Document RJ330bV5KOYpm0DDgeDmn5b4E
A COMPARISON OF FOUR MOUSE STRAINS EXPOSED TO SUBCHRONICALLY INHALED VINYLIDENE CHLORIDE (VDC)
By: J. W. Henck, J. F. Quast and L. W. Rampy
January 12, 1979
Dov Chemical USA
Toxicology Research Laboratory Health & Environmental Science
1S03 Building Midland, Michigan 48640
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SUMMARY
To determine the affect of inhaled vinylldena chloride (VDC) on four different laboratory mouse strains, male and female Ha(ICS) mica, B6C3F1 mice, CD-1 mice, and CIW mice were exposed to 0, 55, 100, or 200 ppm TOC vapor. Exposures were conducted 6 hours/day, 5 consecutive days/week: for a total of 10 exposures. Parameters monitored included appearance and demeanor, body weights, hematology, clinical chemistry, organ weights, and gross patho logical and histopathologi 1 examinations.
Signs of toxicity observed among mice on test Included rough hair coats, palpebral closure, and lethargy. The severity of chase signs of toxicity was exposure level dependant. Mortality, statistically significantly lower mean body weights, increased liver and kidney weights, and an increased activity of serum glutamic pyruvic transaminase also occurred among mice on test; again, these parameters were dependent upon the exposure level. Prom gross and histo pathologic examination, it was determined that mala mice of all exposure levels experienced a marked degree of nephrotoxicity, with renal failure accounting for mortality in the 20Q ppm exposure group. Renal toxicity was in significant In all female mica on test when compared to mala mica of the same strain. However, hepatotoxicity was more prevalent In female mica than in male mice of the same strain and exposure level.
Overall, the data suggest that male mica were affected by exposure to VDC vapor to a greater degree than were female mice of the same strain and expoaura level. Based on pathology of surviving mice, male CD-I mice were the most severely affected at all levels of exposure with moderate to severe degenerative nephrosis seen at all exposure levels (55, 100, and 200 ppm).
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INTRODUCTION
Recent studies have shown a discrepancy In response to Inhalation of vinylidene chloride (VDC) vapors among different strains of mice.
Male and female mice were exposed to 55 ppm VDC 6 hours/day, 5 days/week for up to 9 months in a study conducted by Lae, at al (1978) Although develop ment of 3 hepatic hemangiosarcoma and 6 Instances of bronchioalveolar adenoma and/or acinar proliferation in the lung were reported in the 70 (35/sax) mice examined, the survival rate of these mice was good. The strain of mouse used in fchj-s test was CD-1 (Charles River Breeding Laboratories, Inc., Wilmington, MA).
In a long-term (1-year exposure followed by observation until "natural" death) study conducted by Maltoni (1977 a,b), Swiss-Webster mica have bean exposed to 10, 25, or 50 ppm VDC. Maltoni reported 10 ppm to be a no-adverse effect level. However, tumors of the kidney along with other toxic changes in the kidney were reported at the 25 ppm exposure level, and, in contrast to mica in the Lee, et al (1978) study, the 50 ppm- level was near the lethal dose; 7 of 60 mice survived the exposure, 4 hours/day, for 1 week.
Maltoni (1977a) has also conductad a comparison among 4 strains of mica. These animals were exposed for 2 consecutive days to 200 ppm VDC for 4 hours/day. After 9 observation days, the following survival rata was reported for each strain:
Mouse Strain
Balb/c Swiss-Webster CjH c37si6
Survival Rate
Male
'Patna 1 a
6/30 9/60 13/30 23/30
30/30 60/60 19/30 30/30
The results of the test on the strains used by Maltoni (1977) wera rela
tively comparable with regard to survival. However, a mouse comparable to the
CD-I strain used by Lee, et al (1978) was not used in this study.
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The question of varying responses to VDC among different mouse strains therefore remains unanswered. The purpose of the following study was to Investigate the effects of exposure among strains used in oncogenic studies and the relative degree of such responses.
In this subchronic inhalation study, 4 strains of mice were exposed to VDC vapor. Each strain, and the reason for its choice, is given below.
Strain Ha(ICR) B6C3F1
CD-I
CE-W
Reason for Choice
The strain of mouse used in the Dow Toxicology Research Laboratory in previous VDC vapor studies.
The mouse strain used by the National Cancer Institute (NCI) and currently in use in the Dow Toxicology Research Laboratory.
The strain of mouse used by Lee, at al, in the long-term VDC study (the animals used in the present study were obtained from the same supplier).
A strain of Swiss-Webster derived mouse believed genetically comparable to chat used by Maiconi in his long-term VDC study.
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MATERIAL
Production-grade VDC was obtained from the Michigan Division, Dow Chemical, USA. The material used in this study was analyzed for impurities using a Flanigan 31QQ-D quadrupole gas chromatograph/mass spectrometer (electron impact), with the following results:4'
Component
1.1- dichloroethylane (VDC) chloroethylene 1.2- dichloroethylene 1,1- or 1,2-dichloroethane trichloroethylene
Area Percent
99+2 <0.12
<0.12 <0.12 <0.12*
*Analysed by E. A. Hermann, Dow Toxicology Research Laboratory, SL 068131
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METHODS
Chambers, Vapor Generation, and Analysis.
Exposures were carried out in stainless steel and glass chambers of one
cubic meter volume under dynamic airflow conditions. Air temperature
humidity were monitored daily and controlled to levels acceptable for
laboratory rodents.
VDC vapor was generated by metering the liquid at a controlled rata with
a precision syringe pump into a heated (45*C) vaporiz- ion flash. The vapor
was chen diluted and swept with filtered air into the -ain chamber airflow at a
rate calculated to provide 8-12 air changes/hour. The nominal concentration
of VDC vapor In each chamber was the ratio of the rata at which liquid VDC
was dispensed to Che rate of total chamber airflow. The concentration of
VDC vapor in each chamber was monitored using a Miran I infrared spectrophoto
meter with silver bromide windows and lens. The wavelength was 12.75 u, while
the pathlength was 8.25 M. Each chamber was sampled for 15 minutes of a 60-
minuta time cycle throughout each exposure day. Du Licate air standards of
55, 100, 150, and 200 ppm VDC were used to prepare a standard curve. An air
standard of 100 ppm VDC was analyzed each exposure day to verify the standard
curve. Values for chamber concentration were interpolated from the standard
curve,
time-weighted averages were calculated daily for each chamber.
An-tmAla . ArHTrials used In this study were Ha(ICR) mice (Spartan Research Animals,
Inc., Haslett, MI), B6C3F1 mica (Charles River Breeding Laboratories, Wilming
ton, MA), CD-I mice (Charles River Breeding Laboratories, Wilmington, MA),
and CE-W mice (Charles River Breeding Laboratories, Portage, MI). The. age
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and weight ranges of each 3ax and scraln of mouse upon arrival in this laboratory vara as follows:
Age at
Weight Bangs
Age at
Weight Range .
