Document rerGnM9Z5gvQwGyN379984o2e

civo institutes tno netnenancs organization lor aooited scientific research OX) division for nutrition and food research tno p.o. box 360 3700 AJ zeist netherfands Reporc No. V 83.285/291099 LIFESPAN OR a CARCINOGENICITY STUDY OF VIN!X CHLORIDE IN RATS (Final report) Authors Dr H.P. Til H.R. Immel Dr V.J. Feron Ac the request >f Verband Kunststofferzeugende Industrie E.V., Frankfurt am Main, 3.R.D. Project number B 79-1099 Start of the sttldy August 21, 1979 Termination of the study: June 29, 1982 Study director : Dr H.P. Til Study supervisor : Dr V.J. Feron Approved by : Dr A.P. de Groot Date : September, 1983 SPI-01010 T V 83.285 CONTENTS SUMMARY 1. INTRODUCTION MATERIAL AND METHODS 2.1 Materials 2.2 Preparation and administration of the diets 2.3 Animals and housing 2.4 Identification of Che test system 2.3 Experimental conduct 2.6 Statistical analysis 2.7 Contributors 2.8 Deviations from the protocol 3. RESULTS 3.1 Analysis of VCM in the diets 3.2 Levels of VCM in the faeces 3.3 Actual oral exposure levels of VCM 3.4 Symptomatology and survival 3.5 Body weights 3.6 Food intake 3.7 Haematology 3.8 Glutathione levels of the livnr 3.9 Pathology DISCUSSION CONCLUSIONS I page 8 9 10 11 12 17 18 18 19 19 19 19 20 21 21 22 22 22 25 27 SPI-01011 V 83.285 CONTENTS 6. REFERENCES 7. AUTHENTICATION 3. RETENTION OF RECORDS AND SPECIMENS STATEMENT OF GLP COMPLIANCE TABLES FIGURES ANNEXES page 28 30 31 32 33 70 71 3 SPl-01012 T' V 33.285 SUMMARY 1. the oral carcinogenicity of vL nyl chloride monomer (VCM) was examined in a lifespan study (149 week.; ) with five groups of Wistar rats, each consisting of 100 males and 100 females, except for the top-dose group which comprised 50 males and 00 females. VCM was administered by in corporating polyvinyl chloridf (PVC) powder with a high VCM concent into the diet. The diet was piovided daily for a period of 4 consecu tive hours, whereas food was withdrawn during the other 20 hours. The use of this way of oral VCM administration resulted in the following exposure levels: 0 (control), 0.014, 0.13 and 1.3 mg VCM/kg body weight/day. An extra control group of 100 rats/sex was housed in a separate room. Additional satellite groups of 10 male and 10 female rats, each recelving the same treatment as the main groups were used for determinations of glutathione levels Ln the liver after 9 and 18 months. Observations were made of general appearance mortality, growth, food intake, thrombocyte count, prorhrombin time, glutathione levels in the liver, gross pathology and microscopic pathology of the liver and of all grossly visible tumours or presumable tumours in the abdominal cavity, the glands of Zymbal and the mammary glands. 2. General health, behaviour, bod weight and food intake were not adversely affected by the test substance. In the second half of the expelimental period, mortality in the extra control group was higher than in all other groups. This was most prob-- ably due to a high incidence o chronic respiratory disease in the extra control group. In the fir al stage of the study, the mortality in the top-dose group was slightlj higher than in the lower dose groups and the controls. 4. Thrombocyte count, prochrombin time and liver glutathione levels did not show treatment-related diffle rences among the groups. SPI-01013 T V 83.285 -J- 5. A clearly higher incidence o grossly visible, tumourous, liver nodules was found In boch males and females of the top-dose group chan in any of the ocher groups. Mori over, in females of the cop-dose group the incidence of hepacic cyst s was considerably higher than in controls. 6. Microscopic examination of cha liver revealed increased incidences of liver-cell polymorphism, hepatic cysts, foci of cellular alteration, neoplastic nodules and hepatotellular carcinomas in the top-dose group as compared to the control griup. Moreover, a hepacic angiosarcoma was found in one male and two females of the top-dose group, whereas no such tumours were encountered in any of Che ocher groups. The number of animals bearing foci of cellular alteration in the liver was also statistically signifl cantly increased in females of the mid-dose group as compared to controls. In addition, in females but not in males, the incidence of basophilic foci of cellular alteration in the liver was statistically significantly higher in both the lovand the mid-dose group than in the control group. 7. There was no evidence of VCM-f eding affecting the incidence of abdominal mesotheliomas or the tjrpe and incidence of mammary gland tumours. Mo Zymbal gland tumour uas found. 8. It was concluded that under th conditions of the present experiment: VCM at a level of 1.3 mg/kg lody weight/day induces neoplastic and non-neoplastic changes in Che liver of rats. VCM at a level of 0.13 mg/kg body veighc/day may lead to more female rats bearing foci of cellular alteration in the liver, VCM at levels of 0.014 or O.lp mg/kg body weight/day may result in an increased incidence of basfr philic foci of cellular alteration in the liver of female rats. 0.13 mg VCM/kg body weighc/da) is a "no-observed-adverse-effectlevel" with respect to the ine uction of tumours in rats. SPI-01014 T V 33.285 9. Risk estimation based on the esults of the present rat study and caking inco account the prudence of the linear model applied and a lesser sensitivity of humans to the car i^lnogenic action of VCM in comparison with rats, indicates that the car^.cer risk of a likely maximum oral daily intake of 0.1 pg VCM per person |er day can be practically neglected. SPJ-01015 i V 83.285 LIFE-SPAN ORAL CARCINOGENICITY STUDY OF VINYL CHLORIDE IN RATS 1. INTRODUCTION From a previous life-span oral toyicity study of vinyl chloride monomer (VCM) in raCs with dose levels of 1.7, 5.0 and 14.1 mg/kg body weight/day (Feron et al., 1978; 1981), it appeared that hepatic angiosarcomas occurred at dose levels of 5.0 rng/icg body weight/day and above, while hepatocellular tumours (neoplastic nodules and carcinomas) were found at all dose levels. Zymbal gland tumo irs were found at VCM levels of 5.0 and 300 mg/kg body weight/day. Moreove there was some evidence that VCM en hanced the formation of intra-abdouinal mesotheliomas and adenocarcinomas of the mammary gland. In females o the low-dose group there was still a high incidence of liver-cell tumours, viz. 28/58. Thus, this study showed a) that VCM is a carcinogen in rat when administered orally, and b) that the "no observed-adverse-e::fect level" of VCM in rats with respect to the induction of tumours was lower than 1.7 mg/kg body weight/day. For extrapolating experimental dat to man in a reliable way the information obtained from such a test s; stem ideally should include both a 'minimum tumour-level" and a "no tumour-level". Therefore, a similar life-span oral carcinogenicity stuc y with VCM in rats was carried out, at lower dose levels, viz. nominally C 017, 0.17 and 1.7 mg VCM/kg body weight/day (actual oral exposure le vels 0.014, 0.13 and 1.3 mg VCM/ kg body weight/day) and two control groups. Based on the pathological findings of the previous long-term study, histopathological examinations in the present experiment were focused on the detection of liver lesions. Zymbal gland tumours, mammary gland carcinomas and abdominal mesothellomas. A proposal for the prese nt study - dated 19-02-1979 - was accepted by the sponsor. The presen t experiment and results are described in this report. SPI-01016 V 33.285 2. MATERIAL AND METHODS 3- 2.1 Macerlals Vinyl chloride monomer (VCM), from Akzo Zout Chetaie, Rotterdam, The Netherlands. Physical chemical constants: MW 62.50; m.p. -153.8 *C; b.p -13.37 *C; density * 0.9106; 1.3700. The product (colourless, clear, free of suspended matter) was delivered in pressurized stainless-steel cylinders, and was specified by the supplier as: Vinyl chloride monomer 3- 99.97 wt X min.; acetylene i 2 pl/1 (gas); mono-vinylacetylene ( 15 ;il/l (ga:); 1,3-butandiene 10 pl/1 (gas); methyl chloride 75 pljl (gas); e chyl chloride 4. 50 pl/l (gas); chloro- prene 4 1 )il/l (gas); 1,1-dichlorcethane 4 1 pl/l (gas); 1,2-dichloroeth- ane < 20 jil/1 (gas); acetaldehyde 4 5 mg/kg; hydrochloric acid 1 mg/kg; iron ^ 0.5 mg/kg; water 4 100 mg/kg; evaporation residue 4 10 mg/kg. PVC-powder. commercial name Carina S 65-02, was supplied by Shell Nederland Chemie, Pernis, The Nethsrlands, in closed steel barrels. The particle size distribution (by weisht), specified by the supplier, was: 0.1 X max. > 300 jan; 4 X max. > 20) pm; 90 7. max. > 88 pm; 95 X max. 40 pm. The remaining part of a batch of 500 kg PVC-powder (VCM content 3 ppm) received on January 13, 1977 from Shell, which had been partly used in the previous study (Feron ec al., 1978), was used. Part of this PVC-powder was freed irom residual VCM by keeping it in layers of 4 to 6 cm thick in a vaciun oven at 60 C for a period of 3 to 4 days. The so treated PVC-powder (VCM content less than 0.2 ppm) was used for control purposes. An amount of about 50 kg PVC powder was mixed with a calculated amount of the liquid VCM in a closed steel barrel to raise the VCM content of the PVC-powder to approximately 4600 ppn. This PVC-powder was repacked and st>red in tightly closed steel con tainers (containing about 10 kg PVC) in a freezer at -20 *C until *1 few minutes before mixing wlch each die:. SPI-01017 T V 33.235 2.2 Preparation and adminiscrat: on of the diets 9 Preparation and administration <f the diets were done in the same way as in the previous life-span study (Feron et al., 1978). Only one distinction has to be made. In chat study the dietary levels of VCM were obtained by incorporating into t^e diets 10 Z PVC-powder with varying proportions of VCM--containing and "VCM-free" powder. In the present study, the diets were prepared ts a total concentration of PVC-powder of 1 Z only. The proportions of PVC-powder with or without VCM for each of the diets are specified below: group PVC-powder ii. the diet (Z) PVC-powder cox PVC-powder talning about without 4600 ppm VCM VCM1) control group low-dose group mid-dose group top-dose group extra control group 0 0.01 0.1 1 0 1 0.99 0.9 0 1 1) PVC-powder freed from VCM. The VCM-content was lower than 0.2 ppm Diets were prepared daily - by mi::ing appropriate amounts of PVC-powder (with or without VCM) with the Ins tituce's rat stock diet - just prior to offering the diets to the rats. Tt e composition of the stock diet is presented in Annex 1. The level of nutrients and contaminants in the stock diet are determined twice a year. The contaminants determined are tabulated, together with det' ctior limits and tentative maxima in Annex 2. Actual levels in batches produced on January 24, 1980, September 9, 1980, February 27, 1981, September 9, 1981 and February 9, 1982 are given in Annexes 3 to 7 (nutrients ) and in Annexes 8 to 12 (contaminants), SPI-01018 T V 33.285 - 10 - As In the previous study, the po wdered diets were available to the rats each day for a period of four hou rs (generally between 10.00 a.m. and 02.00 p.m.), in such quantities i:hat the animals did not consume all the feed. At the end of the four-hour feeding period the feeders were removed from the cages and the remainder of the diets was destroyed. The rats had constant access to to ttled tap water. The contaminants in the drinking water which are dete rmined twice a year, are given in Annex 13. The actual levels determined in November--December 1979, January--April 1980, September-November 1980, Mat ch--May 1981, September-November 1981 and January-March 1982 are given in Annexes 14 to 19. 2.3 Animals and housing Five hundred and twenty-five male and 525 female, SPF-bred, weanling rats (Cpb:WU; Wistar random) were obtained from the Central Institute for the Breeding of Laboratory Animals TNO, Zelst, The Netherlands. The animals arrived on August 14, 1979, when :hey were about 25 days old. The body weight range was 38-71 g for males and 42-66 g for females. Upon arrival, the animals were checked for overt signs of ill health and anomalies. One rat showing hydroci phalus, one rat with closed eyes and two rats with a dirty yellow fur rere discarded. The healthy animals were allocated to five main groups by t computer randomisation program. Four of the groups, viz. the control gioup, the low- and mid-dose group and the extra control group, each consisted of 100 males and 100 females. The top--dose group consisted of 50 males and 50 females. To each dietary group a satellite group, comprisirg 10 males and 10 females each, was attached. The rats of the satellite groups, which received the same diets as the rats of the corresponding nain groups, were killed for determinations of glutathione levels in che liver, half of the animals when they had been on their diets for nine months and the remaining half after an experimental period of 18 months. The rats which were not allocated to the main or satellite groups were kept in reserve for a period of four weeks. One female rat of the extra control group showing epileptic fits had to be exchanged for a reserve two days after the start of the study. None of the other reserved were used. SPI-01019 T V 83.285 11 The rats were housed under convfc ntional conditions, five rats per sex per cage, In suspended stainless st sel cages (17 x 44 x 32 cm), fitted wich wire mesh floors and fronts. Animals which were in bad condit ion were housed individually in separate cages until they died or until t hey were killed because their condition was so bad that they were not ejpected to last out the night, (or, when observed on Friday, the weekend). If the condition of the singly housed rats improved they were returned] to their original cage. The male rats of the control-, 1lbw--, mid- and top-dose groups were housed in one room, the females of thess|e groups in a second room and the males and females of the extra control group in a third room. The rooms were ventilated wich about 10 air cha iges per hour. The temperature was kept at 23+1 C, the relative huaidf ty was 40--80 Z and a 12 hour light/dark cycle was maintained (light from 06.00 a.m. till 06.00 p.m.). After an acclimatisation period of 7 days the animals were placed on the test diets for four hours a day during the entire test period. During a period of 3 days, prior to the start of the experiment, the rats received stock diet without PVC for four to six hours each day. This was done to adapt the animals to the daily feeding-period of four hours Drinking water was supplied in gJ ass bottles, which were filled daily with fresh tap water, except for the weekend, and cleaned once weekly. 2.4 Identification of the test system The individual animals were identified in the following way. Each group of rats (the control, low--dose, mLd--dose,' cop-dose and extra control group) was fitted with a lecter aid colour code. A table showing the group letter, colour code, exposure level and number of animals is given on the next pige. SPI-01020 v 33.: 85 - 12 - group letter colour code A white B . blue C green D red E brown nominal actual exposure leve. s exposure levels (mg VCM/kg b.v./day) 00 0.017 0.014 0.17 0.13 1.7 1.3 00 number of rats main groups satellice group-- study no. 125 males females 100 100 study no . 126 males females 10 10 100 100 10 10 100 100 10 10 50 50 10 10 100 100 10 10 Each rat was identified by a si; digit computer reference number, which was even for males and odd for females. Within each subgroup of 10 rats, each rat was individually identified by sex and one out of 10 different V-shaped earmarks according to tie following code: Z zero one right R2 * two right one left L, " two left R1L1 R1L2 R2L1 R2L2 me right plus one left me right plus two left :wo right plus one left '.wo right plus two left Ihree right See also the cross reference listing (Annexes 20 and 21). Each cage was provided with a coloured card showing the computer reference number range, the earmark, ra nge, the cage number, the group letter and the study number. 