Adverse Effects
Flumequine
CAS No.
42835-25-6
 
 

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Activity: Microbiocide
Structure:


Adverse Effects:
Bladder
Blood
Body Weight Decrease
Bone

Eye
Liver
Mitogenic
Potent Photosensitizer
Teratogenic
Contamination / Environmental

European Commission: Not allowed to be used as an active ingredient after July 25, 2003.

-- Flumequine's production and use as an antibiotic(1) and antibiotic feed-additive on fish farms(2) may result in its release to the environment through various waste streams(SRC).
[(1) Budavari S, ed; The Merck Index. 13th ed. Whitehouse Station, NJ: Merck and Co., Inc. p. 732 (2001) (2) Halling-Sorensen B et al; Chemosphere 36: 357-93 (1998)]
-- Authorized or allowed for use in aquaculture (2 day withdrawal time in France). ... Registered or approved for use in aquatic or fishery situations in Japan (20 mg/kg per day)
[Kirk-Othmer Encyclopedia of Chemical Technology. 4th ed. Volumes 1: New York, NY. John Wiley and Sons, 1991-Present.,p. V3 (1992) 618]
--
Ref: Hazardous Substance Data Bank for Flumequine. Available at Toxnet.

Effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish.
Authors: STEFFENAK I HORMAZABAL V YNDESTAD M
Author Address: Dep. Food Hygiene, Norw. Coll. Vet. Med., P.O. Box 8146-Dep., N-0033 Oslo 1, Norway.
Source: ACTA VETERINARIA SCANDINAVICA; 35 (3). 1994. 299-301.
Abstract: BIOSIS COPYRIGHT: BIOL ABS. The effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish was investigated. Salmon containing residues of oxolinic acid and flumequine was boiled or baked in the oven. Samples of raw and cooked muscle, skin, and bone, as well as of the water in which the fish was boiled and juice from the baked fish, were analysed. Oxolinic acid and flumequine did not degrade at the temperatures reached when cooking the fish. However, fish muscle free from drug residues may be contaminated during boiling and baking due to leakage of the drug from reservoirs in the fish.


Bladder (click on for all fluorinated pesticides)

-- PubMed Abstract: In order to elucidate the tumor-initiating potential of flumequine (FL) in the liver, male C3H mice were given dietary administration of 4000 ppm FL throughout the study or for 2 weeks at the initiation stage, and then received 2 intraperitoneal injections of D-galactosamine (Gal) at weeks 2 and 5, with or without 500 ppm phenobarbital (PB) in their drinking water for 13 weeks to provide tumor-promoting effects. Hepatocellular foci were observed in 2 out of 8 and 6 out of 7 animals in the FL/PB + Gal and FL/FL + Gal groups, respectively. In addition, in an alkaline single-cell gel electrophoresis (comet) assay that was performed using adult, infant, or partial hepatectomized male ddY mice to evaluate the potential of FL at 500 mg/kg or less, to act as a DNA damaging agent. FL induced dose-dependent DNA damage in the stomach, colon, and urinary bladder of adult mice at 3 h but not at 24 h after its administration. Similarly, DNA damage was noted in the regenerating liver and the livers of infant mice at the 3 h time point. Furthermore, in in vitro assays that were conducted to investigate the potential of FL to inhibit eukaryotic topoisomerase II, which is responsible for the double-strand DNA breakage reaction as well as bacterial gyrase, inhibitory effects of FL on topoisomerase II were high relative to the influence on bacterial gyrase. The results of our studies thus strongly suggest that FL has initiating potential in the livers of mice that is attributable to its induction of DNA strand breaks.
Ref: Toxicol Sci 2002 Oct;69(2):317-21; Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice; Y Kashida et al.

