1. Materials and methods 1.1 Fate Analysis The value of the fate factor is given from the...
1
1. Materials and methods 1.1 Fate Analysis The value of the fate factor is given from the relationship between the concentration and the emission, and remains the same one for whichever damage category. Where S is the area immediately contaminated because of the substance dispersion Q tot , V is the volume of the room and n is the air exchange rate that is 1h -1 =24gg -1 . From information of the article of Gregis, the probability P c that an amount of ciclophosphamide present in the room comes breathed from the nurse during its every day activity, is given from the relationship between the amount of substance in the urine of nurse and Q tot . 1.2 Effect Analysis After the definition of the fate factor, it must be calculated the damage threshold (SD) of the ciclophosphamide, defined from the relationship between MRL (Minimal Risk Level), that is the level beyond to which the dose becomes unacceptable for the organism, and P i , that is the probability that an individual contracts one disease if exposed to that amount of substance. Therefore we calculate the damage threshold: Unlike the fate factor that remains the same, the damage threshold (SD) will have various values with respect to the considered impact category. Table 1 contains the values of MRL i and P i for the ciclophosphamide for every impact category: Table 1. * values of our elaboration The absence of a limit value beyond which the ciclophosphamide becomes cancerogenous and can induce in the organism the formation of secondary tumors, derives from the genotoxicity of the drug in examination. A cancerogenous genotoxic takes part directly on the cellular genome with a mechanism of action of stocastic type, for which a limit dose couldn’t exist. But, like objet of our study, we have the requirement to define a MRL1 value, without which it is not possible to calculate the threshold of damage SD and the factor of characterization for the impact category Carcinogens. We consider like dose threshold of the ciclophosphamide for the category Carcinogens, the medium value of the every day therapy, that it is of 6mg/kg. The value of the damage threshold for the three impact categories becomes: The reciprocal of the damage threshold is the risk unit (UR). For the Ecoindicator99 method, the unit risk factor for inhalation is a valuation of the probability that an average individual will develop cancer when exposed to a pollution in an environment concentration of one microgram per cubic meter for the individual’s life (70 years). Various, in our study we have replaced to the constant amount of 1mg/m3, the concentration limit MRL, that is the value above which one can be had disease, during one working life of 40 years. The innovation resides in the limit concept: consideration that contrasts with the directed proportionality between the amount of substance and the probability of one disease. P c : probability that the ciclophosphamide dispersed in the atmosphere comes absorbed from the nurse; P i : probability that, in the case in which the ciclophosphamide comes absorbed, this provokes someone disease. Calculating the unit risk for the three impact categories, Carcinogens, Cardiotoxicity and Infertility, we obtained the following values: After the obtainment of the values of the unit risk for every impact category, we obtain the effect factor E (with i=1,..,3) multiplying URi for the population density pd. The population density does not correspond to that one of the Ecoindicator99 method. The term of reference in order to determine pd is the area on which calculate the concentration c: in our case, we consider the surface of the druggist laboratory hospital Damage analysis on the operator because of the emission of ciclophosphamide with LCA method Introduction On demand of the pharmacy unit of the hospital of Correggio (Reggio Emilia), it has been attempted to quantify the damage that can endure a nurse if exposed daily one antiblastic drug amount, the ciclophosphamide, that is dispersed in the surrounding atmosphere during its phase of preparation. But the ciclophosphamide, even if it is a drug of which is assessed the carcinogens by the medical community, it does not appear among the present substances in the used methodologies (Ecoindicator99, EPS2000, Edip 96): this why the three methods consider only those substances that have values of emission that refer to the entire European or world- wide surface. In our case, the surface is extremely reduced: 8m 2 of the room in which the drug is dosed for the supply. Therefore, after to have defined in the new method ENEA-Method 2004 three new impact categories (Carcinogens, Cardiotoxicity, Infertility), in which the ciclophosphamide appears like only substance, we must determine the three factors of characterization for the three indicated impact categories. 