Scribd Logo
Upload

Welcome to Scribd!

  • Final Reg Public Tpe-D-0000003380-83-04 8590 en

    Uploaded by

    ibrahimoviç
    3 views14 pages

    Original Title

    final_reg_public_tpe-d-0000003380-83-04_8590_en

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    3 views14 pages

    Final Reg Public Tpe-D-0000003380-83-04 8590 en

    Uploaded by

    ibrahimoviç

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 14
    eECHA coon Decision number: TPE-D-0000003380-83-04/F Helsinki, 4 November 2013, DECISION ON A TESTING PROPOSAL SET OUT IN A REGISTRATION PURSUANT TO ARTICLE 40(3) OF REGULATION (EC) NO 1907/2006. repaeaigchs ne7as0-0-4 (6c No 231-1880), registration ober: Hl A <<: TTT Ta = ‘The European Chemicals Agency (ECHA) has taken the fellawing decision in accordance with the procedure set out In Articles $0 and 51 of Regulation (EC) No 1907/2006 eancerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH Regulation) 1. Procedure Pursuant to Article 40(1) of the REACH Regulation, ECHA has examined the fllowing testing proposals submitted as pat of the jointly submitted registration dossier in accoréance with Fries 10(a}"i) and 12 (1)(0) thereof for cobalt CAS No 7440-48-4 (EC We 231-158-0), by Ce + Sub-chronic toxicity study (90-days, OECD 408) in rats, oral route, proposed to be ‘carried out withthe analogue substances cabot dichloride, CAS Ns 7646-79°9 (EC No 231-583-4) ana tncobalt tetraoxide, CAS No 1308-06-4 (EC No 215-157-2). ‘+ Pre-natal developmental study (OECD 414 in rts, oral route, proposed to be cariod ‘outwith the analogue substances cobalt dichloride, CAS No 7646-79-9 (EC No 231- 389-4) ond apd Ueeubolt els ouxide, CAS No 2308-06-1 (EC No 235°157°2). ‘+ Two-generation reproductive toxty study (ECD 416 in rats, orl route, proposed tobe carried out withthe analogues substance cobalt cichlride, CAS No 7646-79-9 (ECNo 231-589-8) and and tricobat tetracxide, CAS No 1308-06:1 (EC No 215-157 2. ‘The present decision relates solely to the examination of the testing propasals for sub-chronic toxlety (90-days) and pre-natal developmental studies. The testing proposal forthe two: {generation reproductive toxicity study Is addressed in a seporate decsion although the testing proposals were inialy addressed together in the seme draft decison, “Tas decision is based on the registration dossier as submitted with submission number for the tonnage bond of 1000 tonnes or more per Year. This decision dows not take into account any updates after & March 2013, the date upon which ECHA notified its Graft decision o the Competent Authorities of the Member States pursuare to Article 51(1) of the REACH Regulation. ‘This decision does not imply thatthe information provided by the Registrant in his registration dossier is In complonce with the REACH requirements. The decision does not prevent ECHA from initiating compliance check on the registration ata ater stage. (on 1 July 2011, pursuant to Article 40(1) of the REACH Regulation, ECHA initiated the ‘examination of the testing proposals set out by the Registrant in the registration dossier for the substance mentioned above, €ECHA sonmoewee [ECHA held a thir party consultation forthe testing proposals from 2 September 2011 unt 17 October 2011. ECHA did recelve Information from third parties (see secion Ill below), (on 27 April 2012 ECHA sent the draft decision to the Registrant and invited him to provide comments within 30 days of the receipt of the draft decision. (on 28 May 2012 ECHA recelved comments from the Registrant to ECHA’s draft decision. In his comment the Registrant cid not agree with ECHAS rejection of the testng proposal for]an oral sub-chronic tonety study (80-days). (0n 27 November 2012 the Registrant updated his registration dossier In the updated ‘dossier, the Registrant proposes testing, which Is based on grouping and read-across, Inthe ‘Context of which two substances (Le. cobalt clchlonde and trcobal tetracside) would be tested for sub-chronic toxlcty (90-days), pre-natal developmental toxicity and two- ‘generation reproductive tonlelty, The results ofthe proposed studies are proposed to be used te cover all substances within the ‘cobalt category’, including the substance concerned by the present decision, by means of read-across CHA considered the Registrant's comments received and the updated registration dossier. (On that bass, Section Il was amended and the Statement of Reasons (Settion Il) was ‘hanged accordingly. In that draft decision, the testing proposals for oral sub-chronic toxcty Study (90-days) with cobalt chloride and with tcobaletetraoxide were accepted (On & March 2013 ECHA notified the Competent Authorities of the Member States ofits draft {cision and invited them pursuant to Artcie'1(1) ofthe REACH Regulation to submit. proposals to amend the draft decision within 30 days ofthe recept ofthe notification. ‘Subsequently, Competent Authorities of the Member States submitted progosals for ‘amendment tothe draft decision (On 11 Apri 2013 ECHA notified the Registrant of proposals for amendmen: tothe draft ‘decision and invites him pursuant to arte 51(3) of the REACH Regulation to provige ‘comments on those proposals for amendment within 30 days of the recsit of the notification. ECHA reviewed