Blood (click on for all fluorinated pesticides)

BIOLOGICAL DATA 2.1. Hepatotoxicity and carcinogenicity. In short-term and long-term studies of toxicity that were evaluated by the Committee at its forty-second and forty-eighth meetings, oral administration of flumequine caused dose-related hepatotoxic effects in rats and CD-1 mice. The liver damage was most pronounced in male mice, and included degenerative changes with hypertrophy, fatty vacuolation, focal necrosis and increased mitotic activity. After cessation of treatment with flumequine, the liver damage was reversed. Treatment with flumequine had little or no effect on P450-dependent hepatic drugmetabolizing enzymes or on glucuronyl transferase. Flumequine increased the plasma activities of alanine and aspartate aminotransferases, alkaline phosphatase and lactate dehydrogenase. The overall no-observed-effect level (NOEL) for hepatotoxic effects in mice was 25mg/kg bw per day...
Ref: 2004 - Flumequine (addendum). First draft prepared by Mrs. M.E.J. Pronk, Centre for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment. Bilthoven, The Netherlands.
http://www.fluorideaction.org/pesticides/flumequine.netherlands.2005pdf

Body Weight Decrease (click on for all fluorinated pesticides)

-- the twice daily oral administration of flumequine pellets 200 mg for 3 and 13 weeks at the dose level of 150 mg/kg bw/day induced few clinical signs (vomiting, low food consumption), marked reduction in bodyweight gain for females and minimal to slight arthropathies with cartilage damage. Only slight arthropathy was induced at the dose level of 60 mg/kg bw/day...
Ref: Committee for Veterinary Medicinal Products. Flumequine. Summary Report. EMEA/MRL/104/96-FINAL. June 1996. Study performed by EMEA, London UK for the European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit.

http://www.fluoridealert.org/pesticides/Flumequine.Report.1996.pdf

Bone (click on for all fluorinated pesticides)

-- Teratology studies were conducted in rats (0, 100, 200 or 400 mg/kg bw), mice (50, 100, 200, and 400 mg/kg bw) and rabbits (100, 200 or 400 mg/kg bw). None of these tests showed flumequine to be teratogenic or embryotoxic, but at doses exceeding 100 mg/kg per day it does have an effect on bone formation. The NOELs for the most sensitive species, rats and mice, were 100 mg/kg bw.
Ref: Committee for Veterinary Medicinal Products. Flumequine. Summary Report. EMEA/MRL/104/96-FINAL. June 1996. Study performed by EMEA, London UK for the European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit.
http://www.fluoridealert.org/pesticides/Flumequine.Report.1996.pdf

-- the twice daily oral administration of flumequine pellets 200 mg for 3 and 13 weeks at the dose level of 150 mg/kg bw/day induced few clinical signs (vomiting, low food consumption), marked reduction in bodyweight gain for females and minimal to slight arthropathies with cartilage damage. Only slight arthropathy was induced at the dose level of 60 mg/kg bw/day...
Ref: Committee for Veterinary Medicinal Products. Flumequine. Summary Report. EMEA/MRL/104/96-FINAL. June 1996. Study performed by EMEA, London UK for the European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit.
http://www.fluoridealert.org/pesticides/Flumequine.Report.1996.pdf
• Arthropathy: A rare form of chronic arthritis, reported to occur after attacks of acute rheumatic fever, characterised by an unusual form of bone erosion of the metacarpal heads and by ulnar deviation of the fingers; it resembles rheumatoid arthritis, but with less overt inflammation, and rheumatoid factor is absent. Synonym: Jaccoud's arthropathy.
Defintion from: http://www.books.md/J/dic/Jaccoudsarthropathy.php

Eye (click on for all fluorinated pesticides)

--PubMed Abstract: Flumequine (1 200 mg/day) was prescribed as treatment for infection of the urinary tract to three patients with chronic renal failure, who reported positive scotoma three days later. Ophthalmologic examination evinced bilateral symmetrical macular bullae. A characteristic yellow papule was present at foveal level. In all three cases, visual acuity was impaired (down to 4/10), without any angiographic alteration. Foveolas showed a moderate persistent hyperfluorescence. All patients recovered a normal visual acuity, within two days after treatment cessation, and bullae disappeared without sequelae within 5 days. The chronology and kinetics of clinical manifestations were clearly and reproducibly correlated with flumequine therapy in all patients, and suggest that this drug may be considered responsible for the ocular symptom reported. Chronic renal failure (creatinine clearance lower than 25 ml/mn) most certainly favoured the appearance of visual troubles, but other factors may possibly play a similar role: hepatic failure, individual hypersensitivity... Quinolones used as urinary antiseptics (nalidixic acid, oxolinic acid, pipemidic acid...), and other flumequine analogues may possibly be involved in such side-effects. This was reported by Bouissou et al. in an experimental model with nalidixic acid, where transient bullae appeared on young animals' articular cartilage. Such lesions are related to focal alterations of the C2 intermediary layer of cartilage, with marked edema of the interstitial material. The volume of synovial fluid increases concomitantly. These alterations suggest a direct cytotoxic effect at the intercellular level of target organs, a mechanism possibly also occurring in the retina.
Ref: J Fr Ophtalmol 1983;6(10):829-36.
[Serous macular detachment of the neuro-epithelium and flumequine]. [Article in French]. Sirbat D et al.
• Scotoma definition: An island-like blind gap in the visual field. Taber's Medical Dictionary

