CA-April06-Doc.12.5
EUROPEAN COMMISSION ENVIRONMENT DIRECTORATE-GENERAL ESSENTIAL USE APPLICATION FORM FOR BIOCIDES Directorate B – Protecting the natural environment B.4 – Biotechnology and Pesticides
1. MEMBER STATE
Austria Belgium Cyprus Czech Republic Denmark
Estonia Finland France Germany Greece
Hungary Ireland Italy Latvia Lithuania
Luxemburg Malta The Netherlands Poland Portugal
Slovenia Slovakia Spain Sweden United Kingdom X
2. ACTIVE SUBSTANCE
2.1. Common Ammonia, anhydrous name
2.2. EC and/or EC: 231-635-3. CAS: 7664-41-7 CAS N°
2.3. Molecular and H3N Molecular weight: 17.03 Structural formula (including details on isomeric composition) – molecular mass
2.4. Method of The active substance is not manufactured per se, but produced in-situ through the manufacture (in combination and reaction of sodium hydroxide and ammonium chloride in an aqueous brief terms) environment. 2.5.Specificatio The specified purity of the sodium hydroxide is >/=99%w/w n of purity in The specified purity of the ammonium chloride is >/=99.5%w/w g/kg or g/l as appropriate
2.6. Identity of Ammonium chloride: impurities and Sodium chloride (CAS 7647-14-5), maximum 0.3%w/w Water (CAS 7732-18-5), maximum 0.10%w/w additives – Ash, maximum 0.25%w/w including Iron, maximum 30ppm stabilisers Heavy metals, maximum 20ppm
Sodium hydroxide: Sodium carbonate (CAS 497-19-8), maximum 0.4%w/w Sodium chloride (CAS 7647-14-5), maximum 80mg/kg Sodium sulphate (CAS 7757-82-6), maximum 70mg/kg Silicon dioxide (CAS 7631-86-9), maximum 20mg/kg Total heavy metals, maximum 60mg/kg
2.7. Origin of Not Applicable substance (in case of a natural substance)
2 2.8. Physical Melting point[1]: -78ºC. chemical Boiling point[1]: -33.4ºC. [1] 3 properties in Density : 0.682g/cm at -33ºC. Vapour pressure[1]: 8570 hPa at 20 ºC. accordance Appearance[2]: Colourless gas at 20ºC. with Annex IIA, Solubility in water[2]: 47% at 0ºC; 38% at 15ºC; 34ºC at 20ºC; 31% at 25ºC; 28% at 30ºC, and; Point III, to 18% at 50ºC. Directive Partition Coefficient[1]: -1.14 at 25ºC. Absorption spectra: see appendices 1. [1] 98/8/EC, as Flammability : Lower flammability limit: 16%; Upper 25%. Surface tension[1]: 23.4 dynes/cm at 11.1ºC. appropriate Explosive properties[1]: c. 15 – 28%. Oxidising properties: Chemistry not capable of oxidisation.
References: [1]. IUCLID Dataset, ID: 7664-41-7, Created 19-Feb-2000. [2]. The Merck Index, Twelfth Edition, 1996.
2.9. A summary or toxicological Toxicological summary and Acute toxicity: ecotoxicological Ammonia gas displays a high acute toxicity by inhalation, with LC50 values typically ranging 5 – information for 20 mg/l in studies reported in the IUCLID dataset for Ammonia[3]. the substance Corrosivity (skin): Reports cited in the IUCLID dataset[4] note that; “Ammonia is a gas at ambient temperature and pressure. Thus a standardized skin irritation test in animals is not possible”. According to the source Environmental Health Criteria 54 (Ammonia) WHO, 1986, “ammonia in the form of a gas as well as an anhydrous liquid boiling at low temperatures or as an aqueous solution is a recognized skin irritant based on human data”.
Studies[5] involving aqueous solutions of ammonia (20%) caused effects of oedema and necrosis following application to the skin of a rabbit and a contact time of 5 minutes or longer. No such effects were noted with 2% aqueous ammonia (maximum application time 15 minutes).
Corrosivity (eye): Reports cited in the IUCLID dataset[6] note that; “Ammonia is a gas at ambient temperature and pressure. Depending on the concentration, irritation is observed and effects may be irreversible (i.e. permanent corneal opacity)”. According to the source Environmental Health Criteria 54 (Ammonia) WHO, 1986, “ammonia in the form of a gas as well as aqueous solution is a recognized eye irritant based on human data.”
Upon contact with the eye, a 10% aqueous ammonia preparation applied to the conjunctival sac of the rabbit was reported{7] as causing clear signs of irritation, including oedema and opacity of the cornea.
Sensitisation: No signs of sensitisation were observed during a study[8] involving repeated doses of a 20% aqueous ammonia preparation. No data with ammonia on animals are available as it is a gas at room temperature and pressure.