the proposals for amendment recived for all substances within the ‘cobalt catagory’ and decided to amend the raft decision. (On 22 Apri 2013 ECHA refered the draft decision to the Member State Cemmittee “The Registrant did not provide any comments on the proposed amendments. However, the Member Stata Committze took into account comments that were received or ater substances within the ‘cobalt category’ as these comments apply also forthe substance Subject to the present decision, “The draft decision was spit into two draft decision documents: one relating to the testing proposal for 2 twovgeneration reproductive toxicty study and one relating to the testing Sroposals for an oral sub-chronic toxicity study (90-days) and a pre-ratal developmental toxicity study, [After discussion in the Member State Committee meeting on 11-14 June 2023, a unanimous ‘arcement of the Member State Committee on the draft decision relating to the testing proposals for an oral sub-chronic toxicty study (80-days) and a pre-natal developmental {oxlety study a5 modified at the meeting was reached on 14 June 20:3. ECHA took the decision pursuant to Article 51(6) ofthe REACH Regulation. ECHA = meen ow 1, Testing requited ‘The Registrant has requested to cary out the required tests using analogue substances as part of a read-across and grouping approach, In accordance with Annex XI 1.5. ECHA ‘emphasises that any final determination onthe valety of the ead-across, including the ‘reuping approach proposed by the Registrant would be premature at this pont in time. The {eventual valcity of the read-aross hypothesis and grouping approsch willbe reassessed ‘once the requested studies are submitted. Nevertheless, Dazed on the infermation currently ‘Submitted, ECHA considers thatthe approach proposed by the Registrant is plausibe. In the light ofthis assessment ECHA has taken the following decision ‘The Registrant shall carry out the following tests pursuant to Article 40(3)a) of the REACH Regulation using the indiated test methods and the analogue substances cobalt dihlorige, [CAS No 7646-79-3 (EC No 231-585-4) and trcobalttetraoxide, CAS No. 1308-06-1 (EC No 215-157-2), instead of the substance subject tothe present decison: 1, Sub-chronic toxicity study (90-days) i ras, oral route (Annex IX, 8.6.2. test method: EU B.26/0ECD 408); and 2, Pre-natal developmental toxicity study in rats or rabbits, ora route (Annex Dk, 187.24 test method: EU B-31/0ECD 414), ‘The Registrant shall determine the appropriate order ofthe studies taking into acount the possible outcome and considering the possibilities for adaptations ofthe standard information Fequirements according tothe column 2 provisions of the respective Annex and those Contained in Annex X1 of the REACH Regulation. Pursuant to Articles 40(4) and 22 of the REACH Regulation, the Registrant shall submit to ECHA by 4 November 2035 an update ofthe registration dossier containing the information Fequired by this decision. Data from a second pre-natal developmental toxity study on another species is standard Invormation requirement according to Annex X, 8./-2. ofthe REACH Kegulsvon. Ihe Registrant should fstly take into account the outcome of the pre-natal developmental Toniety ona frst species and all other relevant available data to determine ifthe conditions fare met for adaptations according to Annex X, 8.7. column 2, oF according to Annex XI. the Registrant considers that testing is necessary to full this information rea.irement, he should Include inthe update of his dossier a testing proposal fora pre-natal developmental toxicity study ona second species, [At any time, the Registrant shal take into account that there may be an obligation to make {every effor to agree on sharing of information and costs with other Registrants, IMI, Statement of reasons “The decision of ECHA is based on the examination of the testing proposals submitted by the Registrant forthe regstered substance and scientific information submited by tia parties. In relation tothe testng proposals subject to the present decision, the Registrant has proposed to use @read-across and grouping approach, In accordance with Annex XI, 1.5, and {perform the tests on two analogue substances. To the extent that all poposed testing Felles upon an Identical read-across hypothesis, £CHA has considered fist tne scientific ‘Validity of the propased read-across and grouping approach (preliminary considerations), before assessing the testing proposed (Sections 1 and 2, below). © ECHA coma Read-across and grouping approach (preliminary considerations) Atcle 13(1) ofthe REACH Regulation requlres information on intrinsic prozerties of| Substances on human toxety to be generated whenever possible by means other than Vertebrate animal tests, including fom information from structurally related substances {grouping or read-across), “proved that the conditions set out in Annex 2 are met ‘According to Annex Xl, 1.5 there needs tobe structural similarty among the substances Within 2 group ra category and furthermare, fe s requires that the relevant properties of 2 Substance nithin the group can be predicted from the data for reference substance(s). ‘The Registrants have submitted testing proposals, based on a read-across