Sex Strain Arrival at Arrival First Exposure First Exrosu:
M
Ha (ICS.)
26 days
all 22 grams
F
Ha (Id)
26 days
24-26 grams
M B6C3F1 31 days 16-20 grams
F B6C3F1 29 days 14-16 grains
M CD-I
27 days 18-20 grains
F CD--1
32 days
18-20 grams
M CF-W
31 days 16-20 grams
F CF-W
31 days 14-18 grams
34 days 34 days 42 days 40 days 35 days 40 days 40 days 40 days
24-35 grams 16-28 grams 22-26 grams 18-23 grams 27-34 grams 17-27 grams 22-29 grams 21-26 grains
Exposure. Four groups of mica, consisting of 10 mica/sex/strain/exposure level,
were exposed to 0 (filtered room air), 55, 100, or 200 ppm VDC. All exposures
were conducted 6 hours/day, 5 consecutive days/week for 10 days over a 12-day
period. Mice of each strain were randomly assigned to treatment groups from
single lots of
q using the computer program G3AND. CL1ST (Computation
Laboratory, Dow Chemical, U.S.A.). During exposure, mica vara placed in the
chambers in exposure cages containing 10 animals of the same sex and strain.
Following exposure,
group of 10 mica was placed in plastic holding
cages containing ground corn cob bedding.
Food (Furlma Bat Chow pellets) and water were not available during
exposure periods, but were available ad libitum at all other times. All
mice were exposed to 12 hours of light and 12 hours of darkness each day.
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Body weights of all mica on Cast vara obtainad prior to exposure, and
twice weekly during exposure. Mica ware observed daily for signs of tcxicity and changes in appearance and demeanor, as well as to remove dead or moribund
animals. Organ Weights, Clinical Chemistries, and Pathology.
An effort was made to terminate all moribund animals prior to actual death In order to avoid post-mortem autolysis. Blood was collected from 5 moribund mice of 3 strains from the 200 ppm level for clinical chemistry determinations. All other mice subjected to gross pathological examination
prior to termination were either dead or so close to death that blood samples
were not obtained. On the morning following the tenth day of exposure for each strain, all
surviving mice of that strain were sacrificed. The mice were lightly anesthetized with methoxyflurane; blood samples for clinical chemistry deter
minations were collected from the orbital sinus; and the mice were killed by decapitation. All mice, whether dead, killed in a moribund state, or killed at termini an of the study were given a gross pathologic axaau tion
by a veterinary pathologist. Serum obtained from *1i surviving mice was used for determinations of
blood urea nitrogen (BUN), and the activities of serum glutamic pyruvic transaminase (SGFT) and gamma glutamyl transpeptidasa (Y-GT).a
The eyes of all mice were examined in situ immediately after decapita
tion by
of a glass microscope slide technique and fluorescent illumina
tion. This technique was also applied to those mica presented in a moribund
state.
aCantrifiChem System, 400, Methods File, Union Carbide Corp., Rye, SY.
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Following decapitation, Che liver and kidneys of terminal kill mice were removed and weighed. Selected tissues showing gross pathologic changes in the mice which were submitted dead or moribund were saved in buffered 10% formalin. In all mice from the terminal kill the esophagus, trachea, lung, heart, mediastinal lymphoid tissue, liver and kidneys were saved in buffered 10% formalin.
The lungs, trachea, esophagus, and mediastinal lymphoid tissue from 5 mice/sax/strain/exposure level were embedded as a unit in paraffin, prepared by routine histologic procedures, tissue slides stained with hematoxylin and eosin, and evaluated by light microscopy. In addition, the livers of 5 mice/ sex/strain/level from each mouse strain and a total .of 10 kidneys from each sex and exposure level of each mouse strain were similarly prepared and were evaluated by light microscopy. Statistical Evaluation.
ClipicaT chemistry, body weight, and organ weight data, as well as organ to body weight ratios, were evaluated using an analysis of variance and Dunnett's test (Steel and Torrie, 1960), the level of significance for all cases being p <0.05.
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RESULTS
VDC Vapor Concentration.
Mean analytical concentrations to which each strain of mouse was exposed,
and temperature and relative humidity recorded during exposures are presented in Table 1.
From the mean analytical concentration for each chamber, it can be seen
that all strains of mice vers exposed to basically the same concentration at
each exposure level. ",aily te~. erature and humidity were also quite stable
for each chamber.
Animal Observation.
Mortality of all strains of mice exposed to VDC vapor is given in Table 2.
Regarding mortality, B6C3F1 mice of both sexes were the most sensitive of all
strains tasted. Male mice of the CD-I and CF-V strains were affected to a
greater degree than were female mice of the same strains.
Table 3 gives the signs of toxicity observed in all mice on test.
Many of the mice on test experienced lethargy, rough hair coats, and palpebral
closure; these signs of toxicity occurred with the greatest frequency and
severity among male
female CF-W mice of the 100 and 200 ppm exposure groups.
Male mice tended to be affected to a greater degree than female mice in the Ha(ICR), CD-I, and CF-W strains. Although B6C3F1 mica had the greatest mortality of the 200 ppm exposure group mice, the 55 and 100 ppm exposure groups of this strain exhibited no adverse affects in terms of signs of toxicity observed in
the live animals.
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Bodv Weights. Mean body weights for all male mice are given in Figure 1, while chose
for all female mice are given in Figure 2. The body weight and/or body weight gain of male Ha(ICR) mice was de
pressed co some degree for ell exposure groups compared to Che control group. The weight suppression was apparent in an exposure-related fashion in that the higher exposure groups were affected the most. The mean body weight gains of female Ha(ICR) mice of ell exposure levels were comparable to chose of concrols throughout the study, with the following exception: final body weights of the 55 an4 200 ppm groups were statistically lower chan chose of the control group.
Mean body weights of both male and female 36C3F1 mice in the exposure groups which survived were comparable to those of controls throughout the study.
M>an body weight gains of the surviving group of male CD-I mica were lower rhan controls in an exposure-related manner. By the end of the study the male CD-I mice of the 55 ppm group were statistically comparable, although still lower chan controls. The mean body weight of female CD-I mica of the 200 ppm exposure group was significantly lower than the control at the first weighing. For the remainder of the study, however, the body weight for the 200 ppm group was comparable to the control group. Mean body weights of female CD-I mice exposed to 55 or 100 ppm VDC vapor were comparable to those of controls through out the study.
Mean body weights of mala CF-W mica of the surviving exposure groups were comparable to those of the control group throughout the study. In female CF-W mice, imb body weight of the 200 ppm group was depressed at the first weighing. However, the weight for this group was comparable to tha control group for the remainder of the study. Mean body weights of female CF-W mice
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or the 55 and 100 ppm groups ware statistically significantly grsatar eh*n chose of controls in the early part of the study, but this was thought to be due to a weighing error rather than a treatment related effect. Organ Weights.
