Comments on report on alternatives to brominated flame retardants
2. Compounds
Triphenyl Phosphate (TPP) CAS no. 115-86-6Data availability table: The CAS no. is assigned to TPP and the data is reported from studies that concludes on TPP. Based on the available data the chemical name should not be substituted with the product name.
The chemical synonyms and product names come from Chemfinder, RTECS and similar databases.
Statement in report summary: |
EFRA comments / suggested version: |
Response to comments |
The available data indicate that triphenyl phosphates may have low impact on health, but is quite toxic in the environment. |
Disflamoll TP is practically non-toxic in animal studies but very toxic to aquatic organisms |
The CAS no. is assigned to TPP and the studies reported from concludes on TPP. Based on the available data the chemical name should not be substituted with the product name |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health The available data indicate that TPP has a relatively low impact on health. In rare cases it can induce skin sensitisation and contact dermatitis in humans. Although TPP is a neurotoxin in animals, recent investigations indicate that TPP is not neurotoxic in humans, but persons with preexisting neuromuscular disorders may be at increased risk. |
Health Triphenyl phosphate is practically non-toxic in animal studies after oral, inhalatory (dust) or dermal uptake. The substance is not irritating to skin, but may cause slight irritant effects on eyes. No data from animal studies on the sensitising effect are available. In man, allergic skin reactions have been reported in a few cases after contact with triphenyl phosphate. In animal studies, after repeated oral uptake no substance-related organ damage was found. In tests in bacteria and yeast and mammalian cells, triphenyl phosphate showed no mutagenic effect. No long-term study to clarify a possible carcinogenic effect is available. From a short-term study in mice, no carcinogenic potential of triphenyl phosphate could be deduced. In animal studies, there were no indications of an embryotoxic or fertility-impairing effect of triphenyl phosphate. |
Health The phrasing may be amended, but the conclusion on carcinogenic potential based on short term studies only seem relevant in combination with long term studies. |
Environment The literature reviewed indicate that TPP is very toxic to algae, fish and some crustaceans (typical L(E)C50 <1 mg/l). The compound is toxis to D. magna. NOEC data available for fish are in the range 0,014-0,23 mg/l Bioaccumulation of this compound is high (BCF>100). The biodegradation data available indicates that this compound is readily to inherently biodegradable under aerobic conditions. No data is available for anaerobic degradation. |
Environment On the basis of the ecotoxicological effect data, triphenyl phosphate is to be classified as very toxic to aquatic organisms. The preferred media (target compartments)for triphenyl phosphate are water, soil and sediment. (water 24,4 %, soil 44,2 %, sediment 41,3 %, Mackay Level I). The substance volatilises slightly from water and wet topsoil. Triphenyl phosphate is readily biodegradable. In the atmosphere, a photochemical degradation takes place, and dispersion is possible (half-life t ½ = 33,76 hours). In spite of a bioaccumulation potential, because of the good degradability bioaccumulation is not to be expected. |
Environment EFRA points to the biodegradability as an amending factor for bioaccumulation. In an actual risk evaluation in the environment the bioaccumulation may be less than in bioaccumulation experiments. These are, however, the basis for the conclusion drawn (in coherence with the EU classification Directive). |
Data availability table: The CAS no. is assigned to Tricresyl Phosphate and the data is reported from studies that concludes on Tricresyl Phosphate. Based on the available data the chemical name should not be substituted with the product name.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
The available data indicate that tricresyl phosphates may have impact on health, but is quite toxic in the invironment. |
Disflamoll TKP is harmful if swallowed and in contact with skin and very toxid to aquatic organisms. |
The CAS no. is assigned to TCP and the studies reported from concludes on TCP. Based on the available data the chemical name should not be substituted with the product name |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health The available data indicates that following repeated application tricresyl phosphate is toxic by absorption though the skin. The reviewed test results do not indicate mutagenic or carcinogenic effects of tricresyl phosphates. Tricresyl phosphate may cause effects on the reproduction. The main commercial product is a mixture of various isomers of tricresyl phosphates. Two other tricresyl phosphates (not 1330-78-5) are classified toxic or harmful. |