approach, Intended to fulfl information requirements for oral sub-chronic toxty (90-days; Annex IK 7.5.2.) pre-natal developmental toxicity (Annexes 1X and X, 7.8.2.), and toxiety to reproduction (Annex X, 7.8.3.) It's noteworthy that under the evaluation ofthe testing proposals, ECHA has" not performed a compliance “check on other endpoints. such "as. mutagenicity, carcinogenicity and sub-chronic toxicity via inhalation and may do so at any time at its own Secretion, ‘According to the Registrant, the read-across hypothesis is based on cobat (Co) fon systemic fonity and applies without restriction to all cobalt substances capable of releasing cobalk tons, More speciicaly, the Registrant concludes that cobalt metal and cobalt containing Substances are subject to “corrosion” processes or dissociate in aquat media containing ‘oxygen, liberating cobalt fons; the disolution process ts pH dependent. In addltion the hypothesis fs bases on the fact that in vitro bloaceessbilty in ariel gartrc fu a etter fetimate for bioavalabilty than water solubility. The low pH in the stomach wall couse dissolution of the substances, facitate gastroinestinal absorption, and thereby determine Systemic exposure ‘To support the proposed read-across hypothesis the Registrant has provided experimental data on water solubity, cobalt speciation in the environment, in vitro bloaccessibilty studies {cf all cobalt substances inthe proposed category) in varcus ariel physiological fds, and rour sub-ecute toxicity studies (20-aays). Te results trom the in vtre oaccessIDIy Studies demonstrate thatthe pregicted bionccessblity (gastric release) is high for most, Substances within the category regardless of water solubity. Furthermore, the bioaccessibilty studies show that cobalt substances are likely to be absorbed through the inalaton route, To further support the proposed read-across hypothesis, the Registrant has provided four oral sub acute repeated dose toxilty studies (28-dys all four conducted with cobalt. carboxylates"): cobalt stearate, CAS No 12586"84-0 (EC No 237-016-4); cobalt borate eedecaneate complexes, CAS No 68457-13-6 (EC No 270-601-2); cobalt (If) 4-oxopent-2- fen-2-olate, CAS No 14024-88-7 (EC No 237-895-6); and resin acids and osin acids, cobalt Salts CAS No 68956-82-1 (EC No 273-321-9). Furthermore, three additional oral sub-acute ‘epeated dose toxicity studies on cobalt metal powder CAS No 7440-48-4 {EC No 231-158-0), {obalt sulphide CAS No 1317-42-6 (EC No 215/273-3) and tricabalt ttraokide CaS No 1208 (06-3 (EC No 215-157-2) ae reported as engoing. In addltion, the dossier contains ral non {guideline repeated dose toxicty studies from scientfc literature on cobalt dchlaride. The ‘verall toxicological effects observed in the studies above support te hypathess of cobs on toxity and provide experimental support for use ofthe vitro bicaccessbilty parameter to ‘low prediction of bat fn toxicity within the category, although appicabily of tis information for reproductive toxcity endpoints needs to ba established, @ECHA comes In the dossier update, the Registrant proposes to perform the intended tests on two Substances: cobalt dihloride CAS No 76679-9 (EC No 231-589-4) and tricabalttetraoxide {CAS No 1308-06-1 (EC No 215-157-2). Based on the studies mentioned above, these Substances are respectively the most bioaccessible cobalt substance and the least blosccessible cabalt substance within te cobalt category’ CHA has analysed the dossier update in light of the requirements of Annex XI, 1.5. The fead-acrose hypothesis (based on cobalt ion toxicity) is considered piavslve as the Underining chemical information s supportive and relevant and because the hypothesis is Supported by toxicological data, The data on bosccessibity and the data on lower er only studies suggest that there Is an association among members ofthe category of cobalt substances. The Realstrant has proposed to test two cobalt substances that represent the highest and lowest solubilty/bioaccessibilty of thase cobalt compounds and thereby are ‘oneldered to set the boundaries ofthe propased category ‘Tne prosent decision concerns only a testing plan based on read-across ard grouping hypothesis. This hypothesis Is based on cobalt ion toxity and the fact that in vitro bloaccessbiity in arifctal gastric Fluid isa better estimate for bicavallabilcy than water solubity, ‘The frst Rectal and the fist Article of the REACH Regulation establish the")romotion of ltemative methods for assessment of hazards of substances” as an objecive pursued by the Regulation. In accordance with that objective, ECHA considers thatthe prediction of the relevant properties ofthe registered substance by using the results ofthe proposed tests is Sufficiently plausible based on the information currently avaiable. Nevertheless, ECHA notes thatthe read-across justification shall eventually have to take account ofall aspects that may Influence the hazard characterisation in order to be able to mest the information requirements. Nore specially, the concept ofbicaccessibilty refered toby the Registrant Cannot inal cases be directly translated into bigavalabiity (i.e gactrointstinal absorption) For example, for eabat stearate the NOAEL in the suf-acute stusy does not fllow the trend