Absolute and relative liver and kidney weights of all mica are given in Table 4.
Statistically significantly increased relative liver weights (and increased absolute weights where the superscript "a'* appears) occurred among: Male Ha (ICS.) mice of Che 55,a 100, a and 200 ppm groups; female Ha (ICS.) mice of the 200 ppm group; male B6C3F1 mice of the 55 and 100a ppm groups; female B6C3F1 mice of the 55a 100a ppm groups; female CD-I mica of the 2Q0a ppm group; male CF-W mice of the 55 and 100a ppm groups; and female CF-W mica of the 55,a 100,a and 200a ppm groups. Although there are exceptions in specific groups, overall there appears to be an increase in liver weight relative to body weight that increases with increasing exposure level.
Statistically significantly increased relative kidney weights (and absolute kidney weights where the superscipt "a" appears) occurred among male and female HadCB.) mice of the 200 ppm group; male and female B6C3F1 mice of the 100 ppm group; male CD-I mice of the 100 ppm group; and female CF-W mice of the 55 (absolute only), 100a, and 200a ppm groups.
The increases in relative liver and kidney weights were considerad to be treatment-related and, in general, consistent with pathologic changes described in the Pathology section. Clinjgal Cheasitry.
Mean clinical chemistry values of mice on test are given in Table 5. Although very significant kidney injury was seen upon pathologic examination
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of mala mice, a statistically significant increase in BUN occurred only among male B6C3F1 mice of the 100 ppm group. This indicates that measurement of BUN levels was not a useful criterion of kidney Injury in this case.
Statistically signficant Increases in the activity of SGPT occurred among male Ha(ICR) mice of the 100 and 200 ppm groups, mala and female B6C3F1 mice of the 100 ppm group, female CD-I mice of the 200 ppm group, and female CF-W mice of the 100 and 200 ppm groups. Although not statistically significant (probably because of high variability), values for SGPT activity were clearly high among female Ha(ICR) mice of the 200 ppm group, male and female CD-I mice of the 100 ppm group, and male CF-W mice of the 100 ppm group. The finding of elevated SGPT levels is consistent with the gross and/or histopathologic findings of adverse effects on the liver as reported below.
No pattern of change to indicate a treatment-related affect was seen in y-GT values. Pathology.
The gross pathologic findings in the male mice of the various strains are presented in Table 6. Examination of the data in this table reveals that ail mice of all strains, except the Ha(ICR) strain, exposed to 200 ppm VDC were either dead or moribund when submitted for autopsy. No mice from the 100 or 55 ppm VDC groups showed evidence of a moribund state or died prior to the terminal kill. Treatment-related changes were grossly detectable in the kidneys of all strains of male mice at all dose levels. In addition, the liver showed a treatment-related change in all strains of mice from the 200 ppm group and in most strains from the two lower dose groups. The Ha(ICR) and B6C3F1 male mice appeared to show evidence of
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a decrease In the sire : the thymus. Changes present In the lung were con
sistent with those seen as spontaneous in occurrence and were not directly
effected by treatment. The grossly recognized changes in the gastrointestinal
tract were secondary to the renal failure and probable anorexia associated with
treatment.
Histopathologic findings for the various strains of male mica are presented
in Table 7 (Ha(ICS)), Table 8 (B6C3F1), Table 9 (CD-I), and Table 10 (CF-W), re
spectively. Each table presents the exact histopathologic criteria in the
various organs which were used for evaluation and comparison of the various
strains of mice.
Liver and kidneys were the principal target organs which showed histo
pathologic changes considered treatment related.' These changes were present
at ail exposure levels in all strains of male mica tested. The kidneys show
a greater degree of toxicity Chan the liver at all exposure levels. Although
renal toxicity was still quite severe In all strains at the 35 ppm level, it
was most severe in the CD-I strain. To thoroughly compare the relative renal
toxicity in the various strains of mice, it would be necessary to examine
animals from lower exposure levels.
Findings of lung changes associated with mica exposed to vapors of TOC
were not confirmed in
study. In an occasional control as well as created
mouse there were changes characterized by acute congestion, focal acuta
Interstitial pneumonitis, focal alveolar histiocytosis, or pneumonia. These
were spontaneous in occurrence and did sot show a treatment--relatad effect
in ari-fmatg which survived the exposure. Animals moribund or dying from renal
failure may show a
accentuation of these findings; however, those sur
viving the exposure did not. Therefore these pulmonary effects are not a
direct result of TOC toxicity in the lungs but secondary to the renal failure.
068l>0 SL
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The gross pathologic findings in the female mice of the various strains are presented In Table 11. Examination of the data In this table reveals that nearly all female mice of all strains at all dose levels survived the exposure period, except the 200 ppm Ha(lCS.) and B6C3F1 groups. In general, the livers of female mice of the 200 ppm group only shoved some treatment-related effects. Occasional mice of the 200 ppm group of Ha(IC3.), CF-W and 36C3F1 strains showed suggestive kidney changes. In addition, several B6C3F1 mica from the 100 ppm group showed suggestive kidney changes. The CD-I female mica did not show a grossly detectable kidney change at any level. The Ha(ICR) control and treated mice showed an Increased Incidence of lung changes which vara inter preted to be spontaneous. Many of the treated mica of this strain also showed a decrease in size of the thymus and a decreased amount of adipose tissue within the abdominal cavity.
Histopathologic findings for the various strains of female mice are pre sented In Table 12 (Ha(IGO), Table 13 (B6C3F1), Table 14 (CD-I), and Table 15 (CF-W), respectively. Examination, of Che data in these tables indicates m-fn-tmai renal toxicity In an occasional 36C3F1 or CD-I mouse at the 200 ppm exposure level, only. Significant toxic renal changes were not detected In the kidneys examined from the Ha (ICH.) or CF-W mice at any level of exposure. In contrast to the marked renal toxicity of the mala mice, it appears that the liver In the female mice was Che more sensitive target organ. Pulmonary changes were not present which were considered treatment related In animals which survived the exposure. The cause of death In the Ha (ICS.) and B6C3F1 mice may be associated with the acute hepatotoxicity rather than nephro toxicity, although B6C3F1 mice did show some avldanca of both.
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DISCUSSION
All of che strains of male mice used in this study experienced significant mortality, a finding consistent with Maltoni's (1977) mortality findings in 4 mouse strains exposed for 2 consecutive days to 200 ppm VDC for 4 hours. Maiconi also saw better survival in female mica than males, a finding consistent in general with the present study. It may also be signficant that all the female mice of the strain (Swisa-Webster) used by Maltoni for his long-term studies survived the short mortality experiment as did all the female CD-I mice in the present study. However, Maltoni's mice did not survive at 50 ppm VDC in his long-term study, but CD-I mice were reported to survive long-term exposure to 55 ppm VDC at Che Midwest Research Institute (Lee, et al., 1978).