Health Tricresyl phosphate is harmful if swallowed and in contact with skin. Depending on the tri-o-cresyl phosphate content, tricresyl phosphate can influence nerve conduction functions. No poisoning in man by tricresyl phosphate with a low tri-o-cresyl phosphate content has been observed. Tricresyl phosphate may cause mild irritant effects on skin and eyes. No data from animal studies on a sensitising effect of tricresyl phosphate are available. On the basis of experience in man, a skin-sensitising potential cannot be ruled out completely. In animal studies after repeated uptake of tricresyl phosphate, more or less pronounced neurotoxic effects also occur, dependig on the tri-o-cresyl phosphate content. Tricresyl phosphate shows no mutagenic effect in bacteria and cell cultures. In a long-term study in the rat and mouse, tricresyl phosphate did not have a carcinogenic effect after oral administration. Findings on tricresyl phosphate in animal studies show an impairment in reproductive capacity after administration of doses which are toxic to the parent animals. |
Health The toxicology of tricresyl phosphate isomers is relevant. The amount of each isomer is rarely given in the reviewed data. The safety sheets provided by EFRA may improves this aspect. |
Environment The available effect data originates from tests performed using either the pure compound or a formulation. The tests performed using the pure compound indicates that tricresyl phosphate are very toxic to fish and toxic to algae and crustaceans (L(E)C50 from <1 mg/l to 10 mg/l). Formulations are slightly less toxic, but typically in the 1-10 mg/l. A study of long term acute and chronic effects in fish showd NOECs from 0,0001-0,00032 mg/l for a formulated product. Tricresyl phosphate bioaccumulates (BCF ranges from 165-281). Available screening studies suggest that aerobic biodegradation will occur at moderate to rapid rates with half-lives in the order of several days or less. The mobility in soil is presumably low. |
Environment On the basis of the ecotoxicological effect data, Disflamoll TKP is to be classified as very toxic to aquatic organisms. The preferred media (target compartments) for Disflamoll TKP are soil and sediment. (Mackay Level I: 47,7 % soil, 44,6 % Sediment). The substance volatilises slightly from water and wet topsoil. Disflamoll TKP is readily biodegradable. Because of the ready degradability, substantial elimination of the substance from water is to be expected. Therefore in surface waters, even at constant emissions which lead to concentrations in the region of the effect threshold at the Point of entry, at the most local damage is to be expected. In biological waste water treatment plants, because of the low bacterial toxicity, there is no risk of an impairment of the purification performance. A rapid photochemical degradation takes place in the atmosphere (half-life t ½ = 0,027 day). There is an accumulation potential. |
Environment EFRA points to the biodegradability as an amending factor for bioaccumulation. In an actual risk evaluation in the environment the bioaccumulation may be less than in bioaccumulation experiments. These are, however, the basis for the conclusion drawn (in coherence with the EU classification Directive). The data presented for Disflamoll TKP may improve the screening. |
Data availability table: 14 studies have been submitted by EFRA on the AzkoNobel Fyrolflex RDP. The inclusion of these studies will obviously change the rating of data availability. It should be mentioned that most of these studies were not published at the time of submission the original report.
Regarding the Appendix comments these have not been assessed.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
<Poor data availability for the structurally related resorcinol prohibits conclusions regarding effect pattern> |
Introduce an individual heading for resorcinol bis(diphenyl phosphate) (RDP), as is also done for all the other flame retardants. The text could read: RDP is relatively well studied and indicate that RDP has low impact on health. The chemical is degradable and is not toxic to fish or algae, however is toxic to Daphnia. |
See above |
Statement chapter 5: |
Our comments / suggested version: |
Response to comments |
Health |
Health RDP is not toxic in acute oral, dermal or inhalation studies (1). RDP is not neurotoxic(1). In a two-generation reproduction study no effects on reproductive performance or offspring were found (2). RDP is not teratogenic (3) and not immunotoxic (4). In a 28 day inhalation study a No Observed Effect (NOEL) level of 0.1 mg/l was observed (5). A comparative metabolism study in the rat, mouse and monkey confirmed that RDP is metabolized in an identical manner by rats, mice and primates and that the rat and mouse appear an appropriate model in which to assess RDP toxicity (6). Furthermore from studies with a structurally related chemical RDP is expected not irritating to skin and eyes, not sensitising and also not mutagenic (7,8).
