COMMENTS ON AN ANNEX XV DOSSIER FOR IDENTIFICATION OF A SUBSTANCE AS SVHC AND RESPONSES TO THESE COMMENTS

Substance name:	 Cadmium chloride	
CAS number:	 10108-64-2	
EC number:	 233-296-7	

The substance is proposed to be identified as meeting the following SVHC criteria set out in Article 57 of the REACH Regulation: Art. 57 (a), (b), (c) & (f)

Disclaimer: Comments provided during the public consultation are made available in this document as submitted by the commenting parties. It was the commenting parties own responsibility to ensure that their comments do not contain confidential information. The Response to Comments table has been prepared by the competent authority of the Member State preparing the proposal for identification of a Substance of Very High Concern. RCOM has not been agreed by the Member State Committee nor has the document been modified as result of the MSC discussions. The table does not contain any confidential information.

PART I: Comments and responses to comments on the SVHC proposal and its justification

General comments on the SVHC proposal
Number	Date	Submitted by (name, Organisation/MSCA)	Comment	Response	
10	2014/04/17	International NGO
Health and Environment Alliance (HEAL)
Belgium	The Health and Environment Alliance supports the nomination of cadmium chloride as an SVHC, and in particular that it is nominated for multiple properties (57a, b, c, f). 	Thank you for this support	
7	2014/04/15	Company
Germany	[General]
The report proposes to identify CdCl as SVHC - but no data relating directly to the risk associated to working with the substance is given. 
[p.14]
It is stated that anthropogene sources for cadmium account for up to 90% of the overall Cd exposure, not accounting for the risk taken up by smokers with smoking being identified as the largest single known source for cadmium intake by individuals. Thus, it follows from said numberss that the risks imposed to workers handling Cd containing substances or chemicals like CdCl2 is minimal. This indeed is supported by biomonitoring data from a CdTe PV module manufacturer.

[p.15]
The report presents only data of swedish population based studies, thereby excluding studies from the US with both larger number of probands and also distinguishing workers exposed to Cd, eg. Menke et al (1996), Mannino et al (2003)and references cited therein to give but a few examples. 

[p.15] 
The report states that for the group of swedish probands monitored and indeed the swedish population on the whole, the level of Cd has not changed in the last 2-3 decades. This is in contrast to the statement of the report on [p.27] reporting a substantial increase in imports of Cd from Sweden. It is thus questionable if indeed a relation between the amount of Cd used in manufacturing and other industrial processes poses an additional risk to the population. 

For a sound basis to support the decision making process whether or not to include CdCl2 on the list of SVHC materials it is therefore suggested to first conduct thorough investigations under real working conditions as they can be found in modern production technologies like solar industry.

More information on the health aspects of working with CdCl in a modern production environment is given in the attachment to this response.	General: The justification for SVHC identification is based on intrinsic properties of the substance, not on use, exposure and risk.  The latter is only briefly mentioned in the section on “Societal concern” for 57(f).

p. 14: We agree that intentional uses of CdCl2 contribute to a low extent to the total exposure of cadmium. However, as effects on e.g. bone can be seen in the general population in EU today, all contributing parts of the total exposure, even small ones, need to be diminished, when possible.

Workers exposure can of course vary depending on use, use conditions and implementation of risk reduction measures. These aspects are taken into account in the authorization step.

p.15: The Swedish biomonitoring data should be seen as an example from an EU country. Due to the extremely long time periods both for changing Cd levels in soil, and therefore in food, and the long half-life in humans (10-30 years or longer) changes in use volumes will not result in changes in exposure and effects immediately.	
			See also:
Comment 7 attachment (c571rspcd-official.pdf).pdf		
6	2014/04/15	National NGO
CHEM Trust
United Kingdom	We find the evidence is well presented and provides a convincing case for the inclusion of cadmium chloride on the candidate list.  In addition, CHEM Trust would have liked to have seen the potential endocrine disrupting effects of cadmium chloride given greater emphasis in the discussion on the “equivalent concern” properties.	Thank you for the support. 
	
3	2014/03/21	Member State
Norway	The Norwegian REACH CA supports the proposal to identify cadmium chloride as a SVHC in accordance with article 57 a), 57 b) and 57 c) since cadmium chloride is harmonised classified as carcinogenic (Carc. 1B, H350: May cause cancer), mutagenic (Mut 1B., H340: May cause genetic defects) and toxic for reproduction (Rep 1B H360FD: May damage fertility; May damage the unborn child). 

In addition the Norwegian REACH CA supports the proposal to identify cadmium chloride as a SVHC in accordance with article 57 f) for equivalent level of concern owing to the adverse effects on kidney and bone tissue after prolonged exposure (harmonised classified STOT RE1, H372: Causes damage to organs through prolonged or repeated exposure). Since the toxic effects of cadmium chloride is caused by the cadmium ion, the same justifications for equivalent level of concern given for cadmium applies to cadmium chloride. Cadmium is on the Candidate List identified as an SVHC in accordance with Article 57a) and 57f).	Thank you for the support. 

Specific comments on the justification
Number	Date	Submitted by (name, Organisation/MSCA)	Comment	Response	
13	2014/04/17	International NGO
European Environmental Bureau (EEB)
Belgium	The EEB supports the inclusion of Cadmium chloride in the candidate list due to its concerning properties: carcinogen (and genotox according to genetox database), mutagen, endocrine disrupter (according to Scorecard: http://scorecard.goodguide.com/health-effects/chemicals-2.tcl?short_hazard_name=endo&all_p=t 	Thank you for the support. 
	
12	2014/04/17	Member State
Belgium	Belgium supports the proposal to identify cadmium chloride as SVHC, as the proposal is based on
o	article 57(a) of the REACH Regulation due to the classification as carcinogen cat. 1B.
o	article 57(b) of the REACH Regulation due to the classification as mutagen cat. 1B.
o	article 57(c) of the REACH Regulation due to the classification as toxic for reproduction cat. 1B.   

The substance is also classified as STOT RE 1. The following items are present in the Annex XV dossier to substantiate that the substance fulfills the article 57(f) criteria :
o	Serious organ dysfunction (for kidney : from minor tubular and glomerular dysfunction to an increase risk of end stage renal disease; and for bone : from disturbances homeostasis to actual bone fractures)
o	The health effects  can be irreversible
o	The delay of the effects is very long
o	There is uncertainty about identifying safe exposure levels
o	For the kidney effects : huge cost for the society
o	The exposure (17 countries : biomonitoring Cd) is a societal concern
o	The bioaccumulation

Based on these elements, Belgium also supports the identification of Cadmium chloride as SVHC according to article 57(f) of the REACH Regulation.	Thank you for the support. 
	
11	2014/04/17	Industry or trade association
International Cadmium Association
Belgium	Summary of Comments: 
The Annex XV report on Cadmium chloride highlights two areas of risks: 
1.	risk of increased bone and kidney effect on the general population due to exposure to Cd and its compounds from the environment and to releases of cadmium from cadmium chloride containing articles,
2.	risk to a large number of EU workers occupationally exposed to cadmium compounds. 
These risks are taken forward as a basis to request that cadmium chloride be submitted to the REACH authorization process.
However, no effort is made in this Annex XV to try to link “uses” of cadmium chloride to the risks to the general population.
Moreover, the Annex XV fails to recognize that the vast majority (over 98%) of workers is exposed to cadmium and its compounds present as impurity in commodities.
In these comments, industry will show that:
1.	The contribution of the industry deliberately using cadmium chloride to general population Cd-exposure is insignificant as compared to the contribution of the industry manipulating goods in which cadmium is an impurity.  In other words, the manufacture and use of cadmium chloride containing articles has no influence on general population cadmium exposure,
2.	The use of articles containing Cd and Cd compounds is already under many restrictions, prohibitions and limitations within the EU. Industry will show that exposure from the remaining articles specifically containing chemical CdCl2, including their end of life, is insignificant
3.	The sectors of industry that are deliberately using cadmium and its compounds only employ a small fraction of the estimated number of occupationally exposed workers (1.6%). These sectors deliberately using Cd and its compounds have a solid record of risk management and risk reduction; since 2008 they voluntarily implemented the Swedish Occupational Risk Agency management tools and implemented a DNEL based on the OEL set by SCOEL in 2010 (SUMDOC 136 2010).
In clarifying these points, it will become clear that authorization of CdCl2 uses will not lead to any influence on general population and worker exposure, and as such will be insignificant to “ensure that the risks posed by the substance of very high concern will be properly controlled” (REACH art 55).  Indeed, it will be clear that any Risks are already properly controlled.
In the following, a number of comments on the Annex XV document on cadmium chloride are given. More details on some of these comments are provided in the master-file (uploaded under IV Attachment). This master-file contains also the references. 