2.5 Experimental conduct The experiment (main and satellitt groups) was started on August 21, 1979. Half of the rats of the satsHite groups (assay no. 126) was killed on May 20 or 22, 1980 and the remaining half on February 26 or 27, 1981 for determinations of glutathione in the liver. The final autopsy of the rats In the main groups (assay no. 125) was carried out on June 24 to 29, 1982, when about 80 Z of the contrsl-, low-dose and mid-dose rats had died. The following determinations were nade : SPI-01021 T V 83.285 a' Analysis of VCM In the diets - 13 - The VCM concenc of freshly prepar ed diets was generally determined once every fortnight. During the cours e of the study, 72 determinations for each dose level were carried out At the same time the VCM concenc of Che PVC-powder was determined. The rate of evaporation of VCM f rom the diets was determined by measuring the VCM concenc of the diets at (he beginning of the feeding-period and after 1 hour and after 2, 3 and hours. The diet samples to be analysed were taken at random from the feeders. In this way samples of each of the test diets were taken in week 3, 12, 27, 56, 79, 105 and 132, and were analysed for their VCM content. A t the same time samples from the control diets were taken at the beginning of the feeding-period only and also analysed. The analyses were carried out by leans of gas-liquid chromatography according to a method described by ''eron et al. (1975). b) Analysis of VCM in the faeces Freshly produced faeces from 5 rai s of each dietary group were collected 2U hours after the start of Che feeding-period at about 10.00 a.m. in week 6, 28, 52, 80 and 106. Fresh faeces was obtained by squeezing the lower part of a rat's abdomen. The droppings were weighed, submerged in 10 ml ethylacetate, and stored at 4 *C in j closed vessel until analysis of the supernatant liquid by gas chromatography. c) Calculation of the actual oral Intake and oral exposure levels of VCM The amount of food eaten by the ra :s of each test group (g/kg body veighc/day) was calculated for mal^ s and females separately from the grand averages of body weight (ta e 7') and food Intake (table 9") of each test group over the whole experimental period. SPI-01022 T V 83.285 -li the VCM intake (mg/kg body weight/day) was calculated from the rate of evaporation of VCM from the diets (table 2) and the rate of overall food consumption over the four-hour f eding-period for males and females (table 10). Both the rate of eva >oration and the rate of food Intake were assumed to be linear within each hour of the feeding-period. The actual VCM intake for each group during each of these four periods was calculated by multiplying the ami unt of food eaten during a one-hour period by the average VCM conten of the food eaten in that period. The total actual VCM intake was obca; ned by adding the VCM intakes during the four one-hour periods of the feecing-period To obtain the actual oral exposui e levels of VCM, the actual VCM intakes were corrected for the VCM excreted with the faeces. For that purpose, the faeces production (g/kg body weight/day) was calculated based on an average of 36 g wet faeces/100 g food consumed. The amount of VCM in the wet faeces (mg/kg body weight/day) was calculated by multiplying the amount of faeces produced/kg body weight with the VCM content measured in the faeces (table 3). The amount >f VCM excreted with the faeces, ex pressed in mg VCM/kg body weight/lay, was substracted from the actual oral intake of VCM (also expressed in mg VCM/kg body weight/day) to find the actual oral exposure level of VCM. d) Clinical signs (main groups) The animals were observed daily a r d carefully examined for signs of illness and tumours once every two v< ks. All signs of ill-health or toxicity with any changes in behaviou r were recorded, together with the progression or regression of such ab rmalities, as well as mortality and the time of onset, dimensions and location of palpable tumours. e) Body weight (main and satellite groups) The weight of each animal was reco :ded when the administration of the test substance was started and fur her In week 2 and 4 and once every four weeks thereafter. From these ndividual figures the mean body weight of the animals of each group was calculated. SPI-01023 T V 33.285 f) Food consumption; amount and ate (main groups) 15 - The food consumption was measured in 20 animals/sex/group, in week 1, 2, 3 and 4, 11 and 12, 23 and 24, 3. i and 36, 47 and 48, 59 and 60, 73 and 74, 85 and 86, 97 and 98, 109 anc 110 and 121 and 122. The rate of food consumption was determined by weighing the feeders initially and after periods of 1 hour, 2 hours, 3 hours and 4 hours. This was done for each of the diet grc ups on one day in week 4, 12, 25, 38, 52, 64, 77, 90, 103, 116 and 129 The number of rats involved in these determinations was 20/sex/group. g) Haematology (satellite groups) Samples of blood were collected from the tip of the tail of 10 rats/sex/ group on days 94 and 185 and of f|lve rats/sex/group on day 367. All blood samples were examined for the foltl owing parameters. - thrombocyte count, by means of :he Sysmex Platelet Counter PI 110 using the manual of Toa Medical Elect onics Co., Ltd., Japan - prothrombin time using Normo-te it reagents from Nyegaard & Co. As, Oslo, Norway (Ovren, 1959). h) Glutathione in the liver (sate.. lite group) In week 40 and 80, five rats/sex/j; roup were killed by decapitation. The livers were quickly removed and c cjoled to 0 C and cut into two, about equal, pieces; both were weighed nd stored in a freezer at -20 C until analysis. After thawing, each samil 1 e was homogenised in ice-cold 0.1 M EDTA(Na2) solution. A part of the homogenates was centrifuged at 2800 rpm for 5 minutes. The non-proteir bound sulfhydryl ('glutathione') content of the supernatants was dete ijmined with 5,5'-dithiobis-(2-nitrobenzoic acid) by means of an AutoAn sly ser. SPI-01024 V 33.285 i) Pathology 16 All males still alive In week 14V (June 24 and 25, 1982) and all females in week 150 (June 28 and 29, 198: ) were killed by decapitation, autopsied and subjected to a careful gross examination. At that time a mortality of about 80 X had been reached in tl e control, low- and mid-dose groups. A thorough autopsy was also performe d on rats found dead or killed in ex treals. All superficial tissues, including the urogenital orifices and tail, each pinna, eye and external auditory meatus, were examined visually and by palpation for distortion, swelling or evidence of tumour formation; simi lar attention was given to the mammary tracts and subcutaneous struc- cavity and tongue were then examined, and the cranial roof removed to allow observation of the brain, pituitary gland and cranial nerves. After vsntral midline incision and skin reflec tion, all subcutaneous tissues were examined, including regional lymph nodes, mammary and thyroid/parathfroid glands. The condition of the tho racic viscera was noted, and atteition was given to the thymus, lymph nodes and heart. The abdominal viscera were examin'd before and after removal. The lungs were removed and all pleural surf ices examined. The kidneys were incised and exam.ned. Any abnormalities in the appearance and size of the gonads, adrenals, uterus, intra--abdominal lymph nod is and accessory reproductive organs were recorded. Any lesion suggest .ve of neoplasia was noted, including details of location, size and mul :iplicity. Any evidence of adhesion or possible invasion to adjacent structures was noted. Samples of the following tissues and organs of all animals were preserved in 4 X aqueous neutral phosphate--huffered formaldehyde solution: adrenals aorta ovaries pancreas axillary lymph nodes brain parotid jalivary glands preputia: glands caecum cervix coagulating glands pituitary prostate seminal Resides SPI-01025 V 33.285 colon skelc tal muscle duodenum skin epididymides spinal cord exorbital lachrymal glands spleen eyes sternum (with bone marrow) sciatic nerve stoma :h heart submaciliary salivary glands ileum jejunum kidneys subli igual salivary glands teste ; thymu ( liver thyro. d lungs trachea mammary glands urinary bladder mesenteric lymph nodes uteruc nose ZymbaJ glands oesophagus all gt oss lesions Tissues required for microscopic examination were embedded in paraffin wax, sectioned at 5 pm and stained with haematoxylln and eosin. Histopathology was restricted to the liver, all grossly visible tumours or presumable tumours in the abdominal cavity, the glands of Zymbal, and the mammary glands. As to the liver, of each rat three liver pieces, each taken from a different lobe, were studied; these pieces were always taken from the same three lobes at about the same sites; in addition sections were prepared from liver tissue showing gross changes 2.6 Statistical analysis SP1-01026 Data on body weights were subjectec to one~vay analysis of (co-)variance, followed by Dunnett's multiple comidarlson test. Thrombocyte counts and prochrombln time values were analysed by Che Mann Whitney U--test. Levels of glutathione in the liver were evaluated by che Student c-cest. Data on mortality and microscopical observations were analysed by the Fisher exact probability test. Grossly visible masses were evaluat ed by the Chi square test. V 83.285 2.7 Contributors Major contributions to this studf were made by: Animal handling and: Ms. M.M. Anpringa diet preparation J.M. Blom Ms. A. Dijkitra Ms. G.G.M. I'leer Ms. A.A. vad Tuyl D.C. Veldhujsen Diet analysis A. Schouten Clinical chemistry Dr H.E. Falke J.F. Catsburg Biochemistry Dr D.C. Leeguater Histotechnique Ms. M.T. v ili jswi jk Ms. J. Wisma Ms. A.P.M. v Tuyl-Fonville Ms. N. Hagem syer Pathology H.R. Immel Dr V.J. Feroh Study director Dr H.P. Til Study supervisor Dr V.J. Feroi 18 2.8 Deviations from the protocol - Ac the request of the sponsor, t he glutathione determinations in the liver were carried out after 9 alnd 18 months instead of after 6, 12 and 24 months. - Prothrombin time and thrombocyte count in rats of the satellite groups after 24 moaths could not be carried out, because all rats of the sat ellite group had already been killed before that time. SPI-01027 V 53.285 3. RESULTS 19 3.1 Analysis of VCM in the diecs cables 1 and 2) The average VCM concent of freshly prepared test diets appeared to be 0.49, 4.49 and 44.1 ppm for the 1 olw-, mid- and cop-dose group, respeccively (table 1). The VCM content In all three test diets decreased with time during the four-hour feeding-period (table 2) . The greatest losses were observed during the first hour. Proportions Lly, the losses of VCM were virtually che same in all three test diets a : the corresponding points of time durlng the four--hour period. On averafe e, che cumulative losses were 22, 30, 39 and 38 X after 1, 2, 3 and 4 hon rs, respectively. 3.2 Levels of VCM in che faeces (table 3) The VCM content of the faeces incr < ased with increasing dietary levels of VCM. No appreciable differences in VCM content of the faeces were found within one particular test group, the average amount of VCM found in the faeces expressed as percentage of t|he actual oral VCM incake, was found to be 23.5, 25.9 and 23.9 X for the low--, mid--, and top-dose groups, respectively. 3.3 Actual oral exposure levels of VCM (table 4) SPI-01028 The VCM content of the freshly prep ired test diets (table 1) formed the basis for calculating the average V 2M content of the various diets. Since the loss of VCM from the diet3 duri lg che four-hour feeding-period (table 2), the rate of food intake (cable .0) and the VCM content of the faeces (table 3) were known, the actual oral exposure levels of VCM for each group could be calculated (see secc on 2.5). They were found to be 0.014, 0.13 and 1.3 mg VCM/kg body weight/<|ay for the low-, mid-, and top-dose groups, respectively (cable 4). V 83.285 20 When the accual oral Intake of VCM was expressed as percentage of the theoretical intake, the vain es found were 81.5, 81.2 and 81.3 Z for males, and 80.1, 79.8 and 79 8 2 for females of the low-, mid- and topdose groups, respectively, The overall average for males and females of the various test groups was calculated to be 80.6 2. This percentage was in good agreement with the SO 2 found in the previous life-span study using much higher dietary Li vels of VCM (Feron et al., 1978; 1981). 3.4 Symptomatology and surv: val (tables 5 and 6) There were no overt signs oJ reaction to treatment with VCM. The behav iour of the rats during the first 18 months of the experiment was unre markable. After 18 months ageing symptoms developed in all groups and the number of unthrifty rats increased, more rapidly in males than in fe males. The poor condition started with a humpbacked position and slight emaciation, followed by dyspnoea, pale eyes, lethargy, filthiness and in many cases severe emaciation. Randomly distributed major asnormallties due to ageing included maloc clusion of incisors, staired coats, a bloody discharge around nostrils and eyes, wet stools, focal clopecia, focal dermatitis, paresis of hind legs, loss of one or both eyss and white opaque cornea. SPI-01029 Macroscopically visible or palpable masses occurred in all groups. The total number of racs which showed such a lesion at any time, together with the number of masses is given in* table 5. In females both the inci dence and the total number oi these gross lesions was considerably higher than in males. Taking into account that the top-dose group comprised only 50 rats of each sex, the toccl number of masses in females of the topdose group was higher than ir the other groups. This remarkable differ ence appeared to be caused by the high number of top-dose females with liver cysts (see also cables 13 and 14), which are easily decected by palpation of the abdomen. In the extra control group thle total number and che incidence of masses was relatively low as compare! to the other groups, the control group included. The low figures for the extra control group are undoubtedly related to the relatively higi and early mortality in this group, giving fewer animals of this extra c Jncrol group che time to develop lesions 1 H soa. T V 83.285 >1 _ The cumulative mortality is given in table 6. Up to week 68 mortality was very low. Thereafter, mortality gradually Increased, more quickly in the extra control group chan in the scher groups. The extra control animals which were housed in a separace room - were much more severely affected by chronic respiratory disease than the animals in the ocher groups (see also 3.9.1). This phenomenon undoubtedly explains the higher and earlier mortality in che extra coatrol gioup. 3-5 Body weights (tables 7 and 8; figures 1 and 2) In the three test groups, the mean body weights were generally comparable to those of the controls. Some isolated changes were observed, but there was no evidence of a dose-related response. In the extra control group mean b>dy weights were statistically significantly decreased throughout the s :udy in males and from day 674 and onwards in females as compared to t le standard control group. In males the lower body weights were accompanl d by lower Intake of food (see 3.6). Since the extra controls were housed in a separate room, the lower body weights and food consumption mighi be due to unknown differences in en vironmental condition (see also 3.4), although this separate room was conditioned in the same way as the other rooms. 3.6 Food Intake (tables 9 and 10) Food intake showed wide variations among the different weighings within one group. Theru was, however, no vidence chat food Intake was affected by VCM-feeding (table 9). Males of the extra concrol group had a lower food Intake than che other groups Iron week 3 onward. No appreciable variations were enc iiuntered in the rate of food consumpcion in the various groups (table 0). Females consumed their food slightly less quickly chan males. SPI-01030 T V 83.285 3.' Haematology (cable 11) Thrombocyte count did not show d >se-relaced differences between the test groups and the controls. The slij; ht, though statistically significant increase in females of the top-d <|>se group on day 366 was not apparent when compared to the extra cont r< Is. Prothrombin time of females of t e cop-dose group was slightly increased after 3 and 6 months. However, p i o thrombin time of females of che extra control group was even higher at che same stages. No differences between the groups occurred after a feed! ng-period of 12 months. 