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PubMed1983

Pharmacokinetics and metabolism of inhaled methyl chloride in the rat and dog.

Methyl chloride (MeCl) metabolism and pharmacokinetics were studied in male Fischer 344 rats and male beagle dogs. Apparent steady-state blood MeCl concentrations were proportionate to exposure concentration in rats and dogs exposed to 50 and 1000 ppm. Furthermore, blood MeCl concentrations were similar in both species when they were exposed to the same concentration. A linear two-compartment open model described the blood MeCl data: alpha and beta phase elimination half-times corresponded to approximately 4 and 15 min, respectively, in rats, and 8 and 40 min in dogs. Rats exposed for 6 hr to 0, 50, 225, 600, or 1000 [14C]MeCl were evaluated for tissue nonprotein sulfhydryl (NPSH), total 14C activity, nonextractable tissue 14C activity, and urinary metabolites. MeCl-induced NPSH depletion was dose-related and was greatest in liver. Total 14C in liver and kidney was approximately proportionate to exposure concentrations. Relative concentrations of nonextractable 14C decreased at 600 to 1000 ppm MeCl suggesting a dose-dependent metabolic pathway for MeCl in the rat. Metabolites in urine included N-acetyl-S-methylcysteine, methylthioacetic acid sulfoxide, and N-(methylthioacetyl)glycine. These metabolites are likely to be products of a reaction between MeCl and glutathione. A nonradiometric analysis of a putative MeCl metabolite (S-methylcysteine) was performed in dogs exposed to MeCl; this method was not a sensitive indicator of MeCl exposure.

Animals↗
PubMed1985

An ultrastructural study of lesions induced in the cerebellum of mice by inhalation exposure to methyl chloride.

Female C57BL/6 mice were exposed for 6 h/day, 5 day/wk for 2 weeks, to 1,500 ppm methyl chloride. Focal and diffuse malacia, involving the cerebellar inner granular layer was found while renal lesions were minimal or absent. The cerebellar lesions were most frequently found in the ventral paraflocculus, and less often in other regions of the cerebellum. The earliest ultrastructural changes were seen in the nuclei of scattered cerebellar granule cells, with progression from slight confluence of heterochromatin, to complete nuclear condensation or karyorrhexis. More severely affected areas exhibited severe watery swelling and disruption of granule cell perikarya with less severe changes in other cell types. Blood vessels appeared normal, even in areas of severe malacia. It was concluded that the lesions in the mouse cerebellum closely resemble methyl chloride induced brain lesions previously described in guinea pigs, and that these lesions are not secondary to the renal toxicity of methyl chloride.

Air Pollutants↗
PubMed1989

Metabolism of methyl chloride by human erythrocytes.

Erythrocyte cytoplasm of rats, mice and humans was incubated in head space vials with methyl chloride and the decline in concentration of the substance monitored as a parameter of metabolism. The production of S-methylglutathione was controlled by tlc. Rats, mice, bovines, pigs, sheep and rhesus monkeys showed no conversion of methyl chloride in erythrocyte cytoplasm. About 60% of the human blood samples showed a significant metabolic elimination of the substance (conjugators), whereas about 40% did not (non-conjugators). The production of S-methylglutathione indicated enzymatic metabolism of the substance by glutathione S-transferases. In literature, a "major" and "minor" form of human erythrocyte glutathione S-transferase has been described. The results indicate that the "minor" form is probably responsible for the unique metabolism of methyl chloride in human erythrocytes.

Animals↗
PubMed1985

DNA-binding assay of methyl chloride.

