health perspectives, 115(12), 1717-1726.
Weiner (1977), “Preputial Separation as an External Sign of Pubertal Development in the Male Rat”, Biological Reproduction, 17, 298-303.
Sobotka (2008), Identification and Interpretation of Developmental Neurotoxicity Effects: a Report from the ILSI Research Foundation/Risk Science Institute Expert Working Group on Neurodevelopmental Endpoints, Neurotoxicology and Teratology, 30:
, “Use of SRBC Antibody Responses for Immunotoxicity Testing”, Methods, 41, 9-19.
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No.
Herzyk (2004), “Primary Antibody Response to Keyhole Limpet Hemocyanin in Rat as a Model for Immunotoxicity Evaluation”, Toxicology, 197, 23-35.
422, OECD, Paris.
Gray, L.E., J. Ostby, J. Ferrell, G. Rehnberg, R. Linder, R. Cooper, J. Goldman, V. Slott and J. Laskey (1989), “A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat”, Fundamental and Applied Toxicology, 12, 92-108.
Capitolul B.43 din prezenta anexă, Studiu de neurotoxicitate la rozătoare.
Killian (1978), “Daily Sperm Production and Epididymal Sperm Reserves of Pubertal and Adult Rats”, Journal of Reproduction and Fertility,54, 103-107.
OECD (2000), Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluations, Series on Testing and Assessment, No.
Suarez (1991), “The Method of Sperm Collection Significantly Influences Sperm Motion Parameters Following Ethane Dimethanesulfonate Administration in the Rat”.
19, ENV/JM/MONO(2000)7, OECD, Paris.
Reproductive Toxicology, 5, 39-44.
Capitolul B.53 din prezenta anexă, Studiu de neurotoxicitate pentru dezvoltare.
Wise (1996), “Methods for Assessing Sperm Motility, Morphology, and Counts in the Rat, Rabbit, and Dog: a Consensus Report”, Reproductive Toxicology, 10, 237- 244.
Capitolul B.54 din prezenta anexă, Biotestul uterotrofic la rozătoare:
Russell and S. Schrader (1992), “Methods for Assessing Rat Sperm Motility”, Reproductive Toxicology, 6, 267-273.
un test de depistare pe termen scurt pentru substanțe cu proprietăți estrogenice.
Suarez (1992), “Direct Effects of Ethane Dimethanesulphonate on Epididymal Function in Adult Rats: an In Vitro Demonstration”, Journal of Andrology, 13, 409-421.
Capitolul B.55 din prezenta anexă, Biotestul Hershberger la șobolani:
Perreault (1991), “Rat Sperm Motility Analysis: Methodologic Considerations”, Reproductive Toxicology, 5, 449-458.
un test de depistare pe termen scurt pentru substanțe cu proprietăți (anti)androgenice.
Perreault (1993), “Computer-Assisted Sperm Analysis of Rodent Epididymal Sperm Motility Using the Hamilton-Thorn Motility Analyzer”, Methods in Toxicology, Part A, Academic, Orlando, Florida. pp. 319-333.
OECD (2009), Guidance Document for Histologic Evalution of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No.
Smith (1989), "The Automated Analysis of Rat Sperm Motility Following Subchronic Epichlorhydrin Administration: Methodologic and Statistical Considerations", Journal of Andrology, 10, 401-415.
106, OECD, Paris.
Suarez (1992), “Endpoints of Spermatoxicity in the Rat After Short Duration Exposures to Fourteen Reproductive Toxicants”, Reproductive Toxicology, 6, 491-505.
OECD (2011), Guidance Document on the Current Implementation of Internal Triggers in the Extended One Generation Reproductive Toxicity Study in the United States and Canada, Series on Testing and Assessment, No. 117, ENV/JM/MONO(2011)21, OECD, Paris.
OECD (2008), Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment, Series on Testing and Assessment, No 43, ENV/JM/MONO(2008)16, OECD, Paris.
Extended One Generation Reproductive Toxicity Study, Series on Testing and Assessment, No.
Working, P.K., M. Hurtt (1987), “Computerized Videomicrographic Analysis of Rat Sperm Motility”, Journal of Andrology, 8, 330-337.
151, OECD, Paris.
Bolin, B., R. Garman, K. Jensen, G. Krinke, B. Stuart, and an ad Hoc Working Group of the STP Scientific and Regulatory Policy Committee (2006), “A “Best Practices” Approach to Neuropathologic Assessment in Developmental Neurotoxicity Testing — for Today”, Toxicological Pathology, 34, 296-313.
Măsurile și observațiile incluse în bateriile de teste funcționale bazate pe observație (Cohorta 2A)
Stütz, N., B. Bongiovanni, M. Rassetto, A. Ferri, A.M. Evangelista de Duffard, and R. Duffard (2006), “Detection of 2,4-dichlorophenoxyacetic Acid in Rat Milk of Dams Exposed During Lactation and Milk Analysis of their Major Components”, Food Chemicals Toxicology, 44, 8-16.
Cuști și câmp deschis
Forsythe (2007), “Variations in Phytoestrogen Content between Different Mill Dates of the Same Diet Produces Significant Differences in the Time of Vaginal Opening in CD-1 Mice and F344 Rats but not in CD Sprague Dawley Rats”, Environmental health perspectives, 115(12), 1717-1726.
Manipulare
Sobotka (2008), “Identification and Interpretation of Developmental Neurotoxicity Effects: a Report from the ILSI Research Foundation/Risk Science Institute Expert Working Group on Neurodevelopmental Endpoints”, Neurotoxicology and Teratology, 30:
Fiziologic
OECD (1996), Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test, OECD Guideline for Testing of Chemicals, No 422, OECD, Paris.