Comments
Page 6, section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH”, heading “equivalent level of concern”, 4rd paragraph, 4rd line - 
Comment 1
Annex XV states that ”Deposition from air is an important source to the input of cadmium to soil and must therefore be reduced. In order to achieve this all uses of cadmium and cadmium compounds should wherever possible, be substituted”. This statement ignores (a) the one major source of Cd-input to soil, i.e. use of P-fertilizer (see comment 35), and (b) makes the wrong assumption that (REACH) uses of cadmium contribute to human exposure, which is not the case (see comment 40).  
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 1 and 40.

Page 7, section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH” (cont.), 2nd paragraph - 
Comment 2
Reference is being made to the Council resolution on cadmium of 25 January 1988 -25 years ago- to justify further action on cadmium. The Annex XV fails to consider a) extensive EU legislation that was implemented since then on restrictions of the main cadmium uses, b) the extensive work that has been undertaken by the Commission since then on cadmium, with the EU risk assessment, as a result of which further measures were decided, c) the marked progress that was achieved on limiting documented Cd-emissions to air, water and soil. As such, the annex XV document ignores the significant reduction that has been observed since 1988 related to the cadmium exposure of the general population through the atmosphere (see comment 40 for data). 

Page 8, section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH” (cont.), 7nd paragraph - 
Comment 3
The annex XV document mentions rightfully that there is a continuous publishing of new information on cadmium. It states that this demonstrates that “what can be considered as a safe exposure level is steadily decreasing”. This statement however ignores a number of recent publications that challenge the significance of Cd-U as a marker of cadmium exposure in situations of very low exposure (e.g. at or below Cd-U = 1 µg Cd/g creatinin) for both kidney and bone effects. It is emphasized that the current exposure of the general population is at these very low levels (see comment 6 for details).

Page 9, section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH” (cont.). 2nd paragraph - 
Comment 4
The estimation of annual costs of cadmium exposure in Sweden is based on the lowest estimation of the safe exposure level, measured by Cd-U. Cd-U is however recently challenged by academic research as a biomarker of  Cd-exposure in situations of very low exposure (see comment 6).  The estimation of annual costs therefore needs to be considered with great caution.
For the use of cadmium in pigments a detailed critical review has been made of the economic analysis in the KEMI report (KEMI 2013) and the underlying studies from which the KEMI’s final economic figures were derived (EFTEC 2014).

Page 15, section 3.2: “food”
Comment 5
This paragraph makes reference to a recent EFSA report to conclude that “children and adults at the 95 percentile exposure can exceed health-based guidance values”. As is indicated in the EFSA report itself, this 95 percentile estimate is “speculative and potentially unrealistic” (section 3.2 page 17 of EFSA 2012) because it is based on the unlikely assumption that the same individuals retain the same high exposure throughout their whole life. This 95 percentile should thus be considered as clearly overestimated. The average Cd intake value calculated in this EFSA study is considered conservative as it is higher than recently published values in EU countries. However, it remains below the EFSA dietary intake standard, which is itself lower than the WHO dietary intake standard. Therefore, even following conservative assumptions, current observed dietary intakes in the EU can be considered safe in a life time perspective. See comment 53 for more detail.

Page 17, section 4.2 Kidney toxicity, para 2
Comment 6
Annex XV makes reference to KemI (2011), in which a number of studies were cited, “showing significant associations between cadmium in urine and/or blood and markers of impaired kidney function, mostly impaired tubular function”.  
However, recent evidence questions the causality of these associations between U-Cd and biomarkers of kidney effects (urinary proteins) in populations with low levels of exposure.  
Recent literature, as discussed in Annex XV, is showing that the association between Cd and protein excretion probably represents normal variability in renal physiology resulting in a temporarily increased or decreased Cd excretion, independent of kidney cadmium concentration (Kidney Cd) (Chaumont et al., 2012, Akerstrom et al., 2013a). 
These recent findings suggest that at low environmental exposures, U-Cd would be more a reflection of the functional integrity of the nephron than of the Cd exposure or of the Cd body burden (Chaumont 2012). 
These reverse causality mechanisms might have important implications in the risk assessment of Cd for the general population, which currently largely relies on the use of U-Cd as exposure indicator (Chaumont et al 2012).  
See also comment 48 for more details.
In conclusion, the scientific debate on the causal effect of low Cd exposures (measured as Cd-U) on kidney function is ongoing. Taking this debate into account, it is strongly recommended to consider the anticipated effects on kidney at low Cd exposure with caution. It is emphasized that at higher exposures, the causal relationship is not questioned (Chaumont et al 2011). The use of biological indicators in e.g. worker environment is thus justified. 
Referring to the recent study of (Åkerström et al, (2013b) showing a strong association between kidney Cd and urinary Cd (healthy kidney donors), we would like to emphazise this study should be interpreted very cautiously because the associations shown between concentrations of Cd in urine (or in blood) and the concentration of Cd in kidney are based on the whole population with no distinction between never and ever smokers. 
For more detailed data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 9

Page 18, section 4.3 Bone toxicity, para 3, line 9
Comment 7
Annex XV suggests “that even a urinary concentration around 0.5 µg/g creatinin is associated with increased risk of osteoporosis and fractures”. 
It is emphasized (see also comments 6, 48) that the significance of Cd-U as an exposure marker in situations of very low exposure to Cd, has recently been questioned (Chaumont 2012, Akerstrom 2013a). Consequently, this association between urinary Cd and bone effects must be questioned too. 
Therefore considering these recent elements of scientific knowledge, the suggested threshold for bone effects of Cd ‘at a level around 0.5 µg/g creat for the general population’ exposed by the oral route, is considered highly questionable. 
There is evidence suggesting that low-level urinary Cd in the general population is more a reflection of the recent intake and of the physiological variations in the urinary excretion of creatinine. This is relevant for all studies using urinary Cd as cumulative exposure indicator. 
Therefore, considering these new elements, a cautious interpretation of Cd-U data is needed because it is noted that the link between proteinuria and albuminuria at low Cd-U is physiological rather than causal (Cd-MT and LMW proteins share the same binding sites in the tubuli) (Akerstrom et al 2013a).  Moreover, since proteinuria and albuminuria are well known predictors of bone diseases (Barzilay et al., 2013), a causal relationship between CdU (at low levels) and bone effects is questionable.

Page 18, section 4.3 Bone toxicity, para 4, line 6
Comment 8
The Annex XV document mentions: “it is concluded that the differences cannot be explained by differences in risk of slipping, low calcium intake, vitamin D deficiency or by inactivity”.  No references are given to explain this statement. We anticipate that “slipping risk” and “inactivity” are rather comparable between countries. However, the parameters low Ca and VitD are very important for the bone effect, so clear references should be provided for this statement. 