Repeated dose toxicity: Repeated dose toxicity by inhalation has been reported in a number of studies, ranging a number of species. During these studies, Lowest Observed Adverse Effects Levels were reported as follows:
3 Species Study duration Exposure period LOAEL value Rat[9] 5 days 6h/day 300pm Rat[10] 90 days 8h/day 650ppm Rat [11] 17 weeks 4h/day 1247ppm Guinea pig[12] 90 day 8h/day, 5days/week 610ppm Rabbit[13] 90 days 8h/day 610ppm Pig[14] 5 weeks Continuous 145ppm Dog[15] 90 days 8h/day 610ppm
No Observed Adverse Effects Levels were reported as follows: Species Study duration Exposure period NOAEL value Rat[16] 114 days continuous 0.04mg/l Rat[17] 2 months No data 0.04mg/l Rat[18] 90 days Continuous 0.127mg/l Rabbit[19] 6 weeks 8h/day, 5days/week 0.155mg/l Pig[20] 5 weeks Continuous 0.07mg/l Dog[21] 6 weeks 8h/day, 5days/week 0.155mg/l Monkey[22] 6 weeks 8h/day, 5days/week 0.155mg/l
Carcinogenicity, toxicity to reproduction and developmental toxicity: No carcinogenic effects have been reported in studies cited in the IUCLID dataset for ammonia[23].
According to information reported in the LUICLID Dataset[24] “…. Substantial doses of ammonia are formed by gut bacteria, being subsequently resorbed (>4000mg/day) in humans. Although sufficient [systemic] exposure is given no adverse effects have been reported in humans under physiological conditions.”
Review of human exposure: A very large number of toxicity studies have been documented. The following is taken from a summary presented in the IUCLID dataset for ammonia[25]: Ammonia is an irritant gas that causes severe local effects in the absence of systemic toxicity. Due to its high solubility in water ammonia freely forms NH4OH when in contact with mucous membranes. The high alkalinity of NH4OH causes destruction of cell proteins leading to severe tissue necrosis.
After inhalation, ammonia has most effect on the upper airways. Low concentrations cause pharyngitis, tracheo-bronchitis, nausea, vomiting, anosmia, headache, salivation, coughing and eventually bradycardia. Inhalation of very high concentrations can be fatal and can cause obstruction of the upper airways by formation of an oedema or necrosis. Constriction of the bronchi and interstitial oedema of the lung have also been observed. Ammonia (gas and liquid) is caustic to the skin (colliquation necrosis). Ammonia gas is strongly irritating to the outer surface of the eye, while liquid ammonia and NH4OH are penetrating to the cornea. Depending on the time of exposure and the concentrations, irreversible changes, such as damage to the iris, cataracts or glaucoma can occur after a latency period of up to 10 days.
After ingestion of aqueous ammonia solutions, strong effects of irritation can be observed in the upper gastrointestinal tract and non-lethal doses can result in the permanent damage of the oesophagus. For inhalation exposure assessment, systemic toxicity is of low relevance. Ammonia is a part of the biochemical pathway in humans. Inhalation exposure to doses which show no local irritant effects are not relevant with respect to systemic toxicity, which can only be evoked when the endogenous nitrogen balance is disturbed. This can only be achieved by high doses by inhalation that are strongly irritant or by oral ingestion, particularly of ammonium salts. A concentration of 50ml/m3 in the air would result in the uptake of 350mg/man, however the endogenous formation by intestinal bacteria is quoted as 4200 mg/man/day.
4 Environmental fate and ecotoxicity
Biodegradation (Aerobic): According to data presented in the IUCLID dataset for ammonia[26]: “When ammonia appears in water under normal conditions (aerobic) it is rapidly converted to nitrate by nitrification; the principle water contaminant normally being nitrate. The pH of water is increased by the presence of ammonia ions, in the form of hydroxide ions. Bacteria convert the ammonia to nitrate creating an oxygen demand (BOD) several days after the introduction of ammonia. The bacteria that oxidize ammonia are largely of the genus Nitrosomonas. Conversion of nitrite to nitrate is carried out primarily by the genus Nitrobacter. Temperature, oxygen supply, and pH of the water are factors in determining the rate of oxidation.”
Ecotoxicity: Fish toxicity has been summarised as follows in the IUCLID dataset[27]: + “Ammonia is highly toxic to fish. Elevated ammonia ion (NH4 ) concentrations within the bodies of fish, as also with invertebrates, cause convulsions and death. The concentration of non- ionised ammonia, NH3, in the environment of the fish is important, because ammonia is transferred between the water and the fish largely in this form. Thus, while NH3 is the more + toxic chemical species in the water, within the fish, toxicity is related to the NH4 concentrations….”
An extensive range of acute toxicity studies relating to aquatic invertebrates have been carried out for ammonia. A summary of those reported in IUCLID are produced in the following table:
Species Study duration LC50 value (mg/l) Daphnia magna[28] 48h 25.4 Daphnia magna[29] 48h 189 Daphnia pulex[30] 48h 187 Gammarus pulex[31] 48h 2.52 Nitocra spinipes[32] 96h 70 Ceriodaphnia 48h 131 reticulate[33] Simocephalus 48h 123 vetulus[34] Lymnaea stagnalis[35] 48h 1.5 Physa fontinalis[36] 48h 1.89
References:
ALL STUDIES CITED ABOVE ARE TAKEN FROM THE IUCLID DATASET, CREATED 19TH FEBRUARY 2000, ID NUMBER 7664-41-7.