Pathologically, CD-I mice, especially males, were dramatically affected in this study. With the moderate to severe degenerative nephrosis seen in male CD-I mice (Table 9) after only 10 days of exposure to 55 ppm VDC, it seems unlikely that these mice could survive a long-term inhalation study. Certainly if they did survive, any effects seen would have to have been confounded by the presence of these early extensive kidney effects. The female CD-I mice did not exhibit degenerative nephrosis, but significant hepatocellular degeneration and necrosis along with centrilobular hepatocellular swelling and pleomorphism at the 200 and 100 ppm VDC levels after only 10 days of exposure suggests that longer exposure at the lower level could lead to liver toxicity.
Although it is not passible to carefully rank the 4 strains of mica as Co sensitivity, the results of this study lead to several general conclusions.
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1. A few repeated Inhalation exposures of mice to 200 ppm VDC, as evidenced by the 4 strains of mice In the present study and the 4 strains of mice In the Maltoni (1977a) mortality study, produced significant mortality.
2. Hale mice were more sensitive to VDC than female mice, as evidenced in 7 of the 8 strains of mice tested in either the present study or in the Maltoni (1977a) study.
3. Significant pathological change was seen in the kidney (and liver) of the male CD-I mice (the strain used by Lee, at el (1978)) at levels as low as 55 ppm VDC.
Written By:
Reviewed By:
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1 r* -17 REFERENCES Lee, C. C-, J. C. Bhandari, J. M. Winscon, and W. B. House (1978). Carcinogenicity of Vinyl Chloride and Vinylidene Chloride. Journal of Toxicology and Environmental Health, 4:15-30. Maltoni, C. (1977a). Recent findings on Che Carcinogenicity of Chlorinated Olefins. Environmental Health Perspectives, 21:1-5. Maltoni, C., G. Cotti, L. Mbrisi, and P. Chiaco (1977b). Carcinogen!-ity Bioassays of Vinylidene Chloride. La Medicine del Lavoro, 68:2^ 62. Steel, R.G.D. and Torrie, H. H. (1960). Principles and Procedures of Statistics. McGraw-Hill Booh Company, Inc-, New York.
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v
Table 2
Mortality of Mice Exposed to VDC Vapor*
Exposure Level
Strain
200 PPM 200 PPM
Ha (ICS.) Ha(IC3.)
Sex Male Female
Total # Dead/ Total of Animals For Duration of Study
6/10
4/10
9 of Exposures To Reach
Maximum Mortality
4
3
200 PPM 200 PPM
B6C3F1 B6C3F1
Male Female
10/10 10/10
3 1
200 PPM CD-I
Male
10/10
5
200 PPM 200 PPM
CP-V CF-W
Male Female
10/10 1/10
5 3
55 PPM Ha(ICS)
Female
1/10
3
0 PPM Ha(ICS)
Female
1/10
9
*No mortality was seen in strains or at levels not Included In the Table.
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Table J Signs of Toxicity Exhibited ly Mice Exposed to VUC Vu|>ar
St talu Sex
lla(ICH)
IMICR) lla(ICK) Ha(lCg) llafllttl
M.ile Haiti Hale Female Female Female
U6C1FI U6CIPI gbCJPl
Hale Hale Hale
BbClFI Bfil'.IPI HfcClFl
KuMai 1 e Fewa 1 e Female
CB-I Hale t:-l Hale ail Hale ai-i FtiHhl 1
ai-i Featii 1 e ai-i Female
cf-m
UF-W CF-tl CF-W CF-W tJF-M
Male Hale Hale Female Kewi 1 e IVlHtl 1 *s
Eapsaurt
f.evel
__________________________ Signs of Toalclty_____________________________________________________________ ____ _________
55 PPM 100 ri-H 200 FPH 55 PPH 100 PPM 200 rPH
ill had alightly rough hair coate. All had allghtly rough lialr coate, 20Z had aye Irritation cliarncturlrod by palpebral closure. All ware lethargic, Initially all had Moderately rough hair coate, 20-502 had palpebral closure. All had allghtly rough hair coats. All had allghtly rough hair coata. All wars lethargic Initially, all had Moderately rough hair coats, 20-JOI had palpebral closure.
55 PFH 100 PPH 200 PPH
55 *ph 100 PPH 200 PPH
Ho adverse affects. Ho adverae affacta. All wars lethargic, all had very rough hair coata, 100X had palpebral closure, all were dead following the third uapoauro.
Ho adverae affacta. Ho adverse affacta. All wore dead soon after the first exposure.
55 PPH 100 PPH 200 FFH 55 PPM
100 PPH 200 PPH
All hed slightly rough hair coata. All hed allghtly rough lialr coate; halfway through tire study 201 lied palpebral closure. All were lethargic, all had uodaratsly rough lurtr coata, M-iOOl hud palpabral closure. All had slightly rough hair coata.
All Irad allghtly rough lialr coata, 102 had palpabral cluaura. All wars lethargic, all had Moderate!y rough hair coate, 20-401 had palpebral closura.
55 PPH 100 PPH 200 PPH 55 PPH too PPH 200 PPH
Halfway through the study, all bad slightly rough hair coata. All liad Moderately rough hair coata, 20-502 Irad palpabral closure. All were lethargic, all had very rough hair coata, 1002 had palpabral cloaura. 1/4-wuy through the study, all had allghtly rough hair coata. Halfway through tire study, all had slightly rough haircoata, 10-202 had palpabral closure. All were lethargic, all had vary rough lialr coats, 50-1002 had palpebral closura.
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Figure 1
Mean Body Weight (Grams)
MEAN BODY WEIGHT OF MALE MICE EXPOSED TO VDC VAPOR
Mean Body Weight (Grams)
i iiIIIIi 10 0 2 4 6 8 10 12 14 16 0
Experiment Days
ii t i* 2 4 6 8 10 12 14 16
Experiment Oays
a) Statistically significant by analysis of variance and Qunnett's test, p <0.05. bl Mean body weights wiil no longer be shown due to excessive mortality.
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Figure 2
Mean Body Weight (Grams)
MEAN 300V WEIGHT OF FEMALE MICE EXPOSED TO VDC VAPOR
Mean Body Weight (Grams)
BgCj F, Strain
- Exposure Days
02
5
8 10
--I--|--1--r--L"i--r-H--1
0 2 4 6 8 10 12 14 16 Experiment Days
a) Statistically significant by analysis of varianca and Qunnen s test, p <Q.Q5. bl Mean body weighs will no longer ba shown due to excessive mortality.