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Health See above |
Environment |
Environment RDP is inherently and ultimately biodegradable. Its halflife in water at 20 ºC and pH 7 is 17 days. RDP is therefore not anticipated to bio-accumulate. RDP is not toxic to fish, algae and bacteria. RDP was found to be toxic to Daphnia, however this effect is anticipated to be caused by a physical effect of insoluble droplets in the test rather than by toxicity (1). |
Environment See above |
Data availability table: Only limited data is available on ATH as a compound and no new data has been presented. The rating poor still seems valid.
The (health and) environment assessment of insoluble metals and metals compounds has been a matter of discussion in the EU and OECD for some time. The lack of a firm approach is reflected in the nature of the comments. Briefly, the discussion concerns whether the assessment is to be made on the intrinsic properties the parent bioavailable metal(-ion) or on actual test results with the more or less soluble compounds. The screening reflect a compromise between these two approaches.
Regarding the Appendix comments these have not been assessed.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
Aluminium trihydroxide is generally not toxic in the available tests. Both metal-ions play a metabolic role in mammals, but the data for the metal-ions indicates acute toxic levels for Al to fish and crustaceans at <1-10 mg/l |
The solubility of ATH is about 1,5 mg/l. corresponding to about 0,5 mg/l Al3+-ions, below the toxic level to fish and crustaceans. Since ATH is insoluble, Al-ions present in natural waters are either derived from by natural aluminium sources or soluble aluminium compounds like aluminium sulphate, used in water-treatment. ATH for flame retardancy is not a source of Al-ions in the environment |
See above and below |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health Aluminium hydroxide is often an important source of aluminium in the body. Aluminium compounds can lead to deposition of aluminium in bones leading to decalcification. There are indications that aluminium compounds may lead to lung injuries. Most aluminium compounds may cause irritation of eyes and respiratory tract. |
Health Crystalline ATH is mainly used as flame retardant, raw material for the production of aluminium compounds, polishing agent in toothpaste and as inert filler in weather resistant plastics. It is virtually insoluble over a broad pH-range (3,5 – 10,5). Non-crystalline ATH ( amorphous ATH) is used in antacids. To control hyper acidity of stomachs gel ATH is widely used in anti-allergic treatments. All the applications together do not represent an important source of aluminium in the body. Due to the insolubility of aluminium hydroxide, any aluminium compound in a wet environment reacts to aluminium hydroxide. Even if aluminium hydroxide were the main source of aluminium in the body, its origin is not the flame retardant ATH. Lung injuries may be caused by fine, breathable dust of aluminium hydroxide, like any other inert dust. Eye, skin or respiratory tract irritations may only be caused by excessive amounts of dust, like any other inert dust particles. These statements are only valid for high purity flame retardant ATH’s. Some by products present in standard ATH may be more irritating. |
Health See above ATH is not an eye or lung irritant which is also stated in the Appendix. The text in 5.5 is unfortunately not as clear. |
Environment Very few data was found on the compound Al(OH)3. Since the compound may dissociate in the environment, a limited data set on the Al-ion is presented. The available ecotoxicological data indicates that Al(OH)3 is not toxic to fish, crustacean or bacteria. The data on aluminium-ion indicates that the ionic form is very toxic to fish and toxic to crustaceans. |
Environment The solubility of ATH is about 1,5 mg/l. corresponding to about 0,5 mg/l Al3+-ions, below the toxic level to fish and crustaceans. Since ATH is insoluble, Al-ions present in natural waters are either caused by natural aluminium sources or by soluble aluminium compounds such as aluminium sulphate, used in water-treatment. ATH for flame retardancy is not a source of Al-ions in the environment Statements and point 5.5 p 16 do not comply to the statements in the appendix pp. 49-56: |
Environment Quote from Appendix: A search in [10] on Al resulted in one value on Oncorhynchus mykiis: LC50(24h)=0.16 mg/l ATH is correctly an insoluble compound. Partly due to this fact very few studies report on ATH. ATH in it-self is not a source of environmental Al-ions under normal to basic pH values. However, a dynamic equilibrium between Al-ions and all it’s soluble and insoluble species exist in nature. For this reason a limited data set on aluminium is presented. It is stated that ATH is generally not toxic. |
Data availability table: Only limited data is available on MDH as a compound and no new data has been presented. The rating poor still seems valid.