of the bioaccessbity. Therefore, the sub-acute studies provided by the Registrants do not ‘uly suppor tne nypotesis or eSbat lon oxic or all the substances covered bY the Category. Although the read-across hypothesis ts generally plausible, ECHA considers that estimations of internal systemic exposure fs subject to some uncertainties if based solely on {an in vitro bloaccessiblty. The read-across adaptation based on the results ofthe proposed fests shal ensure that those uncertainties are analysed, minimized, and taken into account forthe purpose of classification and labeling and/or ik assessment. In thelr comments to the MSCAs Proposal for Amendment, the Registrants concemed by the Category have jointly incicated that thelr intention is to divide the cobalt substances into to ‘groups for the purpose of read-across. ECHA points out thatthe eniteria, which the Registrants will use to divde the cobait compounds into two groups have not been sufficiently Canfied. Neither has i been fully explained how the tet result wil be use for setting the Substance and endpoint specific NOAELS/DNELs, The Registrants propose “o use the test Fesults also for classification. However, ECHA emphasises thatthe Registrants have not texplained how the information wil be used to reach conclusions on classification, in particular for the reproductive toxiety. Therefore, the acceptance of the testing proposals does not Imply thatthe application of the read-across strategy in its current form I fully conclusive and acceptable In the case where the tests performed in accordance with the present decision would nat coafirm the read-across hypothesis relied upon by the Registrant, this outcome shal nt alter the obligation ofthe Registrant to meet the standard information requirements. Should the readvacross strategy be inadequate, Ie isthe responsibilty of the Registrant to ultimately Submit reliable information or adaptations which Is used in 8 way that does not underestimate hazards ofthe registered substance in relation tothe relevant endpoint. © ECHA coos In any case, following the update ofthe dossier submitting the infrmatior required in the present decision, ECHA will determine whether the documentation provides ls sufficient to Eatsfactonly address the Information requirement of Annex X for the entie category as Proposed by the Registrant, If, upon furtner consideration, the proposed a2praach does not Entsfy the conditions set out in Annex Xl, ECHA reserves the night to request the information recastary to Tlf the Information requirements fr the substance subject to the present. Secision ECKA notes thatthe reglstered substance isa cobat salt. The total surface area of the particles (le. particle size) Is an important factor that neads to be considered for all Substances inthe category 2s ft wil affect the rte of solubiisation. The Registrant needs to {ake into consideration factors such as particle size, ie. rate of cobalt-fons release from the particles. F appropriate, the Registrant shal justly whether and to wich extent these factors Dffect the prediction from the tested substances fa the substances inthe category, 4, Sub-chronic toxicity study (90-days) 2) Examination ofthe testing proposal Pursuant to Article 40(3)(a) ofthe REACH Regulation, ECHA may require te Registrant to carry cut the proposed test. [A sub-chronic toxicity study (90 day) isa standard information requirement as laid down in Annex IX, section 8.5.2. of the REACH Regulation CHA notes thatthe Registrant has submitted testing proposals for sub-chronic toxicity studies (90-days) to be performed by the ofa route. The Registrant justifas the testing proposal by stating that It is needed for robust risk assessment and as 2 dose-finder for the proposed two-generation reproductive toxicity study. ‘The Registrant has submitted a 13-week inhalation toxicity study (NTP 1991) and a carenogenety study (also via alton, NIP 1998) pertomed using Eobat sulphate, CAS No 10124-43-3 (EC No 233-334-2), which ae in essence consistent withthe respective test guidelines. with regard to oral repeated dose toxicity, ECHA notes thatthe technical dossier contains four reiabie oral sub-acute toxicity studies performed with other member ofthe proposed ‘cobalt category’ Three addtional subacute toxicy studies are reported as an-going (eee fead-across considerations above). In addition, the techrieal dossier contzins a number of ‘ral sub-acute/chronie studies from scientific iterature on primarily cobalt cichlorie which ‘are considered ‘not relable’ by the Registrant as they arent useful for rebust isk ‘assesement. ECHA notes thet there ae no subchronic toxety studies (9C-days) by the oral Foute availabe, neither forthe substance covered by the present decision nor for eabalt Jichioride or tricobalt tetraoxide, which are the roference substances forthe category. “The Registrant has provided several arguments on why an oral 90-day repeated dose toxicity study is necessary f&ECHA a Firstly, according to the Registrant: “The repeated dose tovioty stules va nhaltion with cobalt sulphate are not suitable for use inthe hazard assessment of systemic eects (vid. ‘route to route extrapolation). The respiratory tract of test animols is more susceptible to ‘averse effects by