3 2 0076 0 m m gg , V n S Ε V n Ε S Ε V n τοτ Q Ε C f cases cases ng ng tot Q urine Q c P % 3 03 , 0 1630488 51810 Roberto Pergreffi *, Francesca Falconi*, Germana Olivieri*, Paolo Neri** *Progetto SPINNER c/o ENEA, **ENEA, PROTT-INN via Martiri di Montesole 4, 40129 Bologna, [email protected] , [email protected] c P i P i MRL i SD 3 1600 3 3 , 0 1 80 6 1 6 1 m mg m kg kg mg gg gg kg mg MRL cases m mg SD 3 533333 1 cases m mg SD 3 299880000 2 cases m mg SD 3 179200 3 year 40 1 i MRL c P i P years 40 i SD 1 i UR years mg cases m E UR 3 08 6 , 4 1 years mg cases m E UR 3 11 3 , 8 2 years mg cases m E UR 3 07 4 , 1 3 pd i UR i E 2 375 , 0 2 8 3 m persons m persons pd years m mg m cases E E 2 3 08 7 , 1 1 years m mg m cases E E 2 3 11 1 , 3 2 years m mg m cases E E 2 3 08 3 , 5 3 i E F i IF mg cases E IF 13 6 , 3 1 mg cases E IF 15 7 , 1 2 mg cases E IF 13 9 , 2 3 1.3 Damage Analysis DALY (Disability Adjusted Life Years) indicates the disability and lost life years because of one disease. A DALY is given from the sum between YLD (Years Lived Disabled, that is the number of disease years), multiplied for respective disability rate, and YLL (Years of Life Lost, that is the number of years of life lost), multiplied for mortality rate (mr= 1), and is calculated taking like reference the damage endured from an European medium citizen per Kg of issued substance. The suffering or invalidity rates (dr-disability rate), that derive from different psychophysical conditions, derive from the necessity to quantify the level of incidence of a pathology in the life of an individual, and change inside an interval comprised between enclosed value 0, in case of “satisfactory” health, and excluded value 1, in case of serious chronic diseases. Unfortunately, the cardiovascular diseases and the tumors don't appear among the consulted data to determine dr. Therefore, we must establish a invalidity rate dr for every pathology. The values of dr must be reported to administrations of ciclophosphamide that are greater than those indicated from MRL, for every impact category; otherwise dr and mr assume value zero. The equation for the calculation of the DALY has been modified inserting the probability p. This modification to the Ecoindicator99 method, derives from the necessity to differentiate, inside a same impact category, specific pathologies, on the base of the probability that they have to manifest itself. If in the Ecoindicator99 method to every generic pathology corresponds a specific pathology, in our study this relationship is not respected. Therefore it is had: We reassume in the table 2 the obtained results in the our study, that are necessary in order to calculate the DALY for every impact category : Table 2. We can determine the number of disability or lost life years, for every impact category: 3. Conclusions: LCA of nurse’s risk because of the ciclophosphamide With the LCA method, we calculated the damage that the nurse suffers if he gets the amount of ciclophosphamide corrisponding to the maximum value of damage threshold. The Figs.1 and 2 show the studied process and the results respectively. SimaPro 5.0 Processes Date: 29/10/2004 Project: Antiblastic drug Emissions to air ciclofosfamide-cg (>267mg/m2) 630000 0 0 mg emission of ciclophsphamide (cg: carcinogens) in the working life of the nurse(40 years) ciclofosfamide-ct (>630gr/m2) 630000 0 0 mg emission of ciclophsphamide (ct: cardiotoxicity) in the working life of the nurse ciclofosfamide-if (>504mg/m2) 630000 0 0 mg emission of ciclophsphamide (if: infertility) in the working life of the nurse SimaPro 5.0 LCIA Profile Date: 29/10/2004 Project: Antiblastic drug Method: ENEA Method 2004 / Italia 2004 I/E Value: Impact indicator Per impact category: Yes Impact category Unit Total P_Hospital Infertility DALY 2,33E-7 2,33E-7 Cardiotoxicity DALY 5,04E-9 5,04E-9 Carcinogens DALY 3,4E-7 3,4E-7 4. Main References Benvenuto GB, La Vecchia L, Morandi P, Ruffini P, Mezzena G. Analisi della cardiotossicità da ciclofosfamide ad alte dosi mediante monitoraggio elettrocardiografico, ecocardiografico, e della troponina I in pazienti con tumori alla mammella. Ital Heart J nov. 2000; suppl vol 1: 1457-63. Mattei I. Esposizione a chemioterapici antiblastici e sorveglianza sanitaria . ASL Viterbo. Gregis F. Controlli ambientali e biologici; la sorveglianza sanitaria . Ospedali riuniti di Bergamo. Merler E, Villa L, Lucchini R. Effetti patologici