The (health and) environment assessment of insoluble metals and metals compounds has been a matter of discussion in the EU and OECD for some time. The lack of a firm approach is reflected in the nature of the comments. Briefly, the discussion concerns whether the assessment is to be made on the intrinsic properties the parent bioavailable metal(-ion) or on actual test results with the more or less soluble compounds. The screening reflect a compromise between these two approaches.
Regarding the Appendix comments these have not been assessed.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
Both metal-ions play a metabolic role in mammals, but the data for the metal-ions indicates acute toxic levels ....to fish and crustaceans ..... and approx. 65 mg/l for crustaceans exposed to Mg. |
MDH is nearly insoluble. 9 mg/l correspondent to < 4 mg/l Mg2+-ions, far below the estimated toxic level to crustaceans. This level has to be compared with the app. 1300 mg/l of Mg2+-ions present in the sea-water, still enjoyed by the crustaceans. |
See above. The 65 mg/l is for a freshwater crustacean Gammarus lacustris |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health The available data is not sufficient to conduct a health screening of magnesium hydroxide, but indicate that the substance can be regarded as relatively harmless in small quantities as the substance is used as food additive. Repeated or prolonged human exposure to larger quantities of the substance may imply adverse impact on human health, such as general irritation and malaise. |
Health Ok.
Mg is a Ca-antagonist, therefore the incorporated quantity should be limited.
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Health See above |
Environment Very few data was found on the compound Mg(OH)2. Since the compound may dissociate in the environment, a limited data set on the Mg-ion is presented. Magnesium is an essential element in many organisms. One sufficiently documented LC50 was identified: 64.7 mg/l, which indicates that magnesium is harmful to crustaceans |
Environment See summary |
Environment See summary |
Data availability table: Only limited data was available on APP as a compound. The new data which has been presented will probably change the rating. The data are generally proprietary and more recent than the report.
Regarding the Appendix comment: The data comes from ECOTOX database of the US EPA searchable on the compound CAS no. In general, the original report has only included product or formulation test where no other data was available.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
< none > |
The available data and conclusions from its chemical structure and environmental behaviour indicate that APP is a non-toxic flame retardant with very low impact on the environment if handled in accordance with good working practices. |
Generally, the original report does not include statements on practices. However, in the submitted material such statements may be supported. |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
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Health No relevant data is available. |
Health APP as a pure substance is of low acute toxicity to mammalian species by all three routes of exposure;
Other relevant toxicological test data are;
Phosphoric acids and its salts, including APP, are considered Generally Recognised As Safe by the US Food and Drug Administration. In 1982, World Health Organisation Expert Committee on Food Additives (JEFCA) set an Acceptable Daily Intake (ADI), expressed as a maximum Tolerable Daily Intake (MTDI) for APP of 70 mg/kg/d. This very high figure is an expression of the relative safety of APP. In Germany, the regulatory authority that provides an assessment and sets limits on the allowable concentrations for chemicals that come into contact with foods, the BGVV, also approves the use of APP in food contact materials. If a high molecular weight APP is used as a flame retardant, the consumer /user of a product will be hardly exposed to APP at all, because it is a solid and non-volatile material embedded in a polymer or coating matrix. The low molecular weight ammonium polyphosphate products are water soluble, thus there is some potential for consumer exposure but the toxicity is low as evidenced by the toxicological data presented above. |
Health The submitted data will change the conclusion. The new IUCLID data, the MSDS and proprietary information adds relevant information.
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Environment The available data on a formulated product indicates that this substance may be harmful to crustaceans. |
Environment Ammonium polyphosphates are not labelled as hazardous to the environment. Typical environmental test data are summarized below;
In contact with water slow hydrolysis with release of ammonium phosphate will occur. High temperatures and prolonged exposure to water will increase the hydrolysis rate. Ammonium phosphate is only of environmental concern, if large quantities are spilled into aquatic environments causing eutrophication, since APP can be seen as a classic N-P-fertilizer. Ammonia will be released in contact with strong bases. Major toxic short or long term effects in the environment are highly unlikely. Use as flame retardant – in case of fire: When applied as a flame retardant, APP will not migrate or evaporate from the final product. In an accidental fire or deliberate incineration APP will decompose and mainly form polymeric phosphoric acids which will remain in the slag. Other products may be phosphorus oxides, ammonia, and nitrogen oxides. These products add to the acute toxicity of the combustion products, however, the flame retarding effect of APP is meant to prevent the outbreak of a large fire from small ingnition sources and therefore to avoid the formation of greater amounts of toxic smoke (the main toxic agent is usually carbon monoxide). In flue gas treatment systems of state of the art incinerators the combustion products will be properly removed. |
Environment The submitted data will change the conclusion. The new IUCLID data, the MSDS and proprietary information adds relevant information, although test results for crustaceans already included is <100 mg/l (48h EC50 Daphnia magna). |
Data availability table: In general, the new rating is based on studies not published and not available.