Page 21, section 6.2., 3rd paragraph, 4rd line. 
Comment 9
Section 6.2.  is largely similar to section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH”. The comments 1 to 4 formulated above on this section, are also relevant here. Notably the sentence in paragraph 3, 3rd line “Deposition from air is an important source to the input of cadmium to soil and must therefore be reduced. In order to achieve this all uses of cadmium and cadmium compounds should wherever possible, be substituted” is misleading, since (a) it ignores the main single source of Cd to general population exposure, i.e. the use of P-fertilizer on agricultural land (see also comments 1and 35), and (b) the fact that cadmium (REACH) uses do not contribute to the cadmium deposition from air on crops and soil (see comment 40).
We note that the percentages provided in comment 35 are averages for the EU, and that differences between countries in Cd-sources to soil can occur. Yet, the averages are quite consistent throughout EU member states (OJ 2008/C 149/03), see for more detail comment 35. 

Page 21, section 6.2,  3rd  paragraph 
Comment 10
Again, this section 6.2. is largely similar to section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH”. Comment 1 formulated above on this section, is also relevant here. 

Page 21, section 6.2,  4th paragraph. 
Comment 11
Again, this section 6.2.  is largely similar to section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH”. Comment 2 formulated above on this section, is also relevant here. 

Page 23, section 6.2. , heading “uncertainties on safe exposure” 1st paragraph. 
Comment 12
Again, this section 6.2. is largely similar to section “summary of how the substance meets the criteria set out in article 57(a) and 57(f) of REACH”. Comment 3 formulated above on this section, is also relevant here, see also comment 6 & 7 for more details. 

Page 23, section 6.2., heading “societal concern and impairment of quality of life”. 

Comment 13
See comment 4 made above	The justification for SVHC identification is based on intrinsic properties of the substance, not on use, exposure and risk.  The latter is only briefly mentioned in the section on “Societal concern” for 57(f).

Please see the attached word file for further responses to comments.

			See also:
Comment 11 attachment (CdCl2 Annex XV_Master Comments Document_2014-03-17_final submitted.pdf).pdf		
9	2014/04/16	Member State
Germany	The German CA supports the identification of cadmium chloride (CAS No. 10108-64-2) as an SVHC.	Thank you for the support.	
6	2014/04/15	National NGO
CHEM Trust
United Kingdom	CHEM Trust supports the inclusion of cadmium chloride in the REACH candidate list. It is important to also address the properties of concern (i.e. damage to kidneys and bones) in addition to its CMR effects. In particular the accumulation potential in the kidney is of high relevance. Therefore we support the inclusion of cadmium on the candidate list on the basis of 57(f) as well as 57(a), (b) and (c).  	Thank you for the support.	
5	2014/04/12	Individual
Belgium	As Sweden's Annex XV reports emphasizes, cadmium's risks are exploding in the published literature, contradicting the safe levels established by EFSA and others (and pointing to the total failure of REACh Registrations, which largely and illegally, most not consider this more rigorous science). KEMI: "...Since what can be considered as a “safe exposure level” is steadily decreasing, precautionary community wide actions are warranted."

KEMI: "...Further, it is not clear whether an effect on bone/kidney or carcinogenesis is the critical end-point from a risk assessment point of view...
Because of the associations with multiple health effects observed already at the present cadmium exposure in the general population, it is essential not to increase the exposure further."

In a prospective and large epidemiologic report too new for KEMI to have considered (Environ Health Perspect 2014; DOI:10.1289/ehp.1306587), a median U-Cd concentration of 0.93 (0.55, 1.63) μg/g creatinine was associated with significant elevation of various smoking-related cancers, after control of covariates.  This further solidifies KEMI's conclusions (based on effects at 0.5 to 1 μg/g creatinine in urine) for the strictest possible controls on cadmium, as cadmium shows toxicity at the levels billions of people may take in and retain.  As KEMI notes, this is supported also by Germany's AGS 250-fold lowering (to 16 ng/m3) of acceptable inhalation cadmium exposure level.  Further (Sughis et al. Environmental Health 2011, 10:104 http://www.ehjournal.net/content/10/1/104  – possibly known to KEMI), Cd burdens averaging just 0.50 nmol/mmol urinary creatinine was associated with bone resoprbtion, suggesting a direct osteotoxic effect (not via kidney toxicity); linearly without evidence of a threshold and in young children (if cross-sectional).

It does not matter what the critical end point in cadmium risk assessment is--only that a safe level of exposure (be it zero) be scientifically indicated, and not by its profiteers.	Thank you for providing your opinion and highlighting new data.	
4	2014/03/24	National NGO
ChemSec
Sweden	Page 20

We fully support the identification of cadmium chloride as an SVHC based on the hazardous properties below. Each of them alone being sufficient for SVHC identification:

-	Carcinogen 1B
-	Mutagen 1B
-	Toxic for reproduction 1B
-	Equivalent level of concern; STOT RE1 for having adverse effects on kidney and bone tissue after prolonged exposure
 
Further comments:
ChemSec would have appreciated a deepened discussion about the endocrine disruptive effects of cadmium in the dossier. These effects are described in a number of publications including the recent WHO/UNEP report “State of the science of EDCs” (ISBN: 978 92 4 150503 1).	Thank you for the support.

Since there are no agreed criteria for endocrine disruptors yet (in EU) it was considered premature to address this endpoint for the purpose of SVHC identification.	
2	2014/03/18	Member State
Ireland	The Irish CA notes that the current proposal to identify cadmium chloride as a SVHC relates to carcinogenicity (Article 57a), mutagenicity (Article 57b), reproductive toxicity (Article 57c) and equivalent level of concern (Article 57f). The following comments relate only to the Article 57(f) proposal.

In line with the previously agreed SVHC proposals for cadmium and other cadmium compounds which were based on the intrinsic hazards of cadmium, the Irish CA supports the proposal to identify cadmium chloride as a SVHC in accordance with Article 57(f) for equivalent level of concern, owing to adverse effects on kidney and bone tissue after prolonged exposure to cadmium chloride, and thus cadmium.	Thank you for the support.	
1	2014/03/05	Trade union
European Trade Union Confederation
Belgium	The European Trade Union Confederation supports the identification of Cadmium Chloride as SVHC.
That substance is included in the Trade Union Priority List for REACH Authorisation (see WWW.etuc.org > REACH)	Thank you for the support.	

PART II: Comments and responses to comments on uses, exposures, alternatives and risks

Specific comments on use, exposure, alternatives and risks
Number	Date	Submitted by (name, Organisation/MSCA)	Comment	Response	
11	2014/04/17	Industry or trade association
International Cadmium Association
Belgium	PART II Comments
More details on some of these comments are provided in the master-file (uploaded under IV Attachment)

Page 25, Part II, Conclusions, first bullet point
Comment 14
When it is transformed to another cadmium compound, that CdCl2-use is an “Intermediate” use, out of scope of the Authorization procedure. The single direct use of cadmium chloride is as “activator” of the photovoltaic thin film, e.g. made of cadmium telluride.

Page 25, Part II, Conclusions, second bullet point
Comment 15
Reported manufactured (or imported) tonnages of cadmium chloride in the EU are fluctuating from year to year, depending on the demand of photovoltaïc panels, but are in the range of 5-8 t/y.

Page 25, Part II, Conclusions, third bullet point
Comment 16
This is a minor “intermediate” use of cadmium chloride, but rather a direct industrial use of cadmium metal, reported and discussed as such in the cadmium metal dossier. It is incorrect to associate that use to a “wide use”, actually restricted under REACH to some typical applications (cfr. Entry 23 – annex XVII – cadmium metal plating).

Page 25, Part II, Conclusions, fourth bullet point
Comment 17
CdCl2 “life cycle perspective” to be taken into account is the well-organized recycling scheme of PV-panels; and this in case CdCl2 is deemed to still exist after the initial activation / annealing step of the cadmium telluride thin film.