nhated cobs, showing an inlammatery response at concentrations at luhich systemic effects cannot be observed”. ECHA agrees with the Registrant in tha, due to the reason given above, loca respiratory effects may have prevented accu'ate identification of systemic effects and would not provide a basis for derivation of the DNEL for systemic Toxicity. (ora ute) for the cobalt category. Consequenty, oral sub-ehronk towaty study (G0-days) is considered valuable in aderessing the systemic eects of cobet Secondly, concerning the need to cover both inhalation and oral route of exposure by sub~ hone shies, te Registrant has demonstrated thatthe ie vitro bioaecesibilty (and TkSly also gastrointestinal absorption) ofthe substances within the “cobalt category’ dirs Sepending on the route of exposure, fe. the absorption by oral route is clearly higher than ‘Via the inhalation route. ECHA considers tht this supports the proposal ofthe Registrant to test representative cobalt substances by using the oral route as it wll provde a more robust ‘assessment of systemic effets Finally, al ofthe orl repeated dose toxicity studies in the dossier, with the exception of the recent sub-acute studies, have not been made according to current test guidlines. Although, the NTP studies observed some aspects of systemic toxicity, ECHA considers that 8 new oral ‘sub-chronic toxicity Study (80-days) Is necessary Io order Co fly characterise the systemic ‘effects of cobalt substances. Is noteworthy that according to Annex I of REACH Regulation land according to the ECHA Guidance on information requirements and chemical safety assessment (Chapter .8.), DNELS for both local and systemic effects may need to be derived ‘depending on the substance inthe “cobalt category According to Column 2, Annex 1X, Section 8.6.2, the study Isto be performed using the most appropriate route of administration considering the likely route of human exposure. Based on Information Submitted on uses and exposure, ECHA notes that in the present case the mast likely route of human exposure could be oral and/or inhalation depending on the substance lthia the proposed ‘cobalt eateaory. n the dossier update, the Reaistran: has further justified the route of administration and considers that overall within the oat category’ the ‘ral route of administration isthe most appropriate. For the purpose of testing proposal evaluation, both oral and inhalation exposures are therefore considered as appropriate routes fof human exposure. ‘The hypothesis ofthe proposed read-acrossreles onthe testing of cobalt sicloride and Irlcobat tetraaxide. ECHA has noted thatthe studies which formed the bois for the classification, although, sufficient for hazara wentiication, Is not considered by the Registrant ‘2s sutident to support robust risk assessment across the category. NO information on sub ‘hronic toxtety (80-days) is avaliabe for tricobat tetraoxide. For cobalt chloride, no ‘quideine compliant oral sub-chronic toxety study (80-days) is avaliable. In order forthe Reaistrant to make full use ofthe propased read-across approach for interpolation across the fategory, including the substance concerned by the present decision, its mportant to have {equal quality data at the boundaries of the eategory. ECHA has evaluated se avaiable Information on cabalt dichloride and concluded that addtional testing Is Justified. Therefore, FECHA accepts the testing proposals on both cobalt dichloride and tricobal teraoxtde with respect to oral sub-chronic toxic © ECHA comes ECHA would ke to point ut some adalittonal considerations with ragard te the proposed sub chronic toxicity study (90-days). There is already an identified hazard with regard to male Feproducton for cobalt dichloride. For female reproduction there fs no information avallable, ‘At Teast one of the substances proposed tobe tested Is highly likly to profuce adverse tffects on reproductive organs sufficient for classncation as Repro, 16-1360 nc a result of the proposed tests. Some addtional examinations on reproductive parameters that are ‘ormally performed in the two-ganeration toxicity to reproduction study (lst method: EU £8,35/0ECD 416) can be included into the proposed orl sub-chronic toxicty study (30-days). If these adkitional examinations are included in the proposed oral sub-chrictoxity study {(90-days), and both substances tested produce adverse effects that are sufcient for classiiation as Repro. 18:H360 the proposed two-generation toxcty to reproduction study may not be necessary (see Section I3 and Section Ill). ECHA therefore recommends the Registrant to include adltional examinations of male and female reproducive parameters {cestrous cycle, sperm parameter, and reproductive and other certain organs and tissues) ‘that produce respective information as cullined for P parental animals in EU test method B.35, sections 1.5.3, 15.4 and 1.5.60 1.5.8. »b) Consideration ofthe information received during thiré party consultation ECHA received third party information concerning the testing proposal dueng the public consultation. For the reason’ explained further below the information proved by third parties 1s not sufficient to full this information requirement, “This party information 9: A third party acting on