[3]. Pages 77 to 84; report numbers 145 to 156.
[4]. Page 87; report number 99.
[5]. Page 87; report number 165.
[6]. Page 88, report number 166.
[7]. Page 88; report number 165.
[8]. Page 89; report number 165.
[9]. Page 89; report number 167.
[10]. Page 90; report number 168.
[11]. Page 90; report number 169.
5 [12]. Page 98; report number 176.
[13]. Page 95; report number 175.
[14]. Page 100; report number 178.
[15]. Page 97; report number 175.
[16]. Page 94; report number 170.
[17]. Page 92; report number 147.
[18]. Page 90, report number 170.
[19]. Page 96; report number 170.
[20]. Page 100; report number 179.
[21]. Page 97; report number 170.
[22]. Page 99; report number 170.
[23]. Page 104; report numbers 192 and 193.
[24]. Page 105; report number 190 and 191.
[25]. Page 109 – 110; review of summary made on reports 99, 202, 203, 204, 205, 206, 207, 208, and 209.
[26]. Page 31; report number 34.
[27]. Page 56 – 57; report number 99.
[28]. Page 58; report number 100.
[29]. Page 58; report number 101.
[30]. Page 58; report number 101.
[31]. Page 58; report number 103.
[32]. Page 59; report number 104.
[33]. Page 59; report number 101.
[34]. Page 59; report number 101.
[35]. Page 59; report number 103.
[36]. Page 59; report number 103.
6 3. AVAILABLE INFORMATION ON THE ESSENTIAL USE
3.1. Product type Product type 3; Veterinary hygiene biocidal products. and use(s) for which the The product, OO-Cide, is a surface disinfectant for use in a range of animal housings or derogation is enclosures, and for a range of livestock types (e.g. poultry; game birds; rabbits; cattle; pigs, and; required sheep). It is aimed at reducing the disease challenge of coccidia, cryptosporidia, nematodes* and other protozoa by reducing the environmental load of the disease causing organisms.
*OO-Cide demonstrated efficacy against nematode eggs during in-vitro studies. Nematode larvae and mature to egg-producing adults do not develop in-vitro and are therefore not typically of concern for environmental load.
3.2. Method(s) of Ammonia is delivered through in-situ generation as a result of the combination and subsequent application reaction of the two sachets that make up the OO-Cide product when diluted in water. OO-Cide Pack 1 contains an ammonium salt, Pack 2 contains sodium hydroxide.
OO-Cide Pack 1 is diluted in cold water (1:20 dilution) and stirred until completely dissolved. Following the cleaning routine, this solution is applied to the floor area, posts, walls, etc., up to height of 0.5 metres using a coarse spray, normally with the use of a knapsack sprayer.
Upon completion of application, the contents of OO-Cide Pack 2 are diluted in cold water (1:20 dilution) and stirred until completely dissolved. This solution is sprayed over the area previously treated with OO-Cide Pack 1. Combination of the two solution results in the formation of ammonia within the resulting solution. The treated area will turn pink as a result of an indicator in the Pack 1 solution.
Treated surfaces are not rinsed prior to restocking. Re-entry should not occur before the surfaces are dry and the treatment area is thoroughly vented.
3.3. Number OO-Cide is typically used on a reactive basis in response to an outbreak of coccidiosis, and timing of cryptosporidiosis or other protozoan infection. One application is normally sufficient to achieve the applications desired level of control of the pathogens.
In cases where there is a recurrent problem with protozoan infection outbreaks, the product may be used routinely, typically following clean-down procedures, where animal litter and other organic challenge are removed and surfaces are cleaned prior to restocking.
3.4. OO-Cide Pack 1: Classification Product is composed of greater than 95% ammonium chloride (EC number: 235-186-4), and the & Labelling classification therefore mirrors that defined in Annex 1 to 67/548/EEC for this substance: Harmful; Xn: R22- Harmful by ingestion R36 – Irritating to eyes.
OO-Cide Pack 2: Product is composed of greater than 99% sodium hydroxide solid (EC number: 215-185-5), and the classification therefore mirrors that defined in Annex 1 to 67/548/EEC for this substance: Corrosive; C: R35 – Causes severe burns
Reaction product: No studies on the reaction product have been carried out. However, ammonia itself is classified as follows according to Annex 1 to 67/548/EEC: Toxic; T: R23 – Toxic by inhalation R34 – Causes burns
7 3.5. Available Use of the product results in the in situ formation of ammonia, in a system that is totally inorganic. data on effects While the starting materials are classified as hazardous, they are significantly diluted in water during on human or the use of the product. The product is used only by trained and properly equipped workers. It should animal health be noted that ammonia solution is used as a household cleaner. Similarly, concentrated solutions of and the sodium hydroxide are sold as consumer products for the removal of grease, such as in ovens or environment drains. (including exposure and Sodium hydroxide has no significant effects upon the environment, Although ammonia is harmful to risk aquatic organisms, very large quantities of ammonium salts are used as fertilisers. In fact, all the assessment main components of the system have extensive uses and could be considered as basic active and proposals substances. for risk mitigation) Overall, it can be concluded that the use of this product does not present any significant risks to man from the use or the environment.