Regarding the Appendix comment: The use of CAS no. is based on a previous report as stated above. The CAS number is the one usually used for red phosphorus.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
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Red phosphorus data are limited and conclusions are unclear. The yellow phosphorus is reportedly acutely toxic to humans (fatal dose 1 mg/kg), but the red allotropic form is described as less toxic. Acute toxic concentrations (LC50 or EC50) of unspecified allotropic form in the aquatic environment occurs at 0.009 – 0.012 mg/l for fish and crustaceans. |
[Since there are such extreme differences in physico-chemical properties as well as in toxicologic profiles of red and white phosphorus, the general approach of combining and mixing data of the two is scientifically incorrect and extremely misleading. ] Elemental phosphorus is readily oxidized and this high reactivity results in hazardous properties of the pure material. However, red phosphorus is much less reactive and even more less toxic than yellow (also called white) phosphorus. Nevertheless it require special handling precautions and / or protective pretreatments of the red phosphorus. Whereas yellow phosphorus is deadly to humans and other mammals in doses in the range 1 mg/kg, the LC50 for rats is > 15 000 mg/kg for red phosphorus. Recent toxicology studies revealed an aquatic toxicity (LC50 or EC50) in the range of 10 to 100 mg/L for fish, Daphnia and algae. [studies are not published yet, but will be submitted to the European Chemical Bureau in January 2001 for the classification of red phosphorus]. When properly applied as a flame retardant, red phosphorus is usually completely embedded into a polymer matrix so that it cannot react with air or water. Due to its own polymeric nature it will not migrate or evaporate from the final product. |
The occurrence of different allotropic forms creates interpretation problems similar to those of tricresyl phosphate. In general, the text supplied by EFRA is well phrased, but it is based on studies not published and not available until now. An unclear description of the number of allotropic forms and the appearance of phosphorus is evident in the text of the screening report. A revised information should include
The other physical-chemical properties appear to be similar in range to those suggested by EFRA. The data referred in the data sources as from an ‘unspecified’ form are mentioned as such in the text. It is presumably the more hazardous yellow/white form, but this cannot be verified without consulting the original papers. An important information in the context flame retardants is that Red phosphorus - ignites only after reaching > 260 C. |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
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Health Red phosphorus is often contaminated with white and yellow phosphorus, and information on these two allotropic forms is therefore included. Pure red phosphorus seems to be less harmful than the two other allotropic forms. The substance is classified as highly flammable and may explode when exposed to heat or by chemical reaction with oxidisers. Red phosphorus can also react with reducing materials and represent a moderate explosion hazard by chemical reaction or on contact with organic materials. Large quantities ignite spontaneously and on exposure to oxidising materials. It reacts with oxygen and water vapour to evolve the toxic phosphine. |
Health [Commercial RP does contain trace amounts of yellow phosphorus (which is synonymous to white phosphorus), typically 50 mg/kg (see attachment 5). At this level of impurity, yellow phosphorus does not have a determining effect on the toxicology of RP, therefore this statement is misleading.] Red phosphorus is an amorphous polymeric modification of the the chemical element phosphorus. Elemental phosphorus is readily oxidized and this high reactivity results in hazardous properties of the material. However, red phosphorus is much less reactive and even more less toxic than yellow (also called white) phosphorus. One has to bear in mind that red and yellow/white phosphorus share the same EINECS-number so that care has to be taken when data are extracted from sources based on the EINECS-number. When applied as a flame retardant, red phosphorus is usually completely embedded into a polymer matrix so that it cannot react with air or water. Due to its own polymeric nature it will not migrate or evaporate from the final product. |