SL 068149
Tac.a 4
yaaa (s Standard 3aviacion) Tasainal iody Oaisbta. Orjan Vaisnca and Qrjan ea 3ody Waishe Racdoa of yisa Sxpeaad ca VDC Vapor
Scxaix
3a CCS) 3a Ca) 3a Ca) 3a(:a)
3a(Id) 3a(Id) 3a (IS) 3a Ca)
S6C3F1 36C2F1 36C3T1
86C3F1 36an 36C3FL
a-L cd-i 00*1
CD^l <3^1 CD^L C3-1
aw C2W CIW
CSW W CFW aw
S-r.
yaia Mala Hal* Xala
Fmala Fala Fanala Fault
HaLa Xa-la yala
faaala Faoala Fanala
Hal* Uala Sala
Fanala Fnnala Fanala Fanala
Hala Kala Mala
Fanala Fanala Fanala Fala
Sxpoaura Laval
0 F7K 53 ??!! LOO PPM :oo f?s
0 FW 33 m 100 PPM 200 rra
0 PPM 53 FPU LOO ?FM
0 PPM 55 PPM 100 PPM
0 PPM 35 m 100 7331
a ppm 35 PPM LOO PPM 200 PPM
0 PPM 53 PPM 100 PPM
0 PPH 33 PPM 100 PPM 200 FPU
Fixal Sodv Vaiihc
36s3 33-2 34x2 2S=2
26=2 22*3* 22=3, 222*
26x2 26=1 26=1
22=1 22=1 22=1
34=2 31=2 27x5*
24x4 24=2 25x2 24x1
29x2 28x2 28X1
25X1 26X2 26x1 25x1
Orraa 'Jaizhea
L.ivax
Sidnav
.*
i/ICO 1
l
1/100 3
2.12x0.24 2.46x0.20* 2.47=0.29* 1.33=0.13
3.39x0.38 7.08x0.41* 7.32X0.37*
7.03x0.23*
0.-9=0.06 0.53=0.03 0.51=0.05 0.43=0.09
1.37=0.15
1.53=0.13
1.31=0.13 1.74=0.46*
1.40x0.23 1.20X0.18 1.29X0.16 1.24=0.14
3.38x0.69
3.48x0.31 5.55x0.40 6. yj.40*
0.27=0.04 0.23=0.03*
0.24=0.03 0.26=0.03
1.06x0.10 1.08x0.10 1.04-C.33
1.20=-. 3
1.44x0.16 1.37x0.12 1.70x0.08*
5. J-34 5.. 0.32 6.5--0.23
0.36=0.04
0.36x0.03 0.38x0.02
L.36*. . .1 1.36=0.37 1.45=0.06
1.11=0.08
1.22=0.12 1.34x0.10*
3.02=0.27 3.44=0.35*
6.02=0.43
0.25x0.02 0.26x0.02 0.28x0.02
1.14x0.10 1.16=0.06 1.25=0.10*
1.96x0.21
1.99X0.31 1.73x0.30
5.79=0.36 6.32x0.62 6.27X0.72
0.45x0.03 0.43x0.04
0.47x0.05
1.34=0.12
1.42x0.10 1.40=0.64*
1.16x0.27
1.15x0.15 1.25x0.15 1.43=0.12*
4.37=0.89 4.71=0.41
3.02=0.43 3.87x0.25*
0.28x0.05
0.26x0.03 0.31=0.04 0.29x0.04
1.19x0.23 1.06x0.10 1.23=0.14 1.18=0.13
1.63X0.14
1.77x0.15 1.84x0.18*
3.74x0.31 6.23x0.43*
6.65x0.30*
0.43X0.05 0.39x0.04
0.43=0.06
1.49=0.17 1.39=0.14
1.56x0.16
1.19x0.10
1.28x0.11 1.34x0.11* 1.77x0.19*
4.83x0.30 3.36x0.31*
6.03x0.33 6.97=0.33*
0.28X0.02 0.31=0.02*
0.31=0.03 0.33=0.02
1.13x0.08 1.19=0.06 1.22x0.09*
1.32x0.06
4 Scaclaclnally t*niicaae by analyaia f rarlanca and Dusnacs'a eaac, p <0.03.
SL 068150
Strain Ha(ICR)
Ha(ICR)
B6C3F1 B6C3F1 CD-1 CD-1
CTW CFSW
Table 5
Mean ( S.D.) Terminal Clinical Chamiscry Valuas for Mice Exposed to VDC Vapor
Sex Mala
Female
Male Female
Male Female
Male Female
Exposure Level
0 PPM 55 PPM 100 PPM 200 PPM
0 PPM 55 PPM 100 PPM 200 PPM
0 PPM 55 PPM 100 PPM
0 PPM 55 PPM 100 PPM
0 PPM 55 PPM 100 PPM
0 PPM 55 PPM 100 PPM 200 PPM
0 PPM 55 PPM 100 PPM
0 PPM 55 PPM 100 PPM 200 PPM
BON _N (me/100 oil
10 27l7 10 29x5 10 31i9
4 38X20
9 25i4 S 265 10 29x6 5 24x4
10 28i4 10 27X5 10 34x4
10 26X5 10 24x5 10 21x3
10 25X3 10 32i9
9 62X105
10 24X5 10 21x2 10 18X3 * 10 13x4a
10 38X30 10 30X5 10 32X5
10 26X4 10 25X6 10 23X3
9 26x2
SGPT (mu/al)
22x3 24x5 37115 54x18*
27H5 3016 4013 213x133
27 no 2517 50130
13x5 25no 31112*
1717 37124 71195
1815 26116 29X15 39X13
42131 3214 52111
32X15 28H6 75l30a 111x36
Y-GT (mu/n)
2n in 111 m
2l4 3x1 2X3 2x1
2il 2x1 312
313 1*0 2*0
4l2 3l2 2*2
2*1 3X2 2*0 3x1
m 3*4 lxl
314 2x1 m m
a Statistically significant by analysis
variance and Dunnecc's test, p <0.05
SL 068151
-ii
unx
(BOSS 9ATH0LCCIC OBSSVATIOSS FOR
crosa to tctjes
"3AL STSAErs or &.IS. :GCI -rue vapors
\ > -
.'toua Strain
Oaaacal
Livr
illdaaT
Luna
Can croiatu tmai v* Tract
4 !i
5i
HnCCR)
Cancrnl
33 ?P* LOO ppm 2oo ppn
?!