3.6. Information on Summary of efficacy data carried out on OO-Cide by independent laboratories. efficacy Parasitic Efficacy Order Organism Stage Ref. No Strain Effective Disease Animal Dilution Protozoa Cryptosporidium oocyst 3 1:20 scour Multiple species Protozoa Eimeria acervulina oocyst 1 W102 1:20 coccidiosis poultry Protozoa Eimeria acervulina oocyst 4 W111 1:20 coccidiosis poultry Protozoa Eimeria brunetti oocyst 1 W63 1:20 coccidiosis poultry Protozoa Eimeria chandallis oocyst 2 1:20 coccidiosis sheep Protozoa Eimeria necatrix oocyst 1 W71 1:20 coccidiosis poultry Protozoa Eimeria tenella oocyst 1 W264 1:20 coccidiosis poultry Protozoa Eimeria tenella oocyst 4 W67 1:20 coccidiosis poultry Protozoa Eimeria spp oocyst 3 1:20 coccidiosis cattle/goat Protozoa Toxoplasma gondii oocyst 3 1:20 ovine abortion sheep Nematodes Trichostrongylus colubriformis egg 3 1:20 gastritis sheep/goat Nematodes Haemonchus contortus egg 3 1:20 gastritis sheep/goat Nematodes Ostertagia circumcincta egg 3 1:20 gastritis sheep/goat
References: Report number 1 - Veterinary Investigation Centre, 7th February 1986, “Efficacy of ‘OOCide ‘against avian coccidian”, Ministry of Agriculture Food and Fisheries, Cambridge.
Report number 2 – Department of Clinical Veterinary Medicine, 8th August 1985, “Report on the effectiveness of OO-Cide in destroying coccidial Oocysts”, University of Cambridge.
Report number 3 – Department of Parasitology, no date, “The efficacy of OO-Cide against: - a) cryptosporidium b) 3-species of Ovine gastrointestinal nematodes c) Toxoplasma gondi oocysts d) Ovine coccidian”, Moredun Research Institute, Animal Diseases Research Association, Edinburgh.
Report number 4 – Stichting Gezondheidsdienst Voor Pluimvee, 22nd February 1988, “Efficacy of OOCide against avian coccidian”, Doorn, Netherlands.
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Summary of results obtained from independent efficacy studies carried out by the Ministry of
8 Agriculture, Fisheries and Food, Veterinary Investigation Centre, Cambridge, England.
The purpose of the trials was to study - in vitro - the efficacy of OO-Cide in preventing the excystment of sporulated avian oocysts.
Legend: Excystment prevented - Excystment + Test Test Dilution of Exposure Time to OO- Control temperature OO-Cide Cide Organism 1h 6h 24h 1:20 - - - + + 4oC 1:200 - - - + Eimeria 1:2000 + + - + tenella 1:20 - - - + + 20oC 1:200 - - - + 1:2000 - - - + 1:20 - - - + + 4oC 1:200 + + - + Eimeria 1:2000 + + + + necatrix 1:20 - - - + + 20oC 1:200 + + - + 1:2000 + + + + 1:20 - - - + + 4oC 1:200 + + - + Eimeria 1:2000 + + + + brunetti 1:20 - - - + + 20oC 1:200 + + - + 1:2000 + + + + 1:20 + - - + + 4oC 1:200 + + - + Eimeria 1:2000 + + + + acervulina 1:20 + - - + + 20oC 1:200 + + - + 1:2000 + + + +
CONCLUSION - Eimeria tenella is the most susceptible of the coccidia tested to the effects of OO- Cide. E. necatrix and brunetti showed a similar degree of susceptibility. All three of the strains examined were inactivated by exposure to OO-Cide for an hour.
Eimeria acervulina showed a greater degree of resistance to inactivation but this strain was inactivated by exposure to OO-Cide for between 1 and 6 hours.
It is interesting that at the two exposure temperatures used in the trial there was not a significant temperature related effect. These two temperatures were chosen as representative of winter and summer ambient temperatures.
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9 Summary of results obtained from independent efficacy studies carried out by the Department of Clinical Veterinary Medicine, University of Cambridge, England
The purpose of this trial was to establish the efficacy of OO-Cide against mammalian OO-Cysts.
Test Dilution of Test Organism Exposure Time temperature OO-Cide 1h 6h 24h 1:20 - - - + 4oC 1:200 - - - E. chandallis 1:2000 + + + 1:20 - - - + 20oC 1:200 + - - 1:2000 + - - Legend: Excystment prevented - Excystment +
CONCLUSIONS
At 1:20, OO-Cide prevented excystment under both test temperatures, given an exposure time of one hour. At 1:200, one hour exposure time, excystement was prevented at 4ºC, but not at 20ºC.