3.8 Glutathione levels of the liver (cable 12) There were no significant differe aces in liver glutathione levels between the various test groups and the c ontrols, either after 9 or 18 months. 3.9 Pathology 3.9.1 Gross examination (table 13 The incidence of liver nodules suspected of being tumours was higher in males and females of the top-dose groups than in controls or lower dose animals. Most of these tumourous nasses were small (diameter up to 1 cm), solid and pale or had the same colour as che adjacent liver tissue; some were large (diameter 2 to A cm), soft or firm and occasionally slightly haemorrhagic. Cysts in the liver <f old rats, particularly in females, is a common finding in the strain of racs used. However, the incidence of such cysts was much higher in females of the top-dose group than in females of che ocher groups, the c ontrol group included. The cysts varied widely in size, were often multiple and generally contained a turbid, watery liquid. There was no evidence Chat any of the ocher gross lesions observed and summarised in table 13 were related to che administration of VCM. SPI-01031 V 83.285 - T| . Severe chronic respiratory diseas (CRD) often accompanied by focal emphysema (spongy lungs) was seen much more frequently in the extra concrol group than in the ocher g oups. Many of the rats affected by advanced CRD lost weight and emacia ed before they died or were killed in extremis. Other conspicuous findings in anicials of the extra control group were the high Incidences of bilateral testicular atrophy and atrophy of the coagulating glands and seminal vesicles. Atrophy of the testes and of the secondary sexual glands were ofter seen in the same animals, but these lesions also occurred separately. Moreover, a relatively high number of females of this group showed protrusion of the eye balls; this was almost exclusively observed in severely enaciated rats. 3.9.2 Microscopic examination Liver (table 14) Increased incidences of foci of cellular alteration, neoplastic nodules, hepatocellular carcinomas, liver-cell polymorphism and cysts have been observed in the top-dose group. Moreover, in the top-dose group two females and one male had developed a hepatic angiosarcoma, whereas such tumours have not been seen in any c f the other groups. Since the morphology of che hepatocellular 1 sions was essentially the same as that of the liver lesions described in full detail in our previous report on the long-term effects of oral administration of VCM in rats (Feron et al., 1981), no further discripcion of these alterations is presented in this report. The morphology of VCM-induced hepatic angiosarcomas has also been described in a previous report (Spit et al., 1981). Table 14 also shows that in females, but not in males, of both the lowand mid--dose group the incidence of basophilic foci of cellular alter ation was significantly higher than in controls. In addition, in the id--dose group the number of female > bearing foci of cellular alteration was statistically significantly higiier than in che control group. SPI-01032 V 83.285 - iu There was no evidence chac any o f Che ocher hepaclc lesions observed, was related to the feeding of VCM. lere were a few scaciscically significant differences between test groups ind the control group, but this concerned decreases in incidence in the te st groups (e.g. slight cholangiofibrosis in males), or the differences we e noc statistically significant as coinpared to the extra controls (e.g single cell necrosis in females), or there was no dose-response relat onship (e.g. foci of degenerated hepatocytes in males). As compared to controls lower incidences of several hepaclc abnormalities were found In the extra control droup. Examples of such lesions are cysts, bile duct proliferation, cholangiofibrosis and vacuolisation of periportal hepatocytes in females, and liver cell polymorphism in males. Such changes might be associated with old age and their relatively low incidences in the extra control group is most probably due to the much lower average survival time of these animals (118 weeks) in comparison with that of the controls (129 weeks). Mammary glands (table 15) The number of females bearing a m. irnmary gland tumour was considerably lower in the extra control group , tnd in the low- and mid-dose groups than in the control group. In the same groups the number of females with a mammary fibroadenoma was also lowc r than in the control group. There was no indication that the incidence Af mammary gland carcinomas increased with increasing VCM dose. Abdominal tumours (table 15) All intra-abdominal tumours found at autopsy were examined histologically. The numbers of mesothelioma s detected in rats of the different groups indicace that there was no evidence of a relationship between the administration of VCM and the dev elopment of this type of tumour. Zymbal gland tumours SPI-01033 All gross tumours in the head regip n were studied by light microscopy. No Zymbal gland tumour was found. T V 33.235 4. DISCUSSION In the present study no effects attributable to VCM were observed other than liver changes, and a highe mortality in the top-dose group as compared to the control group duri rS the last 6 to 9 monehs of the exps lmental period. The differences in mortality between the top-dose group and the control group were slight and attained a level of statistical significance only at a few points of time. This si ghtly increased mortality in the top- dose group might be due to the i icreased incidence of neoplastic and non-neoplastic liver changes in :his group. A similar adverse effect has been observed in females, but no in males, of the low-dose group (1.7 mg VCM/kg body weight/day) used in he previous long-term oral rat study with VCM (Feron et al., 1981). SPI-01034 From the previous study (Feron et al., 1981) it appeared that oral exposure to VCM at a level of 1.7 mg/kg body weight/day resulted in a series of changes in the hepatic parenchyma. These changes included an increased incidence of cellular alteration and neoplastic nodules, a few hepatocellular carcinomas, an increased incidence and degree of liver-cell polymorphism, and an increased incidence of hepatic cysts. In the present study the same type oE treatment-related liver changes were found in the top-dose group recei ring 1.3 mg VCM/kg body weight/day. In addition, one male and two female i of the top-dose group had developed a hepatic angiosarcoma; in the prev .ous experiment hepatic angiosarcomas were observed at VCM levels of 5. > mg/kg body weight/day and above but not ac the lowest exposure level of 1.7 mg/kg body weight/day. As compared to controls increased incidences of basophilic foci of hepatocellular alteration occurrec in males of the top--dose group and in females of each of the dose groups . In females the Incidence of this type of foci of cellular alteration in the liver increased with increasing dose levels. Moreover, the number of racs bearing foci of cellular alteration in the liver (all type of foci) was significantly higher in males of the top-dose group and in females of the raid- and top-dose group chan in controls. These findings s jggest a relationship between the oral exposure to VCM at levels of 0.014 and 0.13 mg/kg body weight/day and the Increased occurrence of foci of ce Llular alteration In the liver of T V 33.285 - 26 The Incidence of basophilic foci of hepatocellular alterations in females of the control group (9/98 or 9 ) was clearly lower than Che Incidence of this cype of foci In female controls used in the previous long-term oral rat study with VCM (10/57 >r 18 2; Feron et al., 1981). Similar incidences were also found in females of control groups of three ocher long-term rat studies carried otit in our Institute more or less simultaneously with the study oi Feron et al. (1981); the incidences being 11/95 or 12 2, 3/20 or 15 and 17/99 or 17 2. These data seem to indicate that the incidence of t asophilic foci (9 .1) in females of the control group of the present VCh study is unusually low, and, thus, would seem to throw doubt upon the toxicological significance of the slight increase in incidence of this type of foci of cellular alterations in the low-- and mid-dose groups. However, the incidences of basophilic foci of hepatocellular alterations in fe sales of control groups of other long-term rat studies performed Ln our Institute in the same period as the present VCM-study were: 0/20 or 0 Z, 1/20 or 5 2, 5/69 or 7 2 and 4/50 or 8 2. Compared to these f gures an incidence of 9/98 or 9 2 as found in the present group of fenale controls is not unusually low, and. thus support the suggestion that the feeding of VCM at levels of 0.014 or 0.13 mg/kg body weight/day may hive resulted in more basophilic foci of cellular alteration in the liver of female rats. The directive of the European Comnunity (EC) of January 30, 1978 (78/142/EEC) Imposes a maximum permitted llmic of 1 ppm residual VCM in finished plastic materials or artLcles intended for use in contact with foodstuffs. The same EC-directive stipulates that any migration of VCM to the food must not produce a conce itration in the food of greater than 10 ppb VCM which is or is very close to the detection limit of VCM in foodstuffs. Calculations based on a survey of residual levels of VCM in PVC boctles. films and foods in the period of '.974-1977, suggest that the intake of VCM from the average diet will be less than 0.1 pg per person per day (Crosby, 1982; Ministry of AgricuJture, Fisheries and Food, 1978). What does this maximum oral daily intale of VCM by humans mean in terms of cancer risk? SPI-01035 T V 83.285 Extrapolation of the results of the present rat study to humans using the linear extrapolation model and taking into account an acceptable cancer -- rj risk, from oral VCM exposure for man of 10 , leads to an acceptable oral intake of 0.4 /jg VCM per p rson per day. Since che estimated maximum oral daily intake is only 0.1 pfe VCM/person/day, the estimated cancer risk is at least a factor 4 low* r. Moreover, the extrapolation model used is a conservative and prudent oi e, which implies that the actual cancer risk might be (considerably) low er than chac calculated by means of the linear model. In addition, comp< rison of che results of an epidemiological study of vinyl chlorid* workers with che predicted cancer risk in the cohort of workers based cn che results of VCM studies in rats suggested that humans are less sensitive to the carcinogenic action of VCM than rats (Gehring et al., 1979). Translated into practical terms this means that the cancer risk of a maximum oral daily intake of 0.1 VCM/person/day is small enough to be practically neglected 5. CONCLUSIONS The results of che present oral study allow the following conclusions: VCM at a level of 1.3 mg/kg body weight/day induces neoplastic and non-neoplastic changes in the iver of male and female rats, VCM at a level of 0.13 mg/kg be dy weight/day may lead to more female rats bearing foci of cellular Iteration in che liver. VCM at levels of 0.014 or 0.13 mg/kg body weight/day may result in an Increased incidence of basophill c foci of cellular alteration in the liver of female, but not of malle, rats, and 0.13 mg VCM/kg body weight/day Ls a "no-observed-adverse-effect-level' with respect to che induction of tumours in rats. SPI-01036 T 6. REFERENCES 23 Ministry of Agriculture, Fisherit s and Food (1978). The Surveillance of Food Contamination in the United Kingdom: Survey of Vinyl Chloride Concent of Polyvinyl Chloride fo r Food Contact and of Foods. The Second Report of the Steering Group on 'ood Surveillance - The Working Party on Vinyl Chloride. Food Surveillanc Paper No. 2, p. 6. HMSO. London. Crosby, N.T. Analysis for residual monomer le^els in plastic and in foods Anal. Proc. September 1982, 428-00 Feron, V.J., et al. Life-span oral toxicity study of vinyl chloride in rats CIVO-Report No. R 5788 (1978) Feron, V.J., et al. Lifespan oral toxicity of vinyl c hloride in rats Fd. Cosmet. Toxicol. 19 (1981) 317-333 Feron, V.J., et al. Observations on the oral adminlst ration and toxicity of vinyl chloride in rats Fd. Cosmet. Toxicol. 13 (1975) 63fc-638 Gering, P.J., P.G. Watanabe and C N. Park Risk of angiosarcoma in workers eopposed to vinyl chloride as predicted from studies in rats Toxicol. App. Pharmacol. 49 (1979 15-21 Owren, P.A. Thrombocest; a new method for controlling anticoagulant therapy Lancet, 1959, II, p. 754 Spit, B.J., V.J. Feron and C.F.M. Hendriksen Ultrastruccure of hepatic angiosark oma in rats Induced by vinyl chloride Exp. Mol. Pathol. 35 (1981) 277-28 SPI-01037 V 33.285 29 Squire, R.A. and M.H. Levitt Report of a workshop on classific acion of specific hepatocellular lesions in rats Cancer Res. 35 (1975) 3214-3223 INST. C1VO-TOX. AND NUTR. TNO 83-09-01/AE SPI-01038 V 83.285 7. AUTHENTICATION This report was prepared by: - 30 - (Study director) date H.R. Iamel (Pathologist) date: (Study supervisor. Pathologist) and approved by: M^r/ L^ Dr A.P. de Groot date: (Head Dept. Biological Toxicology) -of - '>J SP1-01039 V 83.285 31 8. RETENTION OF RECORDS, SAMPLES AND SPECIMENS All records concerning the dieta -y formula, dally observations, body weights, food intake, haematology , clinical chemistry and gross- and microscopical examinations and a)1 ocher information relevant to the quality and Integrity of the stuc y have been filed in the archives of the Department of Biological Toxicology together with the master copy of this report. Materials (samples of the test substance, wet specimens, blocks) have been stored, and will be retained for a period of eight years, i.e. till July 1990. The slides will ba retained for a period of 15 years, i.e. till July 1997. SPI-01040 -T V 83.285 32 QUALITY ASSURANCE UNIT TNO - !'. 0. Sox 360, 3700 AJ ZEIST, Netherlands STATEMENT OF GLP COMPLIANCE On Report no. Dace Lifespan oral care: nogenlcity study of vinyl chloride in rats V 83.285/291099 September, 1983 The study was carried out under conditions of good laboratory practice. Within reason there have been na circumstances that might have affected the quality and integrity of th results obtained. Dates and number of inspections: 19 November 1979 22 and 25 February 1980 12 May 1980 12 November 1980 17 November 1980 23 January 1981 3-4 March 1981 14-15 May 1981 (1) (1) (1) (1) (2) (1) (2) (3) 18 August 1981 27 October 1981 (1) (3) 22 January 1982 (3) 12-13 May 1982 24 June 1982 8 July 1982 (2) (1) (3) 8-11 March 1983 (2) 10 March 1983 (1) Draft report audit: 10-11 March 1983 Dates of reports to management: 19 November 1979 25 February 1980 12 May 1980 12 November 1980 18 November 1980 26 January 1981 5 March 1981 18 May 1981 18 August 1981 27 October 1981 26 January 1982 13 May 1982 24 June 1982 8 July 1982 16 March 1983 24 March 1983 24 March 1983 Final report audit: 20 September 1983 (1) 20 September 1983 Drs S. van Straten date SPI-01041 /} 33 T V 83.285 - 33 - CIVO/TNO STUDY NO 125 CARCINOGENICITY iTUDY IN RATS WITH VCM IN THE DIET TABLE 1 LEVELS OF VCM IN THE IIET IMMEDIATELY AFTER PREPARATION OF THE DIETS IT Group Intended oral exposure levels of VCM ___________ (mg/kg b.w./day) A0 B 0.017 C 0.17 D 1.7 E0 Dietary level of VCM (ppm) MEAN SEM N < 0.1 0.487 4.487 44.07 <0.1 0.013 0.097 0.926 72 72 72 72 65 1) The VCM content of the PVC-ppwder with VCM was on average 4582 + 98 ppm. SPI-01042 T 34 TABLE 2 LOSSES OF VCM FROM THE D IE T DURING A PERIOD OF FOUR HOURS th e cages o f the ra ts one hour ( t ^ ) , two hours ( t 2 ) , th re e hours ( t- j) and fo u r hours ( t a fte r preparation The va lu e s are the means o f 7 d iffe r e n t a n a ly s e s . iw 1 <Q 1 TJ 1O (^ 1 t1 41 1 CI1 1 40 1c i 'H i *o 1 41 1 4) 1 ^ /*> O .U VUi 0 41 CO O 4_l c 41 0 <J 4J u 41 a N (A 4_i 41 1 V* "3 13 1 1 J0S 41 a mi 41 0) 0) mm LA 11 1 t- 4J U41 13 a 1o 0 X ( VM 41 (A sj> H \ 4 4J 1 ,c 3 u o 1^ oV 1 40 a 1c 1 'H 1W c i3 1 "O (u U41 41 m fM u o 1 41 U* N i^ i *o *3 6 a. V a 1 4) 1 1w tn CM F"^ <Q 4J o Ie 1| H 1 41 1> 1 4) 1^ *3 4) V W (A 41 t- -- Q. X o 41 V 1X 1o 1> o 4J o \4 t 1- 13 1 (0 lO I 1 a. X g 1 4) > >> "3 |H 1 81 1^ 1O i- -a 1 41 1 "3 C 1 01 1u 1C l *-* u_i 3 O 0 (A CO 4> _* > s>* 41 CO <--i e V o 1 0. 