> t9o 9 -1
9 to 3t1o* --13
*$
LO/LO 0/L0 1/L0 0/L0
3
to
i 3 U
t4o to
3
n
9/XO 0/LO 0/L0 S/LO
1
tt3o3o
1. 99 9> I9f
39
U 99
a
t3o >9
3
t9o t9o to <*
h il
0/10 0/10 0/10 0/10
10/10
10/10
10/10
4/a
aacon
Control 33 n> LOO ppn 200 ppa
L0/L0 2/L0 0/L0 0/L0
0/10 0/10 0/10 9/10
0/10 0/10 0/10 1/10
10/10
3/10
a/a
0/10
CD-I
Cancm! 33 W , Loo ppm 200 ppm
9/10 0/L0 0/9 0/L0
0/L0 0/10
0/9 7/10
0/10 0/10 0/9
3/10
a/a a/io
9/9
o/a
aw
Canera 1 33 ?p* LOO ppn 200 ppm
L0/L0 2/L0 0/L0 0/L0
0/10 0/10 0/10 S/LO
0/10 0/10 0/10 2/10
a/a a/a
10/10
o/a
3
a =i
inn
*x
9y4a
y 3
^W99N*
9to*
--3
9&
to
3
y 3 to
<49tV5o --9a3 mt59^o
4a3a9-3t9yo
to
--a3
5 si
0/10 2/10 3/10
s/a
o/a
1/10 1/10 8/10
0/10
i/a
3/9
6/a
a/a
0/10
o/a a/a
3
4
tta>aa439oao9
9m939
3
0/10
io/a 9/a a/a
0/10 8/10
a/a 9/a
0/10
a/a
9/9
9/a
0/10
a/io
10/10 10/10
a y 3 a 3 3 ttoo
]
to
a
I
o/a
0/10
o/a i/a
o/a o/a o/a o/a
o/a o/a
1/9
i/a
o/a o/a o/a o/a
Suabc \t:*i*d/otmb*c abanrvnd. *0m bu* gncapnd daring uponon and wnn aoe arai-Ubia for aucopnf.
aa 3 i 3 j
1tao
3
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
1/10 0/10 1/9 0/10
0/10 0/10 0/10 0/10
y
9
tao to Jtfot
9aa9 to
^a t3ao t33ov 3
j 3y 3y3
s
tayo
si
tao ato
9 e--
--T-2______
'0/10
0/10
0/10
o/a
0/10 0/10 0/10
o/a
N a
ta99yo
j
0/10 3/10 3/10
2/a
0/10
o/a o/a o/a
o/a
0/10 0/10
0/10
o/a
1/10 1/10
o/a
0/10 0/10 0/9 4/10
0/10 0/10 0/9 2/10
0/10 0/10 0/9 0/10
0/10 0/10 0/10 1/10
0/10 0/10 0/10 1/10
0/10 0/10 0/10 0/10
SL 068152
TABLE 7
HISTOPATHOLOGIC OBSERVATIONS FOR Ha (ICR) MALE MICE EXPOSED TO VimiDENE CHLORIDE VAPORS
Microscopic Observation
Exposure Concentration 0 pom 55 ppm 100 pom 200 ?pn
Liver
(5) (5) (5) (5)
Focal mononuclear cell aggregates,
minimal
5 240
Normal-appearing glycogen deposited
within hepatocyte cytoplasm
5 1 10
Centrilobular hepatocellular swelling 0 3 5 2
Accentuated lobular pattern
00 04
Focal or diffuse hepatocellular
necrosis, minimal
0000
moderate
0003
severe
0000
No change considered treatment
related
5 200
Kidneys
(5) (5) (5) (5)
No change considered treatment
related Focal mononuclear cells
5 00 0 1 00 0
Focus of tubular degeneration and
atrophy - spontaneous
1 00 0
Degenerative nephrosis - treatment
related, minimal moderate severe
0 2 10
0 34
1
0 00 4
Mediastinal Lymph Node
No change considered treatment related
Atrophy Necrosis
(5) (2) (3) (0)
5230 0 0 00 0 000
Thymus
No change considered treatment related
Atrophy Necrosis
(5) (5) (4) (1)
5540 000 1 000 1
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
i
-27
TABLE 7 (Continued)
HISTOPATHOLOGIC OBSERVATIONS FOR Ha(ICR) MALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea
No change considered treatment related
Lungs
Focal acute pneumonia No change considered treatment
related Acutely congested Acute interstitial pneumonitis Focal alveolar histiocytosis
Esophagus
No change considered treatment related
cioosure Concentration 0 ppm 53 ppm 100 pom 200 atm
(5) (5) (5) (3)
<3) (5) (5) (5) 2112 5550 0002 1005 2130
(5) (5) (4) (4)
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068154
4 iV
-28-
TABLE 8
HISTOPATHOLOGIC OBSERVATIONS FOR 36C3F1 MALE MICE EXPOSED TO VINYLEDENE CHLORIDE VAPORS
Microsconic Observation
Exposure Concentration Q p-QTa 53 com 1QQ nom 200 com
Liver
(5) (5) (5) (5)
Focal mononuclear cell aggregates,
miaiTTtal
5 450
Normal-appearing glycogen deposited
within hepatocyte cytoplasm
5420
Centrilobular hepatocellularswelling 0
130
Accentuated lobular pattern
0000
Focal or diffuse hepatocellular
necrosis, minimal
0 100
moderate
0000
severe
0005
No change considered treatment
related
5 4 20
Kidneys
(5) (5) (3) (5)
No change considered treatment
related
S000
Focal mononuclear cells
1000
Focus of tubular degeneration and
atrophy - spontaneous
0000
Degenerative nephrosis - treatment
related, minimal
0100
moderate
0240
severe
0215
Mediastinal Lymph Node
No change considered treatment related
Atrophy Necrosis
(5) (0) (4) (4)
50 42 00 0 0 00 0 2
Thvmus
No change considered treatment related
Atrophy Necrosis
(3) (5) (4) (0)
55 00 00
40 00 00
C ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068155
29-
^ 4 +-
TABLE 8 (Continued)
HIST0P-,'H0L0GIC OBSERVATIONS FOR B6C3F1 MALE MICE ECPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea
No change considered treatment related
Lungs Focal acute pneumonia No change considered treatment
related Acutely congested Acute Interstitial pneumonitis Focal alveola; histiocytosis
Esophagus
No change considered treatment related
Exposure Concentration
0 oom
55 oom
100 ppm 200 oom
(4) (4) C3) (1)
44
31
(5) (5) (5) (5) 0 0-1 0
5551
0000
0004
00 10
(5) (4) (4) (3)
54 4 3
( ) Number in parentheses indicates number or tissues examined. Data listed as number affected.
SL 068156
i -30-
TABLE 9
HISTOPATHOLOGIC OBSERVATIONS FOR CD-I MALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Exposure Concentration
0 doth
55 ppm
100 oom 200 aom
Liver
(5) (5) (5) (5)
Focal mononuclear cell aggregates,
minimal
5530
Normal-appearing glycogen deposited
within hepatocyte cytoplasm
5 2 10
Centrilobular hepatocellular swelling 0 3 2 0
Accentuated lobular pattern
0030
Focal or diffuse hepatocellular
necrosis, minimal
00 10
moderate
0000
severe
0015
No change considered treatment
related
5 200
Kidneys
No change considered treatment related
Focal mononuclear cells Focus of tubular degeneration and
atrophy - spontaneous Degenerative nephrosis - treatment
related, minimal moderate severe
(5)
5 0
1
0 0 0
(5)
0 0
0
0 0 5
Mediastinal Lymph Node
No change considered treatment related
Atrophy Necrosis
(5) (5) (5) <2)
5550 0001 0002
Thymus
No change considered treatment related
Atrophy Necrosis
(5) (3) (5) CO) .