Page 25, Part II, Conclusions, fifth bullet point
Comment 18
Authorization would have no material effect in reducing worker exposure.
The workforce occupationally exposed to cadmium in cadmium production, REACH uses and recycling (which can be regulated by Authorization) totals ca. 3,500 workers within the EU (this number includes ca. 1,000 workers in non Cd-refining Zn smelters, in which Cd is an impurity). For these employees, exposure is monitored and documented, and a high level of compliance with the legally binding DNEL of the REACH registration dossier is observed (see comment 40). 
According to the CAREX data base, another 203,850 EU workers (= 207,350 – 3,500) are occupationally exposed to cadmium as an impurity and would see no benefit in Authorization.
The actual number of employees potentially exposed to cadmium chloride (manufacturing and uses) does not exceed 250.

Page 25, Part II, Conclusions, sixth  bullet point
Comment 19
Main source of general population exposure is through dietary uptake (arising from cadmium in soil) which only marginally originates from deliberate uses of cadmium and even much more marginal if we refer, in this dossier, to the uses of cadmium chloride. An analysis of the origin of cadmium in soil shows cadmium impurities present in commodities and natural releases vastly exceeds deliberate uses (REACH uses) of cadmium. Please refer to comment 35.
 Based on information provided in this comment, authorization would have no effect on the presence of cadmium in soil, and in turn would have no effect on cadmium levels in diet.  Therefore authorization would have no effect in reducing general population exposure to cadmium.

Page 27, Part II, 7.2 general Cd: Table 7,comments and pie-distribution in fig.1
Comment 20
Germany is also a primary producer of cadmium metal (up to 450 t/y capacity)
Cadmium recycling plants (from batteries and PV-modules) are known in France, Germany, Poland and Sweden

Page 27, Part II, 7.2 general Cd: Table 8, European import and export of cadmium in tonnes
Comment 21
This is an unclear summation of all tonnages of cadmium metal and cadmium compounds; roughly ~4600 t/y of cadmium metal are used in Europe (manufactured + recycled + imported – exported): ~100 t/y are directly used and ~3500 t/y are transformed to cadmium compound (essentially transformed to cadmium oxide of which ~2000 t/y are not used but directly exported outside Europe.

Page 28, Part II, 8.1 general in fig.2
Comment 22
The single direct use to be taken into account is the photovoltaïc thin film ‘activator’ function.

Page 29, Part II, 8.2 Industrial and professional uses of cadmium chloride
Comment 23
Only industrial uses are reported.
The four first bullets correspond to industrial “Intermediate” uses as cadmium chloride in solution is transformed to another compound; the fifth bullet correspond to a formulation step and the only direct industrial use is the sixth bullet: component in the manufacturing of PV (photovoltaic) modules.

Page 29, Part II, 8.2.1 Industrial use for production of organic cadmium compounds
Comment 24
The reported use in the production of PVC stabilizers (also in 8.2.2) is restricted since long in Europe (cfr. Entry 23 – Annex XVII).

Page 29, Part II, 8.2.3 Use for cadmium coatings
Comment 25
The characteristics of that use are correctly reported; that use though is covered by a general and severe restriction (<100 ppm) under REACH (entry 23 – annex XVII) with some exemptions, e.g. safety, defense,…

Page 30, Part II, 8.2.4 Component for production of PV (photovoltaic) modules
Comment 26
CdCl2 is routinely applied after the deposition of CdTe thin films in production of thin film PV modules followed by an annealing step in either air or in nitrogen atmosphere. This process is known as “activation process” throughout the industry and among researchers. In general, less than 0,01 g / Wp of produced PV module power is considered sufficient for a complete processing. While it appears to make little difference if CdCl2 is applied as vapour or liquid, it is common knowledge that this process step is vital to obtain high efficiency thin film modules. The exact nature of the physical processes is still under investigation (Hussain, 2004; Terheggen, 2003). It is established that the application of CdCl2 enhances interdiffusion at the p/n junction interface by promoting a recrystallization process (Terheggen, 2003). It is thought that the changes observed in grain size and structure do enhance this process. The influence of CdCl2 on defect levels in CdTe is also established (Hussain, 2004). Depending on the amount of CdCl2 added, it is even possible to change the conduction mechanism in CdTe from p- to n-type. Based on these findings, it is concluded that the CdCl2 added to the thin film structure is not only absorbed, but is consumed up entirely and no free or bound CdCl2 exists in the thin film structure after the activation process is complete.

Page 30, Part II, 8.2.5 End uses of cadmium chloride (excluding the intermediate applications)
Comment 27
See comment 26, laboratory reagents are classified as formulation uses.

Page 30, Part II, 8.2.6 other uses
Comment 28
Those alleged uses are not known nor reported in Europe.

Page 30, Part II, 8.3 Identified uses of cadmium chloride in the EU
Comment 29
See comment 23, the single direct use (< 10 t/y) is as activator of PV- thin films.

Page 31, Part II, 8.5 Recycling
Comment 30
The recycling loop that has to be taken into account are the voluntary recycling schemes in place of photovoltaic panels.

Page 32, Part II, 8.6.2 Lubricants
Comment 31
CdCl2 is not reported to be used in lubricants in Europe; the comments on anti-friction properties rather apply to cadmium metal.

Page 32, section 9, exposure, paragraph 1, line 2
Comment 32
Industrial and professional workers exposed to deliberate uses of cadmium represent a minor fraction of exposed workers.
An estimated 3,500 Industrial and professional workers (including 1,000 exposed workers in Zn smelters which do not deliberately refine Cd), are exposed to cadmium used deliberately. This group represents a small number as compared to the number of workers exposed in scenarios where cadmium is an impurity, which are being estimated at 203,850 workers (207,350 from CAREX database - 3,500 in industries in which cadmium is deliberately used).

Page 32, section 9, exposure, paragraph 2, line 1
Comment 33
It is incorrect to state that “exposure of man via the environment occurs as a result of emissions from industrial and professional processes.”
See comment 35.

Page 32, section 9, exposure, paragraph 2, line 1
Comment 34
It is incorrect to state that “exposure of man via the environment occurs as a result of (…) diffuse releases from private uses of goods.” According to industry, there is no such exposure. If there are data proving the contrary, industry would be interested to see the information regarding the goods which give rise to cadmium releases during their private use, the amount of cadmium released, and the size of the general population exposed to such releases.

Page 32, section 9, 3rd paragraph, lines 2-4
Comment 35
It is correctly stated in the Annex XV document that for non-smokers, food is the primary exposure source of the general population, and that the Cd in food is coming from uptake from agricultural soils. However, contamination via atmosphere and “end use of Cd containing products” are mentioned as the two sources of Cd addition to agricultural soil. This is not correct and incomplete: 
-	the major single source of Cd input to agricultural soils, i.e. the use of P-fertilizer, is ignored in the assessment. P-fertilizer which may have significant Cd-content of natural origin (3-90ppm, see Annex XV document table 9), is directly applied on the soil and as such is the main direct source of Cd into the food chain. The contribution of P-fertilizer to human exposure is estimated to be significant, as is explained below (see figure 35.1 ) This was also recognized by Sweden where, at one time, taxes on fertilizers with high cadmium contents were imposed. (These taxes were dropped later for unknown reason.) 
-	Industrial emissions to atmosphere are also important. These are mainly related to the cadmium that is present as an impurity in mineral commodities that are processed/combusted by industry (see comment 36 and 40).
-	Last but not least, it is emphasized that manufacturing and use of Cd-containing products (including end of life) does not lead to exposure to the general population, as is demonstrated in the next comment 36 and 40. 
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 35. 