Liver (click on for all fluorinated pesticides)

BIOLOGICAL DATA 2.1. Hepatotoxicity and carcinogenicity. In short-term and long-term studies of toxicity that were evaluated by the Committee at its forty-second and forty-eighth meetings, oral administration of flumequine caused dose-related hepatotoxic effects in rats and CD-1 mice. The liver damage was most pronounced in male mice, and included degenerative changes with hypertrophy, fatty vacuolation, focal necrosis and increased mitotic activity. After cessation of treatment with flumequine, the liver damage was reversed. Treatment with flumequine had little or no effect on P450-dependent hepatic drugmetabolizing enzymes or on glucuronyl transferase. Flumequine increased the plasma activities of alanine and aspartate aminotransferases, alkaline phosphatase and lactate dehydrogenase. The overall no-observed-effect level (NOEL) for hepatotoxic effects in mice was 25mg/kg bw per day. The results of long-term studies of toxicity that were evaluated by the Committee at its forty-second meeting showed that flumequine had no carcinogenic effects in rats, whereas in CD-1 mice an increase in the incidence of liver tumours was observed at oral doses of flumequine of ≥400mg/kg bw per day (the lowest dose tested) in an 18-month study. The incidence of tumours in male mice was significantly higher than that in female mice. In male mice, the incidence of liver tumours increased in a dose-related and time-dependent manner, and was paralleled by an increase in the incidence of hepatotoxic changes. The present Committee re-evaluated the three short-term studies in mice, which used a two-stage hepatocarcinogenesis protocol, that were presented to the Committee at its sixtieth meeting. In these studies, treatment with flumequine caused the development of basophilic liver foci, which could suggest that flumequine has tumour initiating potential. However, the Committee also noted that concurrent hepatotoxicity (evidenced by pale, vacuolated hepatocytes with fatty droplets, inflammatory cell infiltration, increased mitotic figures and/or necrosis) was observed, as well as a regenerative response to these toxic changes and indications of oxidative stress.
Ref: 2004 - Flumequine (addendum). First draft prepared by Mrs. M.E.J. Pronk, Centre for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment. Bilthoven, The Netherlands.
http://www.fluorideaction.org/pesticides/flumequine.netherlands.2005pdf

-- PubMed Abstract: In order to elucidate the tumor-initiating potential of flumequine (FL) in the liver, male C3H mice were given dietary administration of 4000 ppm FL throughout the study or for 2 weeks at the initiation stage, and then received 2 intraperitoneal injections of D-galactosamine (Gal) at weeks 2 and 5, with or without 500 ppm phenobarbital (PB) in their drinking water for 13 weeks to provide tumor-promoting effects. Hepatocellular foci were observed in 2 out of 8 and 6 out of 7 animals in the FL/PB + Gal and FL/FL + Gal groups, respectively. In addition, in an alkaline single-cell gel electrophoresis (comet) assay that was performed using adult, infant, or partial hepatectomized male ddY mice to evaluate the potential of FL at 500 mg/kg or less, to act as a DNA damaging agent. FL induced dose-dependent DNA damage in the stomach, colon, and urinary bladder of adult mice at 3 h but not at 24 h after its administration. Similarly, DNA damage was noted in the regenerating liver and the livers of infant mice at the 3 h time point. Furthermore, in in vitro assays that were conducted to investigate the potential of FL to inhibit eukaryotic topoisomerase II, which is responsible for the double-strand DNA breakage reaction as well as bacterial gyrase, inhibitory effects of FL on topoisomerase II were high relative to the influence on bacterial gyrase. The results of our studies thus strongly suggest that FL has initiating potential in the livers of mice that is attributable to its induction of DNA strand breaks.
Ref: Toxicol Sci 2002 Oct;69(2):317-21; Mechanistic study on flumequine hepatocarcinogenicity focusing on DNA damage in mice; Y Kashida et al.