E. chandallis is a very important sheep coccidium and represents an example of a coccidial oocyst that is highly resistant to the environment and can persist under normal conditions for a very long period of time. The OO-Cide was effective even at low temperature of dilution up to 1/200, whereas at a more normal temperature of + 20oC even dilution as high as 1/2000 would kill after 6 hours' exposure or at 1/200 all oocysts were killed after one hour.
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Field Trials:
OO-Cide has also been tested under field conditions, conducted by independent laboratories. (Full reports available on request).
Carried out by Department of Clinical Veterinary Medicine, University of Cambridge, England.
Method summary:
It was decided that four groups would establish the efficacy of OO-Cide.
1. OO-Cide only to be used in the presence of a strong coccidial challenge. 2. A normal coccidiostat to be used in the feed also in the presence of a strong coccidial challenge but without OO-Cide. 3. A combination of the use of OO-Cide and a coccidiostat in the feed with a coccidial challenge. 4. A control without coccidiostat and given no challenge.
In order to satisfy these requirements 80 chicks were reared on normal clean litter, 20 in each experimental group. They were reared together from day-old to 2 weeks of age and then submitted to the following treatments in completely separate accommodation:
1. GROUP 1 was placed on new litter after a treatment with OO-Cide and a challenge on the floor under the litter. The food contained no coccidiostat.
10 2. GROUP 2 was also given a coccidial challenge, there was no treatment with OO-Cide but the birds were given a coccidiostat. 3. GROUP 3 - similar to Group 1 but with the addition of a coccidiostat to the food. 4. GROUP 4, the Control, had birds on new and clean litter; there was no coccidiostat and no challenge.
The 'challenge' with coccidial oocysts was achieved by the use of an application of Eimeria species of coccidia, principally E. tenella, E. necatrix and E. acervulinus, at a concentration of 270,000 oocysts to a square metre of the floor which housed the 20 chicks.
The OO-Cide was applied as follows:
1 litre was made up from the pack supplied by Antec International, the manufacturers, and the concrete floor was thoroughly soaked in the OO-Cide the day after the oocysts application. Litter was placed on the floor to a depth of 15cms after the floor was dried and the chicks were placed on the floor immediately afterwards.
RESULTS
Results were established on the following basis:-
A) 'LESION SCORING'
1. The gut is divided into four regions.
2. Each region is given a score between 0 and 4, o indicating no evidence of coccidiosis from external and internal examinations.
MTLS - Mean Total Lesion Scores are calculated by dividing Total Lesion Scores (TLS) by number of birds in the sample, i.e.
MTLS = TLS/N
(N = No. of birds examined).
Interference values normally set are as follows:
MTLS
<1.5 Below Average 1.5 - 2.0 Average >2.0 Above average 0
Lesion Scoring - the Four Regions
1. The duodenal loop down to just past the end of the pancreas. 2. From end 1 to a point approximately 2 x caecal length from caecal junction. 3. From end 2, to the rectum. 4. The caecal pouches.
11 Results of lesion scoring. Coccidiostat Disinfection with Strong Coccidial Group Legion Scores OO-Cide Challenge in Feed After 10 After 20 days days Group 1 Yes No Yes No lesions No lesions Group 2 No Yes Yes <1.5 <1.5 Group 3 Yes Yes Yes No lesions No lesions Group 4 No No No No lesions No lesions (control)
Results of caecel Oocyst examination. Coccidiostat Strong Caecal Oocyst Estim. Disinfection Group Coccidial with OO-Cide in Feed Challenge Scores After 10 After 20 days days Group 1 Yes No Yes 1 1 Group 2 No Yes Yes 1 1 Group 3 Yes Yes Yes 1 1 Group 4 No No No 0 0 (control) Legend: No. of oocysts Score 0 0 1-50 1 50-200 2 200+ 3
Conclusion: The results of the above field study clearly indicate that in the case of the lesion analysis, OO-Cide reduces the disease challenge by a significant level, whereby no oocyst infection was noted. It is unclear from the results of the second analysis (caecel) whether this is also corroborated, since no positive control was used and exact oocyst counts were not defined.
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Additional information:
In addition to formal laboratory and field studies, OO-Cide has demonstrated a recognised efficacy during more than twenty years extensive use.
4 - JUSTIFICATION OF THE ESSENTIAL USE
12 4.1. Significance of the harmful organism
Coccidia. According to the United States Department of Agriculture in their annual report on coccidiosis programmes[38]: “Coccidiosis is a ubiquitous intestinal protozoan infection of poultry which seriously impairs the growth and feed utilization of infected animals. In poultry, coccidiosis has been particularly problematic where annual losses of over $600 million per year have been sustained by the U.S. poultry industry alone. Each of the more than 30 billion chickens raised annually worldwide is at risk for coccidiosis. Continual emergence of drug resistant parasites in the field, and increased feed costs to producers coupled with reduced weight gain indicate that novel approaches are urgently needed to reduce economic losses from this coccidiosis. Coccidiosis is caused by at least several distinct species of obligate intracellular parasites of the genus Eimeria in chickens. The pathology of coccidiosis is caused by the rapid replication of the parasite during asexual reproduction in the cells of the gut, resulting in diarrhoea, weight loss, and anorexia.”