Health Regarding oral ingestion of Red phosphorus it is stated in the Appendix of the screening report: ‘Elemental red phosphorus is non-volatile, insoluble and thus non-toxic when ingested, unless it is contaminated with traces of yellow phosphorus’. - The information supplied by EFRA on Red phosphorus (rat LD50 > 15,000 mg/kg) strongly supports the ‘non-toxic’ nature of the substance itself. According to EFRA Red phosphorus is contaminated with yellow/white phosphorus at ca. 50 mg/kg. Interestingly, the lethal dose of yellow/white phosphorus is approx. 1.4-4.8 mg/kg, which suggests that the toxicity of Red phosphorus may originate in the contaminating yellow/white phosphorus. The contamination of yellow/white phosphorus at a dose of 15,000 mg/kg Red phosphorus is approx. 0.75 mg/kg, only a factor of two from the lower toxicity range of yellow/white. |
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Environment No ecotoxicological data on red phosphorus were identified. The available data on yellow phosphorus indicates that this allotropic form of phosphorus is very toxic to algae and fish. |
Environment In the environment red phosphorus will slowly degrade by disproportionating and hydrolysis to phosphine (PH3) and phosphorus acids (oxidation levels of I, III, V). Although the intermediate phosphine is toxic, it is also quite reactive and will be oxidized. The final products will be phosphates which are ubiquitous and harmless. From wastewater, red phosphorus is eliminated mainly by adsorption to sewage sludge. In an accidental fire or waste incineration the phosphorus will be oxidized to phosphorus oxides which are properly removed in flue gas treatment systems of state of the art incinerators or which will remain as polymeric phosphoric acid in the bottom ash. Recent toxicology studies revealed an aquatic toxicity (LC50 or EC50) in the range of 10 to 100 mg/L for fish, Daphnia and algae. [studies are not published yet, but will be submitted to the European Chemical Bureau in January 2001 for the classification of red phosphorus]. |
Environment In the open literature and databases no information was found in the screening exercise, but EFRA supplied results on Red phosphorus from
These data sets imply that toxicity in aqueous media occurs above the solubility range of Red phosphorus. The formation of phosphine upon hydrolysis of Red phosphorus is stated to be a relatively slow process. Abiotic transformation has T½ of >10 days. In an oxidising environment the toxic phosphine is readily transformed to phosphates. |
Data availability table: In general, the new rating is based on studies not published and not available at the time of submission of report. The data submitted may significantly change the rating.
Regarding the Appendix comments these have not been assessed.
The (health and) environment assessment of insoluble metals and metals compounds has been a matter of discussion in the EU and OECD for some time. The lack of a firm approach is reflected in the nature of the comments. Briefly, the discussion concerns whether the assessment is to be made on the intrinsic properties the parent bioavailable metal(-ion) or on actual test results with the more or less soluble compounds. The screening reflect a compromise between these two approaches.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
There is practically no data on the compound. Based on comparison with sodium borate and boric acid the possible main effects in humans are expected to be irritation of skin, eyes and throat, and harm to the unborn child. In the environment zinc-ion is very toxic to crustaceans |
Borax Europe Ltd has both physical chemical data , and helath and environmental toxicological data on zinc borates. This data can be submitted to the Dansih EPA. |
The submitted data may change the data rating. |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health & Environment The health screening on zinc borate show that only few data sets are available. Boric acid can be formed, if zinc borate gets in contact with water e.g. body fluids. Based on comparison with sodium borate and boric acid, respectively,
the possible main effects are expected to be: No data was found on the compound ZnO(B2O3)2. Since the compound may dissociate in the environment, limited data sets on the Zn-ion and Sodium tetraborate are presented. The effect concentrations of zinc borate are estimated from the effect concentrations of disodium tetraborate (CAS no. 1330-43-4). This approach is based on the assumption that the total toxicity of disodium tetraborate and zinc borate originates from the boric acid formed upon dissolution. Zinc is an essential element for many organisms, however, for crustaceans zinc is very toxic. |
Health & Environment Borax Europe has several acute toxicity studies on zinc borates which indicate that zinc borates are not skin, eye irritants.
Borax Euopre has some data on ecotoxicological effects of zinc borates.
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Health & Environment The submitted data adds information and may amend the conclusions of the screening report. |
Data availability table: OK
Regarding the Appendix comment: The conclusion is taken from HSDB. No consultation of original paper included in original report.