53 50 00 0 0 00 00
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068157
-31-
4 4-
TABLE 9 (Continued)
HISTOPATHOLOGIC OBSERVATIONS FOR ID-1 MALE MICE EXPOSED TO VUTCLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea No change considered treatment
related
Lung;'
Foca_ .cute pneumonia No cc .ge considered treatment
related Acutely congested Acute interstitial pneumonitis Focal alveolar histiocytosis
Esophagus
No change considered treatment related
Exposure Concentration 0 ppm 55 ppm 100 pom 200 tom
(3) (1) (0) (3)
3 103
(5) (5) 00
3) (5) 10
5550 0004 00 0 3
0000
(4) (5) (4) (3)
45 43
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068158
TABLE 10
HISTOPATHOLOGIC OBSERVATIONS FOR CTO MALE MICE EXPOSED TO VtNTLIDENE CHLORIDE VAPORS
Microscopic Observation
Exposure Concentration 0 oom 55 oom 100 ppm 200 ppm
Liver
Focal mononuclear cell aggregates, minimal
Normal-appearing glycogen deposited within hepatocyte cytoplasm
Cantxilobular hepatocellular swelling Accentuated lobular pattern Focal or diffuse hepatocellular
necrosis, moderate severe
No change considered treatment related
(5)
3
5 0 0
0 0 0
5
(5)
0
0 0 0
0 0 5
6
Kidneys
No change considered treatment related
Focal mononuclear cells Focus of tubular degeneration and
atrophy - spontaneous Degenerative nephrosis - treatment
related, minimal moderate severe
(5)
5 2
0
0 0 0
(5)
0 0
0
0 0 5
Mediastinal Lvmoh Node
No change considered treatment related
Atrophy Necrosis
<4) (5) (5)
45
5
ooo
00
0
(4)
0 1 4
Thymus
No change considered treatment related
Atrophy Necrosis
(5) (5) (3) (0)
5530 0000 0000
( ) Number in parentheses indicates number of tissues examined Data listed as number affected.
SL 068159
--33-
+ 4
TABLZ 10 (Continued)
HISTOPATHOLOGIC OBSERVATIONS FOR CTff MALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea No change considered treatment
related
Lungs
Focal acuta pneumonia No change considered treatment
related Acutely congested Acuta Interstitial pneumonitis Focal alveolar histiocytosis
Esophagus
No change considered treatment related
Exposure Concentration 0 oom 55 pom 100 ppm 200 oom
(3) (0) (2) (3)
30 23
(5) (5) 00
(5) (5) 00
5550 0005
0000
0000
(1) (1) (4) (3)
114
3
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
0&8^
* t>
;I4
f-ia
XtfU LI
G30SS PATHOLOGIC OHSISlVAtlOMS FOR SEVI3AL 3TSAIKS OF HMALS HICS CT0SE3 TO VOTUDE3E CHLORIDE VAPORS
Central
Ll'rr
Kldaity
Lao*
Msu* de7**d
In ii vied d*-
eTM*i ai?o*
Cancraincutdnal
eljiu* in jo-
Sv
Trace
gyvgua dceir.al cavder
** 2 C 2? X -*
s1 a 11
-3 *21 M3 y9 23
-*9 *3--
1
a I *3 39 a
0 y'
11 5 *33
1*
s i
y 3
4 >
3X9
-a ays
9g ay ya
'a a Xa
t3y >3 <3y 93
y i* y *6
9* 1_JJL
1 |a
^ x3
Taucral 53 ppa 100 7pa 200 ppn
a/io
3/10
4/10 0/10
1/10 1/10 0/10 4/10
0/10 0/10 0/10 1/10
9/10 1/10 0/10 Q/10
5c:n
Zouesol 55 ?pn 100 ppa 200 ?pa
10/10 10/10
3/10 0/10
0/10 0/10 0/10 10/10
0/10 0/10 0/10 0/10
10/10 10/10
2/10 0/10
O-l
Canesnl 55 ?po 100 ppn ZOO ppa
9/10 10/10 10/10
5/10
TV
Canenol
55 ppm 10O ppm ZOO ppm
10/10 10/10 10/10
0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 1/10
0/10 0/10
0/10 0/10
10/10 10/10 10/10 10/10
0/10 0/10 0/10 0/10
10/10 10/10 10/10
9/10
;uabr *ffM*d/tt*b*t aftnnrry.
aay9 a<ya9w
a9^x
y3a3
9 m3y
dS ^a
m
yyaayya Au a9
aU --xaa* y3 9ayaaa9
--9a& yy3y3ya-a^ y4*
S'i
g 52
0/10 0/10 0/10 7/10
0/10 0/10 1/10 9/10
0/10 0/10 0/10 4/10
0/10 0/10 0/10 10/10
W*4 a9y !