causati da chemioterapici antiblastici nei lavoratori addetti alla loro produzione, preparazione o somministrazione. Med Lav 1996; 87, 3; 207-221 Federico M, Artioli M E, Rashid I,Cirilli C, Fracca A, Maiorana A, De Girolamo G. I tumori in provincia di Modena nel 2001 . Associazione Angela Serra per la Ricerca sul Cancro, Modena, nov 2003. Impact categories MRL i for the ciclophosphamide P i Carcinogens MRL 1 = indefinite value P 1 =1/10cases* Cardiotoxicity MRL 2 =7g/m 2 every day for 3 months=630g/m 2 P 2 =1/2,38cases Infertility MRL 3 =6mg/m 2 every day for 12 weeks=504mg/m 2 P 3 =3/4cases Impact cat. General pathology Specific pathology dr YLD mr YLL Carcinogens Cancer Leukaemia 0,7 1year 1 17 years 0,5 2years 0 0 Tumor to the blister 0,7 1year 1 19,5years 0,5 2 years 0 0 Cardiotoxicit y Cardiotoxicity Haemorrhagic myocarditis Effusion of pericardium 0,6 14days 1 25 years Espansive myocardiopathy 0,3 25years 0 0 Infertility Infertility Chronic 0,24 10years 0 0 Temporary 0,12 2 years 0 0 YLL dr YLD YLL dr YLD mr YLL dr YLD DALY * ) 1 * ( ) * ( ) * ( ) * ( )) ( ) (( 1 i i i i i i n i p mr YLL p dr YLD DALY case years DALY 51 , 1 1 case years DALY 7 , 4 2 case years DALY 26 , 1 3 mg years E Fc 13 4 , 5 1 mg years E Fc 15 8 2 mg years E Fc 13 7 , 3 3 2. Results: factors of characterization We calculate the three factors of characterization like product between the Incidence factor and the number of DALY: In order to make to take part the limit value concept (MRL) on the factor of characterization, the operator must insert the values that are advanced to the damage threshold for every impact category.
-
Upload
silvia-butler -
Category
Documents
-
view
215 -
download
2
Transcript of 1. Materials and methods 1.1 Fate Analysis The value of the fate factor is given from the...
1. Materials and methods
1.1 Fate Analysis
The value of the fate factor is given from the relationship between the concentration and the emission, and remains the same one for whichever damage category.
Where S is the area immediately contaminated because of the substance dispersion Q tot, V is the volume of the room and n is the air exchange rate that is 1h-1=24gg-1. From information of the article of Gregis, the probability Pc that an amount of ciclophosphamide present in the room comes breathed from the nurse during its every day activity, is given from the relationship between the amount of substance in the urine of nurse and Q tot.
1.2 Effect Analysis
After the definition of the fate factor, it must be calculated the damage threshold (SD) of the ciclophosphamide, defined from the relationship between MRL (Minimal Risk Level), that is the level beyond to which the dose becomes unacceptable for the organism, and P i, that is the probability that an individual contracts one disease if exposed to that amount of substance. Therefore we calculate the damage threshold:
Unlike the fate factor that remains the same, the damage threshold (SD) will have various values with respect to the considered impact category. Table 1 contains the values of MRL i and Pi for the ciclophosphamide for every impact category:
Table 1. * values of our elaboration
The absence of a limit value beyond which the ciclophosphamide becomes cancerogenous and can induce in the organism the formation of secondary tumors, derives from the genotoxicity of the drug in examination. A cancerogenous genotoxic takes part directly on the cellular genome with a mechanism of action of stocastic type, for which a limit dose couldn’t exist. But, like objet of our study, we have the requirement to define a MRL1 value, without which it is not possible to calculate the threshold of damage SD and the factor of characterization for the impact category Carcinogens. We consider like dose threshold of the ciclophosphamide for the category Carcinogens, the medium value of the every day therapy, that it is of 6mg/kg.
The value of the damage threshold for the three impact categories becomes:
The reciprocal of the damage threshold is the risk unit (UR). For the Ecoindicator99 method, the unit risk factor for inhalation is a valuation of the probability that an average individual will develop cancer when exposed to a pollution in an environment concentration of one microgram per cubic meter for the individual’s life (70 years). Various, in our study we have replaced to the constant amount of 1mg/m3, the concentration limit MRL, that is the value above which one can be had disease, during one working life of 40 years. The innovation resides in the limit concept: consideration that contrasts with the directed proportionality between the amount of substance and the probability of one disease.