behalf of the Registrants has communicated to ECHA that the Registrants intend to update the testing strategy and test cobalt dichloride, CAS No 7646-79: 9 (EC No 231-589-8) rather than cobat sulphate, CAS No 10124-43-3 (EC No 233-3342). EECHA considered the corresponding infermation provided by the Registrants in the updated technical dossier “hist pary information 10: [A third party has proposed a read-across approach for ECHA to take into eccount before further tests on vertebrate animals are required. As part ofthis approach, the third party provided results from the US National Toxicology Program (NTE). The tiré party has pated thatthe registration dossier contain resits from NTP L0S-week carcinogenety studies in ‘mice and rats, which were perlrmed withthe read-across substance cobet sulphete heptahydrate (CAS No 10026-24-1) using inhalation exposure. The third garty has noted that the results from 16 day and 13 week range-finding studies are available @ Separate report but are not included in the registration dossier. The third party propases Cat the information from the range-finding studies may be sufficient to fully adress the data equirement, with the consequence thatthe proposed 90-day arl toxicity study i nat scientiealy Justiied [ECHA has taken the information proved into account and concludes thatthe information provided by the third party is provided by the Registrant. The information has been Eonsidered in relation to the endpoint (see Section I-18). ECHA concludes thatthe Information provided Is sufficient to fut the information requirements for Annex IX, Section 1816.2 forthe inhalation route for ‘highly soluble" category members. Honever, i light of the vera, read-across approach, testing strategy and the availabe information by the orl route, ECHA considers tht testing for sub-chronic toxlety i required also by the ora route in forder to support robust risk assessment ofthe cobalt category’ €f€ECHA soxmeewe ee “Tied pare information 21 ‘Athied Party polnts out that cobalt sulphate and several other cobalt containing compounds ‘already are classified as Car. 18 and Ropro.18 and sted in the Candidate List 3 3 ‘Substance of Very High Concer, asthe fist part ofthe Authorisation procass. The third party argues thatno testing Is necessary Tor cobalt sulphate because a caranagenic ‘Compound will subject to very rigorous exposure controls and Authorisation (once completed) ‘il prohibit some uses and only allow those uses where the exposure can de demonstrated to be safe (or because of adequate socio-economie justification}. The third party further argues thatthe rsk management measures requlred to contr the risks fram carcinogenic, lhc is non-threshold effect, wll be much more restrictive than those whieh would result from the additional tests and the resulting DNELs. Furtnermore, the thie party argues that, because ofthe read-across and category approach proposed by the Regist ant, all cobalt Should be considered to have the same carcinogenicity hazard as cobalt sulphate and therefore no addtional testing Is required. On this basis, the third party considers the ‘ditional toxily tasting on vertebrates le unnecessary, and proposes rejection of them in the Interest of animal welfare. “Third parties were invited, as specified by Article 40(2) ofthe REACH Reguation to submit “scientifically valid Information and studies that address the relevant substance and hazard end-point, addressed by the tasting proposal". As the proposal fora strategy or for Waving {3 such cannot be regarded information or studies, ECHA concludes that this fe not 2 Sufficient basis to full the data/information requirement. ECHA also paint cut that nt al substances in the ‘cobalt category’ are classified for carcinogenity, ‘hie party information 12: ‘A third party has submited two studies by Grice et a and Domingo et an which rat were ‘exposed sub-chronically to cobalt (sulphate and chloride, respectively). In these stules, Increased heart weight and degenerative hear lesions ware ebserved. third party also referred to an international assessment report (CICAD 89, Cobalt and Inorganic cobalt Compounds) published by the Worla Health Urganlzation Although ECHA recagnises thatthe information as provided by the third party might be Sclentifally relevant, ie does not fulfl as such the Annex IX, Section 8.6.2 requirements, because these studies have been classed as “not reliable” by the Registrant an they have of been made and reported according to respective test guidelines. Therefor, the studies are not sutiient to allow ECHA to reject the testing proposal solely onthe basis ofthese Studies. 