9 9 ya9* aa3t a9*3 3
0/10 0/10 0/10 3/10
0/10 0/10 3/10 3/10
0/10 0/10 0/10 0/10
0/10 O/10 0/10 2/10
yaa aU ay a 9 s y i a
A a 1
2/10 2/10 1/10 0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
m
3
yg*
I
0/10 0/10
o/ia
o/io
o/io
o/io
0/10
0/10
1/10 0/10
0/10
1/10
0/10 0/10 0/10 a/io
A V
m3
3
9 yy I =3 =a
-ue s--
o/io
o/io
0/10
2/10
0/10
0/10
0/10
1/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10
0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 1/10
0/10 0/10 0/10 1/10
Ma
9
0/10 6/10 6/10 5/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
0/10 0/10 0/10 0/10
0/10 5/10 5/10 5/10
0/10 0/10 0/10 0/10
0/10
0/10 0/10 0/10
0/10 0/20 0/10 0/10
SL 068161
-35-
^4 V
TABLE 12
HISTOPATHOLOGIC OBSERVATIONS FOR Ha(ICR) FEMALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Exposure Concentration 0 pom 53 ppm 100 pom 200 pom
Liver
(5) C5) (5) (5)
No change considered treatment
related
55 40
Focal mononuclear cell aggregates,
minimal
55 50
Normal-appearing glycogen deposited
within hepatocyta cytoplasm
2000
Decreased amount of glycogen within
hepatocyta cytoplasm
00 00
Accentuated lobular pattern, minimal . 0 0 0 4
marked
0
0
0
0
Centrilobular hepatocellular swelling
and pleomorphism
00 15
Hepatocellular degeneration/necrosis
0
0
0
2
Acute congestion without necrosis
0
0
0
1
Kidneys
(5) (5) (5) (5)
No change considered treatment
related
3555
Focal mononuclear cells
0000
Focus of tubular degeneration and
atrophy -spontaneous
0000
Degenerative nephrosis - treatment
related
0000
Mediastinal Lymph Node
No change considered treatment related
Reactive hyperplasia
(0) ' Cl) (4) (2)
0 13
2
00
10
Thymus
No change considered treatment related
(5) (5) (4) (2)
55
42
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068162
TABLE 13
HISTOPATHOLOGIC OBSERVATIONS FOR B6C3F1 FEMALE MICE EXPOSED TO VTNYLIDENE CHLORIDE VAPORS
Microscopic Observation
_______ Exposure Concentration 0 ppm 53 ppm 100 ppm 200 oom
Liver
(5) (5) (5) (5)
No change conside treatment relaced
Focal mononuclear -11 aggregates, minimal
Normal-appearing glycogen deposited within hepacocyca cytoplasm
Decreased amount of glycogen within hepatocyta cytoplasm
Accentuated lobular pattern, aKnimai marked
Cencrilobular hepatocellular swelling and pleomorphism
Hepatocellular degeneration/necrosis Acute congestion without necrosis
5
5
5
0 0 0
0 0 0
5
5
5
0 0 0
0 0 0
20
50
30
20
10 00
30
10
05
Kidneys
(5) (3) (5) (5)
No change considered treatment
related
5 5 50
Focal mononuclear cells
0 0 00
Focus of tubular degeneration and
atrophy -spontaneous
1000
Degenerative nephrosis - treatment
related
0005
Mediastinal Lymph Node
No change considered treatment related
Reactive hyperplasia
(5) (0) (4) (0)
50 00
4 0
0 0
Thymus
No change considered treatment related
(5) (5) (5) (0) 5 5 50
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068164
TABLE 13 CContinued)
HISTOPATHOLOGIC OBSERVATIONS FOR B6C3F1 FEMALE MICE EXPOSED TO VIMYLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea
No change considered treatment related
Acute tracheitis
Lungs
No change considered treatment related
Focal acute pneumonia Acutely congested Acute interstitial pneumonitis Focal alveolar histiocytosis Inflammatory cells within bronchi
Esophagus
No change considered treatment related
Exposure Concentration
0 ppm
55 ppm
100 ppm 200 oom
(5) (4) (2) (2)
5 420 0002
(5) (5) <5) (4)
5550
100 1 0000
0003 0020 0004
(5) (4) (5) (3)
3
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068165
-39-
* .** f"
TABLE 14
HISTOPATHOLOGIC OBSERVATIONS FOR CD-I FEMALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Exposure Concentration
0 pom
55 pom
100 ppm 200 opts
Liver
(5) (5) (5) (5)
No change considered treatment
relaced
5 5 00
Focal mononuclear cell aggregates,
minimal
3 550
Normal-appearing glycogen deposited
within hepacocyte cytoplasm
3 200
Decreased amount of glycogen within
hepacocyte cytoplasm
1 000
Accentuated lobular pattern, minimal 0 0 5 4
marked
0
0
0
0
Centrilobular hepatocellular swelling
and pleomorphism
0 054
Hepatocellular degeneration/necrosis 0 0 2 5
Acute congestion without necrosis
0
0
0
0
Kldnevs
(5) (5) (5) (5)
No change considered treatment
related Focal mononuclear cells
55 53 2 0 00
Focus of tubular degeneration and
atrophy -spontaneous
1 0 10
Degenerative nephrosis - treatment
related
0 0 02
Mediastinal Lymph Node
No change considered treatment related
Reactive hyperplasia
(5) (4) (5) (5)
5555
0000
Thymus
No change considered treatment related
(4) (3) (5) (3) 43 53
( ) Number in parentheses indicates number af tissues examined Data listed as number affected.
SV
4 by
-40-
TABLE 14 (Continued)
HISTOPATHOLOGIC OBSERVATIONS FOR CD-I FEMALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Trachea
No change considered treatment related
Acute tracheitis
Lungs
No change considered treatment related
Focal acute pneumonia Acutely congested Acute interstitial pneumonitis Focal alveolar histiocytosis Inflammatory cells within bronchi
Esophagus
No change considered treatment related
Exposure Concentration 0 non 35 soa 100 ppm 200 oom
(4) (4) (3) (5)
4 435 0 000
(5) (5) (5) (5)
5 55 5 0 01 0 0 00 0 0 000 0 000 0 00 0
(4) (5) (5) (4)
455 4
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068167
--41-
*.4 ^
TABLE 15
HISTOPATHOLOGIC OBSERVATIONS FOR CFW FEMALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscopic Observation
Erasure Concentration
Oppa
55 ppm
100 ppm 200 ppm
Liver
(5) (5) (5) (5)
No change considered treatment
related
5 100
Focal mononuclear cell aggregates,
minimal
5 4 20
Normal-appearing glycogen deposited
within hepatocyte cytoplasm
5 100
Decreased amount of glycogen within
hepatocyte cytoplasm
0000
Accentuated lobular pattern, minimal 0 3 0 0
marked
0
0
5
5
Centrllobular hepatocellular swelling
and pIsomorphism
0455
Hepatocellular degeneration/necrosis 0 0 2 5
Acute congestion without necrosis
0
Q
0
0
Kidnevs
(5) (3) (5) (5)
No change considered treatment related
Focal mononuclear cells Focus of tubular degeneration and
atrophy -spontaneous Degenerative nephrosis - treatment
related
5 3
0
0
55
11
20
00
5
0
0
0
Mediastinal Lymph Node
No change considered treatment related
Reactive hyperplasia
Thymus No change considered treatment
related
(5) (5) (5) (3)
5553
00 0 0
(5) (4) (5) (1)
54
5
1
( ) Number in parentheses indicates number of tissues examined Data listed as number affected.
06168 SL
4 >
-42-
TABLZ 15 (Continued)
HISTOPATHOLOGIC OBSERVATIONS FOR CFW FEMALE MICE EXPOSED TO VINYLIDENE CHLORIDE VAPORS
Microscooic Observation
Trachea
No change considered treatment related
Acute tracheitis
Lungs
No change considered treatment related
Focal acute pneumonia Acutely congested Acute interstitial pneumonitis Focal alveolar histiocytosis Inflammatory cells within bronchi
Esophagus
No change considered treatment related
Exdosura Concentration
Q pop
55 onm
100 ppm 200 oom
(2) (4) (4) (4)
24 4 4 00 0 0
(5) (5) (5) (5)
55 00 00 00 00 00
(4). (4)
5 0 0 0 0 0
(5)
3 0 0
2 0 0
(4)
4 55
4
( ) Number in parentheses indicates number of tissues examined. Data listed as number affected.
SL 068169