Data on the economic significance of coccidiosis on both a global and national level is scarce. This is presumably due to the difficulty in deriving a single monetary value to represent the global or even national cost of this disease as a result of the huge range of variances and uncertainties of the values required to be obtained for a suitably reliable calculation, and the dynamic nature of these values.
However, a robust estimation made of the impact of coccidiosis on the poultry industry in the United Kingdom has been derived by R.B. Williams in his report[37] on compartmentalized modelling for the estimation of cost of coccidiosis, where he reports that: “The total cost for 1995 may have been at least GB£38,588,795, of which 17.5% was the cost of prophylaxis and therapy of commercial broilers, and 80.5% was due to sub clinical effects on their weight gain and feed conversion. The total cost of chemoprophylaxsis and therapy of broilers plus losses attributable to coccidiosis-induced mortality, reduced live weight and increased FCR [Feed Conversion Rate] amounted to 98.1% of the total losses due to coccidiosis, or 4.54% of the gross 1995 UK broiler market revenue of GB£834,852,638…. The impact of such losses on the profitability of the UK broiler industry is put into perspective by the fact that in 1995, the profit per bird processed was only 7.02% of the cost of the chick and its rearing…”
Further Information on the economic impact of coccidiosis on the poultry industry has been reported by the United States Department of Agriculture, concerning global economic impact[39]: Globally - $1.5 Billion
Coccidiosis is also a serious disease in cattle, sheep and goats, in which the liver as well as the intestine can be affected[40]. “Infections with some species of Eimeria are one of the most economically important diseases of sheep”[41].
Coocidial challenge can lead to direct damage to the intestinal lining, predisposing the host animals to co-infection, such as Necrotic Enteritis (Clostridium perfringens), which is normally non-infective due to the unfavourable environment of the gut where they are commonly found.
Cryptosporidium. A report issued on the Department of Environment, Food and Rural Affairs (UK) website[42] states that: “Oocysts are remarkably resistant to common disinfectants, including chlorine-based compounds. The inherent resistance both to antimicrobial compounds and environmental stress has increase the prevalence of cryptosporidiosis in the UK, which rose nearly 10-fold in cattle and 5-fold in sheep between 1983 and 1994 (Svoboda et al. 1997)….. cryptosporidium is now ubiquitous amongst mammals in the UK. It appears that there is now an irreducible, minimum background level of the organism in UK wildlife and this reservoir would act as a continual source of reinfection of domestic livestock (Sturdee et al 1998).”
A general summary of clinical findings and prognosis is provided in The Merck Veterinary Manual[43], as follows: “The disease in calves, characterized by weight loss and watery diarrhoea, is clinically indistinguishable from many other causes of calf diarrhoea. Unless the immune system is compromised, it is self-limiting. Cryptosporidium parvum infections from animals and other people pose a significant risk to immunocompromised people [and to animals*], who can develop protracted diarrhoea and die.”
*Cryptosporidium parvum is not host-specific.
Nematodes. According to the Merck Veterinary Manual[44]: “About 100 worm species have been recognized in wild and domestic
13 birds in the USA. Nematodes (roundworms) are the most significant in number of species and in economic impact. Many field studies show that poultry maintained under free-range conditions may be heavily parasitized; therefore, control measures such as preventing infections or chemotherapy are likely to improve weight gain and egg production. In surveys of birds raised under nonconfinement conditions in other countries, an incidence of infection >80% is not uncommon.” Symptoms of infection in young animals are lack of growth and loss of condition.
Environmentally resistant larvated eggs on the ground are the main environmental load for infection[45]. ……………………………………………………………………………………………………………………………………..
References: [37] – Section 8, para. 4, “A Compartmentalized model for the estimation of the cost of coccidiosis to the world’s chicken production industry”, R.B. Williams, 31st May 1999.
[38] – Fine-Mapping and Characterization of Quantitative Trait Loci (Qtl) That Affect Coccidiosis Broilers, Annual Report 2003, United State Department of Agriculture website : http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=405388&fy=2003
[39] - Viral vector vaccine carrying an immunogenic protein of Eimeria and chicken IL-2 induces protective immunity, United States Department of Agriculture Website : http://www.ars.usda.gov/research/programs/programs.htm? np_code=103&docid=390&pf=1&cg_id=43
[40] – Adapted from The Merck Veterinary Manual (Eighth Edition), p140 – 141, 1998.
[41] – Coccidiosis of sheep, p145, The Merck Veterinary Manual (Eighth Edition), 1998.
[42] – Department of Environment, Food and Rural Affairs, website: http://www.defra.gov.uk/science/Project_Data/DocumentLibrary/PS0430/PS0430_356_FRP.pdf
[43] – Cryptosporidiosis, p145, The Merck Veterinary Manual (Eighth Edition), 1998.