13 1o 1u 1O < 00 UP vO vn rs. vO r-s fs. v 00 fCM O oo sr sO ST >o FM fS On Cs un ns CM O sO wn y> CM rs m-4 00 o cn ON w> fM CM r*s CM CM O Oo sT CM CN O o Oo o\ rs cn !--1 O oo ,-"S cn rs CO *T con oo o ns CM CM o cn O fH <n o m C"1 <N cn o vO CM sT O NO n. %o MO fH CM o O' rs. O' fH CM m cn CO m fH m sT cn O' fM M PS fM rs. o fM ps. * oO SPI-01043 03 o a CM nO CM vO o Or-N O V O V n O V O V fM O V O c <0 41 X co un U1 u c uV) F*s CD o 41 u6o U 4) u 3 3 C CT3 O U(A 41 o -4C> o c c u(0 (o0. u4) & u 41 u4) 0 T3 4) E E O) .X rg u> 41 a S (T3 C/J r CIVO/TNO STUDY NO 125 CARCINOGENICITY STUDY IN RATS WITH VCM IN THE D IE T D E TJ 1 01 0) at at a Cu 0t 1 <0 GC C z lT\ m W) uO ii 1 41 "3 XV 0) U-t C *4 r*4 CM sO sO -- u V z < oo CM m o O i-k td CM u* X V V x 41 > to 0> u X3 O X <M CO LzJ o u 4) < Ui Cu 3 to EJ o /""s a. T. <0 H X G *3 at > V, z #"4 no 3 r*fM r o > u X O r-^ o OC O o o X 3 at u* at > o o c a> OaC to 0t i_i UJ c t-4 u X m W a. -J 3 00 0 o at Xa ., <0 cc at 0o *3 0 JO <0 X (0 <9 *0 *3 u at t- at o Xw to *** c O at X LJ 4J u 3 3 aC <a 1m at 3 3 AJ cO <9 4J 4J at at at u w cX CD ow >% u c00 X 4_i r -Jfc at CJ N> at at e 3 a* o at x aw to u >s c o X VM 3 "3 to at at w 00 VJ U i- >\ at at s <9 o u X t3o c CO at >s *4 u at at e 3u3 <0 (A -4 at a V at at ast 09 <0 s at u. *4 > *4 SPI-01044 CIVO/TNO STUDY NO 125 CARCINOGENICITY STUDY IN RATS WITH VCM IN THE D IE T 1 X0 01 --. 0J 00 ro > J l CJ X <9 *3* 0 PM 00 s <PM pm -M "1 pm CJ VM <9 u 3o o 3 3 pH u Cfl <T JJ u oX < a CJ > J c g <0 > u P"N 00 PM r-. 0 4M o -Q >N to o pH r pH -o o o p* o <3 CJ 00 3 pX -X OC XJ CO aUJ U xj oo <E sw o CU CJ > pH Ucu <Q /*s cm o z o5 z pH 3> (0 CM >--1 u 4M 3 CM pH < f-t * UzH Ht CJ o A0 >> <Q o PM p" 0J TJ o o o CM o 00 CJ 0 (0 CJ CO -C c 00 H M s UJ w pH a a HI UJ 5 w U to > HI 00 PH CO c S H a W QJ *Q a q2 <0 CJ w 4J H o z CJ <4M *1* HH u "" a-as un pH JZ-o <0 CJ TJ o o 3* xO CJ pH to 4pi H > fl H >M o 3 CJ <4M Cl bu 4J > O a. 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S3 s CJ CJ s P. ro 4-4 4-4 4* 44 CJ -j n ro ro ro ro s s s Ul Ul >- >- > >- >- >- >- >- - > *- >- >- >- >- > >- V >" >- >- <r I <t <t <r <r <r <r <r X <x <Z <x c <x <z D 44 1-- -- 1 1 1 to : r- : tn ; Ld 1 P- 1 ! rJ P-- 1 UJ 1z iz :x 1 W4 J j -rl 1 <X 1 r~> 1 *i 1 1 03 tU 44 1 : ui ; ' 1 ! 1 'i 1 - -6 - SPI-01055 CIVO /TNO STUDY MO 1 2 6 18-MONTH STUDY IN RATS WITH VCM IN THE D IE T --E o u: in Nz o u z <z UJ r >3 -- <> 0* > ro <r'^)^'XOCDO''0*rrOrsv -- O -- Ci Cl fi <T if) <* U*J ifl if) if) S3 If) SS g3 gl S3 ul S3 ^ n o n ^ o o cs c ro rv o n n n ci o O 111 ^ r | O N T < U1CD-b*)*ONNOCt ^ ^5 ^4 44 ^ ^ ^4 ^4 ---- p J -- -- rj cj cj cj ri rj rj ci cj cj z a zz \u o cn X X o o o o O O U*3 IfJ go m llY go go U"> in tn 44 44 44 44 -0 > ro 03 03 W 44 o S3 44 ro cn U0 o* S3 O n ro Cl ro tp U0 lH S3 S3 If) s: -4 ^4 O o O o 44 w 44 Cl 44 44 1 * 44 z b0 CN J o X S3 4-4 CK CN o <r ro fO x S3 U0 CN cn CD r x in CD 44 S3 X CD 0" CD > CN CN o o o o O' o b o O r4 44 4 44 CJ cj Cl rj 44 ci cj Cl cn c X Z 3 X UJ z a \u CD U) z o o o O O o o D O UO W in in in W If) W in in ................................................................................................... ^HrJMMCTCCn^NCD'OCDfflfflNCDCOO' cn o 3 oz UJ z rv rj 44 r) IjO CN IX o r. r) 44 CJ m CJ X S3 O X CJ ro -r UD r) S3 03 UT o i4 S 1 -4 UD CJ CN CD CD CN o CJ in CN ri in S3 rs 03 CN 0 O 0* o > O' O' O o o o 4-4 ^4 H 44 44 4 <N ^ CJ 44 44 44 44 CJ CJ Ci CJ a b) 2 <z tz o CJ w --v CD cn NX CD 1-4 UJ 3 NA O A Z <r u X cn u -J CO < LJ x --1 A UJ C N` u- z CD Z Xz o UJ r cn x^4 *z o <r UJ z z r ou l cn Nz a u z < UJ r T o O o CN CN CN CN CN CN CN CN IjT on in in in m in in in uo 4*4 ^4 4-4 r rs CD fS S3 r <T CN <r S3 CJ O 44 in ^4 4T CD 03 CN p4 4-4 ri CN ro ro n r) PD ro to ro ro UT 4T in S3 S3 -o X X CN n ri r) liT CN Ul ro n O CN a b ro CJ ro in S3 44 44 Cl S3 n CN <r CD ii*) n n in <T b ro o S3 in X <N m S3 un 0s- m >0 fN CD CN > o O O 44 r< 44 ^4 ^4 Cl tj ^4 4-4 4 ^4 H 4-4 H ^4 M CJ Ci CJ Ci CJ r-J CJ CJ CJ CJ ooo o o o o Ooo 4--| p4 r4 ^4 44 ^4 4-4 1--4 44 --4 j") IjD m m U*3 go go in in <r CD un rv CD CN ^4 <r UD rj ci in o CJ ro m CN <r in o 4-1 tj r-j r) s* \n UD UT 0 PO r ro uo m <n go S3 ID X m 03 ro rs M CD CD rx ) X n X X 44 03 <r O CO go m in o -4 CJ fN r- ul rx n \n X CD ro CD 44 03 0* O' in 0* -4 \n S3 rs PS Ou CD CO O' O' o O' o O 44 1-4 44 44 44 44 44 * 44 44 4S CJ CJ 44 CJ CJ CJ PJ o S3 o 03 S3 4-4 ro in 03 --V Cl < 44 "l CO S3 r O' CJ --i 44 Cl i' " Cl o CD -0 pj O 03 < *T m 44 ro S3 CN ri UD X o ro ri r) ro ro ro r 4T m UD > N- >- >* X >> >- >- >- >- * >- >- X >* >- > >- >- X >- c <X <r <t <x <r <z c c <c <x <x <z <1 < <c <z <. <X b--1 * 44 U4 A N- -- A A A 44 W4 A *- * b- J t <-4 Io 1o 1 \ Cl. I j 1 l l i uo 1o t i 1V t u. 1 I l 1 1 l 1 l 03 1 V-- i cn 1 UJ 1 H* i i -- i i-- l UJ 1z lz 1X 1A l I s1 i <r i 1o 1z 1 1 i cn 1o i *-- i Hi cn 1 44 I Pi x )-- cn - i7 SPI-01056 11 11 1t 11 11 11 1 11 1 J1 1 OS in CO rs. <r 'O ON c m rs. sO n fH fN P4 P- _O m , NT O rs. m Cs sO m ph PH pH p4 rs. nO CO in m m sT UH m pH PH I1 1 11 I1 vO r-i rs tf"\ NO w\ ON so" m ^H SO pH in pH CMH 1 J* 0> at UO 5 r*> e *h >N < Q CM *0 *S^ w m u n 00 CM V m 00 wn c\ m m in <n ph pH pH pH pH o SO oo Cs o PH ON pH pH pH pH m m >7 m NO rs PH CN pH pH pH pH at .* 03 H u CM U C pH ch a "O w o H bu pH pH 2 ch r O > *7 pH m NO cn r-t sO "T m m m p>4 pH pH pH pH o NO PH m nO HT m sr CM HpH pH pH p pH O m PH m m *T m < m Hp pH pH pH rN*H O P< On pH 2 ro CM pH pH CN CM c/i ^HpH pH pH pH H oS CS Cs o *r cn 2 CM o 0> o o o pH pH pH pH > O 2 H to O' -T CO . rs PH PH 00 pH HI >H o at >> PH ui r (Q 2 U] C.3 1 O 2 < H1 Z 1--* 4J cH CJ > u-* 0 s*--o* CO u --i J U as Q O at "D --(0H < 60 X o LOl CM pH W2< 4J at 00 rc- <-h 'wS' o 22 X1 OS 1 \H O > >Q2hCO 1 1 t i ujoa: < H 1 \1 1 ao3. o < rs PH Ot pH rn o o pH 1 3 CO u a t J Os sO o CN a O' CN o o1--4 o CM 33 sO *T Os . o ON o o Os sO o PH PH 00 o CN o ON Os CO m rn rs Os o' pH ^H Os pH r"> m PH 00 Os as O o o Os pH pH pH CM 'O SO CM ON ON O ON Os pH CM o CO PI pH ON On o Os Os pH CM O ao Cs P-J oooO O PH pH pH pH pH *o CM o a o o opH pH pH pH p^HH ON PH o o sC ON O pH CM o Os HpH pH pH Os sy m <T CM Os O pH o o pH pH pH pH o CO rn sT m o Os Os Os Os pH Os <r\ m P'N P*N CO CO CO CO ao to U3 -J rn < r bJ u. O pH O o Cs. pH o rs p- O < CO u u SPI-01057 V) 11 11 11 1 1 1 1 1 1 1 1 1 CM CN -4 CM 44 _ o ao 00 m sO m in in CN 44 -4 "* 44 ON MD CO CM cn lA *0 m O* CN 44 44 44 ^4 o m P* CN l 44 44 4^ 4** 44 -- 1 1V 1 1) ol 3 on 1 1 c i--1 1 44 CN *T f** ^4 m m m sO 44 44 ^4 44 44 ^4 1 *"N 1 >N l CO 00 I on 1 'n 1 1 <0 1u 1 "s* f-t 1 60 r-. til 1 On M1 a 1 0) 1 -si S H 1 4_l 1 c 1 *44 00 Z1 44 1 TJ 1o s 1o o 1 u- m > 1 00 1 l CN CN O' SO sO in m m 44 -H 44 --4 44 p-* MO vr Cm cn *0 m n CN 44 44 -- 44 44 CM O cn ON v *0 sO CN -- i--4 44 44 44 MJ s o fM o cn m iA m 44 ^4 44 44 t 3 1 MT 1 r*. V5 1 MD 44 cn m m V0 r*> n r4 ^4 44 44 "4 H1 oi 1 1 cn z 1 pm >--i 1 in ON m CN vO m pm CO H -H ^4 n n -4 1 > i a1 --s | H cn H l o sO CN CN 44 00 sO m M3 uA ^4 ^4 44 44 o N 4 Z1 >H* Ou 1I --i N.4 1 CJ 1 01 >s G--* ill 1 r CQ z 4 1 CO *0 f- 1UJ < 1 4J > *--* O O e Z 1 44 U-. 3 tn r*. Z 1-4 1 O ui 1 *0 -Q ml o--4 Cm 44 r* o o oo Q ai to O I -D 44 60 2 ^4 o <t CJ 1 un <N --4 oo zZ 1 1 1 i O1 U- 1 Z1 <1 Bj A> 1 1 O' 1 C 0) 4J c 4 0) > QC B *W H \ > o > =3 4M f-- u C/J 1 1 1 1 1 UJ 1 1 as 1 <1 *- 1 a. 3 O < 50 a u oco 44 sO cn o PM ** 44 <n 4-4 4* CO r>. *-T cn o o 44 44 44 44 4H 4* 44 PM ^9* -r in CN -- -- -- r-. 44 un O CN o 4 o 44 ON 44 44 ^4 SO 00 ON ON Ps. ON 44 o o CO 44 4H 44 rs. <9* N" ao 00 oON O O oo 44 44 44 r-s. cn 00 Oi CN * oON ON On ON 44 Oi ON 00 44 CN o oo ON ON O 44 oO m N0 cn * ON o 44 o 44 44 44 44 oON 44 CO ** o o PM ON 44 ofM ON P*. cn o0 Oi * ON ON ON 44 to b3 -J Pm o< 4* ^4 ps. bJ U*' o o o ^4 a< aa u UJ SPI-01058 t/i H ui o UJ H X u CO H 2 2 >* Q 3 H W >H 2 u Oo o ec < O oo zz H ^ >* oa >3 ^CJ Hco a. 3 0) s 1 <-- 1u (0 10 1 JZ 1& 1c 10 I Sh 10 1 Cfl 1 -0 1o 1 Iu 1V ia i jtu i> 1o i -o lo i *h 1w tv ia </> C O U3 0 o -- O U0u 1 fA S4>M 3 CO --U 1 JO JZ CN ^1 0 4i 01 itri z 0 aj u _1* 00 H <0 > LJ O 1 Nu CQ -- (n u i (Q O "O 0) CQ CO 01 u a. X < CO Os sO uO in O | 00 1c i t *T3 1U 1V t Sk4 1 4) \ > \ *> -j < H O (NC\0N (NP>HN|SOs0inDiA O OSON 030fNO*|r>OQOO'XO H 1 oo 1c 1^ tu 13 1 *o r- I \o cs m v? ON Cn CO -H |r*M H O N vO H 1 cn -H O *4 01^ O cs O O 1v o 1 -X 0 I <a I 01 1 c UJ 1 H Cm 1 "O OI 0 2t 0 I-m 1 U, Q UJ bJ b- a& 3 O T os 3 O u *- u oo (0 <0 o u (0 (0 4) W a. X t> ri OCr%NflH-h lI iAmrsncuNo fsHfs 1 CN in O cs Ol O cs O h O O' ON CN rs CN CN cs in vfl n cs <-< cs O O O O <-> O cm O CN fN sO CO O 'O i CO O sO iO h O' CD <C oh I ,-H O & o O O O 03 O o UJ ia H i -* 1 (Q 1u 1c 1 **H os 31H 3 I <Q 1w bJ 1 O * < 1 *u H1 o Z13 1c i ai QI u O1 c O1 Urn >, X <Q C-J *U >N VM 3 0 J0 CQ --4 QO 0* >N V 00 -H B *w CO UJ -J o d o UJ 1 o. J 1 3 CQ 1 0 <1 U H1O 3 **7 --t CN o vO in H ^OO*r'-AiI n n O* f\S'j n^0 Cf-NH o CN O C*"HN O CN O >"*-H* O nc%s0uNChO iO>NT iOnh* Ocho o *"* O o ^h ^ o O Cs r. ^ i H O *"4 O CO nO H CO H (O H O ^4 O ^ O M OH' c C(NO O. -- c"> N n CN h -i cnOcnOcnOcnOcnO onfN /i'j'^noH'ojNno sOO'OO'OOr^O'OO CO UJ mJ < X UJ u. o O-* r*-<- SPI-01059 >o < veral 1 ^ Food In ta k e fig u re s a re th e means o f 11 d i f f e r e n t d e te rm in a tio n s . ^ S ta n d a rd e r r o r o f th e mean ii - 'll x o MEAN HAEHATOLOGICAL F IN D IN G S RECORDED AT DAY 9 4 r l8 5 AND 3 6 7 x u m h- CJ >-- UJ >- u cn Ci 33 a 1- CJ )-- LJ >- tU C*j <r Cl -s CS Hb-- !J Ul >- u. 03 -X W U4 < 33 CS <r 33 O c-j 33 3" S3 <r CO cj a o ^4 33 Cu a o S3 o cj r a 33 o m iv S3 cs 1s O i' O fs o n o fV O 33 TH ^4 33 cs 33 o H ca 33 < Cl cs M cj u a n o H-4 o ^4 L3 7 8 33 C.J 33 cj ^ un O 33 O * tH cs o m ci n a <r c-j 33 : 1 l UJ M N-l 1 03 1 ia i3 {H j i CJ io J; c 5O j ) u. J 1 1 rv U -s S3 O -J C N. 2 cs U3 S3 n 1)3 n 33 T IS rH * 33 Om - 33 CJ CJ >- O UJ <r C-l 33 -T o cj m S3 rv m -r ui O cn a a cs a c r-- in u ~ 03 C _i H c\ a: cs sc is r-4 1)3 ro > C UJ cs i"* HT <E lie O a cs C X- r-- N--' o 33 S3 S3 33 T"H rH cj 33 a Cn th rs ro a CJ Q _l CN o * o a o . . ,> > x cs au CN a fs Ci H S3 M mn klJ 3 o "J S3 L3 H Cn CJ S3 o S3 33 <x c u: o T"H cn o ^4 o --4 Cn a H- X2 <1 Ui u cn x 2X2 <t u u 03 X 2 u2 u 1i Jn X 2 X A. t UJ UJ cn X 2X2 <1 UJ uj cn X oa -J 2 \ !* \ ajl -J cn a a a \ a aX X a a UJ H- X H* _j 2 C rv fv ^4 /v 2 a CJ ^4 * o <x x 1 CJ 1o ;* 1o i V' u. 1 l i \n !O * 1O S V` J u. 1 J m IK s cn ! UJ } r >; UJ ia i X i >- l UJ i ZU 1 r- H* ! hh > CCi i ru x i 3a a 1 vs CCi l 2X i 2a i <r a c 1 XX 1 1-- i cn ii 1 : u i-s u >- o : cn cu l --X : - a Ccr SPI-01060 T TADLE l c 2 2 'X 'I S3 n -- a n S3 O T <r cm 33 S3 rs u3 0- T H- LJ > u. 03 o - ,~3 r-j O' *--4 CO x r T n r*i 3 x u 5. MEAN HAEMATOLOGICAL F IN D IN G S RECORDED AT DAY ? 7 1 8 4 AND 366 IS <T G3 rH >- u n 33 O' CO <r o- O O CO rj rs o> (S. O' H* LJ X .n o Cl o .~3 S3 ^ rs o <r n n ro n n i ii l n i3 S} G3 O c-4 ca o m -c o S' ri O .~3 O' r-j o o o ^C <T oo <r n^ <r rs n <T 4 TH UO i S3 n aa 22 O I SD cj S3 o -J n AN 2 cs O' S3 > o UJ rs ri 2 uC o a iJ r- w o S3 Mo O' sr CJ 03 o r*4 A \ 2 cs M rs ri r-j >- a u rs r-i Mn <X Ci o O' O Ci 22 rH r*4 >-- CJ rv a .j Cs CO \ 2 cs fS Cs 1-4 U3 rs > <r a UJ CL o C-J r^ CS rj O' iZd i y-t <T <r o r-j >> S3 o a Cl cs rn Cs rr nn Cs rH --4 m sn a CD M Hn o ri o o Cs r-4 rH CJ o T r4 0 r4 s m <r r4 >0 n a o nw <r C-J Cs 2<r 2 U L, ua 2 222 <1 UJ U 03 2 y E Z u 2 Ja 2 22 'X UJ UJ a 2 2 2 22 X Lu UJ 03 2 03 a <3 UJ 2 : a N. 2 -1 _l o a < ) s o CL r : a cl <r >-- 2 H- r2 a rs ! F 2 Tv a o J u C <: i : rj 1o io i u. 1 { 1 1 t \n !O :o : Cl. ! 1. l H- i cn 1u : r- } UJ ia 1 1> 2 J-i S- iu 1 2U 2 J S- H- >--* 1 -4 V A 1 2U 2 : 3a a : \a A 21 2 2 'r i a SJ CL a 1 2 I u: I H u. i an 1u 1 hh u 1 1- c : on a i hr i >- a i a Co M SPI-01061 T' - 53 - TABLE 12 MEAN NON-PROTEIN BOUND SULFHYDRYL "GLUTATHIONE") CONTENT OF LIVERS OF RATS FED VCM FOR 9( AND 18 MONTHS .58 CO JuZ CO a c u a> > 4? 4) CO eo H J= 4-1 4-1 3 oct o a2 C sCc/3 t:4) o> O u \* c z u 3 0 O. o X4> ftNo T3 4) V> -e3 41 VO <o vo o On > m GO cn CN NT CO T CO 04 nO CN 'T r-i 0 r*-. o p-n. fN 2 nT CN D 00 ON o CN fN NO VO CO CO i CO CN CO CN CO CO fN r-N < 5 PN O P-*. O fN^ o r*-. fn r- O OO O < a CJ Q uj C V > 00 CQ c (9 4) s 4J .fi O w VO Uuol V 4J o c uSJ M0) cm 3 lj 9 JuZ u -4O) c <Q a3 4) C a .c u 9 .4*) U u T3 XuCOi C e SPI-01062 CIVO/TNO STUDY NO 125 CARCINOGENICITY STUpY IN RATS WITH VCM IN THE DIET TAIM.E 13. MACROSCOPIC PATHOLOGY Sice and type of observations* 1 Initial number of animals Effective number of animals MODE OF DEATH: a. found dead b. killed in extremis c. terminal sacrifice AUTOLYSIS/CANNIBALISM: a. slightly autolytic' b. partially lost c. completely lost SKIN / SUBCUTIS 1. tumour or suspected of tumour 2. alopecia 3. edema 4. haemorrhage 5. injury AXILLARY LYMPH NODES 1. tumour or suspected of tumour 2. enlarged 3. reddish PREPUTIAL -/CLITORAL GLANDS 1. tumour or suspected of tumour 2. evidence of inflammation 3. enlarged 4. small 5. cyst SPI-01063 MAMMARY GLANDS 1. tumour or suspected of tumour 2. evidence of secretory activity 3. haemorrhage ABDOMINAL CAVITY 1 . tumour or suspected of tumour 2. ascites T Incidence of observations MALES mg VCM/kg b w * /day 0 . 017 0.17 1 .7 0 FEMALES mg VCM/kg b.v. /dav 0 . 017 0.17 1 .7 0 100 100 100 50 100 100 100 100 50 100 99 100 99 49 100 98 100 96 49 too 26 26 25 16 10 54 54 57 27 90 20 20 18 7 0 8 15 9 5 8 71 62 67 41 92 21 23 24 4 0 ! 0 15 13 3 9 11 4 4 9 1 i01 10 36426 06425 204 1 0 5 7 93 3 53323 4 1 7 2 3 10 9 9 4 8 232 1 0 1 1 1 00 00 1 00 0 0 00 0 0020 1 0000 1 3 2000 2 2000 1 0000 000 1 0 0 1 20 1 00000 352 1 2 7 6 11 2 2 0 1 1 00 0 0 2 0 0 0000 0 3 1 020 55 1 35 00 1 1 0 0000 0 0 1 00 0 8 14 7 3 3 39 25 28 18 23 1 2 6 8 2 6 53 35 4 1 21 29 00 1 00 00000 12 1 10 353 20 6852 6 5554 6 ^..... -n- _--. STUD\' MO ! 25 CARCINOGENICITY S~ dy ::: ?j~s vhth vc. i: TAIU.i' ! 3. MACKOSCOP! C PATHOLOGY CONTINUED I) Site and type of observjtions SPLEEN 1. Cumour or suspected of tumour 2. splenomegaly 1 3. atrophy 4. granular surface 5. small 6. small nodule 7. dark ADRENALS 1. tumour or suspected of tumour 2. small (unilateral) 3. haemorrhagic 4. discoloured a. pale b. dark 5. spotted 6. enlarged a. unilateral b. bilateral KIDNEYS 1. tumour or suspected of tumour 2. granular surface 3. unilateral hydronephrosis 4. discoloured a. pale b. dark c. greenish d. reddish 5. cyst(s) 6. enlarged 7. small 8. spotted 3PI-01064 STOMACH 1. enlarged/swollen 2. haemorrhage/erosion 3. rough inner surface 4. tiiickened cardial/fundic wall 5. thin fundic wall 6. trichobezoar incidence of observations MA1.KS mg VCM/kg b w. /day 0 . 01 7 0. I 7 . 7 0 I'KMALES <(,V VCM/kg b . w. / dnv o . 01 7 0. 17 1 . 7 0 01010 8 14 7 3 2 00Q0 1 20 I 1 0 1 00 1 I 0000 1 00000 0 1 003 42432 000 I 0 00 1 1c 0 0 200 0 0000 0 1 000 7520 I 5 520 1 10101 t 1 000 00000 1 1 1 00 1 0 1 1 13 20 1 2 1 36 I 02 4 2747 9 8 7 1 2 26 25 27 14 23 6 2 8 2 1 21 9 6 4 7 3222 1 1 1514 02 1 1 10 11 52 10 !1 00 4 32 00 10 30 91 01 7' 2 20 20 00 42 40 00 00 0 8 0 3 1 0 1 4 2 0 1 0 .2 0 0 0 5 2 200 3 2300 3 1 1 00 0- 1 0 0 I 3 3 l 30 00000 1 430 1 1 1 200 0 1 000 0 000 1 41 636 1 654 1 1 0000 0 1 000 00 1 00 -- - I 4 3 20 061 22 0 0000 1 0000 00000 STUDY NO 125 CAKCINOCI'.NTCITY STUPY IN RATS WITH VCM IN THE DIET tai'.; i: n. macicunoih' 11 I'ArnoLorY iCONTINUEO ?.