Page 32, section 9, exposure, paragraph 1
Comment 36
In order to assess the effectiveness of the regulatory measure envisioned, it is important that for each exposure situation described further in section 9, the contribution of each origin of cadmium is properly assessed. 
In this context, it must be kept in mind that Authorization (or a denial thereof) only has an impact on REACH uses (essentially “deliberate anthropogenic uses”) but not on anthropogenic origins in which cadmium is an impurity, and not on natural releases of cadmium.
In this comment, we will redefine the categories of origin, while in comment 40 we will present quantitative data that allow the identification of the relevant sources to human exposure.
Industry disagrees with the description and number of these categories mentioned in this section. Dietary intake essentially stems from cadmium present in soil, and direct atmospheric deposition on edible crop parts (comment 35). Cadmium present in soil originates from atmospheric deposition and physical additions, which can be broken down in four categories (see below). The most important single source, i.e. P-fertilizer addition (see comment 35) is ignored in Annex XV.
1)	Anthropogenic atmospheric deposition from deliberate use: industrial processes in which cadmium is deliberately used. These are cadmium refining, specialty cadmium compounds including pigments (the latter being non-hazardous) manufacturing, manufacturing of cadmium containing articles (batteries, thin film PV panels…), recycling.
2)	Anthropogenic atmospheric deposition as impurity: industrial processes in which cadmium is an impurity. These are ferrous and non-ferrous metals refining (including Zn refining), fossil fuel incineration (such as coal and fuel power plants), cement and glass manufacturing. 
3)	Natural atmospheric deposition: naturally occurring atmospheric releases and deposition.
4)	Soil amendments: addition of phosphate fertilizers, manure, and sewage sludge onto agricultural soil.

Page 33, Part II, 9.1 Releases and exposure during industrial and professional uses
Comment 37
In the updated version of the cadmium chloride registration file, it will appear clearly in the IUCLID structure 5.5, that only industrial uses are reported, most ‘Intermediate’ uses and one single direct use in the manufacturing of PV-thin films.

Page 33, Part II, 9.2 Release from use of professional use
Comment 38
No professional use has been reported and the alleged industrial use as PVC stabilizer is strongly restricted since long in Europe (cfr. Entry 23 – Annex XVII)

Page 34, Part II, 9.3 Release during service life
Comment 39
Releases from PV-panels (fully glass protected) are very unlikely.
For the release linked to the alleged use as PVC-stabilizer, see comment 38

Page 34, section 9.5, releases from natural sources
Comment 40
As follows from the analysis under comment 35 on sources of cadmium to general population exposure, the Cd inputs to atmosphere are an important contributing factor, because they are a direct source of crop/food cadmium content. The annex XV fails to make a quantitative analysis of the relative importance of the different origins of cadmium going into the atmosphere and being deposited on/taken up by the crops. As such, Annex XV fails to assess the importance of the different atmospheric Cd-sources in the perspective of human exposure. 
The inventory of current atmospheric emissions from the different sources in the EU shows that the main sources are: a) public power generation, b) industrial combustion, c) small combustion; d) industrial processes (EMEP inventory (2012)).
It follows from these data that the major part of cadmium emissions to atmosphere is from anthropogenic use where Cd is an impurity (category 2 in comment 43). The emissions from deliberate Cd production and use (category 1) are further discussed below. 
Overall, Cd emissions to the atmosphere decreased by >60% over the period 1990-2010 (EMEP 2012). It should be noted that the EMEP inventory does not report natural emissions. These have been estimated at ca. 15T/yr (Cd/CdO RAR ECB 2008).
The emissions from the companies manufacturing Cd-products (Cd-production, Cd-recycling, production of Cd compounds, manufacture of NiCd batteries, pigments, and thin-film photovoltaic panels) are minimal (0.18% of EU total emissions). Consequently the contribution of this industrial activity to the total anthropogenic Cd-exposure of the general population is only of the order 0.08% (= 0.18 x 0.42). 
Considering the above, it is emphasised that the production and use of CdCl2 is only a small fraction of this industrial activity related to cadmium in general. Therefore, the contribution of the CdCl2 production and use to cadmium exposure of the general population is entirely insignificant. 
During service life, emissions from Cd-containing products are negligible; there is no emission of consumer exposure at all (see also comment 46). 
At end of life, most of the Cd in products is recycled (e.g. industrial NiCd batteries, photovoltaic panels). The small amount that ends up in the municipal waste stream and can be incinerated, results in <0.8% of total Cd-emissions to the atmosphere (EMEP 2012, Arche 2012). It is noted that CdCl2 containing products are only a very small fraction of the waste stream related to cadmium in general. Therefore, the contribution of the CdCl2 production and use to cadmium emissions from waste is considered entirely insignificant.
All EU Cd-emissions taken together i.e. from production, processing, use and end-of-life incineration of Cd products account for <1% (= 0.18% + <0.8%) of the anthropogenic Cd-emissions to the atmosphere and, accordingly, for <0.42% of the Cd-exposure of the general population (sum of Cd-industry emissions + emissions from incineration <1% x 0.42) 
In other words, the emissions from deliberate Cd production and use are minimal compared to the total emissions, and therefore their impact on general population exposure is negligible. Therefore the effect of measures taken against the use of Cd-products on general population as a whole and, notably, the effects of measures taken against CdCl2 are considered to be insignificant and disproportionate. 
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 40.

Page 36, heading cadmium exposure over time, 3rd paragraph, line 2
Comment 41
This section concludes that “Cd exposure based on biomarkers of exposure and measured dietary intake in Sweden shows no decrease over the last 2-3 decades”. A generalisation of this conclusion of “no change” is challenged, for the following reasons:
For Sweden, there are 3 studies available on kidney-Cd content of general population. Most relevant for comparing the general exposure are the data on the “ever non-smokers”, since the smokers/ever smokers data are dominated by smoking behaviour. The “never smoker” data show that between the 1970s and 1990s, there was a rather significant decrease in Cd-content of forensic autopsy kidney samples (compare Elinder et al 1976) with Friis et al 1998). Kidney Cd values were subsequently evaluated by Barregard et al 2010), related to the period 2003-2006. These samples had Cd content that was not different from the Friis data, and, while still lower, the differences with Elinder et al (1976) were smaller in the comparable age groups. When considering these kidney Cd data, it needs to be taken into account that the number of samples was small (order of magnitude ~=10) in all studies. Moreover, the time lapse between the period considered by Friis et al 1998 (period 1995-1996) and Barregard et al 2010 (period 2003-2006) was probably too small to allow indication of any further trend. 
-No dietary intake data are presented in this section at all, so it is impossible to check this part of the statement.
-The interpretation of the Swedish Cd-U data presented in figure 4 of Annex XV is odd: of the 12 populations, where a comparison was made in Cd-exposure (measured via Cd-U) between 2002-2004 and 2008-2009 (in the areas of Vastra Gotaland, Stockholm, Vaster och Naarbotten), a decrease was observed in 10 out of 12 cases; while in 2 cases there was an increase. The decreases are sometimes quite large (reductions can amount to -40%), but are put in doubt because of “analytical differences that are still under investigation”. We consider this a weak argument to refuse the data. Moreover, we consider that nowadays differences in analytical performance between labs leading to such differences would be unacceptable. 
-In the section Cadmium exposure over time, second paragraph p48: the lack of trend in Cd-B levels in Sweden is mentioned. However, this statement probably (no reference given) refers to table 2 in Bilaga 3 ‘Health effects of cadmium in Sweden’, in Kemi 2011, where Cd-B data are summarized as a function of time. It is noted that the data in this table are not comparable, since a) smokers and non-smokers, b) rural and urban populations and C) different age groups are all mixed. 
In conclusion, and in contrast to what is concluded in this section of Annex XV, the data show that the exposure of the general population in Sweden to Cd has decreased over the last 2-3 decades.  
Dietary Cd-intake data are also an indication of the exposure of the general population. 
The decrease in Cd exposure of the general population can be explained by the parallel decrease of Cd-emissions to atmosphere, observed over the same period. Due to the direct relationship between atmospheric Cd emissions/deposition and crop Cd-content. Cd emissions to atmosphere have decreased significantly, not only in Sweden (Rühling and Tyler 2001) but also in the EU over the last decades as follows clearly from the yearly data between 1990 and 2010 from EMEP (2012).
The general decrease of atmospheric Cd-emissions in the EU (>60% reduction) over the last 2 decades (EMEP 2012) is anticipated to have resulted in a decrease of Cd-deposition on exposed edible plant parts, and, as a result, in a general decrease of Cd-content of food in the EU, and consequently, a decrease in Cd-intake through food in the EU. 
Such decrease in cadmium content of crop is confirmed by the continuing decrease of the Cd content measured in 2 base cereals (wheat and rye) with about -40% over the period 1975-2004 in Germany (BfR 2009). Cereals are a general basis for food products, and a main source (33% of total) of dietary Cd intake by the general population (BfR 2009). Given the central geographical position of Germany in the EU, these data put the time trend of Cd-exposure to the general population in a broader EU-perspective. 
In conclusion, the statement in annex XV that “there is no evidence for a decrease in Cd exposure over time during the last 2-3 decades in Sweden” is is in conflict with the weight of evidence suggesting a decrease of Cd-exposure to the general population in the EU and also in Sweden. The main factor for this is most probably the general decrease of  atmospheric Cd-emissions observed all over the EU, having resulted most probably in a decrease of Cd content of food and thus of intale through the diet. The main cause for this decrease in atmospheric emissions is the decrease of industrial Cd-emissions to the EU atmosphere. In other words, a decrease of environmental exposure to Cd through the diet (the objective of the current Annex XV exercise) is ongoing in the EU.
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 41.