Fischer-344 rats and B6C3F1 mice of both sexes were exposed in closed chambers to 14C-labeled methyl chloride. Different clearance values from the gas phase of the system indicated that, based on body weight, mice metabolized the test compound much faster than rats. After isolation of DNA and nucleoproteins from liver and kidneys radioactivity was found in all macromolecular samples; this was ascribed to metabolic C1-incorporation. Radioactivity incorporation was particularly high in DNA of mouse kidneys, suggesting a high turnover to active C1 bodies (formaldehyde, formate) in this tissue. Analyses of DNA samples from kidneys of female and male mice showed neither 7-N-methylguanine nor O6-methylguanine. Hence, the formation of tumors in B6C3F1 mice exposed to high concentrations of methyl chloride is not based on methylation of DNA in this tissue.

Animals↗
PubMedDate not supplied

Long-term follow-up after methyl chloride intoxication.

In this study, the authors investigated mortality and cancer patterns among a group of individuals accidentally exposed to methyl chloride 32 y earlier. This group of 24 persons had survived the immediate intoxication, which had occurred on a trawler during a fishing trip. The authors selected a reference group, which contained five times as many individuals as the study group, from registers of crews, and they controlled for age, occupation, social class, and lifestyle factors. The authors established a record linkage through personal identification numbers with the national death register and cancer register, thus securing 100% follow-up. The Mantel-Haenszel point estimate (M-H) was 2.2, and the 95% confidence interval (CI) was 1.3-3.1 for all causes of death. There was an excess of deaths from cardiovascular diseases (M-H = 2.1, 95% CI = 1.2-3.8). This excess mortality was more prominent among deckhands who had been subject to higher exposure; risk ratios (RRs) were elevated for all causes of death (RR = 2.5, 95% CI = 1.0-5.7), as well as for cardiovascular diseases (RR = 3.9, 95% CI = 1.0-14.4). In addition, the authors noted elevated risks for all cancers (M-H = 1.5, 95% CI = 0.3-5.6) and for lung cancer (M-H = 2.7, 95% CI = 0.1-52.6). The authors concluded that exposure to methyl chloride may have contributed to the risk of cardiovascular disease. Investigators need to conduct further studies on groups exposed to methyl chloride to refute or confirm this result.

Aged↗
PubMed1983

Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure.

One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.

Air↗
PubMed1994

Polymorphic distribution of glutathione transferase activity with methyl chloride in human blood.

Interindividual variation in the in vitro conjugation of methyl chloride with glutathione by erythrocyte glutathione transferase was investigated in 208 healthy males and females from the southern and central parts of Sweden. It was found that 11.1% of the individuals lacked this activity, whereas 46.2% had intermediate activity and 42.8% had high activity. This distribution of three phenotypes is compatible with the presence of one functional allele with a gene frequency of 0.659 and one defect allele with a gene frequency of 0.341. The proportion of non-conjugators in this Swedish material was considerably smaller than that previously found in Germany (Peter et al., Arch Toxicol 1989: 63, 351-355). The polymorphic distribution of another glutathione transferase, GST mu, was determined in the same individuals with a PCR method. No connection between the genotype for GST mu (GSTM1) and the glutatione conjugation with methyl chloride in erythrocytes was found.

Adult↗
PubMed1990

Formation and repair of DNA lesions in kidneys of male mice after acute exposure to methyl chloride.

The time-course of DNA lesions (DNA-protein cross-links, single-strand breaks) induced by high concentrations of methyl chloride (1000 ppm) was measured in renal tissue of male mice by means of the alkaline elution assay in order to gain an insight into repair processes. DNA-protein cross-links were removed at a fast rate, whereas single-strand breaks appeared to accumulate, even during repair of DNA-protein cross-links. However, 48 h after exposure to methyl chloride, neither of these lesions were detectable in mouse kidney. Both types of DNA damage were ascribed to the action of formaldehyde, an intermediate in methyl chloride metabolism which may react with nucleic acids and protein and interfere with DNA repair.

Animals↗
PubMed2000

Natural methyl bromide and methyl chloride emissions from coastal salt marshes.