} Silo and type of observations SMALL INTESTINES 1. Cumour or suspected of tumour 2. prominent Peyers's patches 3. enlarged/swollen 4. haemorrhage 3. reddish 6. filled with watery fluid COECUM 1. tumour or suspected of tumour 2. enlarged/swollen 3. small 4. filled with watery fluid COLON 1. tumour or suspected of tumour 2. enlarged/swollen 3. filled with watery fluid 4. accreted to the cervix MESENTERY 1. tumour or suspected of tumour 2. edema 3. dilated blood-vessel 4. thrombus in blood-vessel 5. haemorrhage PANCREAS 1. tumour or suspected of tumour 2. discoloured a. pale b. dark c. reddish 3. edema 4. spotted 5. small haemorrhages MESENTERIC LYMPH NODES 1. tumour or suspected of tumour 2. enlarged 3. sma11 SPI-01065 4. edema Incidence of observations MALES mg VCM/kg b-w./day 0 .017 0.17 1.7 0 FEMALES mg VCM/kg b .w./day U .017 0.17 1.7 0 02000 34000 333 1 0 I 22 I 0 1 0 1 00 00 1 0 1 00000 1 00 1 2 3 1 000 0 1 000 00000 0 0000 00 85 0I 00 00 53 00 0 00000 3 3 0 00 0 0 0 00 0 0 0 00 0000 2220 000 1 00 0 0 0 0 00 0 0 00 0 0 00 0 00 0 2 00 004 00 443 1 0 00 1 00 000 0 0 2 2 403 1 0 0 00 54 1 1 3 0 0 0 00 0 0 00 21 10 200 2 4030 1 I 0 1 00 01 1 00 30000 000 0 0 4 4 2 45 0 0 0 12 1 2 2 02 o 0 0 10 0 0 0 00 0 0 0 00 0 0 00 22 3I II 02 0 1 0 0 32 00 11 03 STUDY NO 123 CARCINOGENICITY S7U3'( IN RATS WITH 7 CM IN THE DIE** TAIK.F. 13. MACROSCOPIC PATHOLOGY (C 0N7INUED 3) - Sice and cype of observations 6. discoloured a. pale b. dark c. greenish d. reddish URINARY BLADDER 1. tumour or suspected of tumour 2. haemorrhage 3. enlarged/swollen 4. calculus/concrements SEMINAL VESICLES 1. tumour or suspected of tumour 2. evidence of inflammation 3. enlarged 4. atrophy COAGULATION GLANDS 1. tumour or suspected of tumour 2. evidence of inflammation 3. enlarged 4. atrophy PROSTATE 1. tumour or suspected of tumour 2. evidence of inflammation 3. enlarged 4. atrophy TESTES 1. tumour or suspected of tumour 2. atrophy a. unilateral b. bilateral 3. enlarged (unilateral) 4. crypcochismus EPIDIDYMIDES I. tumour or suspected of tumour 2. evidence of inflammation 3. atrophy 4. haemorrhage Incidence of observations MALES mg VCM/kg b.w ./day 0 . 017 0. 1 7 1. 7 0 1-0 on o> FEMALES mg . W . /dav 0 . 017 0. 17 1 .7 0 1 001 0 1 0 1 00 0 0 000 0 0 200 00000 00000 00 ! 00 002 1 1 0 0 1 00 1 2000 1 2002 00 I 00 1 1 000 00 2 00 3 2 1 00 00000 0 1 000 2 1 1 00 I 0000 4 5 10 3 27 ------------- ---- l 1 000 1 0000 0 0 0 00 3 5 9 3 27 - ---- - - -- -- - ---- -- - - - 0530 1 1 2000 1 1 00 I 4 1 218 --------- --- - - - -- 304 14 10 18 10 9 6 202 101 00 57 5 22 10 12 ----- ------------- --- 1 0000 00 1 00 2000 I 1 0000 ----- --- - SPI-01066 ........ * ~T .... --. -- --------- 8 sr.'ov mo : i; cam.'::study IN RATS WITH VQi IN THE DIET TAftt.M 13. MACROS;'OM! C RATH0L0GY (C0i TINUED 4) Sice und cvpu of observations OVARIES 1. tumour or suspected of tumour 2. cyst(s) 3. enlarged 4. reddish UTERUS 1. tumour or suspected of tumour 2. hydrometra 3. evidence of inf lamination 4. pyometra 5. enlarged/swollen LIVER 1. tumour or suspected of tumour 2. prominent lobular pattern 3. swollen/enlarged 4. discoloured a. pale b. dark 5. cyst(s) 6..small 7. small surface lesions (rosette, constriction) 8. spotted 9. granular surface / Incidence of observations MALES mg VCM/kg b-w./day 0 .017 0.17 1.7 0 FEMALES mg VDl/kg b.w./dav 0 .017 0.17 1 .7 0 ------- - 64235 811153 7 5 27 2 1 0 21 29 28 1 I 33 2 1 1 32 1 000 0 000 10 2 2 7 I 1 127 23 I 1 420 0 0 3 2451 0 3 2 0 3201 0 13 3 300 1 00 2154 0 17 14 01 10 2 00 0 0 0 1 0 3 0 I1 0 1 0 1 5 6823 I2 0 0 2 0 30 21 01 0. 1 22 00 THORACIC CAVITY 1. tumour or suspected of tumour 2. hydrothorax 3. haemothorax THYMUS 1. tumour or suspected of tumour 2. enlarged 3. spotted HEART 1. enlarged (atria) 2. thrombus 3. pale SPI-01067 |0 000 0 0 0 00 13 830 262 10 |4 740 5 1 000 000 1 000 0000 0 0 0 20 10 00 1 00 000 1 < 19 16 76 3 67 50 1 0 45 400 0 00000 1 0 12 C i. Vu / i'NU STUDY NO 1li CARCINOGENICITY SHI )Y IN RATS WITH VCM IN THE DIE T tan: :j. :!ackoscopic pathology CONTINUED 5) - Site and type of observations MEDIASTINAL LYMPH NODES 1. tumour or suspected of tumour T. enlarged " LUNGS 1. tumour or suspected of tumour 2. evidence of CRD 3. spongy 4. spotted 5. haemorrhage 6. discoloured a. pale b. dark c. reddish 7. atelectasis (partially) 8. pleuritis TRACHEA 1. filled with blood AORTA 1. dilated 2. calcified diaphragm 1. tumour or suspected of cumour 2. spotted surface CERVICAL LYMPH NODES 1. tumour or suspected of tumour 2 enlarged SUBMAXILLARY SALIVARY GLANDS 1. tumour or suspected of tumour 2. edema 3. discoloured a. dark b. reddish 4. enlargid/svollen Incidence of observations MALES mg VCM/kg b w. /day 0.017 0.17 .7 0 FEMALES mg VCM/kg b w. / d:iv 0 . 017 0. 1 7 . 7 <3 31 I '2 0 2 '' 0 0 1 00 000 0 '2 2 ' 2 ~0 010 464 6 8 11 18 18 26 1 04 1 20 1 00 131 1 24 000 01 5 72 I 50 96 01 42 00 00 00 02 000 4 3 10 554 20 17 9 00 I 564 000 020 1 03 1 00 01 9 67 3 36 64 01 02 00 00 22 01 0 1 000 00 000 5991 0 1 0000 52 1 1 2 00000 1 0000 0 00 1 0 01 10i 00000 1 0000 01 1 00 00000 00000 1 1 1 00 1 21 I 1 1 0000 00 1 00 1 1 000 0000 1 000 ! 0 00000 0 1 000 00000 * CRD chronic respiratory diseas *: SPI-01068 .............. "T ' 4^ . ..... _ ______ ____ . STUDY NO 125 CARCINOGENICITY SIJudy in rats with vcm in the DIET tak: n. MAC'NOSi 'I'M' 1 > ATHOLOCi (CONTINUED 6) Siu- and t v])0 ol obaiTvat ions | | I SUBLINGUAL SALIVARY GLANDS 1. tumour or suspected of tumour I 2. enlarged/swollen 3. haemorrhage 4. edema 5. discoloured a. pale b. reddish PAROTID SALIVARY GLANDS 1. discoloured, pale 2. spotted 3. enlarged THYROID 1. tumour or suspected of cumour 2. enlarged 3. discoloured a. pale b. dark PARATHYROID c. reddish 1. enlarged EYES 1. haemorrhagic scabs around eyes 2. evidence of inflammation 3. protruding 4. pale 5. opaque ERAIN 1. tumour or suspected of tumour 2. haemorrhage 3. a pale spot MENINGES I. haemorrhage Incidence of observations MALES mg VCM/kg b.v./duy 0.0170.171.70 FEMALES mg VCM/kg b.w./Jav 0.0170.171.7 0 1 0000 0 1 000 1 0 .0 0 0 0 ] ] 00 0000 0000 0 0000 00000 00000 00000 00000 0 1 000 3 00 1 0 000 1 3 0 ] 000 0 0 0 00 00000 I 0000 263 0 30 1 1 0 1 0000 2 1 30 0000 1 2000 0 0 0 01 00000 0 1 0 0I 00 1 00 0 24 02 11 623 2 2 10 1 3 3 C02 6 9 9 2 21 8 6 2 0 12 12 3 7 3 ! 3 13 7 9 16 2 14 3 5 0 000 0 I 10 0 0I0 0C00 0 0 0 00000 SPl-01069 S'l'MiV NO I.''j CARCINOGENICITY ST 11) Y !N RATS CV!! VO! N THE Dll ' m:: ! n. :'ac::;)scoio c pathology (c ONTTNIIF.D 7) - Site .md typo ut observations PITUITARY I. tumour or suspected of tumour 2. haemorrhagic (cyst) 3. discoloured a. pale b. dark 4. enlarged/swollen NOSE 1. tumour or suspected of tumour 2. haemorrhagic scabs around nose ORAL CAVITY 1. malocclusion of incisors EXORBITAL LACHRYMAL GLANDS 1. pale 2. granular appearence ZYMBAL's GLANDS 1. tumour or suspected of tumour 2. enlarged 3. evidence of inflammation A. haemorrhage ABDOMINAL/LUMBAL LYMPH NODES 1. tumour or suspected of tumour 2. enlarged ABDOMINAL WALL 1. small cysts TAIL 1. ulcer 2. abscess EAR DUCT 1 . compact debris 2. evidence of inflammation LIMBS I. tumour or suspected of tumour 2. abscess 3. deformed SPI-01070 Incidence of observations MALES mg VCM/kg b . V . /day 0 .0 1 7 0. 1 7 . 7 0 FEMALES mg VCM/kg b .w. /dnv 0 . 017 0. I 7 . 7 0 8 9 10 5 3 13 13 17 10 5 ! 23 1 1 5 10 1 1 4 2 31 1 10 24000 1 1 001 000C 1 1 0201 1 1 00 1 00000 662 1 1 00300 43200 532 1 1 2 1 00 1 18 12 10 69 6 8 13 17 00000 00000 010l0 00 0 00 0000 1 000 0 0 00000 1 01 00 00000 0 1 000 1 I 000 2 1 000 00 1 00 o. 0 0 0 0 00000 1 0000 21 1 10 000 0 0 00000 00 1 00 0 1 000 00 1 00 00 0 0 0 00000 20 0 00 000 0 1 42! 0 1 000 0 0 000 1 0 1 1 I 00 --- -.. - -- "T ;:o i c; rv SiulJV IN KATS U'lTlI VCi IN ; i it. iJ it'. :,athoi.o ;y (continued 8 . . ( .mo ! . p> viii-v vv .1 ( urns MISCELLANEOUS >. emaciated 2. deformed spine 3., deformed dorsal vertebrae Incidence ot observation:. _________ ___________________ _ riCMM.KS m(' VCM/k|> |).w.7d.iy ni)4 Vt.'M/Ivi* Li. ~ 0~ . 0 I 7'7)~.~l / i*.~7 ~0~........ 0 ' U~~7 0.1 7" I 15 19 13 00 17 7 00 10 48 0 0 J2 22 26 14 55 0 10 0 0 00000 SPI-01071 12*** 7** 31* 27 5 ** 19 23*** 15 16 12 CIVO/TNO STUDY NO 125 CARCINOGENICITY STUDY IN RATS WITH VCM IN THE DIETS O as as r*-. >> ^4 as W 01 X *4 a 00 e ' -X a u. z u r r*. so i-4 a X as O O (0 V 0c0 0a0s CO X au Ul > 4 44 0 -J o oo 0) uu Xc H a TJ z *4 c44 U C/5 44 r*** as CQ -a U oz 3 2 r-* CO X as 0} as r*4 00 <X <0 -X X N* uX 44 o> o X 00 ^4 o E as as H < 0- O eto Os as -- u* o X z o> UJ c a 4* a oz <0 X 44 01 a /--s z < CO- X a. 0c0 > C9 HX u *T 44 o UJ X 01 A Cl <X H cn co S c m o 01 x e z3 o '*y CM 1 P4 1 * <* * 4C 4C cn X O' CN ao cn * Xo CM 44 <n in o 44 X CM cn m Os X o ax 44 in o O o n * * X <n X o CM 44 o 44 cn cn CN CN 1 n 44 00 CN 44 -4 CN 1 CM c 0 p4 *J (Q u 0) LJ CQ 4 3 JV U 3 IM <Q 44 CQ 3H ^4 ^ * 4 w <Q LI 0 u J 01 u 0) > 4cV ** s 0 (0 0J 44 ) 4*4 44 u 0 u. 9 3 u <V O Um4 CQ U <4 u o X 01 CL c 0o (0 <Q X 44 X' 4 <Q u 01 > 01 (0 44 44 44 CJ 3 0 01 1*4 44 CQ 44 01 U u0 0) oc Xo 4 e 44 u 1 P4 1 SPI 4 uo 3 *4 01 Cl4 44 CJ a CQ .0 ^4 44 w X O 1*4 Q. 0 01 o e e 0) o*4 & o(0 >> *4 ^4 41 44 CQ 44 w 44 O < f-- 1 44 u o M4 <44 0 u 0> X 8 3 Z b e a rin g a n im a ls 2 T o pm >S (Q oO oo HC HC OHC ' *M CO CN cano in M cn hc m <n as <N Xo CN nr CN Ht PM n. HC CN <r r"i pH ao CN PM 5 CO pm 43 X pm ^h s<0 00 O J* 4) u. 5 ^H o opm say* ao m CN PH as X O pH CH pH a w X z PM CO H 43 z o oc c u (Q X u > r-. 00 PH ao d o oOo o o pH o >pHT cn pH m X pH CN a> ao cn CN pH r-> <n pH PH CN X CN PCmN H AC V44 uo > pH 01 .J C/3 u c S-- u oj U X o PM H H au ze UJ PM pm X H to u o pm >N pm (Q --T3 oo oo m4 CM mHC pH CHN ^H o pH H6 as o^H <n pH O o pH / O pH O OO Hr He HC HC CpHN pH #H a cn o Za PM z 3 5 CJ > X 3; < Hu pm PM pm CO X M 0) M 00 o CQ X "N, X o oo oo sCON r** pH pH cn o mcn ao o 3 CJ o pj Ho > PM 0a0 o oo Oo CcNn nT M CN o <r o XCN as o H < Z arM C o SPI-01073 H > to oM x o oo oo pm. CN a M M pH xT o Pm cn as CN H C/3 a. o >- u PM CJ> <D z HM UJ z Q UJ PM o o u z z PM PM u as Q z << co CJ UJ in a. o cO r <N > <q -- H X o O z --i <+* > UJ o a -J X CQ f-- < 4 o. > to h- f-- CO pH CO Ma 3 O c u ^H u (0 bCHQ a. o z 3 4c3 *44M3 o cq <Q <Q 0s -C8O Mc PH X u<J ua. IQ o U8 5s u ^M M<a CQ oa. M3H pH 8 o ^H CJ PH 4J 4 44 CQ a; u 41 X U u o 44 IQ CQ CO voH ul h 4> MM00 CO 0) o8o Q. oco *>h = < m3 CQ X pH a> u H CQ M *4a1 0 (0 JUL C3 CQ S pCHO 0J 4J 4) u u cX <Q w a 4) oo 4) >V(A C MPH 8 (0 O8 * u0 <J 0m <Q X 4CCOO>S U OC41 <Q 344Jp Q X c M404 uCQ VMVH M wo a. 4> 4J 44 44 <Q CJ X u >s c CQ 8 3 *a 4) PoHo M to 4) o8u MpH U s CQ X uV 4>3 4CO3 U .. ! 04 **y in . PM ao TABLE 14 TYPE AND INCIDENCE OF HISTOPATHOLOGICAL CHANGES IN THE LIV E R CONTINUED- b. several 13. S lig h t h a e m a to p o ie tic a c tiv ity oo >s in o oo CM <0 01 OC C J<=0 u -a0:0 00 s oo oo oo mO T3 3 * * JQ O QO ocm .X00 oX > 00 CM O e 'TOO CM O O pH CM O CM O O moo ch O O mOO ao mm cm O CM O O cm in m ao m CM o cm m mo O r-. m CM o m oo SPI-01074 O CM yj 0) 00 c <0 U 0 01 >os. H - no - O*N <N o oooo x --< o C/3 H tC-s4J a ui P Z H 5 CO H >O E-- CO > H CJ MM z bJ o o z -- CJ os < V CN mm oO zz H >oo >o MM h- '^ UQ2 H (00) Z oc CoJ c CO X u as tu > UZ H CbO: oz S u X < o o o X o p 0<4 o H CO bu o X CJ 1Z 1X 1Q 1i-- | CJ Zi NM | 1a i Z Hl 1T -m | X| X| 1SB I < E-- 03 040> c<0 X u 0'MM V a. >> " 0< "> CN X O c oooo to 5 * X <**> <T X CN i- ao O OO 5 > r*** ao| mh O **T CN CN mM >s| eo -o 3 X ao cn r"i *-m mh cn <T *T O O OOOO OO CN O CN cn o cn o ^O O CN O ^O O >T O O On X O CN CN CN O CN *T m CN ''TOO cn o O -m ur\ X CN -M --o 3 343 043 SPI-01075U 0mm 03 4 43 03) 03O U 43 43u 0 <3 43u > 43 4 03 0 8) 03 4 03c mM 03 03 4 303 3 03 00 13 4cm o ) 4 3 4 00 43 "3mH Ju w 4 <3 4 <0 1 *0 3 0 0 41 u J m 41 0 0 8 03u X u Xu 4 00 00 4 4 03 4 03) Mi "O -4 03-m o c) Mi a iM o 00 8 03 8 03 4 43 8 --4 3CO to 4 00 41c u 4 43 43 8 4M * O <0 <0 "3 /3CO X bu X CO uw Mm K ) u U QO OC > H fO >% MM Mi u X c Mi CL U J o Mi *Mi )m ' ft M u V C z sM J to to C u J* M o to X uw --M o o Mi M M > MM Mm > MM C u Mi > a; X u w A mM u ) Mi >o u m u c ) (Q X U) u N u u Mi oo M Im M O C o o mM o Mi >> c. ) U Mi OU NM a> MM MM <Q CL MM MM MM cV ) mM ffl U CL ) a; C / U CJ o Z &. C >X to <r u-\ ---- 00 sD r- . . O' O Mi -- --* MM CN rsj T TABLE 14, TYPE AND INCIDENCE OF H1STOPATHOLOCICAL CHANCES IN THE LIV E R CONTINUED 4- o r- -o CO 3t 01 -a m u0S** j? > oof 40 0> QO C -Ctc CJ o V c 0/ a u c I o rv Ji 0) (V X c o evj oo o oo o oo o o o o I P o o o o o O O I 4/5 I 0/ I 00 Ic Ii 3 IV I >*- Io I 0/ t a, iI f->*s T SPl-01076 TABLE 15 TYPE AND INCIDENCE OF TUMOURS OF THE MAMMARY GLANDS AND INCIDENCES OF ABDOMINAL MESOTHELIOMAS m u ltip le * * 00 CM O ON WN O <"* .O <M SOO' QO o e 00 o> o On >> <0 *0 oON to 00 CM * * * m sO ^ wn cm m CM . O OO OO OONn On On T3 V C a CXOOJ a. -Uco3 >s <0 oa a <0 a to <V CQ c8O u a> *T3 C QG U> (hA t0oo 00 3 e o 3 -c -<ooo 0c0 <80 Cv CO 4_J 4i--* -021 63 03 C<0 < c CQ l ** 1 CO 1< l I1 M -J 1u 1 H CO UJ z < Z44 z < 1 1 1 )1 o r-. 5N C0 O r-s. CO u 3 CO 6 L0*0 U0*) 5 P-* o o -< o --o O cs 1 u* 0 CO 1 UJ z UJ HQH fZ--< (0 u \3 0 a3 VM 0 > O 00 O S O o 00 mo <v U O o 00 UHJ z < c a CO "MO uj z z H <--i CJ c PS, *-H o o 00 NZL 0 >* DC CO ""S* X <; 2* 3 rs >2 cn QJ o 00 22 X 00 hH-4 3 ~UJ <0 L* Z z CO H H U, > r*s c<* O CO 00 E ,0 D -I Z as O > z a H 'O' O o <~* H CO U- O >- Hi--* C-J4 UJ UzJ CO z UJ 1-4 L 3 0 0 z*0-- z 3E w 0 OS UJ z 4- < < Mz O U"> UJ H Z C) CN >* >> <0 a qj 0 c ^4 0) a cj CJ ** u <- H 11 0z O z in -- I 1C H > 1 1 UJ 1 1 <0 M> f- 03 < V 00 H CO <o s 00 c 5 4j <0 CJ 00 LO ow (0 I 3 S 0 4 c cr 3 CJ u. <0 TJ u < CO- <r lH "3 0 <0 O) c CN o u) V r-i o <0 Xqj CuO qj "3 u. 0) o rsj 00 c -uo o (J u <0 o o CL 4*C o o V o< * lA o vy G- SPI-01078 FIGURE \ (MA! MoftlIOWl 344.3 343.4 31. 3 334.4 310.7 334. 323. f 310.4 313.1 311.3 307. J 303.4 iro. j .7>03.4 lot 107.1 1*3.* 1*0.0 174.1 173.3 140.3 144.4 140.3 134.4 133.7 14*. 144.* 141.0 137.1 i33.: 130.3 133. 131.3 117.0 113.7 I0*.l 103. * 1*003..10 O . J 4.4 3.3 '*.4 7 4..* *0.0 4.* 4J . 0 JO. J u.: 31 . J I* * 1*7 1*0 49 :*4 j*i 30? C Jwo/raO Ituo* avfttct - 133 totcict * 1 9.017 OOOUA iCDICf ooeuf '.cocao: * coaraot - a*/*o e* o.i7 40# 11* 1M 037 ill *19 r4 aQAlMAt. 04* la r< ITUO* D) 7 a/io (. coaraoc PERCENTAGE COMPOSITION OF JASAL DIET FOR RATS AND MICE soya bean oil meal fish meal meat and bone scraps vheac (whole ground) maize (whole ground) brewer's yeast grass meal whey powder defacced bone meal sale with trace elements^) 2 B-vitamin mixture ) vitamin ADEK mixture^) soya bean oil .1 7 4 .16 :;9.7 3 3 2 0.4 0.5 0.1 0.3 3 10D.0 Trace elements in sale MnS04.H20 ZnCl2 KJ FeS04.7H20 CoCI26H2O CuS04.5H20 NaCl 2) B-vitamin mixture Thiamin-HCl Ribof1avin Pyridoxin-HCl Niacin Ca-pantothenate Biotin Folic acid Vitamin B]_2-prep. (0.1 21) Ground sucrose 3) Vitamin ADEK mixture Vic. ADj-prilla (Farmix): 2250 IU vit. A, 750 IU vit. D3/g Vic. E-dry powder (Merck) 50 2 Menadion-Na-bisulphite (Vic. k3) Wheat search B tch 2 80 l 50 20 i: 50 20 i 00 45< 80 50C 00 g g g g g g g g B< tch 25 g 30 g 1 00 g 1 25 g 75 g 1.5 g 5g 50 g 95 38.5 g 100 )0 g Ba :ch 250 00 8 00 ::7 8 (10 g g g g added to 1 kg diet 41 mg Mn 12 mg Zn 1. 5 mg J 25 mg Fe 0. 7 mg Co 8 mg Cu added to 1 kg diet 2.5 mg 3.0 mg 10.0 mg 12.5 mg 7.5 mg 0.15 mg 0.5 mg 5.0 mg (* 5 added Co 1 kg diet 6339 IU vit. A 2112 IU vit. D3 45 mg vit. E 3 og vie. K3 SPI-01080 CONTAMINANTS REGULARLY DETERMINED IN 3ASAL DIET Contaminants in basal die1; contaminant - inorganic substances (me /kg) arsenic cadmium lead mercury selenium tin potassium nitrate sodium nitrite - organochlorine compounds (mg/kg) HCB lindane (y-HCH) ct-HCH S-HCH heptachlor heptachlorepoxide a-chlordane y-chlordane aldrin dieldrin endrin methoxychlor p, p'-DDE p.p'-TDE o ,p 1-DDT p, P'-DDT PCBs - organophosphorus compounc s (mg/kg) chlorpyrifos diazinon dichlorvos fenitrothion malathion mevinfos parathion sulfotep - dithiocarbamates, in total , determined as carbondi sulfide (mg/kg) ferbam nancozeb maneb nabam thiram zineb ziram --- - detection limit 0.01 0.005 0.05 0.005 0.01 1 25 5 0.005 0.01 0.01 0.02 0.01 0.02 0.02 0.02 0.01 0.01 0.02 0.05 0.02 0.03 0.03 0.04 0. 