Postura corpului
Chapter B.43 of this Annex, Neurotoxicity Study in Rodents
Scoatere ușoară
OECD (2000), Guidance Document on the recognition, assessment, and use of clinical signs as humane endpoints for experimental animals used in safety evaluations, Series on Testing and Assessment, No 19, ENV/JM/MONO(2000)7, OECD, Paris.
Temperatură
Chapter B.53 of this Annex, Developmental Neurotoxicity Study
Mișcări clonice și tonice involuntare
Chapter B.54 of this Annex, Uterotrophic Bioassay in Rodents:
Manipulare ușoară
A short-term Screening Test for Oestrogenic Properties
Închidere palpebrală
Chapter B.55 of this Annex, Hershberger Bioassay in Rats:
Tonus muscular
A Short-term Screening Assay for (Anti)Androgenic Properties
Reacția pupilei
OECD (2009), Guidance Document for Histologic Evaluation of Endocrine and Reproductive Test in Rodents, Series on Testing and Assessment, No 106, OECD, Paris.
Erecție piloasă
OECD (2011), Guidance Document on the Current Implementation of Internal Triggers in the Extended One Generation Reproductive Toxicity Study in the United States and Canada, Series on Testing and Assessment, No 117, ENV/JM/MONO(2011)21, OECD, Paris.
Reacție la apropiere
Extended One Generation Reproductive Toxicity Study, Series on Testing and Assessment, No 151, OECD, Paris.
Dimensiunea pupilei
Measures and observations included in the functional observational battery (Cohort 2A)
Salivație
Home Cage & Open Field
Reacție la atingere
Manipulative
Lăcrimare
Physiologic
Reacție auditivă
Posture
Vocalizări
Ease of removal
Reacție la ciupirea cozii
Temperature
Ridicare pe labele din spate
Involuntary Clonic & Tonic
Reacție de îndreptare
Ease of handling
Anomalii de mers
Palpebral Closure
Alunecarea piciorului la aterizare
Muscle Tone
Excitare
Pupil response
Forță de apucare cu laba din față
Piloerection
Stereotipie
Approach Response
Forță de apucare cu laba din spate
Pupil size
Comportament bizar
Salivation
Pete
Touch Response
Anomalii respiratorii
Lacrimation
Substanță chimică
Auditory Response
o substanță sau un amestec de substanțe.
Vocalisations
Substanță chimică de testat
Tail Pinch Response
orice substanță sau amestec de substanțe testat utilizând prezenta metodă de testare.
Rearing
B.57.
Righting Response
TESTUL DE STEROIDOGENEZĂ A H295R
Gait Abnormalities
Prezenta metodă de testare este echivalentă cu Orientarea OCDE privind testarea (OT) nr. 456 (2011).
Landing Foot Splay
În 1998, OCDE a inițiat o activitate cu un nivel ridicat de prioritate pentru a revizui orientările existente și a elabora noi orientări pentru depistarea și testarea posibililor perturbatori endocrini.
Arousal
Cadrul conceptual al OCDE pentru testarea și evaluarea perturbatorilor endocrini din 2002 cuprinde cinci niveluri, fiecare nivel corespunzând unui nivel diferit de complexitate biologică (1).
Forelimb Grip Strength
Testul de steroidogeneză H295R in vitro (H295R) descris în prezenta metodă de testare utilizează o linie de celule adenocarcinom umane (celule NCI-H295R) și constituie un «test in vitro, furnizând date mecaniciste» de nivel 2, care se utilizează în scopuri de depistare și prioritizare.
Stereotypy
Dezvoltarea și standardizarea testului ca test de depistare a efectelor chimice asupra steroidogenezei, și anume, asupra producției de estradiol 17β (E2) și testosteron (T), s-a efectuat printr-un proces cu mai multe etape.
Hindlimb Grip Strength
Testul H295R a fost optimizat și validat (2) (3) (4) (5).
Bizarre Behaviour
Obiectivul testului de steroidogeneză H295R este depistarea substanțelor chimice care afectează producția de E2 și T. Testul H295R este destinat identificării substanțelor xenobiotice care au ca țintă (ținte) componentele endogene care alcătuiesc mecanismul biochimic intracelular începând cu secvența de reacții de la colesterol la producerea de E2 și/sau T. Testul H295R nu este destinat identificării substanțelor chimice care afectează steroidogeneza din cauza efectelor asupra axului hipotalamic-pituitar-gonadal (HPG).
Stains
Scopul testului este de a oferi un răspuns DA/NU în ceea ce privește potențialul unei substanțe chimice de a induce sau a inhiba producerea de T și E2;
Respiratory Abnormalities
cu toate acestea, în unele cazuri se pot obține rezultate cantitative (a se vedea punctele 53 și 54).
Chemical
Rezultatele testului sunt exprimate ca modificările relative la nivelul producției de hormoni în comparație cu martorii pentru solvent (MS).
A substance or a mixture.
Testul nu este menit să furnizeze informații referitoare la mecanismul specific privind interacțiunea substanței de testat cu sistemul endocrin.
Test Chemical
Cercetările au fost efectuate utilizând linia celulară pentru a identifica efecte asupra unor enzime specifice și hormoni intermediari, cum ar fi progesteronul (2).
Any substance or mixture tested using this test method.
Definițiile și abrevierile utilizate în prezenta metodă de testare sunt descrise în apendice.