Atmospheric methyl bromide (CH3Br) and methyl chloride (CH3Cl), compounds that are involved in stratospheric ozone depletion, originate from both natural and anthropogenic sources. Current estimates of CH3Br and CH3Cl emissions from oceanic sources, terrestrial plants and fungi, biomass burning and anthropogenic inputs do not balance their losses owing to oxidation by hydroxyl radicals, oceanic degradation, and consumption in soils, suggesting that additional natural terrestrial sources may be important. Here we show that CH3Br and CH3Cl are released to the atmosphere from all vegetation zones of two coastal salt marshes. We see very large fluxes of CH3Br and CH3Cl per unit area: up to 42 and 570 micromol m(-2) d(-1), respectively. The fluxes show large diurnal, seasonal and spatial variabilities, but there is a strong correlation between the fluxes of CH3Br and those of CH3Cl, with an average molar flux ratio of roughly 1:20. If our measurements are typical of salt marshes globally, they suggest that such ecosystems, even though they constitute less than 0.1% of the global surface area, may produce roughly 10% of the total fluxes of atmospheric CH3Br and CH3Cl.

Atmosphere↗
PubMed1983

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride.

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.

Abnormalities, Drug-Induced↗
PubMed1985

Reproduction in Fischer-344 rats exposed to methyl chloride by inhalation for two generations.

Male and female Fischer-344 rats were exposed to methyl chloride by inhalation (0, 150, 475, or 1500 ppm, 6 hr/day, 5 days/week, 40 males and 80 females per group). The only treatment-related clinical signs were a 10 to 20% body weight gain depression (BWGD) in both males and females exposed to 1500 ppm at all weekly weighings after 2 weeks of exposure and a 5-7% BWGD in 475-ppm exposed animals after Day 57. After 10 weeks the exposure schedule was changed to 6 hr/day, 7 days/week and each male was mated to two exposed females. The mating period was ended after 2 weeks, at which point 10 males/group were necropsied. The only treatment-related lesions found were severe bilateral testicular degeneration (10/10) and granulomas in the epididymis (3/10) in the 1500-ppm males. The remaining 30 males per group were then removed from exposure and mated during a 2-week period with 60 unexposed females. The exposed females were continued on exposure from the start of mating to Postnatal Day 28 (6 hr/day, 7 days/week). The females were not exposed from Gestation Day 18 to Postnatal Day 4, and the pups were never directly exposed prior to weaning. There were no significant differences between groups in the number of exposed or unexposed females that mated, as evidenced by copulation plugs. No litters were born to exposed or unexposed females mated to the 1500-ppm males. There was no significant difference in the number of litters produced by the 150-ppm groups when compared to the control groups. Fewer litters were born in the 475-ppm groups than in the control groups. No differences in litter size, sex ratio, pup viability, or pup growth were found among the 475-ppm, 150-ppm, or control F0 groups. When bred 10 weeks after the cessation of exposures, 5 to 20 1500-ppm F0 males had regained the ability to sire normal litters. The same number of 475-ppm F0 males proved as fertile (15/20) as control F0 males (13/20). After weaning, F1 pups from the 475-, 150-, and 0-ppm groups were exposed to the same concentrations of methyl chloride for 10 weeks and then mated. A trend toward decreased fertility was found in the 475-ppm F1 group.

Animals↗
PubMed1986

Role of epididymal inflammation in the induction of dominant lethal mutations in Fischer 344 rat sperm by methyl chloride.