3 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.01 0.5 tentative maximum 0.25 0.05 1 .0 0.05 0.5 25 500 10 0.02 0. 1 0. 1 0.02 0.02 0.02 0.02 0.05 0.01 0.01 0.02 0.5 0.02 0.03 0.05 0.05 0.5 0.05 0.05 0.05 0.05 0.5 0.05 0.05 0.05 1.0 SPI-01081 -1 " ANNEX Contaminants in basal diet (cont.) contaminant - poi^cvciic_aromatic irocarbons_ (ug/Jcg) benzo(b)fluoranthene benzo(k)fluoranthene benzo(a)pyrene fluoranthene indeno(1,2,3-cd)pyrene - nitroso compounds (yg/):g) nitrosodiethylamine nitro sodimethy1amine nitrosodipropylamine nitrcsomethylbutylamine nitrosomethylpropylamir e nitrosomorpho1ine nitrosopiperidine nitrosopyrrolidine - raycotoxins (mg/kg) aflatoxin Bi miscellaneous determinat ions oestrogenic activity (Ti ecco test) urease activity (ApH) trypsin inhibitors (mg trypsin/g food) haemagglutinins negative reaction it dilution detection Limit 0.2 0.4 0.2 1.0 0.4 0.5-1.5 0.3-0.9 1.5-4.5 1.5-4.5 1.0-3.0 3.0-9 1.5-4.5 1.5-4.5 0.01 tentative maximum !0 10 10 50 10 10 10 10 10 10 10 10 10 0.05 negative 0.3 8.0 1:200 SPI-01082 T X 3 - 74 NUTRIENT COMPOSITION CF BA:AL DIET FOR RATS Analyses of a 1000 kg batch produced January 24, 1980 moisture L .6 % crude protein (N x 6.25) 2( .9 % crude fat .9 % crude fibre TJ .6 % total ash 5 .6 % calcium c .89 % phosphorus 0 .72 % magnesium 0 .14 % potassium 0 .75 * sodium 0 .28 * iron manganese copper zinc cobalt chromium selenium 175 ppm 95 ppm 15 ppm 50 ppm 2 ppm 3 ppm 0.24 ppm vitamin A vitamin 0 vitamin E carotene vitamin K3 5200 1380 44 20 l.< i I.U./kg I.U./kg mg/kg mg/kg mg/kg SP1-01 83 vitamin vitamin B2 vitamin niacin pantothenic acid folic acid choline biotin vitamin B^ 4.7 5.8 12.0 66 mg/kg mg/kg mg/kg mg/kg 15.5 1.25 1600 0.22 8 mg/ kg mg/kg mg/kg mg/kg ug/kg isoleucine leucine lysine methionine cystine phenylalanine tyrosine threonine tryptophan g/100 g 0.85 1.60 1.03 0.39 0.36 0.89 0.64 0.81 0.21 /16 g N 4.1 7.7 5.0 1.89 1.75 4.3 3.1 3.9 1.01 valine arginine histidine alanine aspartic acid glutamic acid glycine proline serine g/100 c 1.00 1.16 0.45 1.09 1.74 3.69 1.11 1.40 1.10 g/16 g 4.8 5.6 2.2 5.3 8.4 17.9 5.4 6.8 5.3 ANNEX 4 NUTRIENT CC MPOSITION OF BASAL DIET FOR RATS 75 Analyses of a 1000 kg bat ch produced September ?, 1980. mois Cure n. 9 Z crude protein (N x 6.25) 22 , 2 Z crude faC 64 Z c rud e f ib re 31 Z total ash calcium phosphorus 5.<* Z .0 90 Z .0 78 Z magnesium 0. 15 Z potassium sodium 0. 32 Z .0 19 Z iron manganese copper zinc cobalt chromium selenium iodine L35 ppm 95 ppm 16 ppm 55 ppm 2 ppm 2 ppm 0.40 ppm 2.0 ppm vitamin A vitamin D vitamin E carotene vitamin isoleucine leucine lysine me chionine cystine phenylalanine tyrosine threonine trypcoph an 700 3 1.0./kg I.U./kg 5 1 mg/kg mg/kg .8 mg/kg vitamin vitamin vitamin B^ niacin pantothenic acid folic acid choline biotin vitamin 6.2 mg /kg 5.4 mg/kg 11.8 mg/kg 74 mg/kg 11.5 mg/kg 2.4 mg/kg 1600 mg/kg 0.20 mg/kg 16.5 yU/g/kg g/100 g 0.98 1.78 1.13 0.41 0.38 0.98 0.69 0.95 0.23 8' L6 g N *.4 II.0 1.1 .8 : .7 i .4 3.1 3.9 1.0 valine arginine hist idine alanine aspartic acid glutamic acid glycine pro line serine g/100 g 1.14 1.21 0.44 1.19 1 .93 4.20 1.12 1.42 1 . 17 g/16 g N 5.2 5.4 2.0 5.4 8.7 18.9 5. 1 6.4 5.3 SP1-01084 NUTRIENT COMPOSITION OF iASAL DIET FOR RATS Analyses of s 1000 batcn produced February 27, 1981 - ,0 - tnoi a cure crude protein (N x 6.25) crude fat crudefiber cocal ash calcium phosphorus magnesium potassium sodium 12.6 2 20.6 Z 6.1 Z 3.8 X 5.6 X 1.05 X 0.74 X 0.13 X 0.75 X 0.32 X iron manganese copper zinc cobalt chromium selenium iodine 150 90 17 45 0.6 3 0.4 1.5 ppm ppm ppm ppm ppm ppm ppm ppm vitamin A vieamin 0 vitamin E carotene vitamin isoleucine leucine lysine me Chionine cystine phenylalanine tyrosine threonine tryptophan to 's U) a 66 )0 .1) 7 1.6 I.U./kg I.U./kg mg/kg mg/kg mg/kg vitamin B^ vitamin vitamin niacin pantothenic acid folic acid choline biotin vitamin Bj^ 7.5 5.7 12.1 55 14.7 5.1 1500 0.25 15.5 mg/kg mg/ kg mg/kg mg/kg mg/kg mg/kg mg/kg Ug/kg g/100 g 5/16 8 N 0.81 >.0 1.52 '.5 1.03 ! .1 0.38 : .9 0.33 : .6 0.88 i .3 0.63 3.1 0.78 3.8 0.19 0.9 valine arginine histidine alanine aspartic acid glutamic acid glycine proline serine g/100 g g/16 g N 0.95 4.7 1.13 . 5.6 0.46 2.3 1.08 5.3 1. 74 8.6 3.70 18.2 1.13 5.6 1.46 7.2 1.06 5.2 not analysed CIVO-TNO, June 1981 SPI-01085 e.o NUTRIENT COMPOSITION OF CLVO-flASAi DIET FOR 3AT5 Analyses of s 4000 kg bat:h produced by Hope Farms on Sepc. 9, 1981 moisture crude protein (N x 6.25) crude fac crude fiber coral ash calcium phosphorus magnesium potassium sodium LI.3 Z 10.2 6.9 3.9 Z r z 5.3 i 0.65 z 0.7 z 0.21 z 0.8 z 0.32 z iron manganese copper zinc cobalt chromium selenium iodine 220 105 18 55 1 1 0.25 3.0 ppm ppm ppm ppm ppm ppm ppm ppm vitamin A vitamin D vitamin E carotene vitamin isoleucine leucine lysine me thionine cystine phenylalanine tyrosine threonine tryptophan 57( 0 .1) 16 ]3 <3 I.U./kg I.U./kg mg/kg mg/kg mg/kg vitamin vitamin B2 vitamin Bg niacin pantothenic acid folic acid choline biotin vitamin B^ 9.0 7 12 70 18.6 3.3 1700 0.24 13 mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg g/kg g/100 g 5/16 8 H 0.81 k.O 1.60 .9 1.07 Ji.3 0.40 ; .0 0.34 1.69 0.89 4 .4 0.65 3.2 0.78 3.9 0.23 1.14 valine arginine histidine alanine aspartic acid glutamic acid glycine proline serine g/100 g 1.05 1.13 0.49 1.14 1.73 3.51 1.07 1.27 1.01 g/16 g 5.2 5.6 2.4 5.6 8.6 17.4 5.3 6.3 5.0 ^not analysed CIVO-TNO, June 1981 SPI-01086 ANNEX 7 NUTRIENT COMPOSITION OF CIVO-E A SAL DIET FOR RATS Analyses of a 4000 kg batch pro duced by van Eck, Cochen, on Febr 9, 1982 moiscure crude procein (N x 6.25; crude fat crude fiber total ash calcium phosphorus magnesium potassium sodium 11.3 X 19.8 2 6.2 Z 4.1 Z 5.5 z 0.9!. z 0. 6< z 0.1< z 0.7: z 0.32 z iron manganese copper zinc cobalt chromium selenium iodine 315 95 19 65 0.5 1.0 0.3 0.9 ppm ppm ppm ppm ppm ppm ppm ppm vicamin A vitamin D vicamin E carotene vitamin K. 8000 _1) 56 12.5 <2 I.U./kg I.U./kg mg/kg mg/kg mg/kg vicamin B,1 vicamin vicamin B^ niacin pantothenic acid folic acid choline biotin vitamin 7 5 12 55 15 4 1600 0.21 26.8 mg/kg mg/kg mg/kg rag/kg mg/kg mg/kg mg/kg mg/kg ug/kg isoleucine leucine lysine me Chionine cystine phenylalanine tyrosine threonine tryptophan g/100 g g/16 g N 0. 79 4.0 1.52 7.7 0.99 5.0 0.40 2.0 0.32 1.62 0.84 4.3 0.51 2.6 0.77 3.9 0.22 1.11 ^not analysed valine arginine histidine alanine aspartic acid glutamic acid glycine proline serine g/100 g g/16 g N 1.00 5.1 1.08 5.5 0.43 1.02 2.2 5.2 1.65 8.4 3.48 1.06 1.22 17.6 5.4 6.2 0. 94 4.8 CIVO-TNO, June 1982 SPI-01087 - 'T ------- .*. ANNEX 8 CONTAMINANTS IN BASAL DIET FOR RATS AND MICE Sanple of a 1000 kg batch produ:ed on January 24, 1980 lead cadaiua mercury tin arsenic seleniua organo-P-compounds organo-Cl-compounds 0.95 0.06 0.02 2 0.4 0.24 ag/kg mg/kg mg/kg ag/kg ag/kg ag/kg ND NO dithiocarbaaates (as CS^) aflatoxin B]/B2,Gi,G2 oestrogenic activity (Tiecco tept) 0.5 ag/kg < 5 ug/kg ND benzo< a)pyrene benzo(b)fluoranthene indeno (l,2,3-c,d) pyrene benzo(k)fluoranthene fluoranthene K-nitrate Na-nitrite nitrosodiaethylamine nitrosopyrrolidine other nitrosaaines urease activity trypsin inhibitor haeaagglutinins positive ililution 2.5 4.4 2.8 2.6 12.0 ug/kg ug/kg ug/kg ug/kg ug/kg 163 ag/kg 1 mg/kg < 0.4 <2 ND 0.15 < 0.6 none ug/kg ug/kg A pH ag tryps/g sample ND " not detectable CIVO-TNO-May, 1980 SPI-01088 19 CONTAMINANTS IN 3ASAL DIET FOR RATS (1000 leg batch produced 2 7 February lead cadmium mercury tin arsenic selenium organo"P~c otnpound s organo-Cl-compounds PCB's dichiocarbamates aflatoxin oestrogenic accivicy (Tiecc a Cest) benzo(a)pyrene benzo(b)fluoranchene indeno (l,2,3-c,d) pyrene benzo(k) fluoranthene fluoranchene K-nitrace Na-nitrite nicrosodimechylamine nicroaopyrrolidine ocher nitrosamines urease accivicy crypsin inhibitor haemagglucinins posicive dilucion negative dilucion NO " noc detectable CIVO-TNO, June 1981 0.3 0.07 0.25 < 1.0 0.35 0.4 mg/kg mg/leg mg/kg mg/kg mg/kg mg/kg NO ND ND ND <5 U g/kg ND 0.8 0.9 0.6 0.3 5.7 y g/kg U g/kg y g/kg y g/kg u g/kg 77 mg/kg 1 mg/ kg 1.2 y g/kg 1.7 u g/ kg ND 0.05 4 pH < 0.6 mg tryps/g sampl 1 : 10 1 : 20 SPI-01089 T........................................................ t 'Ju N7AMIN ANTS sAc-Au OlZT' c OR RATO iiGOO icg bacon. produced 9 September 1980) Oi lead cadmium mercury tin arsenic selenium 0.25 0.045 0.025 < 1.0 0.45 0.40 mg/kg mg/kg tng/kg mg/kg g/kg mg/kg organo-P-compounds organo-Cl-c ompound s ND ND dithiocarbamaces ND aflatoxin B1,B2,G1, and G2 oestrogenic activity (Tieccj test) <5 Ug/kg ND benzo(a)pyrene benzo(b)fluoranthene indeno (l,2,3-c,d) pyrene benzo(k) fluoranthene fluoranthene K-nitrate Na-nitrite 2.0 2.7 2.0 1.0 16.0 Ug/kg Ug/kg Ug/kg Ug/kg Ug/kg 80 mg/kg 1 mg/kg nicrosodimethy1 amine nitrosopyrrolidine other nitrosamines 0.5 U g/kg 1.5 U g/kg ND urease activity trypsin inhibitor haemagglu tinins positive dilution negative dilution 0.05 <0.6 none A pH mg tryps/g sample ND not detectabli CIVO-TNO december 1980 SPI-01090 !1 CONTAMINANTS IN CIVO BASAL DIET FOR RATS (4000 kg batch, produced by Hop s Farms on September 9, 1981). lead cadmium mercury tin arsenic selenium 0.9 mg/kg 0.07 mg/kg 0.005 mg/kg < 1.0 mg/kg 0.45 mg/kg 0.25 mg/kg organo-P-compounds malathion organo-Cl-compounds PCB's dithiocarbamates (as CS2) aflatoxin oestrogenic activity (Tiecco tes t> benzo(a)pyrene benzo(b)fluoranthene indeno (l,2,3-c,d) pyrene benzo(k)fluoranthene f1uoranthene benz(ghi) perylene ND 0.08 ND ND < 0.5 mg/kg mg/kg <5 ug/kg ND 0.4 0.7 < 0.5 0.1 0.9 0.3 ug/kg ug/kg ug/kg Ug/kg ug/kg ug/kg K-nitrate Na-nicrite 83 <l mg/kg mg/kg nitro8odimethylamine nitrosopyrrolidine other nitrosamines 0.9 1.0 ND U g/kg U g/kg urease activity trypsin inhibitor haemagglutinins positive a Llution negative d ilution ND " not detectable *1... u - lOOl 0.05 A pH 0.51 mg tryps/g l : 50 1 : 100 SPI-01091 ANNEX 12 CONTAMINANTS IN CIVO BASAL DIE" FOR RATS (a000 kg bacch, produced by vat, Eck, Cothen, on Febr. 9, 1982) - 33 lead cadmium mercury tin arsenic selenium 1. 4 .0 09 0. 005 t. 0. 0. mg/kg mg/kg mg/kg mg/kg mg/kg mg/kg organo-P-compounds organo-Cl-compounds PCB's dichiocarbamaces N) N) N!> < 0. i mg/kg aflacoxin B1,,B2,,,G1.,G2,, oestrogenic activity (Tiecco test) <5 NI Ug/kg benzo(a)pyrene 0.5 benzo(b)fluoranchene 0.1 indeno (l,2,3-c,d) pyrene < 0.1 benzo(k)fluoranchene < 0.2 fluoranthene 0.2 benz(ghi) perylene < 0.3 Ug/kg Ug/kg Ug/kg Ug/kg Ug/kg Ug/kg K-nitrace Na-nitrite 34 ND mg/kg nitrosodime thylamine nitrosopyrrolidine other nitrosamines ND 0. 7 U g/kg ND urease activity Crypsin inhibitor haemagglutinins 0.0(1 4 pH 1.4 mg trypa/g sample positive di lution none negacive di lution ND * not detectable SPI-01092 ANNEX \2 Contaminants in drinkinq water contaminant - inorganic substances (i ig/1! arsenic cadmium chromium copper cyanide lead mercury selenium zinc potassium nitrate sodium nitrite ammonia - organochlorine compound s (ug/1) 1,1-dichloroethane dichloromethane tetrachloroethene tetrachloromethane 1,1,1-trichloroethane trichloroethene trichloromethane HCB lindane (y-HCH) a-HCH 8-Hca heptachlor heptachlorepoxide a-chlordane Y-chlordane aldrin dieldrin endrin methoxychlor p,p'-DDE p, p1 -TOE o,p'-DDT p,p1-DDT PCBs - organophosphorus compou ids (ug/1) chlorpyrifos diazinon dichlorvos fenitrothion malathion mevinfos parathion aulfotep detection limit 10 1 10 1 100 1 1 1 1 1,000 1,000 500 tentative maximum 50 5 50 50 100 50 1 10 100 50,000 1,000 1,000 1 5 1 0.1 0.1 0.5 0.3 0.01 0.01 0.01 0.03 0.01 0.02 0.03 0.03 0.02 0.03 0.05 0.15 0.03 0.06 0.06 0.1 0.8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 0.1 0.1 0.1 0.1 0.1 0.1 0.2 0.1 0.2 0.1 0.1 0.1 0.2 0.1 0.1 0.1 SPI-01093 ANNEX 13 (CONT.) Contaminants in drinkinc water (cont.) contarninant - polycyclic aromatic hydrocarbons (ng/1) benzo(b)fluoranthene benzo(k}fluoranthene benzo(ghi)perylene benzo(a)pyrene fluoranthene indeno(1,2,3-cd)pyrene detection limit -ab - tentative maximum 5 200 5 200 5 200 5 200 10 200 5 200 1 Nov. 1979 SPI-01094 ANNEX lu 36 CONTAMINANTS IN TAP WATER ( determined in period Nov. -Dec 1979 lead CAdailllfl oercury arsenic selenium copper chromium zinc cyanide Ob <1 <1 <5 2 <1 SO <1 . 5 3 ammonia nitrate nitrite chloride sodium calcium potassium iron 22 < 0.01 9.6 < 0.01 23 14.5 31 1.2 o o o V 22b di chlorousthane 1,l-dichloroethane <5 absent' chloroform 1,1,1-trichloroethane te trachloromsthane trichloroethane te trachloroethene 0.8 0.2 0.5 absent absent SSI benzo(a)pyrene < benzo(b)fluoranthene < lhdeno (l,2,3,-c,d) pyrene< benzo Oc) fluoranthene < fluoranthane benzo (g,h,i) perylene < 5 5 5 5 5 HCB a-aca lindane m heptachlor heptachl. epoxide aldrin dieldrin a-chlordane y-chlordane endrin p,p'-DDE O,p'-DDT p,p'-TDB p,p1-DDT e-Hca PCB's DDVP aevinfoa iiazinon nalathion sarathion :hlorpyrifos i lulfotep SPI-01095 2b < 0.01 < 0.01 < 0.01 < 0.01 < 0.02 < 0.02 < 0.03 < 0.03 < 0.03 < o.os < 0.03 < 0.06 < 0.06 < 0. 10 < 0.03 < 0.8 < 0.1 < 0. 1 < 0. 1 < 0.2 < 0.2 < 0. 1 < 0.1 . .... . . ' T ' " ANNEX 15 D7 CONTAMINANTS IN TAP WATER (determined in period Jan.-April 1980) lead cadmium mercury arsenic selenium copper chromiurn zinc cyanide 2b '1 <0.1 0.1 <l 55 <1 3 <2 ammonia nitrate nitri te chloride sodium calcium potassium iron E2E 0.01 u < 0.01 30 18.5 31.0 1.3 0.08 b dichloromethane 1,1-dichicroethane chloroform 1,1,1-trichloroethane tetrachloromethane trichloroethene tetrachloroethene <5 <1 0.3 < 0. 1 < 0.1 0.3 < 0.2 t benzo(a)pyrene <5 benzo(b)fluoranthene <5 indeno (l,2,3,-c,d) pyrene < 5 benzo OO fluoranthene fluoranthene <5 < 10 benzo (g,h,i) perylene <" HCB a-HCH Lindane leptachlor leptachl. epoxide ildrin iieldrin -chlordane -chlordane ndrin , p ' -DDE ,p'-DDT ,p'-TDE j ,p '-DDT 'CH p :b s d; jvp nx'vinfos d. azinon malathion p^rathion lorpyrifos sdlfotep SPI-01096 gob < 0.01 < 0.01 < 0.01 < 0.01 < 0.02 < 0.02 < 0.03 < 0.03 < 0.03 < 0.05 < 0.03 < 0.06 < 0.06 < 0.10 < 0.03 < 0.8 < o. 1 < 0. 1 < 0.1 < 0.2 < 0.2 < 0.1 < 0.1 16 CONTAMINANTS IN TAP WATE (determined in period Sepc.- Nov. 1980) lead cadmium mercury arsenic selenium copper ch romium zinc cyanide PPb <1 < 0.1 0.1 1 <1 50 <1 10 <1 ammonia nicrace nicrite chloride sodium calcium potassium iron 2W < 0.01 8.0 < 0.01 25 15.0 28.5 1.2 0.01 dichlo romechane PPb <5 1,1-dichloroeChane chloroform 0.3 0.3 1,1,1-Crichloroethane 0.1 cecrach1oromeChane < 0.1 Crichloroechene 0.4 Ce Crachloroe Chene < 0.2 PPC benzo(a)pyrene <5 benzo(b)fluoranthene <5 indeno (1,2,3 ,-c,d)pyrene < 5 benzo(k)fluoranthene fluoranthene <5 < 10 benzo(g,h,ilperylene <5 HCB a-HCH lindane heptachlor hepcachl. epoxide aldrin dieldrin a -chlordane y-chlordane endrin p,p1-DDE o,p'-DDT p.p'-TDE P,P'"DDT B-HCH methoxychlor PCB's SPI-01097 CIVO-TNO December. 1980 DDVP mevinfos diazinon malathion parachion chlorpyrifos sulfotep fenitrochion PPb < 0.01 < 0.01 < 0.01 < 0.01 < 0.02 < 0.02 < 0.03 < 0.03 < 0.03 < 0.05 < 0.03 < 0.06 < 0.06 < 0.1 < 0.03 < 0.15 < 0.8 < 0.1 < 0. 1 < 0. 