6) Outcome CHA has examined the testing proposal considering all the relevant and zvallable data in the Context of the proposed read-aeross approach and the information submited by third partes {during the public consultation, The availabe information is not considered a suficent to permit a robust conclusion on sub-chronic toxcty (90-days), to serve as 2 starting polnt for fobust risk assessment across the proposed ‘cobalt category’, including the substance Concerned by the present decison, Ite thus necessary to generate additional data or this endpoint, in accordance with the provisions of Annex Dk, seetion 8.6.2, elumn 2. ‘Therefore, pursuant to Article 40(3)(a) ofthe REACH Regulation, the Registrant is required to carry out the proposed study: Sub-chronic toxicity study (90-days) in rats oral route (Annex 1, 8.6.2.; test method: EU 8.26/OECD 408), using the indicated test method and the ‘analogue substances cobalt cieloride, CAS No 7646-79-9 (EC No 231-589-4) and treobalt tetraoxide, CAS No 1308-06-1 (EC No 215-157-2) instead ofthe substance subject to the present decision eECHA corso 2. Pre-natal developmental toxicity study 2) Examination ofthe testing proposal Pursuant to Article 40(3)(a) of the REACH Regulation, ECHA may require the Registrant to carryout the proposed test {A pre-natal developmental toxicity study fora first species is a standard information requirement as laid down in Annex IX, section 8.7.2 of the REACH Regulatan. The information on this endpoint isnot avaiable for the registered substance fut neds to be present in the technical dossier to meet the information requirements. Corsequenty there is {2m information gap and itis necessary to provide information for this endpoint FECHA notes thatthe Registrant has submitted four relevant studies (published scientific Journals) n relation to this information requirement. Three studies were performed in rats ‘and one in mice using cobalt dichloride or cobalt sulphate. Each ofthese studies covers some ‘aspects ofthe pre-natal developmental toxic. In addition, the Registrant has also ‘Submitted testing proposals for a pre-natal developmental toxicity study (test method: EU B.31/0ECD 414) to be performed by the ofa route, While ECHA notes that some relevant data is availabe in the dossier on pre-natal developmental toxkity, these studies are not considered sufficient to Tlf the information Fequirement. More specially, ECHA considers that the studies submitted do nak cover all the Parameters and observations according tothe current test guideline (EU B21, OECD 24). In ‘sition, the size of animal groups used in the studies is smaller than stipulated within the test guidelines and therefore, the statistical sensitivity ofthese studies is compromised. [EGHA also notes that this information originates from published literature, where the ‘adherence to standard test guidelines and the robustness of reported study results may not be as stringent as in study reports specially designed for regulatory purposes. ECHA ‘scknowledges Uae the tastes provided do not enabled the Registrant to Frepare appropriate bust study summaries in accordance with REACH Regulation requirements since the felevant information on the methods applied and detalied results are not zlways given in the scientiie publications, ‘Annex IX 8.7, Column 2 of the REACH Regulation stipulates: “ira substance is known to have an adverse effect on fertility, meeting the eriteria for Classification as Repro. 1A or 1B: H360, and the available data are adequate to Support a ‘robust risk assessment, then no further testing for ferity wil be necessary. HOWever, testing for development toxicity must be considered” (emphasis added) ‘Testing or pre-natal developmental toxic Is therefore proposed by the Registrant as he considers that, due tothe limited data available, a test using the appropriate guideline is ecessary. As previcusly explained, the information on pre-natal developmental toxic is ‘current insufficient to cover the cobalt category’. ECHA acknowledges that the Registrant legitimately considered that pre-natal developmental toxicity data perforrred according tothe accepted test guideline was necessary to suppart.a robust risk assessmen. Furthermore, the tests proposed will provige a more adequate basis for derivation of the DEL for the “cobalt category" ‘The Reglstrant didnot specify the species and route to be used for testing, According to the test method EU B.31/OECD 414, the rats the preferred rodent species, the rabbit the preferred non-rodent species and the test substance fs usually administered orally. ECHA Eonsidars these default parameters appropriate and testing shauld be perormed by the oral outs with the rator tha rabbit as a frst species to be used. GECHA = ome For the sake of clarty, ECHA highlights that only the information requirement concerning the testing with "Tst™ species has Been considered at this stage. 'b) Consideration of the Information racelved during third party consultation ECHA recelved third party information concerning the testing proposal during the third party consultation. At the time of the consultation the testing proposal indicated cabal sulphate 3s the substance tobe tested. Later the Registrant updated tne dossier and proposed cobalt Chloride to be tested. For the reasons explained further below the information provided by {hid parties is not suffelent to fulfl this information requirement “Tied party information 1 For this information requirement, a third party have submitted information that i ential to that addressed in Third party information 9 forthe pre-natal developmental toxicity study ‘above (see Section IL.1-b). ‘Third party information 2: [Athi Party highlights that cobat sulphate and several other cobalt containing compounds are currently classified as Care. 18 and Repro. 