This study assessed the possible relationship between methyl chloride (MeCl)-induced epididymal inflammation and the formation of dominant lethal mutations in sperm of Fischer 344 rats. Groups of 40 males were exposed to MeCl (3000 ppm 6 hr/day for 5 days), with or without concurrent treatment with the anti-inflammatory agent 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW 755C; 10 mg/kg, i.p. 1 hr pre- and postexposure); BW 755C was shown previously to inhibit MeCl-induced epididymal inflammation. Control groups (n = 20) were either untreated, injected as described above with BW 755C, or injected on the afternoon of day 5 with triethylenemelamine (0.2 mg/kg), a known dominant lethal mutagen. Each male was caged with one female weekly for 3 weeks; 12-18 days after mating, females were killed to assess dominant lethal parameters. In females bred to MeCl-exposed males, significant increases were observed in postimplantation loss at postexposure week 1 (0.84 dead implants per female vs. 0.29 in untreated controls) and in dead implants/total implants at both week 1 (0.10 vs. 0.04 control) and week 2 (0.24 vs. 0.06 control). These increases were not observed in females bred to males treated with BW 755C during MeCl exposure. Coadministration of BW 755C to males along with MeCl also reduced the percentage of mated females with two or more postimplantation losses from 31% to 8% (week 1) and 30% to 12% (week 2). Therefore, the dominant lethal mutations induced by MeCl appear to be a consequence of its induction of inflammation in the epididymis. These data demonstrate the potential genotoxicity of inflammatory processes in vivo.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

Reproductive effects of inhaled methyl chloride in the male Fischer 344 rat. II. Spermatogonial toxicity and sperm quality.

Studies were performed to assess the effects of inhaled methyl chloride (MeCl) on sperm quality and testicular histopathology in the Fischer 344 rat. Adult male F-344 rats were exposed to 1000 or 3000 ppm MeCl 6 hr/day for 5 days, or received an ip injection of 0.2 mg triethylenemelamine (TEM)/kg on the afternoon of Day 5. Five males from a control group and each of the three treatment groups were killed weekly for 8 weeks, and five more from the control and 3000 ppm groups at Week 16 postexposure. Male rats from the 1000 ppm MeCl- and TEM-exposed groups exhibited no consistent difference from control males in any parameter measured. In the 3000 ppm MeCl group, over 50% of the males had uni- or bilateral sperm granulomas in the cauda epididymis. Testes weights were significantly depressed in these males by 3 weeks postexposure, and remained depressed as late as 8 weeks after treatment. Testicular spermatid head counts were significantly lower by 2 weeks postexposure, and the testes showed a characteristic cytotoxic response to MeCl exposure, including a delay in spermiation, chromatin margination in round spermatids, epithelial vacuolation, luminal exfoliation of spermatogenic cells, and multinucleated giant cells. Counts of repopulating seminiferous tubule cross sections and of testicular sperm heads at 7 weeks postexposure indicated that 60 to 70% of the spermatogonial stem cells had been killed by MeCl exposure. Sperm isolated from the vasa deferentia had significantly depressed numbers and an elevated frequency of abnormal sperm head morphology by Week 1 postexposure, and significantly depressed sperm motility and an elevated frequency of headless tails by Week 3 postexposure. All parameters measured in the testes and in vasa deferentia sperm showed varying degrees of recovery, and all were near the normal range by Week 16 postexposure except sperm count. These data suggest that the previously reported high preimplantation loss caused by methyl chloride exposure may be primarily due to cytotoxic effects on the testis and epididymal epithelium, rather than to direct genotoxic effects on the sperm.

Animals↗
PubMed1987

Role of testicular versus epididymal toxicity in the induction of cytotoxic damage in Fischer-344 rat sperm by methyl chloride.