Page 37, section 9.7, worker exposure to cadmium, paragraph 2
Comment 42
Sectors of EU industry which deliberately use cadmium total 3,500 employees out of a grand total of 208,350 cadmium exposed employees as indicated by CAREX (CArcinogen EXposure 1990-1993).
The following sectors of EU industry which are deliberately using cadmium (Cd refiners, specialty cadmium compounds manufacturers, including pigment manufacturers, battery manufacturers, thin-film PV cells manufacturers and recyclers), beyond complying with the mandatory DNEL of the registration dossiers, have consolidated their knowledge and experience regarding employee exposure, ways to minimize it, and results.
The number of cadmium exposed employees in the EU in these sectors is approximately 3,500.
Most of the remaining 203,850 employees exposed to cadmium (as estimated by CAREX) work in industrial sectors in which cadmium is an impurity.

Page 38, section 9.8, consumer exposure, 3rd paragraph, line 2-3
Comment 43
The Annex XV document states that “…given the wide range of potential uses for Cd it cannot be completely ruled out that some consumer exposure from articles containing cadmium may still take place”. No evidence is however given in Annex XV to support this statement. 
Cd and Cd-substances are in general, physically and/or chemically contained in a stable matrix, or present in massive metallic form, and as such not available for exposure of the consumer. In the EU risk assessment (RA), an analysis for consumer exposure was made, integrating exposure from all Cd substances (RA Cd/CdO, ECB 2007). 
According to the EU RA, the consumer uses of cadmium oxide, metal (and compounds) fall into five categories corresponding to at least 5 scenarios of exposure. For these scenarios consumer exposure is considered to be “very low” Two scenarios were an exemption on this general observation:
-significant concentrations of cadmium (conceivably cadmium metal) were encountered in jewels ("silver" bracelets) imported from South and South East Asia. 
-Brazing material containing up to 20% w/w Cd can be purchased by the consumer through Do-It-Yourself shops. All consumer uses of Cd metal involving brazing sticks that could result in exposure of consumers were advised against in the REACH registration of Cd (cadmium consortium, 2010). 
Referring to the EU risk assessment, it is concluded that consumer exposure through the use of Cd-containing products is negligible. The statement made in the Annex XV file is thus not supported by any facts. 
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 43

Page 38, section 10, alternatives
Comment 44
The only direct use of CdCl2 is as activation substance in the production of PV modules (see comment 14, 26). 
Calyxo GmbH, a European downstream user, founded in 2005, has been looking from the start, into alternatives to CdCl2 as activation substance (Calyxo, 2009). Among the alternatives tested extensively has been NH4Cl. Results have yielded conversion efficiencies up to 65% below the level obtained using CdCl2, rendering the eventual modules not sellable. 
In addition to the work by Calyxo, there have been numerous attempts to employ different activation processes reported by research institutes or other CdTe manufacturing companies worldwide (McCandless et al., 2005). It is concluded that while alternatives have been tried none is equivalent to the use of CdCl2 in terms of initial efficiency and stability of the modules (Rangaswamy, 2003). ANTEC, a german SME employed chlorine gas ca 2006 to activate the CdTe thin films (Oelting, 2006), a process that has also been investigated with respect to the microstructural changes (Terheggen, 2003). Results were poor from a commercial perspective with ANTEC reporting 5-6% conversion efficiency of their modules initially. Since the use of chlorine gas having been used infamously as a chemical weapon in WWI on a large scale industrial base has been deemed to pose a major EHS and safety risk, this route has not been investigated further. 
Another alternative substance has been suggested by an Italian start-up company ARENDI (ARENDI, 2007, Romeo et al. 2006). It was proposed to use the FREON F22 as activation gas. Results with respect to the conversion coefficient of the modules were mixed as confirmed by Flores et al 2012. Moreover, since F22 has a GWP of 1810 (one of the highest known) its use is not considered in production at Calyxo. Indeed, it is already being banned in several countries like Austria or the US.

To conclude, while there have been a wide range of alternatives to use of CdCl2 as activation material have been proposed, none of the alternatives has shown equal performance or are even more detrimental to the environment than CdCl2. Therefore, work on alternatives has been discontinued for time being.

Page 39, section 11.1, risk for workers, para 1, line 4
Comment 45
Industry wishes to clarify that data indicated as respirable fraction in the CSR are indeed measured as respirable fraction. In absence of such measured respirable data, the respirable fraction was derived from inhalable measurements by applying a factor of 2.5, which is expressed in the CSR.