[44] - The Merck Veterinary Manual (Eighth Edition), p1917-1918, 1998.
[45] – Adapted from The Merck Veterinary Manual (Eighth Edition), p317, 1998.
4.2. Importance of the intended use and estimated scale of use - maximum quantity of active substance per year
It is widely noted that clinical coccidiosis disease is staging a comeback with the emergence of resistant or tolerant strains. The United States Department of Agriculture reports[40] that: “Traditional drug-based control strategies are no longer effective due to drug-resistant Eimeria species and consumer’s demand for chemical-free poultry meat.” The discovery of new chemicals is a long and expensive business. It is essentially a random process to try and find a novel and effective product. When coupled with increasing environmental concerns and perceived human health implications of in-feed products, the likelihood of new chemicals for coccidiosis control is remote.
The current control strategy requires a practical approach, both to reduce challenge from infectious oocysts as well as controlling sub-clinical disease. The aim must be to use the drugs that are left effectively and strategically. This can be achieved by shuttles and rotations to preserve the population of oocysts sensitive to the products in use at any one time. Some potent chemicals may even help to actively restore the sensitivity to other products where resistance or tolerance had built up.
However, for such an approach to be successful, the pressure must be taken off this rapid selection of resistant strains by reducing challenge and exposure in the first place. The degree of pathogenicity (disease causing damage) of coccidia is mostly dependent upon the numbers of oocysts ingested by the host at one time. For example, up to 100 eggs of Eimeria tenella (the cause of caecal coccidiosis) causes infection but no disease. Up to 1000 eggs causes mild coccidiosis lesions, morbidity and loss of pigmentation in corn fed birds. Challenges in excess of 1000 eggs are capable of causing disease and death.
14 When it is known that oocysts will persist in the environment longer than most viruses, and may survive in moist soil for over two years, reducing the level of challenge on a site is not easy.
The use of a product such as OO-Cide, with a proven ability to remove environmental contamination within the farms specific coccidial burden allows the producer to "wipe the slate clean". In doing so, this should cut down the challenge dose on site, taking the pressure off the coccidiostat as well as deselecting the emergence of resistance or tolerant coccidial strains and reducing/controlling disease outbreaks.
The use of coccidiostats to control one of the most economically important poultry diseases worldwide will continue. Their success will be protected and extended by the strategic control of challenge. Reducing environmental contamination through stringent bio security and effective disinfection will be the cornerstone of that control.
Since the active ingredient is generated in-situ it is difficult to determine exact quantities. Approximately 18 tonnes of OO-Cide was sold into the French Market place in 2004. Assuming maximum conversion of ammonium chloride to ammonia, this equates to approximately 8.5 tonnes of ammonia. We may estimate that future use of the OO-Cide product will be less than 30 tonnes per annum in each of the two Member States for which an application for essential use is being made.
The walls of the oocyst consist of an electron-dense, 10nm outer layer and 90nm inner layer. The former constitutes 25% of the total wall mass and contains fatty acids, fatty alcohols, phospholipids and cholesterol. P-Hexacosanol makes up 23% of the oocyst wall allowing passage of only small uncharged molecules. The inner layer is readily soluble in any agents that are capable of breaking disulphide linkages. It is mainly composed of glycoprotein with a molecular weight of 10,000. Cysteine is not found in the free glycoprotein but is associated with the fraction of low molecular weight after solubilisation. Since the outer layer, the protective barrier, will only allow the passage of small uncharged molecules, it is very resistant to current disinfectant technologies, such as quaternary ammonium compounds, Iodophors, peracetic acid, other acids and alkalis, etc. Being small and uncharged means that ammonia is capable of diffusing the cell wall and membrane, enabling it to kill the oocyst.
[40] - Viral vector vaccine carrying an immunogenic protein of Eimeria and chicken IL-2 induces protective immunity, United States Department of Agriculture Website : http://www.ars.usda.gov/research/programs/programs.htm? np_code=103&docid=390&pf=1&cg_id=43
4.3. If the essential use is not permitted, what would be the consequences for health, safety, protection of cultural heritage or the functioning of society (including cultural and intellectual aspects)?
The problem for disinfectants is the inherent resistance of the coccidial oocyst to virtually all products. This relates to the very thick coating of the egg, giving highly efficient waterproofing and making liquid disinfectants ineffective.
There are very few products that can claim to kill the coccidial spore. However, OO-Cide has been proven to be able to destroy oocysts under laboratory and field conditions.
OO-Cide uses a principle of a double application. The first, the ammonium salt, with surfactant, ensures that it penetrates organic material and sticks to the cysts. The second activator combines and releases ammonia gas exactly where it is needed. This low molecular weight gas rapidly gains access through the coating, into the cyst and destroys it. The product also contains a colour indicator that gives practical help in locating where the product has been applied and confirming that activation has taken place.