1 < 0.2 < 0.2 < 0. L < 0.1 < 0.2 CONTAMINANTS IN TAP VATZ& (determined in period March - May 1981) Lead cadmium mercury arsenic selenium copper ch romi urn zinc cyanide b 1 < 0.1 < 0.1 2 <1 30 c1 2 6 ammonia nitrate nitriCe chloride sodium calcium potassium iron om < 0.01 16 < 0.01 25 14.0 30.0 1.1 0.03 dichioromethane 1.1-dichloroethane chloroform 1.1.1-CrichloroeChane Ce trachloromechane trichloroethene cecrachloroechene b :5 :1 : 0.1 : 0.1 : 0.05 1.0 0.4 benzo(a)pyrene benzo(b)fluoranthene 221 5 <5 indeno (1,2,3,-c,d)pyrene < 5 benzo( It) fluoranthene <5 fluoranthene <10 benzo(g,h,i)perylene <5 HC3 a-HCH lindane heptachlor heptachl. epoxide aldrin dieldrin a-chlordane T-chlordane endrin p, p'-DDE o, p'-DDT p.p'-TDE p,p'-DDT S-HCH methoxychlor SSl < 0.01 < 0.01 < 0.01 < 0.01 < 0.02 < 0.02 < 0.03 < 0.03 < 0.03 <0.05 < 0.03 < 0.06 < 0.06 < 0.1 < 0.03 <0.15 PCB's < 0.8 SPI-01098 CIVO-TNO May 1981 DDVP mevinfos diazinon malathion parathion chlorpyrifoa sulfotep fenitrochion < 0.1 < 0.1 < 0.1 * 0.2 < 0.2 < 0.1 < 0.1 < 0.2 ANNEX ; 3 CONTAMINANTS IN CIVO TAP WATER determined in period Sept. - Nov. 1981) so -- 1 ead - cadmium mercury arsenic selenium copper chromium zinc cyanide Ob <1 <1 <5 < 10 <1 50 < 10 5 < 10 ammonia nicrate nitrite chloride sodium calcium potassium iron om < 0.01 9.3 < 0.01 30 17.5 30.0 1.2 0.03 -- ppb b dich1orome thane <5 - 1,1-dichloroethane < 1 HC8 a-HCH < 0.01 < 0.01 chloroform < 0.1 lindane < 0.01 1,1,1-trichloroethane 0.2 heptachlor < 0.01 te trachiorome thane 0.2 heptachl. epoxide < 0.02 trichloroethene 1.5 aldrin < 0.02 te trachloroe thene < 0.5 dieldrin < 0.03 ppt o-chlordane < 0.03 benzo(a)pyrene <2 Y~chlordane < 0.03 benzo(b)fluoranthene <2 endrin < 0.05 - indeno (1,2,3,-c,d)pyrene <10 p,p1-DDE < 0.03 benzo(k)fluoranthene <2 o, p1-DDT < 0.06 fluoranthene benzo(g,h,i)pery lene <1 <3 p.p'-TDE p,p'-DDT 8-HCH < 0.06 < 0.1 < 0.03 me thoxychlor < 0.15 PCB 1 s < 0.8 __ SPI-01099 CIVO-TNO May 1982 DDVP mevinfos diazinon malathion para chion chlorpyrifoa sulfocep fenitrothion < 0.1 < 0.1 < 0.1 < 0.2 < 0.2 < 0.1 < 0.1 <0.2 ANNEX !? CONTAMINANTS IN TAP WATER (decelrmined in period Jan - March USD lead cadmium mercury arsenic selenium copper ch rotnium zinc cyanide b <L <L <5 < 10 <1 40 < 10 10 < 10 ansnonia nitrace nicrite chloride sodium calcium potassium iron 222 < 0.01 8.3 < 0.01 23 13.0 30.0 1.1 0.02 dich1orome thane ppb <5 1,1-dichloroethane chloroform <5 < 0.5 1,1,1-trichloroethane < 0.2 teerachioromethane < 0.1 trichloroethene 0.4 te era ch1oroe Chene < 0.2 benzol a)pyrene benzolb)fluoranthene PPt < 1.3 < 0.5 indeno 11,2,3,-c,d)pyrene < 1.3 benzollO fluoranthene < 0.7 fluoranchene < 0.5 benzolg,h,i)pery1ene < 5.4 SPI-01100 CIVO-TNO May 1982 HCB a-HCH lindane heptachlor hepcachl. epoxide aldrin dieldrin a-chlordane Y-ehlordane endrin p,p'-DDE o,p'-DDT p,p'-tde P P ' "DDT B-HCH methoxychlor PCB's DDVP mevinfos diazinon malathion para chion chlorpyrifos sulfotep fenicro chion 22k < 0.01 < 0.01 < 0.01 < 0.01 < 0.02 < 0.02 < 0.03 < 0.03 < 0.03 < 0.05 < 0.03 < 0.06 < 0.06 < 0.1 < 0.03 < 0.15 < 0.8 < 0.1 < 0.1 < 0.1 < 0.2 < 0.2 < 0.1 < 0.1 < 0. 2 ANNEX 20 L'l VG/TNO 92 CROSS REF E R E N C E L I S T I N G ASSAY NO. 125 (.1 MALES SPI-01 101 ZERO REFERENCE DATE ~ 2 FEMALES COMR 770002K 770004K 770006D 770008N 770010D 770012K 7700140 770016D 7700181 770020D 770022D 7700240 770Q26D 770028D 7700300 7700320 7700340 770036K 770038D 7700400 7700421 7700440 7700460 7700480 7700500 7700520 7700540 7700560 7700580 7700600 7700620 7700640 '70066N 7700680 7700700 7700720 7700740 770076K 770078N 7700800 7700820 7700840 7700860 7700880 7700900 7700920 7700940 770096K 7700980 EXF'ft A ') A4 A6 A8 A 10 A 12 A 14 A 16 A 18 A 20 A 22 A 74 A 26 A 28 A 30 A 32 A 34 A 36 A 38 A 40 A 42 A 44 A 46 A 48 A 50 A 52 A 54 A 56 A 58 A 60 A 62 A 64 A 66 A 68 A 70 A 72 A 74 A 76 .A 78 A 80 A 87 A 84 A 86 A 88 A yo A 97 A 94 A 96 A 98 K - ki lied SGP CAGE EAI6R COMR (0) n (0) CO) (0) n n y (0) 2 7 61 62 -1 2 (0) 4 r; -1 (0) 4 R3 2 (0) 4 r:.i.1 (0) 4 r:i_n (0) 4 63 (0) 6 Z (0) 6 6.1 (0) 6 62 (0) 6 LI (0) 6 L.2 (0) 8 R1 -1 <0) 8 R1 n (0) 8 K2 _i <0) 8 R2 n <0> 8 63 CO) 10 7 (0) 10 61 (0) 10 \^ (0) 10 (0) 10 .1 2 (0) 12 R1 .1 (0) 1 2 R1 r> CO) 12 R2 .1 CO) 12 R2 2 CO) 12 CO) 14 :3 Z CO) 14 1 <0) .1. 4 h2 0 ) 14 L1 0) 14 L2 CO) 16 R1 L 1 CO ) 16 R 1 12 CO) 16 R2 L 1 CO) 16 R2 CO) 1 6 63 CO) 18 7. CO) 18 61 CO) :iH R7 CO) 18 LI (0) 18 l: CO) 20 R1 L 1 CO) 70 R1 L 1 (0) 20 R7. L L C 0 ) 20 R2 L2 770001D 770003).! 770005D 770007D 770009b 77001IK 770013))! 770015D 770017K 770019D 77002in 77002311 770025K 770027D 770029D 77003ID 770033K 770035D 770037K 770039D 770041K 770043D 770045K 770047K 770049D 770051K 770053)1 770055H 770057D 770059D 770061H 7700631 770065N 7700671 770069D 770071D 770073D 770075D 770077D 7700791 77008 ID 770OH3K 770085D 770087D 770089D 77009 ID 770093).! 770095D 770097D D dead I - il 1 - ( H A art 'l EXF'R AI A3 A5 A7 A9 A 11 A 13 A 15 A 17 A .19 A 21 A 23 A 25 A 27 A 29 A 31 A 33 A 35 A 37 A 39 A 41 A 43 A 45 A 47 A 49 A 51 A 53 A 55 A 57 A 59 A 61 A 63 A 65 A 67 i 6V ,) 71 A 73 A 75 A 77 A 7V A 81 A 83 A 85 A 87 A 89 A 91 A 93 A 95 A v7 SGP CAGE EARR C0) CO) CO) CO) CO) CO) (0) (0) CO) <<>> (0) CO) CO) CO) CO) CO) CO) CO) (0) (0) CO) CO ) CO) (0) CO) (0) CO) (0) CO) (0) CO) CO ) <0 ) CO ) CO ) CO) CO) CO) CO) CO ) (0 ) CO ) CO ) CO ) CO) C0) C0) C0) <0) 17 1 K1 1 R2 1 LI 1 L2 3 R1L1 3 R1L2 3 1621-1 3 R2L2 3 R3 5 co Z R1 R2 5 L1 5 L2 7 R1L1 7 R1L2 7 621.1 7 62L2 7 R3 9Z 9 R1 9 R2 9 LI 9 L2 11 R1L1 11 R .1 L.2 11 R2L.1 1.1 R2L2 11 R3 13 7. 13 R1 .13 R2 13 LI 13 L 2 15 R1L1 15 R11..2 15 R2I...1 .15 R2L2 15 R3 17 1 17 RY 17 R2 17 LI 17 L.2 19 R 3 L 1 19 R 11. 2 19 R2I. .1 l 9 R2L2 ANNEX 20 (CONT. 1) 1YO/TNO - 93 ROSS REF E R E N C E L I STING SSAV NO. 125 0 MALES SP-01102 2 h K(J kKTEkfcNC E DAT FEMALES -- COMR 770100D 770102D 770104D 770106D 770108D 770 HOD 770112D 770114D 770116D 770118D 770120D 770122D 770124 D 770126D 770128D 770130D 770132D 770134D 770136D 770138K 770140K 770142D 770144D 770146D 770148D 770150D 770152D 7701541 770156D 770158D 7 7016 0 D 770162N 770164K 770166K 770168K 770170K 770172D 770174D 770176D 770178N 770180N 770182D 770184D 7701 SAD 7 7 018 8 D 770190K 770192D 770194N 7701960 770198D 770 2001' EXPfi A100 A102 A104 A106 A108 A110 A112 A114 All 6 A118 A120 A122 A124 A126 A128 A130 A132 A134 A136 A138 A140 A142 A144 A146 A1 48 A150 A152 A I 54 A156 A158 A160 A162 A1 64 A 166 A168 A170 A1 72 A 1 74 A 176 A178 A 1 80 A182 A 1 84 A186 A 1 88 A 1 90 A 1 9? A1 y4 A3 96 A 198 A 7 00 SGP CAGE E ARR (0 ) 20 <0) *y*y (0 ) 'vr> (0 ) n (0) *yn (0) nn R3 2 R1 R2 L.l L.2 (0) 24 K 1L1 (0) 24 R 1L2 (0) 24 R 2L1 (0) 24 R (0) 24 R3 (0 ) 26 Z (0) 26 R1 (0) 26 R2 (0) 26 I..1 (0) 26 L.2 (0> 28 R 1L1 <0) 28 R 1L2 (0) 28 R 21.1 (0) 28 R 2L (0) 28 R3 (0) 30 Z (0) 30 R1 (0 ) 30 R2 (0) 30 1. 1 (0) 30 L2 (0) 32 R LL1 < 0 ) 32 R LL2 (0) 32 R 2L 1 (0) 32 R :l;2 (0 ) 32 (0 ) 34 R3 z < 0 ) 34 R1 < 0 ) 34 R2 (0 > 34 1. 1 ( 34 L.2 ( w ) 36 R .LI ( 0 ) 36 R .L2 ( 0 ) 36 R 'L 1 (0) 36 R 21.2 ( 0 ) 36 R3 (0) 38 Z (0) 38 R1 <0 ) 38 R2 (0) 38 L.l <0 ) 38 L2 < 0 > 40 R :,li ( 0 ) 40 R :,L2 ' 0 ) 40 R 2L 1 ( 0 ) 40 R 'M n ( 0 ) 40 R3 COMR 770099H 770101D 770103D 770105H 77010711 7701OVD 7701111 7701131 770115K 770117D 770119D 7701211 7701231 770125K 770127H 770129D 770131D 770133K 770135D 770137D 770139D 770141K 770143D 770145D 770147D 770149D 77015ID 770153D 770155 JJ 770157D 770159K 770161D 770163D 770165D 770167K 7 7 016 9 D 7701711' 770173K 770175D 770177D 770179 E' 7 7 0181D 7 7 018 3 D 7701 BSD 7 7018 7 D 770189N 770191K 7 7 0 1 9 3 L' 770195).' 770197D 770199K EX PR A 99 A 1 01 A.103 A.105 A107 A109 A11 1 All 3 A115 A117 A119 A121 A.123 A125 A127 A129 A131 A133 A135 A1 37 A139 A1 41 A143 A1 45 A1 47 A149 A151 A153 A155 A157 A159 A1 61 A.163 A165 A167 A1 6 9 A1 71 A .1 7 3 A175 A1 77 A179 A1 81 A.1.H3 A185 A187 A189 A191 A 193 A.t 95 Al V / A i,99 SGP CAGE EARR (0 ) (0) (0) (0 ) (0) (0) <0 ) (0) (0) (0) (0) (0) (0 ) (0) <0> (0) (0) (0) (0) (0) (0) (0) (0 ) (0) (0) (0) (0) (0 > <0 ) (0 ) (0) <0) (0 ) (0) (0 ) <0) (0) <0) (0) (0; (0) (0) (0) (0) (0) (0) <0 ) <0) (0) (0) (0) 19 21 21 >. a1. 21 21 23 23 23 23 23 25 25 25 25 25 27 27 27 27 27 29 29 29 29 ^<9 31 31 31 31 31 ' 33 33 33 33 33 35 35 35 35 35 37 37 37 37 37 39 39 39 39 39 R3 V. R1 R2 l.l I..2 R1I..3 R1L2 R21 1 R2I..2 R3 Z R1 K2 I..1 L2 R1L1 R1L2 R2L1 R2I..2 R3 z R1 R2 1. 1 L2 K1.L1 R1L2 R2L1 R2I..2 R3 Z R1 K2 1.. ,i 1. 2 R1L1 R1L2 K2L.1 r R3 z R1 k :/ I. l L. 2 R1L1 R1L2 R2L.1 R2L2 R3 ' ,, .. .... ANNEX 20 (CONT. 2) C I 'JO/TNG CROSS REF E R E N C E L ASSAY NO. 125 U MALES COMR 7702020 770204D 770206D 770208D 770210D 770212D 7702:4D 770216D 77021SD 770220K 770222D 770224D 770226K 770228D 770230D 770232D 770234K 770236H 77023SD 7702A0D 770242K 770244D 770246K 7702A8D 770250D 770252K 770254D 770256D 770258K 770260D 770262D 77026AD 770266D 770268D 770 270 Ei 770272 D /70274K 770276K 770278D 770280D 770782D 77028AD 770286D 7702881 770290K 770292D 77029AK EXPR B2 B4 B6 B8 B 10 B 12 B 14 B IS B 18 B 20 B 22 B 24 B 26 B 28 B 30 B 32 B 34 B 36 B 38 B 40 B 42 B 44 B 46 B 48 B 50 B 52 B 54 B 56 B 58 B 60 B 62 B 64 B 66 B 68 B 70 H 72 B 74 B 76 B 78 B 80 B 82 B 84 B 86 B 88 B 90 B 92 B 94 SGP CAGE <0) <0 ) (0) (0) (0) (0) (0) (0) (0) <0> (0) (0) (0) (0) (0) (0) (0) <0> (0 ) (0) (0) (0 ) (0) (0 ) (0) (0 ) (0 > (0 ) (0) (0) (0) (0) (0) (0 ) (0 ) (0) (0) (0 ) (0 ) (0) (0) (0) LO ) <0) (0) (0) <0) 42 42 42 42 42 44 44 44 44 44 46 46 46 46 46 48 48 48 48 48 50 50 50 50 50 52 52 52 52 52 54 54 54 54 54 56 56 5 ft 56 56 58 5R 58 58 58 60 60 EA RR -r Ri R2 LI L2 R1 l.l Rl I..2 R2 LI R2 L2 R3 Z Ri R2 LI L2 RI LI R1 I..2 r: L.l r: L2 R3 Z Ri R2 LI L.2 r: LI R1 L2 r: LI RE L2 R3 Z RI R2 L.l L.2 R1 l : RI L2 r: LI r: L.2 K3 2 R.t R2 L.l L.2 r: I..1 R1 1.2 - 54 - STING ZERO R E F E R ft. N! (. h ).i A I K - ' FEMALES COMR EXPR SOP LALjP EAkk 77020IK 770203K 770205D 770207D 770209D 77021ID 770213D 770215D 770217K 770219D 770221D 7702231 77022511 770227D 770229D 77023.ID 770233D 770235D 770237D 770239K 77024.Ui 7702430 770245D 770247K 770249B 770251D 7702530 770255D 770257K 7702590 770261K 770263K 770265D 770267K 770269D 77027IK 7702730 770275K 770277D 7702/9M 770281 J.i 7702830 770285D 770287K 77028VD 770291 Ei 7 7 0 2 9 3 Ei B1 B3 B5 B7 B9 B 11 B 13 B 15 B 17 B 19 B 21 B 23 B 25 B 27 B 29 B 31 B 33 B 35 h 37 B 39 B 41 B 43 B 45 B 47 B 49 B 51 B 53 B ir e JJ B 57 B 59 B 61 B 63 B 65 B 67 B 69 B 71 B 73 B 75 B 77 B 79 B 81 B 83 B 85 B 87 B 8V B 91 B 93 L 0) (0) <0) <0) (0) (0) (0) <0> (0) (0) (0) (0) (0) (0) <0) (0) (0) (0) (0) (0) (0) (0) (0) (0 ) (0) (0) (0) (0) (0 ) (0) <0) (0) (0) (0) (0) (0) (0) (0) (0 ) (0) (0) (0) (0) (0 ) (0) (0 ) (0) 41' i 4 i ki 41 R2 41 LI 41 L2 43 RI L.l 4 3 R1I..2 4 3 R2I. 1 43 R2L2 43 R3 45 Z 4 5 RI 45 R2 45 LI 45 L2 4 7 RI L.l 47 R1L2 4 7 R2L1 47 R2L2 47 R3 49 Z 49 Ri 49 R2 49 LI 49 L 2 51 RI LI 51 K1I..2 51 K2L1 51 R2L2 51 ft'3 53 ' '/. 53 RI 53 R2 53 LI 53 L.2 55 R11. j 55 K1L2 33 R2L1 55 R2L2 55 K3 57 7 57 ft.'l. 5 7 R2 57 L 1 57 1. 2 3V K l t L \;9 KM. 1 2 SPI-01103 ANNEX 20 (CONI. 3) CIVO/TNQ CROSS REF E R E N C r L I STING ASSAY NO. 125 0 MALES SPI-C 1104 ZK Rl) KLM-. KK Nl L DATE hEMAILS COMR EXPR SliP CAGE Ei RR COMR EXRR Slip CAGE EARR 770296D B 96 (0) 60 r: LI 770298D B 98 (0) 60 HI L2 770300D B100 (0) 60 R3 770302D B102 (0) 62 770304D B104 (0) 62 2 Rl 7703060 B106 (0) 62 R2 770308K B108 (0) 62 1.1 7703ion B110 (0) 62 L.2 770312D B1 12 (0) 64 R] LI 770314D B114 (0) 64 Rl L2 7703161 B116 (0) 64 r: LI 770318D B118 (0) 64 r: 1.2 770320D B120 CO) 64 R3 770322D B122 (0) 66 Z 770324D B124 (0) 66 Rl 7 70 3 2 6 D B126 (0) 66 R2 770328D B128 <0> 66 I..1 770330D B130 <0 ) 66 1.2 770332D B132 (0) 68 R3 LI 770334D B134 (0) 68 RJ L 2 770336D B136 (0) 68 k: I...1 770338D B138 (0) 68 r: 1.2 7703401 B140 (0) 68 R3 770342D B142 (0) 70 2 7 7 0 3 4 4 D B144 (0) 70 Rl 7703460 B146 <0> 70 R2 7703480 B148 (0) 70 1. 1 770350K B150 (0 ) 70 L2 770352D B1 52 (0 ) 72 R 3 LI 770354K B 154 CO) 72 Rl L 2 770356D B156 (0) 72 r;. 1. i /703580 B158 (0) 72 Rl L.2 770360N B160 <0 ) 72 7703620 B 1 62 <0) 74 R3 Z 770364K B 1 64 (0) 74 Rl /70366D B 1 66 CO ) 7 4 R2 7703680 B 168 (0) 74 1 .1 7703700 B 170 (0 ) 74 L2 770372K HI 72 (0) 76 Rl LI 7703740 B 1 74 (0) 76 Rl L.2 7703760 B 176 (0) 76 r: 1 1 77037SK B178 (0) 76 ft1 L.2 770380N B1 80 (0) 7 <i R3 7703820 HI 82 (0 ) 7b Z 7703840 B184 (0) 78 Rl 7703860 B 186 (0 ) 78 R2 7703880 B188 (0) 78 11 7703901 B 1 90 (0 ) 78 L2 7703920 B 1 9 2 (0 ) 80 ft 1 LI 7703940 B 19 4 CO ) 80 K L2 7703960 HI 96 ( 0 ) HO ft 1:li 770398N B 1 98 < 0 ) 80 ft 1:l:.' 7 70-100 0 B200 CO > 80 K3 770295K 7 702.9 70 770299D 77030 ID 7703031 770305K 7703070 770309K 77031 ID 7703131 7703150 7703170 7703190 7703210 7703231 7703250 770327K 7703290 77033ID 7703330 7703350 7703370 7703391 7703410 7703430 7703450 770347K 7703490 770351K 770353K 7703550 7703570 7703590 7703610 7703631 770365K 7703670 770369K 7703710 7703730 7703750 7703770 7703790 7703810 7703830 7703850 7 7 0 38 7 K 770389K 7703910 7 703930 7703950 7703970 770399 1 B 95 B 97 B 9? h i. o i B103 BIOS B107 B109 Bill B113 B115 B117 B119 H121 B123 B125 B127 B129 P131 B133 B135 B137 B139 B141 El 143 B145 B147 B149 B151 EH 53 B155 B157 B1.59 B161 B163 B165 B167 B169 B1 71 EH 73 B175 B1 77 HI 79 EH HI EH 83 B185 B187 EH 89 HI 91 B1 9 3 HI 95 Bi 97 B l 99 (0) c 0) (0) c0) (0) CO) (0) CO) CO) CO) CO) CO) CO) CO) CO) CO) CO) (0) (0) (0) CO) CO) (0) (0) CO) CO) (0) (0) CO) CO) (0) CO) CO) 1<>) CO) CO) CO) CO) C0) CO) (0) C0) (0) (0) CO) (0) CO) (0) (0) C0) (0) (0) (0) 59 59 59 6.1 61 61 61 61 63 63 63 63 63 65 65 65 65 65 67 67 67 67 67 69 69 69 69 69 71 71 71 . 71 71 73 73 73 73 73 75 75 75 75 75 77 77 77 77 77 79 79 79 79 7'-' R2L.1 KOI. 2 R3 Rl R2 1. :i I. 2 R1L1 R1L2 R2L.1 R2I..2 R3 uy. Rl K2 1. .1 L2 R1L1 R1L2 R2L.:i R2I. 2 R2 7 Rl K2 l..:i L2 R1L1 R1 L 2 KOI. ROLL R3 Z Rl R2 1. I L2 R1L1 R1L 2 R2I. KOI. 2 R3 l Ri k 11 L2 R 1 L. 1 Kll . R2I 1 R^l. . ft' . * ...... 'T ' .. W v. < ........ ANNEX CIVQ/TNG (CONT. 4) - 90 CROSS REF E R E N C E L I STING ASSAY NO. 125 0 ZERO F:F FFRENC F On IF COHR 770402D 770404K 770406D 7704080 77041 on 770412K 770414K 770416K 770418K 770420D 770422D 770424D 770426D 7704230 7704300 7704320 770434D 770436D 770438D 770440D 770442D 770444D 770446D 770448D 770450K 770452D 770454D 770456D 770458D 770460D 770462K 770464D 770466K 7704681s 770470K 770472D 770474K 770476D 770478D 7704800 770482D 7 70484 D 7704860 770488D 770490D ALES EXFR Cn c4 c6 i: a V. 10 c 12 c 14 c 16 c 18 c 20 c 70 c 24 L 26 C 28 c 30 c 32 c 34 i; .56 c 38 c 40 C 42 L 44 (. 46 c 48 c 50 c 52 c 54 c 56 c 58 c 60 c 62 (.: 64 L 66 C 68 C 70 c 72 (. 74 c 76 0 73 c 80 c 87 i: B4 i; B6 <:: 88 c 90 SGF CAGE 15 ARR CO) B7 Z (0) 87 R1 (0 ) B7 R2 (0) 82 L1 (0) 82 L2 (0) 84 R lLl (0) 84 R 1L2 (0) 84 R 2L1 (0) 84 R 2L2 (0) 84 **R3 (0) 86 Z (0) 86 Rl (0) 86 R2 <0> 86 L1 (0) 86 I..2 (0) 88 R :l!.. 1 <0) 88 R 1L2 (0) 88 R 2L1 (0) 88 R :>L2 (0) 88 K3 (0) 90 Z (0) 90 Rl (0) 90 R2 (0) 90 LI CO) 90 I..2 (0) 92 R lLI (0 ) 92 R ,L2 (0) 92 R 2L1 (0; 92 R 11.2 (0) 92 R.5 (0) S'4 2 (0) 94 Rl < 0 ) 94 R2 (0) 94 1. 1 <0> y4 1. 2 < 0 ) 96 R : L l (0) 96 R : L2 (0) 96 R 7L1 (0) 96 R 71.2 <0 ) 96 R3 (0) 98 Z <<)) 98 (0 ) 98 (0 ) 98 Rl R2 1 .1 < 0 ) 9B 1. 7 C8MK 77040IK 7704030 77G405D 7704070 770409K 77041in 770413D 770415K 770417U 7704190 77042ID 770423D 7704251 770427D 770429 )i 77043IK 770433D 770435.1 770437K 77043VK 770441D 770443D 7704450 7704470 77044VK 770451D 770453D 7704550 7704570 7704590 770461K 770463K 77046.51 7704671s 7704690 7704710 770473D 770475K 7704770 7704790 7704810 7704830 7704H5K 7704870 7704890 FEMALES EXPR C1 C3 (. ks.j t; / c9 c 11 c 13 0 15 <: 17 c 19 c 21 c 23 i; 25 c 27 c 29 c 31 c. 33 8 35 8 37 C 39 C 41 C 43 8 45 C 47 c 49 c 51 c 53 8 55 C 57 C 59 c 61 t: 63 <; 6 3 L 67 c 69 c 71 r: 75 t: 75 L 77 c 79 c 81 i; B3 c B5 i; 87 c 89 SGF (0) c0> (0) (0) CO) CO) (0) (0) (0) (0) CO) CO) CO) CO) CO) (0) CO) CO) (0) (0) (0) (0) (0) <0) (0) CO) CO) (0) CO) (0) (0) (0) .<<>) (0) CO ) (0) < 0) CO) CO ) (0) C0) co; (0 ) CO) <0) UABF H AKK HI 8 :i. Rl HI ft 2 81 L 1 81 L 2 83 ftll.,1 83 K1.L2 83 R2L1 83 R2L2 83 R3 85 Z 85 Rl 85 R2 85 L.l 85 L2 87 ft .1L1 87 R1L2 87 R2L1 87 R2L2 87 K5 8 V 7. 89 Rl 89 R2 89 LI 89 I..2 91 R1I...1 91 R1L2 91 R2L1 91 K2L 2 91 ft 5 93 ' V 93 Rl 93 R2 92 LI 9 3 I..2 9 5 R1L1 95 R1L2 95 R2I. 1 95 R2I. 95 ft 3 97 3 97 Rl 97 H? 97 1 i 97 i. SPI-01105 T . [ V\j / i r^O 9? CROSS REF R E N C E LISTING ASSAY NO. 125 0 MALES COMR EXPR 770492B 770494D 770496N 7704931 770500K 7705021 770504D 770506K 770508B 770510D 770512D 770514D 770516D 770518D 770520D 770522D 770524D 770526D 770528D 770530K 770532D 770534D 770536D 770538D 770540D 770542D 770544K 770546D 770548D 770550D 770552K 770554D 770556D 770558D 770560D 770562D /70564D 770566D 7705681 770570D 770572D 770574D 770576D 770578D 770580D 770582K 770584D 770586I 770588 Ei 770590D 770592D 77059 4 Li 770596D 770598D / 7 0 6 0 0 Li C 92 C 94 C 96 C 98 Cl 00 Cl 02 Cl 04 C106 C108 C3 10 C112 C114 C116 Cl 18 Cl 20 Cl 22 C124 C126 Cl 28 Cl 30 Cl 32 C134 C136 Cl 38 Cl 40 C147 Cl 44 C 1 46 Cl 48 C 150 Cl 52 C 154 C156 Cl 58 Cl 60 Cl 62 C 164 C 1 66 Cl 68 Cl 70 C 172 C 1 74 C 176 Cl/8 C l 80 Cl 2 C 184 C18` 1.188 C 190 C 19 7 (.194 C 1 96 C 198 C 200 SCR (0) (0) (0) <<>> (0) (0 ) (0) (0) (0) (0) (0) (0) (0 > (0) (0) (0 ) (0) <0 > <0 ) (0) <0) (0 ) (0) <0 1 (0) <0> (0) (0) CO) CO) CO) CO ) CO) <0 > CO) CO) <0) (0) CO ) (0) CO ) (0) (0) <0) (0) (0) C0) (0) (O) (0) (0) (0) i0) (0) (0) SPI-C11106 CAGE EAF 100 100 100 100 100 102 102 102 102 102 104 104 .104 104 104 106 106 106 106 106 108 103 108 108 108 110 1 10 110 110 110 117 1 17 Il i ** 112 3 14 134 l i4 :l 1 4 114 ) 16 116 ! i6 116 116 ) )8 l 18 l ,iH 1 )8 1 18 t 70 120 1 20 ! 