Pc: probability that the ciclophosphamide dispersed in the atmosphere comes absorbed from the nurse;
Pi: probability that, in the case in which the ciclophosphamide comes absorbed, this provokes someone disease.
Calculating the unit risk for the three impact categories, Carcinogens, Cardiotoxicity and Infertility, we obtained the following values:
After the obtainment of the values of the unit risk for every impact category, we obtain the effect factor E (with i=1,..,3) multiplying URi for the population density pd. The population density does not correspond to that one of the Ecoindicator99 method. The term of reference in order to determine pd is the area on which calculate the concentration c: in our case, we consider the surface of the druggist laboratory hospital worker, that is 8 m2.
when
Now, we can calculate the Effect factor for the three impact categories:
The incidence factor per mg of emission, is given from the product between the Fate factor and the Effect factor, that is:
Damage analysis on the operator because of the emission of ciclophosphamide with LCA
method
IntroductionOn demand of the pharmacy unit of the hospital of Correggio (Reggio Emilia), it has been attempted to quantify the damage that can endure a nurse if exposed daily one antiblastic drug amount, the ciclophosphamide, that is dispersed in the surrounding atmosphere during its phase of preparation. But the ciclophosphamide, even if it is a drug of which is assessed the carcinogens by the medical community, it does not appear among the present substances in the used methodologies (Ecoindicator99, EPS2000, Edip 96): this why the three methods consider only those substances that have values of emission that refer to the entire European or world-wide surface. In our case, the surface is extremely reduced: 8m 2 of the room in which the drug is dosed for the supply. Therefore, after to have defined in the new method ENEA-Method 2004 three new impact categories (Carcinogens, Cardiotoxicity, Infertility), in which the ciclophosphamide appears like only substance, we must determine the three factors of characterization for the three indicated impact categories.
32
00760m
mgg,VnS
ΕVnΕS
ΕVn
τοτQ
ΕCf
casescasesng
ng
totQurineQ
cP %303,01630488
51810
Roberto Pergreffi *, Francesca Falconi*, Germana Olivieri*, Paolo Neri***Progetto SPINNER c/o ENEA, **ENEA, PROTT-INN via Martiri di Montesole 4, 40129
Bologna, [email protected], [email protected]
cPiPiMRL
iSD
31600
33,0180616
1 mmg
mkg
kgmggg
ggkgmgMRL
casesmmgSD
3
5333331 casesm
mgSD
3
2998800002 casesm
mgSD
3
1792003
years401
iMRL
cPi
P
years40i
SD1
iUR
yearsmgcasesmEUR
3086,41 yearsmg
casesmEUR 3113,8
2 yearsmgcasesmEUR
3074,13
pdi
URi
E 2375,0
283
mpersons
mpersonspd
yearsmmgmcasesEE
23087,1
1 yearsmmgmcasesEE
23111,3
2 yearsmmgmcasesEE
23083,5
3
iEFiIF mgcasesEIF 136,3
1 mg
casesEIF 157,12
mg
casesEIF 139,23
1.3 Damage Analysis
DALY (Disability Adjusted Life Years) indicates the disability and lost life years because of one disease. A DALY is given from the sum between YLD (Years Lived Disabled, that is the number of disease years), multiplied for respective disability rate, and YLL (Years of Life Lost, that is the number of years of life lost), multiplied for mortality rate (mr= 1), and is calculated taking like reference the damage endured from an European medium citizen per Kg of issued substance.
The suffering or invalidity rates (dr-disability rate), that derive from different psychophysical conditions, derive from the necessity to quantify the level of incidence of a pathology in the life of an individual, and change inside an interval comprised between enclosed value 0, in case of “satisfactory” health, and excluded value 1, in case of serious chronic diseases. Unfortunately, the cardiovascular diseases and the tumors don't appear among the consulted data to determine dr. Therefore, we must establish a invalidity rate dr for every pathology. The values of dr must be reported to administrations of ciclophosphamide that are greater than those indicated from MRL, for every impact category; otherwise dr and mr assume value zero. The equation for the calculation of the DALY has been modified inserting the probability p. This modification to the Ecoindicator99 method, derives from the necessity to differentiate, inside a same impact category, specific pathologies, on the base of the probability that they have to manifest itself. If in the Ecoindicator99 method to every generic pathology corresponds a specific pathology, in our study this relationship is not respected. Therefore it is had:
We reassume in the table 2 the obtained results in the our study, that are necessary in order to calculate the DALY for every impact category :
Table 2.We can determine the number of disability or lost life years, for every impact category:
3. Conclusions: LCA of nurse’s risk because of the ciclophosphamideWith the LCA method, we calculated the damage that the nurse suffers if he gets the amount of ciclophosphamide corrisponding to the maximum value of damage threshold.