Without effective support to reduce disease challenge using a proven disinfectant, not only are incidences of coccidiosis likely to persist, but also coccidiostat drugs will become more rapidly obsolete through resistance, with the combined effect of rapid increases in coccidiosis. This will result in greater economic losses for farmers, more disease and suffering in farm animals and the potential for more intensive treatments with anticoccidials, which could give rise to unacceptable residues in food products.
15 4.4. Need for the biocidal product / active substance in resistance or other pest management programmes (for example integrated pest management) See above.
OO-Cide is a preventative treatment that reduces the potential for infection by inactivating coccidia in animal housing. It thus reduces the incidence of disease and reduces the need for treatment of existing disease in animals.
5 - WHY THE USE OF THIS ACTIVE SUBSTANCE IS ESSENTIAL
5.1. Active substances currently used [elsewhere in the EU/worldwide) to control the problem described in 4.1. and their approval/authorisation status
Neopredisan 135-1. Manufactured and marketed by Menno GmbH, Germany.
Kilcox. Manufactured and marketed by Kilco International, UK.
Bi-OO-Cyst. Manufactured and marketed by BioLink, UK.
All of the above products contain the active ingredient: p-chloro-m-cresol (CAS 59-50-7). p-chloro-m-cresol is included in the review programme for existing active substances under the BPD transitional arrangements.
No other disinfectants for this use are known to exist.
Vaccines for the prevention of coccidiosis are available.
Various veterinary medicinal products and feed additives are approved within the EU for the treatment of coccidiosis.
5.2. Evidence that there are no available technically and economically feasible alternatives or substitutes that could be acceptable from the standpoint of environment and health
It is very difficult to judge objectively the comparative effectiveness of one product to another. However, by limiting the options available for the environmental control of coccidiosis, potentially to one active ingredient type (p-chloro- m-cresol), the incidence of resistance is likely to significantly rise, resulting in additional pressure on coccidiostat drugs. Furthermore, the efficacy of this product is not known, and such products have the drawback of potentially tainting feedstuffs.
Furthermore, the intensive livestock industry will be reliant on the success of a single active substance dossier under the Biocidal Products Directive review programme. There is no guarantee that a complete dossier will be submitted; furthermore, given the known toxicity and environmental effects of chlorophenols, an acceptable risk assessment of this substance is not assured. If the application for Annex I inclusion is unsuccessful, no other options for anticoccidial disinfectants will be available, again putting pressure on coccidiostat drugs and feed additives, which may expedite further resistance of this drug type, which is already under pressure (see above).
Some vaccines have been developed for the protection of animals against protozoan parasites. However, such vaccines tend to offer protection only against a narrow range of pathogens, such as only a single species of Eimeria. Furthermore, the use of vaccines is expensive and labour intensive, such use therefore being limited to high value, such as breeder, stock. The development of resistant strains is also a potential limitation of vaccine use.
Various anticoccidal compounds have been developed and these can be applied directly to animals as either veterinary medicinal products or utilised as feed additives. Although a vital part of disease control, these products have several drawbacks. Firstly, they are used to treat rather than to prevent disease, with the resulting stress and suffering to animals, and economic losses to farmers. Furthermore, the development of resistance is an ever- present problem, only partially constrained by shuttle programmes. Finally, the use of these products is limited by their toxicity to the target species and the presence of residues that could have adverse effects upon consumers. Hence the use of these products is already subject to a number of restrictions and their utility is potentially limited in
16 the longer term by the development of resistance.
6 - PROPOSED PLAN FOR A MORE PERMANENT SOLUTION
6.1. Evidence of a plan to submit a dossier for the evaluation and inclusion of the active substance in one of the annexes to Directive 98/8/EC
See below.
6.2. Any outline of work carried out to develop an alternative or substitute to the active substance
During preliminary independent efficacy trials, a product currently in the latter stages of the development process has shown comparable efficacy against cryptosporidium to OO-Cide. Results from independent efficacy studies against coccidia are expected by December 2005.
The product includes only actives supported under the Biocidal Products Directive review process.
Further testing is necessary to establish the efficacy of the product and define conditions of use. Once this has taken place, and assuming that a product can be developed successfully, it will then be necessary to meet any national regulatory requirements. Given that the deadline for the withdrawal of biocidal products that contain only identified active substances, and the need to ensure that products are removed from the supply chain by the deadline, it is not possible to have a replacement product on the market in sufficient time to replace OO-Cide by September 2006.
Nevertheless, subject to the success of the development process and the requirements for national registration, an alternative product should be available before May 2010.
7- OTHER INFORMATION
E.g.: - Steps that are being taken to minimise the proposed uses - Steps to minimise the emissions and human exposure associated with the proposed uses and waste management related to the biocidal product - Acceptability of the active substance in light of the criteria in Annex VI of Directive 98/8/EC
The active substance is only generated in situ, in solution at the place of use.
The product is marketed for a very specific purpose and is neither available nor suitable for other uses. The product is currently on the market in a number of EU countries, with regulatory approvals where appropriate.
Revision of requirements for listing of basic substances into Annex IB could offer a means of continual use of this substance, given the ubiquitous nature of the active substance.
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