The (health and) environment assessment of insoluble metals and metals compounds has been a matter of discussion in the EU and OECD for some time. The lack of a firm approach is reflected in the nature of the comments. Briefly, the discussion concerns whether the assessment is to be made on the intrinsic properties the parent bioavailable metal(-ion) or on actual test results with the more or less soluble compounds. The screening reflect a compromise between these two approaches.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
Health The substance is teratogenic. |
This substance has produced reproductive toxicity. It has not been found to be teratogenic within the realm of the conventional definition that is does not produce gross malformations. |
Phrasing can be discussed. Conclusion based on pre implantation loss and fetal growth retardation. |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health & Environment The overall evaluation from IARC is: Antimony trioxide is probably carcinogenic to humans. The substance is reportedly teratogenic in rats. |
Health & Environment The IARC classification is Group 2B: This should be interpreted as a possible human carcinogen.
Based on the cited toxicological data the substance cannot be concluded to be a teratogen in rats. |
Health & Environment This is the conclusion of HSDB. The original publication has not been consulted.
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Data availability table: There is a lack of long term toxicity tests, but otherwise acceptable coverage. This has been assessed as medium.
Comments to Appendix: The information appears to be the original.
Statement in summary: |
EFRA comments / suggested version: |
Response to comments |
Melamine seems to be only mildly toxic when ingested by animals. The available data does not show evidence of cancer induction by melamine. One experiment indicates that melamine may be harmful to crustaceans, but otherwise the reviewed toxicity data show little aquatic toxicity. The bioaccumulation of this compound is presumably low in the natural pH range (pH 6-8). The available biodegradation data indicates that this compound is persistent both under aerobic and anaerobic conditions. |
Melamine has been extensively studied in repeated-dose toxicity studies. According to the labelling guide (European Commission Directive 93/21/EEC of 27 April 1993) melamine has not to be classified as a dangerous substance on the basis of the results of the available toxicological studies. On the basis of these data melamine has been concluded to be a non-toxic substance. Bioaccumulation does apparently not occur because the acute and chronic toxicity for fish is in the same order of magnitude. Also model calculations do not indicate a hazard for bioaccumulation. The biodegradation rate of the substance is low. |
The phrasing of the original report may be overconservative, and can be amended to the text of EFRA
The evaluation of intrinsic properties is based preferentially on the test results from guideline tests. The statement on bioaccumulation does seem to overinterprete results. |
Statement chapter 5: |
EFRA comments / suggested version: |
Response to comments |
Health & Environment Melamine seems to be only mildly toxic when ingested by animals. There is no sufficient data to predict acute toxicity from dermal application in humans. The available data does not show evidence of irritation, cancer induction or mutageneity by melamine. Based on animal tests it seems there is a risk of formation of stones in the urinary bladder. A risk of inducing dermatitis in humans exposed to melamine among other chemicals in the working environment has been reported, however, the data was obtained in a formaldehyde-rich environment. The LD50 for application of melamine on rabbit skin is found in one study to be slightly larger than 1 mg/kg (1mg/kg implicates a high risk of adverse effects on skin of humans). |
Health & Environment Melamine has been extensively studied in repeated-dose toxicity studies (International Uniform Chemical Information Database IUCLID version 2000). According to the labelling guide (European Commission Directive 93/21/EEC of 27 April 1993) melamine has not to be classified as a dangerous substance on the basis of the results of the complete toxicological studies. On the basis of these data melamine has been concluded to be a non-toxic substance for man and environment. Bladder stones were observed in some rodent studies at levels above 1000 ppm in the diet and is caused by exceeding solubility of melamine salts in the urine due to excessive dose levels (> 50 mg/kg). A level of 50 mg/kg is equivalent with a dust level of 350 mg/m3 in occupational exposure. This level will reduce visibility to less than 1 meter and will never occur in occupational practice. The nuisance dust level is in the OECD-countries between 5 and 10 mg/m3. So a risk of bladder tumours under normal use conditions does not exist at all. NB: if melamine is non-toxic in oral studies, it will be certainly non-toxic via the dermal route due to a lower dose rate. The rabbit study quoted by the Danish EPA might be caused by misreading. The IUCLID-database 2000 reports a dermal LD50 > 1000 mg/kg for the rabbit. Melamine has been shown not to be a skin sensitiser in animal and human volunteer testing (IUCLID 2000) |
Health & Environment The bladder study may be out of context due to the exceptional high doses.
IUCLID 2000 were not available at the submission of the original report. |