Page 39, section 11.1, risk for workers
Comment 46
In addition to the information provided in Annex XV, ICdA wishes to provide the following additional information.
Risk management measures have been developed by industry in two stages.
Stage ONE: adopting and disseminating the Swedish legislation throughout the EU
In 2006, the cadmium producing, using and recycling industry, represented by ICdA built an industry Guidance on the Protection of Occupationally Exposed Workers. This Industry Guidance was built on the basis of the Swedish legislation developed by ARBETSMILJÖVERKETS FÖRFATTNINGSSAMLING (the Swedish Work Environment Agency), amended and published in MEDICINSKA KONTROLLER I ARBETSLIVET (Medical Surveillance in Occupational Setting) publication AFR 2005:6.
Implementation of this legislation had been on-going (under version 2005, following previous versions) in a large industrial Ni-Cd battery manufacturing plant since its inception, and has proven excellent at keeping exposure of workers extremely low.
This Industry Guidance (available upon request) was published in 2006, dissemination followed, and implementation started in 2007.
Industry sectors who have committed to implementing this program are Zn producers, Cd refiners, specialty cadmium compound manufacturers, pigment manufacturers, Ni-Cd battery manufacturers, thin-film PV panel manufacturers, Ni-Cd battery recyclers.
This industry Guidance is built along three pillars; 
-keeping the workplace clean,
-implementing collective and individual hygiene policies,
-ensuring individual exposure is properly controlled by means a medical surveillance program which takes advantage of: 
o	exposure bio-markers: [Cd-U] for cumulated exposure and [Cd-B] for recent exposure,
o	as well as effect biomarkers: measurement of the urinary excretion of specific proteins.
CdB and CdU based action levels, taken over from this Swedish regulation, determine what added surveillance must be implemented should an employee exceed these action levels. Removal from exposure is decided should a certain threshold be exceeded. 
Stage TWO: selecting risk based OEL (set by SCOEL) as the DNEL for workers
As mandated after the conclusion of the Cd/CdO RAR (ECB 2007), a COM Risk Reduction Strategy was agreed, and the setting of an OEL (and possibly a BLV) was decided. SCOEL was therefore tasked with developing a health based proposal. 
SCOEL published its (health based) OEL recommendation of [Cd-air] = 4 µg/m3 (respirable fraction) in February 2010. Industry therefore decided to take this OEL forward as its worker DNEL in the cadmium registration dossier.
Since that date, this is the workplace air quality standard that industry is legally bound to comply with.
Results of Industry Guidance implementation; current exposure of workers in industry deliberately using cadmium
Two sets of Cd-U distributions (the biomarker which integrates all routes of exposure) are tracked.
First set of data: 
This data tracks the distribution of exposure of workers from 15 industrial sites (deliberately using cadmium) whose occupational doctors have started reporting anonymous data since the inception of the program in 2008. The size of this exposed workforce is 2,605 workers.
This data shows that in 2012, 79 workers (3.0%) have a [Cd-U] greater than the maximum value allowed under the Swedish regulation (5µgCd/g creatinine). This number was 142 in 2008.
As strongly recommended by the Swedish regulation, most of these workers are removed from exposure. Only in limited cases will the occupational doctor allow such employees to continue work in exposed positions.
This data also shows that 288 workers (11.0%) of workers have a [Cd-U] greater than the BLV proposed by SCOEL in February 2010 (2µgCd/g creatinine). This number was 373 in 2008.
Both numbers are being reduced at a rapid pace.
Second set of data:
This second set of data tracks the distribution of exposure of all workers from all industrial sites (deliberately using cadmium) whose occupational doctor have started reporting anonymous data, either in 2008 or at a later date. In 2012; 25 sites have reported data for 3,296 workers. It is estimated that the whole industry employs ca. 3,500 workers.
This data also shows a strong decrease of both categories of workers, those with a [Cd-U] greater than 5 and those with a [Cd-U] greater than 2. In 2012, the first category represented 2.6% of workers (down from 7.7% in 2008), and the second category represented 9.5% of workers (down from 20.3% in 2008).
It can be concluded from this data that as of 2012, 9.5% of the workforce exposed to cadmium in a deliberate use of this substance have a biomarker in exceedance of the SCOEL health-based threshold of 2 µg Cd/g creat. In this respect, it is noted that Cd-U is a marker for life time accumulated exposure; in other words the higher Cd-U levels observed today can be a reflection of higher exposure in the past. Nevertheless, within the framework of the OCdBio (Observatory of cadmium biomonitoring in the European industry) program, industry has set clear objectives towards a further reduction of occupational exposure of the employees in the cadmium industry:
•	95% of European employees subject to medical surveillance and bio-monitoring should have a urinary cadmium level below 2 μg Cd/g creatinine by the end of 2017, 
•	98% of European employees subject to medical surveillance and bio-monitoring should have a urinary cadmium level below 2 μg Cd/g creatinine by the end of 2020 

Based on the progress observed at present, and the continued implementation of strict risk reduction measures, it is expected that cadmium exposure at the workplace will continue to decrease and that these objectives will be met.

Page 40, section 11.2., 1st paragraph, line 5-7.
Comment 47
It is stated that “a critical review of the database on biomarkers of Cd-exposure provides no evidence for a decrease in Cd exposure over time during the last 2-3 decades in Sweden”. 
This statement is challenged, not only for Sweden, but also for the EU, as there is clear indication for decreasing exposure, see comment 41.

Page 40, section 11.2, para 3
Comment 48
Annex XV states that “There is the debate concerning the causality and the health significance of the associations between urine-based biomarkers of cadmium exposure and kidney effects that occur at very low cadmium concentration. Thus, it is difficult to ascertain the exact lowest effects dose for a clear adverse effect. However, several recent mechanistic studies support effects at low exposure.”
It is emphasized that there is indeed recent debate on the significance of Cd-U as indicator of exposure at very-low Cd-exposure levels: (Chaumont 2012, Akerstrom 2013) concluded that “There is evidence of non-causal associations between low-level urinary Cd and urinary proteins”. The co-variability observed between Cd-U and urine based biomarkers would have a strong physiological basis. This evidence is suggesting that low-level urinary Cd (e.g.for Cd-U at or below 1 µg Cd/g creatinine) in the general population would be more a reflection of the recent intake and of the physiological variations in the urinary excretion of creatinine and of the renal function (diuresis, renal handling of proteins and glomerular filtration rates). This is relevant for all studies using U-Cd as cumulative exposure indicator.
In conclusion, the threshold for kidney effects of Cd < 1 µg/g creatinine for the general population exposed by the oral route should be questioned because of the non-causal associations between low-level U-Cd and urinary proteins mentioned in recent reports. 
Consequently, the major hypothesis of the Annex XV document that there may be risk of impaired kidney function already at urinary Cd-levels below 1 µg/g creatinin has also to be questioned. 

Page 40, section 11.2, para 5, line 4-5
Comment 49
The threshold for bone effects of cadmium concentration in urine around 0.5 µg/g creatinine for the general population exposed by the oral route should be questioned because of the non-causal associations between low-level U-Cd and low Cd-exposure mentioned in recent reports (see also comment 6-7)
Consequently, the major hypothesis of the Annex XV document suggesting that already a cadmium concentration in urine of around 0.5µg/g creatinine is associated with increased risk of osteoporosis and fractures and the estimated societal cost related to that (see comment 4) has also to be questioned. 

Page 41, section 11.2, para 1,  line 4-6
Comment 50
Annex XV suggests that results from experimental and epidemiological studies are raising concern that cadmium might have estrogen-like effect and possibly increase the risk of hormone-related cancers. It is emphasized that although there are indications that this is the case, this needs to be confirmed by other studies, for several reasons (see also comment 55 for more details): 
-most positive in vivo studies were conducted with acute Cadmium exposures. Kortenkamp (2011) emphasized in his review that a key issue that needs to be resolved in the context of human risk assessment is whether the estrogenic effects of Cd occur at dose levels that are lower than those known to be associated with kidney dysfunction or pulmonary carcinogenesis.
-most studies apply non-physiological routes of Cd-administration e.g. peritoneal injection. When relevant physiological routes of exposure (e.g. oral) were used, no positive effects were observed (Höfer et al 2009)
-CdCl2 is used for most studies; however no effects were observed after oral administration of dietary Cd
-Finally, it is noted that in the general environment, humans are simultaneously exposed to metals (cadmium and others), but also to organic compounds that might also be endocrine disruptors. There is a need to study the possible additive, synergistic, or antagonistic effects on the endocrine system following exposure to such substances. 

Page 41, section 11.2, para 3, line 3-4
Comment 51
Annex XV states: « Causal relationships are supported by mechanistic experimental studies”. 
No references are given. In comment 6, references are given which strongly suggest non-causal relationships. 

Page 41, section 11.2 para 3, line 4-6
Comment 52
Annex XV emphasises on bone effects of cadmium and their relationship with Cd-U as a marker for cadmium exposure. 
As indicated, the significance of Cd-U as a biomarker of exposure in situations of very low Cd exposure (like in general population) is currently under scientific debate. Therefore the relationship between bone effects and Cd-U levels in the general population is questioned. 