The Figs.1 and 2 show the studied process and the results respectively.
SimaPro 5.0 Processes Date: 29/10/2004 Project: Antiblastic drug
Emissions to air
ciclofosfamide-cg (>267mg/m2) 630000 0 0 mg emission of ciclophsphamide (cg: carcinogens) in the working life of the nurse(40 years)
ciclofosfamide-ct (>630gr/m2) 630000 0 0 mg emission of ciclophsphamide (ct: cardiotoxicity) in the working life of the nurse
ciclofosfamide-if (>504mg/m2) 630000 0 0 mg emission of ciclophsphamide (if: infertility) in the working life of the nurse
SimaPro 5.0 LCIA Profile Date: 29/10/2004 Project: Antiblastic drug Method: ENEA Method 2004 / Italia 2004 I/EValue: Impact indicatorPer impact category: Yes Impact category Unit Total P_HospitalInfertilityDALY 2,33E-7 2,33E-7Cardiotoxicity DALY 5,04E-9 5,04E-9
Carcinogens DALY 3,4E-7 3,4E-7
4. Main References
Benvenuto GB, La Vecchia L, Morandi P, Ruffini P, Mezzena G. Analisi della cardiotossicità da ciclofosfamide ad alte dosi mediante monitoraggio elettrocardiografico, ecocardiografico, e della troponina I in pazienti con tumori alla mammella. Ital Heart J nov. 2000; suppl vol 1: 1457-63.
Mattei I. Esposizione a chemioterapici antiblastici e sorveglianza sanitaria. ASL Viterbo.
Gregis F. Controlli ambientali e biologici; la sorveglianza sanitaria. Ospedali riuniti di Bergamo.
Merler E, Villa L, Lucchini R. Effetti patologici causati da chemioterapici antiblastici nei lavoratori addetti alla loro produzione, preparazione o somministrazione. Med Lav 1996; 87, 3; 207-221
Federico M, Artioli M E, Rashid I,Cirilli C, Fracca A, Maiorana A, De Girolamo G. I tumori in provincia di Modena nel 2001. Associazione Angela Serra per la Ricerca sul Cancro, Modena, nov 2003.
Impact categories MRLi for the ciclophosphamide Pi
Carcinogens MRL1= indefinite value P1=1/10cases*
Cardiotoxicity MRL2=7g/m2 every day for 3 months=630g/m2 P2=1/2,38cases
Infertility MRL3=6mg/m2 every day for 12 weeks=504mg/m2 P3=3/4cases
Impact cat. General pathology Specific pathology dr YLD mr YLL
Carcinogens Cancer
Leukaemia
0,7 1year 1 17 years
0,5 2years 0 0
Tumor to the blister
0,7 1year 1 19,5years
0,5 2 years 0 0
Cardiotoxicity Cardiotoxicity
Haemorrhagic myocarditis Effusion of pericardium 0,6 14days 1 25 years
Espansive myocardiopathy 0,3 25years 0 0
Infertility Infertility
Chronic 0,24 10years 0 0
Temporary 0,12 2 years 0 0
YLLdrYLDYLLdrYLDmrYLLdrYLDDALY *)1*()*()*()*(
))()((1
iiiiii
n
i
pmrYLLpdrYLDDALY
case
yearsDALY 51,11
case
yearsDALY 7,42
case
yearsDALY 26,13
mg
yearsEFc 134,51
mg
yearsEFc 1582 mg
yearsEFc 137,33
2. Results: factors of characterizationWe calculate the three factors of characterization like product between the Incidence factor and the number of DALY:
In order to make to take part the limit value concept (MRL) on the factor of characterization, the operator must insert the values that are advanced to the damage threshold for every impact category.