70 i 70 R11 1 R i.l -2 K2i -1 k 21.2 *3 Z *2 -1 -2 r: 1 R3 -2 r:;i -1 r:i-2 *3 7- *1 *2 ^ -2 R) D ri -2 R2 -1 R2 -2 <3 2 '1 <2 1 2 K1 LI K1 2 R2 * 1 R2 1-2 F3 2 1 ' E2 LI L2 R1 l 1 R 1 12 K7 LI R2 L2 R3 2 Rl R2 L 1' R1 L: ft 1 L2 R7 1 K71 2 k' COMR 770491 Jj 770493D 770495K 770497K 770499K 770501)1 770503K 770505D 770507K 770509D 77051 IK 770513D 770515D 770517K 770519D 77052.:lD 770523K 770525K 770527D 770529] 770531)1 770533)1 770535D 770537D 770539D 77054ID 770543K 7705451 770547D 770549D 770551D 770553D 770555D 770557D 7705391 /7056ID / 7056 3D 770565D 770567D 770369H 7705 71)1 /70573D 770575D 770577D 7/0579D 7 70581)1 770583D 77058SK 770587D /70589D 77059 IK 770593D 770595D 770597K TJAcnor, 7R.R0 REFERENCE DALE = 2 !- K M 01. FS EXPR C 91 C 93 C 95 C 97 C 99 Cl 01 Cl 03 C105 Cl 07 Cl 09 cm Cl 13 C115 Cl 17 Cl 19 Cl 21 C123 C125 C127 Cl 2 V Cl 3.1 Cl 33 C135 Cl 37 Cl 39 Cl 41 C143 C1 45 Cl 47 Cl 49 Cl 51 C153 C153 Cl 37 Cl 59 Cl 61 C1 63 C 165 (; i 6 7 Cl 69 Cl 71 C1 73 Cl 73 0177 Cl 79 CJ 81 Cl 83 C185 1,18/ C 189 C191 1, 1. 9 6 Cl 93 C 19 7 --- - COP CAGE EAftR (0) <0 ) CO) (0) CO) CO) CO) CO) (0) CO) (0) (0) CO) C 0) (0) (0) (0) (0) ( 0) CO) (0) CO) CO) (0) <0> CO) CO) CO) <0) CO) CO) (0) (0) CO ) CO) CO ) (0) 10 ) C0) CO) CO ) CO) CO) CO) CO) CO) C0) CO) (0) C0) (0) (0) C0) ( 0) 99 99 99 9V 99 101 101 103 1 01 101 103 103 .103 103 103 105 105 103 105 105 107 107 107 1 07 107 109 109 .109 .1 09 109 111 3 13 1 .11 111 111 113 l :i 3 1 I3 1 1A 113 115 :l :t li;. :!. 15 115 11 / li/ 1 .i 7 3 17 1i/ .1 1 V 11 V 139 1 IV R3 L3 K11. 2 R2I..3 K7L2 R3 7. KM R2 LI L2 ft 3. LI R1I..2 R2L1 R2L2 ft 3 7 Fc1 R2 LI L2 ft] L.1 ril:2 R2L1 R2L2 ft 3 Z KM R2 LI L2 R 1 L 3. K11..2 ' K2I. 1 R2L2 R3 7 R :l ft 2 Ll L2 ft 11.1 Kil 2 K2L1 R2L2 ft 3 7 Kl R2 Ll 1. 2 R 1L 1 ftl L2 ft.'! .1 k:*i 2 ANNEX 20 (CONT. 6) GIVO/TNQ CROSS R E F E R E N C ASSAY NO. 125 0 L nALES COMR 770602D 7 7060 4D 770606H 770608D /70610D 770612D 770614D 7706loD 770618K 770620D 770622D 770624D 770626D 770628K 770630D 7 70 6 3 2 D 770634D 770636D 770638D 770640D 770642D 770644K 770646D 770648D 770650D 770652K 770654D 770656D 770658D 770660D 770662D 770664K 7 70666D 7 70 6 6 8K 770670k 770672U 770674k 770676D 770678D 770680D 770682D 770684M / 70 6 8 61 770688D 7 70 6 ?0 D /70692D 7 7 0 6 9 4 ti EXF'R LI )i 4 )J 6 D8 D 10 n 12 D 14 ii 16 D 18 D 20 D n '"t Li 24 n 26 D 28 D 30 Li 32 r.i 34 11 36 D 38 D 40 n 42 D 44 D 46 D 48 D 50 n 52 D 54 D 56 D 58 li 60 u 62 I.l 64 D 66 D 68 n 70 n 72 ji 74 D 76 D 78 H 60 u H2 ).l 64 D 86 ).i HH H 90 D 92 Li 94 SGF' (0) <0 ) 10) (0) <0> (0) (0) <0) (0) (0) (0) (0) <0> (0) (0) (0) (0) <0 ) <0) (0) (0) (0) (0) (0) <0> (0) :o) (0) (0 ) (0) <0) (0) <o <. < o ; <0) (0) (0) (0) (0) <0 ' (0) (0) (0) <0 ) (0) (0) CAGE 1 2.7 122 122 3.22 122 124 124 124 124 124 126 126 126 126 126 128 128 128 128 128 130 130 130 130 130 132 132 132 132 132 134 134 134 134 1.34 136 136 3 36 1 36 136 138 3 38. 3 38 138 138 140 14 0 <k Z il *2 .1 .2 Rll-1 Rll n R2 ..1 R2 K3 Z R3 <2. .1 _2 R1 _1 Rl n R2 -.1 R2 n <3 Z Cl <2 -1 2 Rl .1 R3 2 K2 1 R2 L.2 :3 Z 3 2 1 LRl . 1 Rl 2 R2 . 1 R2 L. 2. R3 Z hi R2 LI .2 Rl . 1 Rl : 98- STING ZERO kh1- h Kh Nl>: l.ih l> - i>i OUMK 77060 ID 770603)1 7706058 770607D 770609K 770611D 77061 3D 77063 5D 7706171 770619D 770621D 770623D 770625K 770627D 770629D 770631D 770633D 770635H 770637D 770639D 77064ID 770643D 7 7064 5 J.i 770647D 770649D 770651D 7 7 065 3 JJ 7 70655 Li 770657D 770659D 7706611 770663K 7706651 V0667D '0669K 770671D / 706731.1 770675D 7706771 770679D 770683 D /70683J.I 7706850 770687D / /0689)1 / 7069 ID 7706930 FEMALE'S EXPR D1 ).i 5 D W ) D7 D? Ii 3 1 ).i 13 D 15 D 17 D 19 D 21 D 23 D 25 D 27 D 29 I) 31 ).i 33 D 35 D 37 D 39 n 41 D 43 D 45 D 47 D 49 D 51 D 53 D 55 D 57 Ii 59 D 61 D 63 D 65 D 67 H 6V ).i 7 :i ).i 73 n 75 D 77 D 7V H 81 I.i 83 D 85 )i 87 n 89 D 91 D 93 SGF (0) 0) C0) (0) (0) CO) CO) CO) CO) CO) CO) (0) CO) CO) CO) CO) (0) CO) CO) (0) CO) CO) CO) CO) CO) (0) CO) C0> CO ) CO) C0) CO) CO) (0) CO ) i 0) C0) (0) CO) C0) C0) (0) (0) C0) c0) .0) C0) CAGE t 23 121 121 121 1 21 123 123 123 3 23 123 125 125 125 125 125 127 127 127 127 127 129 129 12? 3.2 V 12 V 131 131 3 33 133 131 133 133 133 3 33 133 135 135 3 35 135 1. 35 137 137 3 37 137 137 3 3? 139 FARR im kl k2 1. ,i 1.2 R1L1 R1L2 K2I. 1 k2L2 R3 LT. R3 R2 LI L2 R1L1 R1L2 k.'/Ll K2I. 2 R3 Z R3 R2 1. 1 L2 R1L1 R3.L2 K2I. 1 R2L2 R3 Z M k2 1.. .1. L2 i . LI K1L2 k2l. :i k2l. 2 R3 7 KM k:> Ll l2 K11 i R1L2 SPI-01107 ANNEX 20 (CCMT. 7) CI'JO/TNO CROSS REFERENCE LISTING SPI-01108 99 ASSAY NO. 125 0 ZEKU REFERENCE DATE MALES EEMALES COMR EXRK CAGE. E*RR COMR E.XF'K HI6R CAGE EARR 770696D 77069SD 770700D 770702K 7707Q4K 770706K 770708K 7707101?; 770712K 770714K 770716K 770718K 770720K 770722K 770724K 770726K 770728K 770730K 770732K 770734K 770736K 770738K 770740K 770742K 770744K 770746K 770748K 770750K 770752K 770754K 770756k 77C-758K 770760K 770762K 770764K 770 7 66k 770768k 770770K 770772K 770774K 770776k 770778K 770780k 770782K 770784N ' 70 786k 770788K 770790k . 70 7V?l\ /0794K 7 /0 796N 770798K 770800N Ji 96 D 98 ru oo D102 D104 niOA D108 DUO D112 Dll 4 Dll 6 D118 D120 D122 D3 24 D13A j.uca D130 D132 D134 D13 6 D3 38 D140 D142 D14 4 D3 46 D1 48 D150 D152 DIM LULA LU 28 D160 D16 2 D1A4 0.1 A A 0168 D1 70 D17? D17 4 01 76 D17 8 D180 0182 D1H4 0186 01 hH hi yo li 1 72 0174 0196 UJ VH LU'OO (0 ) (0) CO) CO) (0) (0) (0) (0) (0) (0) (0) (0) <0) CO) CO) (0) (0) (0) CO) (0) (0) <0> CO) (0 > CO) CO) (0) (0) CO) (0) (0) (0) CO) CO) <0 ) C0) CO) (0) <0 ) (0) iO> <0 ) (0 ) CO) CO ) CO) CO) C0) l0) CO ) C0) <0> (0) 140 140 140 142 142 142 142 3 42 .144 144 144 144 3 44 146 146 146 146 346 1 48 148 148 148 148 150 150 150 150 150 152 152 152 152 152 1 54 154 154 154 154 156 156 156 156 156 15H 3 58 158 158 158 160 160 160 160 160 R 2L1 R >L2 R3 2 R1 R2 LI L2 R: LI R3L2 R'Ll RIL2 R3 2 R1 R2 1. 1 n R1 .1 R1 .2 R2.1 R2 2 C3 7 R1 U2 11 1.2 k.1.1 3 R1L 2 R2L 1 R21 2 E3 2 F1 R2 1. 1 1. 2 K 3 L1 R1L2 R2L 3 K2L 2 K5 4 RL. l:: K3 l . k ll. 3 R2V. R2LC r; 770695D 770o97D 770699D 77070 IK 770703K 770705K 770707k 77O709K 77071IK 770713K 770715K 77073 7K 770719K 77072 IK 770723K 770725K 770727K 77072 S'K 77073IK 770733K 770735K 770737K 77073VK 770741k 770743k 770745K 770747k 770749k 77075IK 770753K 770755K 770757K 770759K 770761k 770763k 7707651 770767k 7/07A9K 770771k 770773k 770775k 770777K 770779k 770781k '70783K 770785k 770737K 770789K 770791k 7 70 7V3K 770795K 770797k 770799k )) 95 D 97 D 99 D101 D103 D1 05 D10 7 D109 Dill D113 D115 Dll 7 D119 D121 D3.23 D :i 25 D127 D129 0131 D133 0135 D137 It 139 D141 ru 43 D145 D14 7 t'l 49 D151 D 3 53 1.U55 M 57 D159 D161 HI 63 D165 D.1.67 D169 D172 D1 73 D175 )J3 77 0179 D18.1 LU83 0185 U J H7 D1 HV Di91 D193 D 1 95 Li 19 7 Li 199 (0) CO) CO > (0) (0) <0> (0) (0) CO) (0) CO) (0) (0) CO) CO) CO) (0) CO) CO) (0) (0) <0> CO) CO ) CO) CO) CO > CO) (0) (0) CO) CO) (0) CO) (0) (0) (0) (0) CO) (0) CO) CO) (0) (0) CO) (0) CO) CO ) (0) (0) C0) C0) (0) 139 139 139 I4 i 141 141 141 141 143 1 43 343 143 143 145 145 145 145 145 147 147 147 147 147 149 149 149 149 149 151 153 151 151 3 51 1 53 153 153 153 3 53 155 3 55 155 155 155 157 157 15 7 157 157 159 159 159 159 159 R2L1 R2L2 K3 7 R1 R2 LI L2 R1L1 K1L2 R2L1 R2L2 R3 /. R1 R2 1. .1 1.2 R11.3 R1L2 R2L1 R2L.7 R3 l R1 R2 1. X 1.2 R 11.1 R1L2 R2L1 K2I.2 k`3 2 ftl R2 1. I 1. RJ Ll R1L2 R2L1 K2I..2 R3 Z R1 R2 Ll L2 k 11. 1 Ki1 7 k 21. i R2L2 R3 ANNEX 20 (CONT. 8) CI yO/TNCl CROSS REF E R E N C E L I STING 100 - ASSAY NO. 3 25 0 ZERO RE. FERENC I- U A MALES females CQMR 770802D 770804D 770806D 770808D 77081OD 7708120 770814D 7708160 770818D 770820D 770822D 770824D 7708260 770828D 770830D 770832D 770834D 7708360 770838D 7708400 770842D 770844D 7708460 770848D 7708500 770852D 770854D 7708560 770858D 770860D 7708620 770864D 770866D 7708680 7708700 7708720 7708740 7708760 7708780 7708800 7708820 7708840 7708860 7708880 7708900 7708920 7708940 EXPR En E4 E6 E8 E 10 E 12 E 14 E 16 E 18 E 20 E E 24 E 26 E 28 E 30 E 32 E 34 E 36 E 38 E 40 E 42 E 44 E 46 E 48 E 50 E 52 E 54 E 56 E 58 E 60 E 62 E 64 E 66 E 68 E. 70 E 72 E 74 E 76 E 78 E 80 E 82 E 84 E 86 E 88 E 90 E Y2 F 94 SGP CAGE fc hk'k (0) 162 (0) 3 62 C 0) 162 (0) 162 (0) 162 (0) 164 (0) 164 (0) 164 (0) 164 (0) 164 (0) 166 (0) 166 (0) 166 (0) 166 (0) 166 (0) 168 (0) 168 (0) 168 (0) 168 (0) 168 (0) 170 (0 ) 170 (0) 170 (0) 170 (0) 3 70 (0) 172 <0) 172 (0) 3 72 (0) 3 72 ( 0 ) 3 72 (0) 174 (0) 174 (0 ) 174 <0 ) 174 <0) 3 74 ( 0 176 < 0 3 76 (0 ) 176 ( 0 ) 176 (0) 176 ( 0 ) 178 (0) 3 78 ( 0 ) 178 ( 0 ) 178 ( 0 ) 178 (0 ) 180 ( 0 ) 3 80 7. R1 R2 LI L2 k 11.1 R 1I..2 R 2L1 R 2L2 R3 Z R1 R2 LI L2 R 1L1 R 11.2 R 2L1 R 2L2 R3 Z R1 R2 LI L2 R 1L.1 R 1L2 R 2L 1 R R3 7 R1 R2 L.l 1.2 R 1L3 R 1L2 R 2L1 R 2L 2 R3 Z Kl R2 L1 L2 R 1L 3 R 11. 2 LOMR 7708010 7708030 7708050 7708070 7708090 7708110 7708130 7708150 7708170 7708190 7708210 7708230 7708250 7708270 7708290 7708310 7708330 7708350 7708370 7708390 770841D 7708430 770845D 7708470 7708490 7708510 7708530 7708550 7708570 7708590 7708610 7708630 7708650 7708670 7708690 7708710 7708730 7708750 770877D 7708790 7708810 7708830 7708850 7708870 7708890 7708910 7708930 EXPR E1 E3 E cu E7 E. 9 E 11 E 13 E 15 E 17 E 19 E 21 E 23 E 25 E 27 E 29 E 31 E 33 E 35 E 37 E 39 E 41 E 43 E 45 E 47 E 49 E 51 E 53 E 55 E 57 E. 59 F 61 E 63 E 65 E. 67 E 69 E 73 E 73 E 75 E 77 E 7V E. 81 E 83 b. 85 E 87 E 89 l: 91 F 93 SGP (0) (0) (0) (0) (0) (0) (0) <0> (0) (0) (0> (0) (0) <0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) <0> (0) (0) (0) (0) (0) <0) (0) <0) (0) (0) <()) (0) (0) (0) (0) (0) <0) (0 ) (0 ) (0) CAGE 161 1 63 i. 61 161 161 163 163 163 163 163 165 165 165 165 165 167 167 167 167 167 169 169 169 169 169 171 171 171 171 171 3 73 . 173 1.73 173 173 3 75 3 75 175 175 3 75 177 1 77 3 77 177 1 77 1 79 1 79 e Akk 2 R1 R2 LI L2 R1L1 R.t L2 R2L1 R2L2 R3 Z R1 R2 LI L2 R1L1 R1L2 R2L1 R2L2 R3 Z R1 R2 LI L2 R1L1 R1L2 R2L1 R2L2 R3 Z R1 R? LI l.:> R1L.3 R1L2 R2L1 R21.2 K.S / K1 ki' L1 L. 2 k 11.1 kill. 2 SPI-01109 ,ruNnC*\ ;;: vo/tno v '- w\ i. CROSS REF E R E N- c E ASSAY NO. i:.";- a L COMR MALES EXPR SGP CAGE EAF R 770896D 770898D 7709000 7709020 7709040 7709060 7709080 7709100 7709120 7709140 7709160 7709181 7709200 7709220 7709240 7709261 77092SI 7709301 7709320 7709340 7709360 7709381 7709401 7709420 7709440 7709460 7709480 7709500 7709521 7709540 7709560 . 770958D 7709600 7709620 7709640 7709660 7709680 7709700 /70972D 7709740 7709761 7709780 /70980I 7709820 7709840 / 70986D / 709880 7709901 7709920 7/09940 7709960 77099Q0 7710000 E 96 F 98 F 100 FI 02 104 1106 F108 F 3 10 FI 12 El 14 F.116 fe 1 18 E120 El 22 E124 F126 El 28 El 30 El 32 E134 F136 E 138 E 1 40 E14 2 El 44 E 146 E 148 E 1 50 E 152 El 54 E 156 E 158 t 160 F 162 FI 64 FI 66 t 1 68 E170 E172 fc .174 E 1 76 h 178 E180 fc 1 87 fc 184 E186 E 188 E 1 90 E 192 fc 194 f 196 F 3 98 E 700 rnr*i ^ IT (_' - c, (0) (0) (0) (0) <01 (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) (0) 10) (0) (0) (0) (0) <0> (0) (0) (0) (0) (0) (0) <0 ) (0) C0> <0) (0) (0) (0) (0) C0) <0> <0 ) (0) (0) <0) (0) (0) (0) CO > (0) (0) (0 ) (0) <0) CO ) (0) 180 .1 80 180 182 182 182 182 182 .1 84 184 184 184 1 84 186 186 186 186 186 188 188 188 188 1.88 .190 190 1 90 3 90 190 192 192 192 3 92 3 92 .19 4 194 194 19 4 1 94 196 1 96 196 196 196 198 1 v;< 1 VH ;t 98 700 700 700 700 700 R21 1 R21 F3 7. X Fn L1 L ri R1L .1 K1L n R2L 1 R2L 2 F3 7 F1 F l1 ln R1L 1 R1L, n R2L 1 R2L 2 k3 7. F\ 1 Rn L1 Ln R1L 3 R1L 2 R2L 1 R2L 2 h3 Z E1 o 11 L Kll 1 R1L > R2L 1 R2L '*> h3 7. a <7 l1 L -> Rll 3 R .1L > K21 1 R2L ) R* ING SPI-01110 ZERO REFEkf.NO. UA i ( '.lx/ 8/ FEMALES COMR EXPR SGP CAGE EARk 770895D 770897n 770899D 77090ID 77 0903D 770905D 770907D 770909D 7709 lire 7709 3 3D 770915D 770917D 770919H 770923 Ii 770923D 770925P 770927D 770929U 77093ID 770933D 770935D 770937D 770939D 77094 ID 770943D 770945D 770947D 770949D 77095 3 D 77095311 770955D /70957D 770959D 770963D 770963D 770965} /70 96 7IJ / 70 9 6 911 770971D 770973D 770975D /70977D / 709791) 77098 ID 770983D 770985D 770987D 770989D 77099]D 770993D /70995D 770997D 770999D F 95 P 97 fc 99 E .10 3 E103 E105 El 07 El 09 E3 13 El 13 El 15 Ell 7 E 3.19 fc.121 El 23 fc 3 25 E 127 E 129 fc. 3 31 El 33 El 35 fc 137 E.l 39 E14 1 E143 F14 5 E .147 E 149 E3 53 El 53 fc. 3 55 E 157 fc 159 E 161 F3 63 fc 165 E 167 E169 E3 71 fc. 17.4 fc l 75 fc 177 E179 E 3 8.1 (-183 El 85 fcl 87 fc 1HV fc 191 fc 3 93 El 95 fc 1 97 fc 199 (0) CO) CO) (0) C0) (0) (0) (0) CO) (0) CO) (0) (0) CO) CO) (0) CO) CO) (0) CO) CO) CO) (0) CO) CO) CO) CO) CO) CO) co) CO.' CO) CO) CO) CO ) CO > co : C0) (0) CO ) C0) C0) CO) (0) ( 0 .' (0*) CO ) CO ) CO) CO ) <0) (0 ) (0) 3 79 1 7V 179 181 3 83 181 183. 181 183 183 3 83 3 33 183 3 85 185 3 85 3.85 185 3 87 187 3.8 7 187 187 189 3.89 189 189 3 89 3 93 3 91 3 91 191 3 91 3 93 .3 93 193 1.93 3 93 3 95 3 95 195 195 1 95 197 197 I 97 3 97 1 97 199 1 99 3 V9 3 VV 1 79 K7I..1 fc'71.. 2 R3 7. K1 R2 L3 1.2 Rll. 1 K1L2 K2L 1 R2.L2 R3 2 K 3. R2 L1 L2 Kll. 3 K1 L 2 R2L1 R2L2 K3 2 Fcl R2 L1 1. 2 K1I..1 R1L2 R2L1 K2I. 2 K.4 Z kl K7 ll 17 K 1 1. 3 K 3 L2 R2L1 R2L2 K.4 / k3 R7 LI i; Kll 1 k 11. 7 K7I 3 R2L2 K3 f rt TAJ C L uAI r t r / /\ .-u ' 11 A i; I v 0 / T N 0 u. Ul CROSS R E ft E N C E ASSAY NO. i: 6 0 L I S'T I N G SPI-01111 hales COMR 780002 780004 780006 780008 780010 ' 780012 780014 780016 780018 780020, 780022 780024 780026 780028 780030. 780032 780034 780036 780038 780040 78004*5" 780044 780046 780048 780050 780052 780054 780056 780058 780060 780062 780064 780066 780068 78007 a. 780072 780074 780076 780078 730082. 780082 780084 780086 780088 78009&. 780092 780094 780096 780098 780100 EXFR A ri A4 A6 A8 A 10 A 12 A 14 A 16 A 18 A 20 Bn B4 B6 B8 B 10 B 12 B 14 B 16 B 18 B 20 C2 C4 c6 c8 c 10 c 12 c 14 c 16 c 18 c 20 Dn DA B6 D8 D 10 D 12 n 14 D 16 B 18 n 20 En E 4 E6 E8 E 10 E 12 E 14 E 16 E 18 F 20 TOTAL MALES 1? o SGP (0) C0> CO) (0) CO) (0) (0 ) (0) CO) (0) CO) (0) (0) (0) CO) CO) CO) CO) (0) CO) (0) (0) (0) (0) (0) CO) (0) CO) CO) CO) CO) CO) (0) CO) CO) CO) CO) CO) CO) CO) CO) CO) CO) CO) CO ) CO ) CO) CO) CO) CO) CAGE -> n n 4 4 4 4 4 6 6 6 6 6 8 8 8 8 8 10 .10 10 10 10 12 12 12 12 12 14 14 14 14 14 16 16 16 16 16 18 18 18 18 18 20 20 20 20 20 EA ft ft 2 Rl R2 LI L2 ft L LI ft L L2 r:: LI r:: L2 *5Z Rl R2 LI L2_ Rl LI Rl L2 ft: LI R2 L2 PCi Z Rl '<2 .1 -2Rl .1 Rl n ft 2 .1 R2 .2 'i_ z :i 1:2 l.l 2. Rl L 1 Rl L 2 R2 L 1 ft 2 L 2 R3, r Rl R2 LI _t Rl Jl Rl L 2 R2 LL R2 L 2 ft 5 females COHft EXPR SGP CAGE EARR 780001 780003 780005 780007 780009 78001T 780013 780015 780017 780019 780021 780023 780025 780027 780029 780031 780033 780035 780037 780039. 78004" 780043 780045 780047 780049 780051 780053 780055 780057 780059 780061 780063 780065 780067 780062L 780071 780073 780075 780077 780079 780081 780083 780085 780087 780089^ 780091 780093 780095 780097 780099 A1 A3 A C- A7 A9 A 11 A 13 A 15 A 17 A 19 B1 B3 B5 B7 B9 B 11 B 13 B 15 B 17 B 19 C1 C3 C5 C7 C9 C 11 C 13 C 15 C 17 c 19 D1 D3 D5 D7 B9 D 11 D 13 D 15 D 17 D 19 E1 E3 E5 E7 E9 E 11 E 13 E 15 E 17 E 19 CO) (0) (0) (0) (0) (0) CO) CO) co) CO) <0> CO) CO) CO) CO) CO) CO) CO) CO) CO) CO) CO) co> (0) CO) CO) (0) (0) (0) (0) (0) (0) (0) (0) CO) (0) CO) CO) CO) (0) C0) (0) CO) CO) (0) CO > co) CO) co) (0) 11 1 Rl 1 R2 1 LI 1 Lg. 3 R1L1 3 R1L2 3 R2L1 3 R2L2 3 R3_ 52 5 Rl 5 R2 c* LI 5 L2^ 7 R1L1 7 R1L2 7 R2L1 7 R2L2 7 R3_ 9Z 9 Rl 9 R2 9 LI 9 L2_ 11 R1L1 11 R1L2 11 R2L1 11 R2L2 11 R3 13 Z 1'3 Rl 13 R2 13 LI 13 L_ 15 R1L1 15 R1L2 15 R2L1 15 R2L2 15 R3 17 Z 17 Rl 17 R2 17 LI 17 Li. 19 R1L1 19 R1L2 19 R2L1 19 R2L2 19 R3 TOTAL FEMALES = 50 .. T -- -- ....... ............ --