Exposure of male Fischer-344 (F-344) rats to methyl chloride (MeCl) results in testicular and epididymal toxicity and the induction of both pre- and postimplantation embryonic loss; the preimplantation loss is caused by cytotoxic damage to sperm that leads to failure of fertilization (Toxicol Appl Pharmacol 1986; 86:124-130). The present study examined whether the cytotoxicity of MeCl to sperm is due to the testicular or epididymal toxicity of MeCl. Groups of 18 males were exposed to 3000 ppm MeCl 6 h/day for 5 days, with and without concurrent treatment with the anti-inflammatory agent 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW755C; 10 mg/kg, i.p. 1 h pre- and postexposure); BW755C was used to inhibit the epididymal toxicity of MeCl. Control groups were untreated or injected as described above with BW755C. Six males from each group were killed weekly for 3 weeks. Toxic effects of MeCl on the testis were demonstrated by decreased relative organ weight (week 3), testicular histopathology (weeks 1-3) and decreased daily sperm production (weeks 1-3); these effects were not prevented by BW755C. In both the MeCl and the MeCl + BW755C treatment groups, tubules devoid of sperm were observed in regions 4 and 5 of the epididymis at week 2, and in regions 6A and 6B at week 3. Sperm were present in the vas deferens of both groups at week 3 in decreased numbers and had decreased motility and more frequent morphologic abnormalities compared to untreated controls. In conjunction with known epididymal transit times for F-344 rat sperm, these data indicate that the induction of preimplantation loss by MeCl at weeks 2 and 3 postexposure is likely to result from cytotoxic effects on sperm located in the testes at the time of exposure.

Animals↗
PubMed2001

The General Harmonic Force Field of Methyl Chloride.

The complete general harmonic force field of methyl chloride has been recalculated using the most recent literature frequency, Coriolis zeta, and centrifugal distortion data for (12)CH(3)(35)Cl, (13)CH(3)(35)Cl, (12)CD(3)(35)Cl, (12)CHD(2)(35)Cl, (12)CH(2)D(35)Cl, (12)CH(3)(37)Cl, (12)CD(3)(37)Cl, (12)CHD(2)(37)Cl, (12)CH(2)D(37)Cl, and (13)CH(3)(37)Cl. The anharmonic corrections applied to the observed frequency data are considered to be more realistic than those used hitherto. There is excellent agreement between the fitted force constants and literature high-quality ab initio force fields. The results of the least-squares refinement of the full-harmonic force field is compared with least-squares refinement of only the scale factors for an SCF calculated force field since the latter approach may be useful for larger molecules where more sophisticated calculations are impractical. The results of a refinement of only the scale factors for an MP4 calculated force field are also reported. Copyright 2001 Academic Press.

Journal Article↗
PubMed1984

Glutathione depletion by methyl chloride and association with lipid peroxidation in mice and rats.

Inhalation of methyl chloride (CH3Cl) by male B6C3F1 mice resulted in a concentration-dependent depletion of glutathione (GSH) in liver, kidney, and brain. Exposure for 6 hr to 100 ppm CH3Cl decreased the concentration of GSH in mouse liver by 45%, while exposure to 2500 ppm for 6 hr lowered liver GSH to approximately 2% of control levels. For those exposures which decreased liver GSH to less than 20% of control levels, the extent of liver GSH depletion was closely correlated with the capacity of a 9000g supernatant fraction from the liver to undergo lipid peroxidation in vitro. GSH was depleted to a lesser extent in mouse brain and kidney, compared to liver, and no relationship to peroxidation was observed for single exposures to CH3Cl. A dose-dependent decrease in liver GSH was also produced by diethyl maleate, although a nearly lethal amount (2 ml/kg) was required to lower liver GSH to less than 10% of control levels. Under these conditions the amount of lipid peroxidation was 3.5-fold less than in mice exposed to 2000 ppm CH3Cl. Exposure of rats to 2000 ppm CH3Cl reduced liver GSH to 20% of control levels, compared to 4.5% in mice similarly exposed, and under these exposure conditions the amount of lipid peroxidation measured in vitro was 40-fold greater in mouse liver than in rat liver. During exposure of mice to 2500 ppm CH3Cl, ethane expiration increased to an extent comparable to that produced by administration of 2 ml/kg of CCl4. These findings suggest that GSH depletion in liver may be an important component of CH3Cl-induced hepatotoxicity.

Animals↗
PubMed2004

Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

PURPOSE: To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). METHODS: PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. RESULTS: Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. CONCLUSION: PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

Animals↗