18 and listed inthe Candisate Uist as, Substances of Vary High Concern, as the first part ofthe Authorisation procss. The third Party argues that ne testing is necessary for cobalt sulphate because a carcinogenic Eompaund will be subject £0 very rigorous exposure controls and Authorsston (ence Completed) will prohibit some uses and only allow thase uses where the exposure can be ‘demonstrated to be safe (or because of adequate socio-economic justification). The third party further argues thatthe risk management measures required to conta the sks from Eareinogentety (a non-threshold effect) will be much more restrictive than those which would Fesul from the additional tests and the resulting DNELs. Furthermore, the third party argues hat, because of the real-aurons ai ualayury approach props Uy Ue keylsiant, all ‘cobalt compounds should be considered ta have the same carcinogenicity nazar as cobalt Sulphate and tharefere no additional testing Is required. On this basis, the third party Considers thatthe adsitional toxet testing on vertebrates Is unnecessary, and proposes rejection of them inthe interest of animal welfare ‘Third parties were invited, as specified by Article 40(2) of the REACH Regulation to submit “selentifcaly valid information and studies that address the relevant substance and hazard ‘end-point, addressed by the testing proposal’. As the proposal fora strategy or for waiving {25 such cannot be regarded information or studies, ECHA concludes that this isnot a Sufficient bass to ful the data/information requirement. However, ECHA has considered the arguments provided by the third party, Testing proposal exarminaton under REACH is 9 process that i formally independent ofthe Authorisation process. The Authorisation process Is ongoing and ECHA can not predict the outcome of this process. Therefore risk management ‘measures and the levels of exposure cannot be assessed at present. In aalition, the third party suggests that additional testing for reproductive toxicity is not recossary as the substance proposed to be tested is classified as Carc. 15, the associated hazard phrase is H350i “May cause cancer by inhalation”, ECHA agrees win the third party that appropriate risk management measures should be In place with regard to inalation ‘exposure. However, some ofthe cobalt substances included within the prepesed category also have oral exposure as a route of human exposure and therefore, ECHA considers the testing to be necassary EECHA orem me “Third party information 3: [A thied party suggests that addtional tasting for reproductive toxicity isnot necessary as the proposed test substance Is classified as Care. 18, H350) "May cause cancer By inhalation”; uta. 2, H341 “Suspected of causing genetic defects" and therefore testing should only be necessary if appropriate nsk management measures are net in pace. ECHA agrees with the third party in that according to Annex IX, 8.7. reproductive toxily studles would not be required if the substance s known to be 3 genotoxic carcinogen and apprepriata risk ‘management measures are implemented. However, the Registrant did nox clarify whether the isk management measures (RIMS) are implemented and therefore ECHA cannot assess the implementation of the RHMs in the context of te testing proposal examination, Furthermore, some cobalt compounds are listad in the Candidate List as Substances of Very High Concern, a= the fist part of the Authorisation process, ana their RMI will depend on {this process. Appropriate risk management measures shouldbe in place with regard to inhalation exposure. However, some ofthe cobalt substances Include in te proposed Category also have oral exposure as raute of human exposure, therefore, ECHA considers the testing to be necessary (see also Section II.1..11). ‘Thin party information 4: [A thid party has submitted one study (Szakmary eta.) on the effects of cobalt sulphate on prenatal development of mice, rats, and rabbits, and on early post-natal development of rats; Bnd an international assessment apart (CICAD 69, Cobalt and inorganic exbalt compounds) published by the World Health Organization. The study provided by the thed party ls already Eonsidared by the Registrant. Although the study investigates pre-natal developmental effets Following orl exposure to cobalt sulphate in three species thera are several methodological and reporting deficiencies inthe study. In particular, multiple study desigrs are used and the fetal number of animals used in each study design 1s too low for regulatory purposes. The CICAD report confirms the Registrant's claim that there isa limited database on prenatal ‘developmental toxicity of cabal and thatthe results are somewhat cantrasctory. Therefore, Standard information requirements as laid dawn in Annexes IX and X, section 8.7.2. of the REACH Regulation ©) Outeome ECHA has examined the testing proposel considering all the relevant and avaliable data in the Context of the proposed read-across approach and the information submited by third partes ‘uring the public consultation. The avaiable information is not considered as suiclent to permit a robust conclusion on the pre-natal developmental toxicity potential of the Substances within the ‘cobalt category’ including thes substance subject te the present

    You might also like