Page 43, section 11.3.  risk via food intake
Comment 53
The Annex XV document presents the abstract of the EFSA study on dietary Cd intake in the European population (EFSA 2012). Calculated lifetime cadmium dietary exposure was estimated at a middle bound overall weekly average intake of 2.04µg Cd/kg BW, and a potential 95 percentile value of 3.66µg Cd/kg BW. 
The following comments are made on the EFSA study:
-the dietary intake was calculated from food Cd-content data and dietary information. It has been observed that such approach may overestimate the Cd-intake, since considerable loss of Cd can occur during food preparation (Fouassin & Fondu 1981).  
-the authors of the EFSA-report themselves note that the 95 percentile estimate is “speculative and potentially unrealistic” because it is based on the unlikely assumption that the same individuals retained the same high exposure throughout their whole life”. The 95 percentile should thus be considered with caution, since it appears that it is clearly an overestimation.
-the EFSA-report notes also that “many of the reported results for meat and edible offal…might include a high proportion of samples targeting potential problem areas and thus might not reflect the average situation”.
Recent (post year 2000) values reported for weekly dietary intake in a number of EU member states show lower values than the average reported by EFSA. The points raised above may explain why. Even for a country like Belgium, which has a historical contamination of Cd, the 95 percentile value is only just at the level of the EFSA-average. These country data suggest that the EFSA average is slightly overestimating current dietary Cd-intake. 
The weekly intake data mentioned above are general figures, which are related to the average exposure of general populations. Such data make sense for a cumulative toxicant such as cadmium, where critical exposure levels relate to chronic Cd accumulation at the level of the kidney cortex and therefore relate well to chronic average exposures. For that reason also, worst-case estimates may not be realistic, since such situations are unlikely to proceed for longer time. Yet, situations of consistent enhanced exposure can occur in particular related to specific dietary habits involving systematic consumption of high-Cd food. 
In conclusion, recent (post-2000) weekly dietary Cd-intakes in the EU are of the order 1 -2 µg/kg BW. and as such below the WHO PTWI standard of 5.8 µg Cd/kg BW, and below the more stricter EFSA standard of 2.5 µg Cd/kgBW. Calculations of dietary intake based on life-time continued worst case are considered unrealistic. 
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 53.

Page 47, section 13.1 Developmental toxicity, para 3
Comment 54
The studies of Ciesielski et al (2012) and Kippler et al (2012), showing associations between low-level environmental cadmium exposure in children (measured as Cd-U) and adverse neurodevelopmental outcomes should be interpreted with caution, in light of the recent literature data challenging the significance of U-Cd as biomarker of cumulative exposure in situations of low exposure (see comment 6). 

Page 47-48, section 13.2 Endocrine effects
Comment 55
The Annex XV document mentions experimental studies that suggest that cadmium may have oestrogen-like effects. Swedish epidemiological studies have shown associations between estimated dietary exposure and increased risk of hormone-related cancers (endometrial, breast cancer). However, as noted in Annex XV, this needs to be confirmed by other studies (see also comment 50), for the following reasons: 
To date, most cadmium in vivo studies have largely focused on acute cadmium exposures and there are only two studies on the effects of chronic exposure to low levels of cadmium. They suggest breast cancer development and progression (Alonso-Gonzales et al., 2007, Höfer et al 2009). 
The observed effects are very much dependant not only of dose but also of route of administration. In the in vivo study from Höfer, it was explained that when cadmium was administered by physiological relevant routes (oral ingestion by gavage or drinking water), no effects were seen. The effects were seen only when cadmium was administered by non-physiological routes (e.g. intra-peritoneal injection).  It should be noted that only few studies used the main relevant human exposure route, i.e. ingestion, as the route of Cd administration. Most studies apply non-physiological routes of exposures, e.g. intraperitoneal injection. 
It is noted that the studies of Ali et al (2013), as cited on page 48, para 3 in which the mechanism of the oestrogen-like effects of cadmium were investigated, are also acute exposure cadmium studies, in which transgenic ERE-luciferase reporter mouse were exposed subcutaneously for 3 days. This study design might be questioned in examining whether chronic, low-level exposures to cadmium can directly result in the development and progression of hormone-related cancers.
Moreover, in most in vivo studies to date, the estrogenic effects of Cd were estimated after exposure to inorganic Cd salts dissolved in a buffer or saline by injections or gavage (Höfer et al 2009, Ali et al 2010; 2012), while human populations are exposed to Cd mainly through diet. This difference was shown in the study of Ramachandran et al (2011) where oestrogen-like effects were only observed after oral administration of CdCl2 and not after dietary exposure. 
In conclusion, the elements listed above show the need for more basic, physiologically relevant research is needed (a) on the mechanisms of interaction between Cd and oestrogen signalling, (b) biologically active species of Cd, and (c) biomarkers of oestrogen-like effects of Cd in vivo, before conclusions on possible  hormone disruptive effects of Cd can be drawn. 
The reference to the meta-analysis of Cho et al (2013), showing statistically significant positive associations between dietary cadmium intake and hormone-related cancers in humans, should be interpreted cautiously. In this meta-analysis, for example for breast cancer [RR: 1.15 (95% CI 1.04-1.28)], data of not comparable studies were combined. In fact, for the studies of Itoh et al. (2014) and Sawada et al. (2012), the data of all women were used and not only the data of postmenopausal women as is the case for the studies of Julin et al 2012 and Adams et al 2012. Furthermore, since this meta-analysis of Cho et al (2013), the group of Adams et al. has published a more recent paper that shows lower values for postmenopausal women [RR: 0.90 (95% CI 0.81-1.00)], n = 1,328) (Adams et al 2014) than his earlier article [RR: 1.00 (95% CI 0.72-1.41)], n = 224) (Adams et al 2012).
For data and references supporting the analysis above, see in uploaded attachment under IV Attachment, comment 55. 	Thank you for your comments and the information provided.
Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
			See also:
Comment 11 attachment (CdCl2 Annex XV_Master Comments Document_2014-03-17_final submitted.pdf).pdf 		
8	2014/04/16	Company
Germany	The applications are routine analytical uses for reference in a laboratory within the scope of scientific R&D. The risk for the environment and consumers is very low. Usually the volumes and the concentration of the substance are low. The disposal of the substance is also controlled.
Therefore, the use of cadmium chloride as analytical standard should be exempted from authorisation (scientific R&D) as well as the formulation of mixtures for R&D purpose and packaging/refilling of the pure substance and mixtures into small packages for this use.
	Thank you for your comments and the information provided.

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
7	2014/04/15	Company
Germany	[p.30]
While it is correct that CdCl is used as raw material in manufacturing of thin film PV modules, it is not valid to suggest that CdCl2 is directly responsible for improving the efficiency of PV modules.

Instead, CdCl in its pentahydrate form is dispersed onto the semiconductor layers, dried and in a subsequent annealing step is consumed up entirely in the CdTe solid state matrix to heal defects and and form electricallly active states to increase lifetime of carriers in the semiconductor. It is thus consumed up entirely during this annealing step. Any residual cadmium containing species on the surface are washed away immediately after the anneal step.

Thus, the end product is entirely free of CdCl2 species. Moreover, any Cd containing film is safely packaged in a PV module to both ensure the safety of the environment and population as well as to promote longterm stability of the electrical performance of the module. No risk is perceived for the end user of a pv module.	Thank you for your comments and the information provided.

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
			See also:
Comment 7 attachment (c571rspcd-official.pdf).pdf		
5	2014/04/12	Individual
Belgium	Battery technologies are exploding.  Is there thus any need for cadmium batteries, the most easily controlled source of exposure)?	Thank you for your comment.

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	
4	2014/03/24	National NGO
ChemSec
Sweden	P 38

The main release of anthropogenic cadmium comes from release of cadmium ions from articles. ChemSec would have appreciated a deepened discussion about alternatives to the general use of cadmium and its salts in articles and in the production of articles.

The following example of an alternative to cadmium is available, as presented in the SUBSPORT database:
 
Alternative for PVC stabilisation
Hydrotalcite, synthetic
CAS No. 11097-59-9 EC No. 234-319-3
Information from the following report:
http://www.subsport.eu/case-stories/294-en?lang	Thank you for your comments and the information provided.

Comments regarding use, exposure, alternatives and risks may, where relevant, be considered at later stages of the risk management process.	

Attachments

Comment number	Public attachment	
7	
Comment 7 attachment (c571rspcd-official.pdf).pdf	
11	
Comment 11 attachment (CdCl2 Annex XV_Master Comments Document_2014-03-17_final submitted.pdf).pdf