-- 1999 PubMed Abstract: It has been reported that flumequine (FLU) induces hepatic tumors in mice when given orally for 18 months. We investigated possible underlying mechanisms using a two-stage mouse hepatocarcinogenesis model. After initiation with a single intraperitoneal injection of 100 mg/kg body weight diethylnitrosamine (DEN) or saline, male CD-1 mice were given 4000 ppm FLU in the diet or 500 ppm phenobarbital (PB) in drinking water for 9, 19, 24 or 30 weeks. Toxicity, evidenced by centrilobular swollen and polar hepatocytes with fatty droplets, infiltration of inflammatory cells and increased numbers of mitosis in hepatocytes, was apparent in the livers of mice treated with FLU at all time points, but its severity declined towards the termination. FLU did not induce cytochrome P-450 enzymes such as 1A1, 2B1 and 3A2 as assessed immunohistochemically, while positive expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) was increased in hepatocytes of both DEN + FLU and FLU groups compared with the relevant controls. In animals given PB, eosinophilic swelling of hepatocytes was prominent, and the hepatocytes showed strongly positive reactions for CYP 1A1 and 3A2. Altered cell foci were induced in the livers of FLU-treated animals both with and without DEN initiation, especially the former, and their development paralleled the degree of hepatic toxicity. These results suggest that FLU hepatocarcinogenicity in mice is dependent on hepatotoxic damage and consequently increased cell proliferation. Oxidative damage to DNA may also be a crucial factor.
Ref: Cancer Lett 1999 Jul 1;141(1-2):99-107.
Hepatotoxicity and consequently increased cell proliferation are associated with flumequine hepatocarcinogenesis in mice. Yoshida M et al.

-- Maximum Residue Limits. In calculating MRL values for flumequine, the following factors were considered: á An ADI of 0-30 m g/kg, based on a toxicological end-point, was established by JECFA. This will yield a daily intake of 0-1800 m g/kg for a 60-kg person. á The parent drug was selected as the marker residue. á Muscle and kidney were proposed as target tissues. For practical reasons, however, liver is the proposed target tissue for chickens in place of kidney.
Ref: Flumequine.
http://www.fao.org/docrep/W8338E/w8338e0a.htm#TopOfPage

-- In the 90-day subchronic toxicity carried out on CD-1 mice, flumequine was administered to at level doses of 0, 25, 50, 100, 400 and 800 mg/kg bw/day for males and dosages of 1, 100, 400 and 800 mg/kg bw/day for females. In the two high doses groups, the histopathological examination of the livers revealed, in both males and females, periacinar single cell necrosis and inflammation, periacinar pigment laden macrophages, increased ploidy of hepatocytes, hepatocytic intranuclear inclusions, increased periacinar hepatocytic fatty vacuolation. However, a periacinar hepatocytic hypertrophy was only observed in males : in 7 of 12 animals of the 800 and 400 mg/kg bw dose group, in 5 of 12 animals in the 100 mg/kg bw dose group and in 1 animal in the 50 mg/kg bw dose group and these lesions were dosage-related. In addition, an inhibition of the activity of NADPH-cytochrome P450 for females of the two highest dose grop and of UDP-glucuronosyltranferase for males at 50 mg/kg bw was also reported... 25 mg/kg bw/day was considered as the NOEL for hepatotoxicity in mice.
-- In an 18-month carcinogeniciy study in mice, flumequine was administered in the feed at 0, 400 or 800 mg/kg bw. The combined incidence of benign and malignant liver tumours was dose related : 37 % in the 400 mg/kg bw dose group, 88 % in the high dose group vs. 9 % in the control group for males and 13 % in the high dose females vs. 0 % for the contrl and the low dose groups. Dose related changes in the hepatocytes which paralleled the liver tumour incidence occurred in the low dose males and in the high dose males and females.
-- There is evidence of compound-related tumorigenic efffects in the liver of mice. In order to explain the mechanism of liver tmour induction, the dosage of a preneoplastic markter yGT and of a detoxification enzymes, GSH S-transferase, were performed on liver samples collected in the 90-toxicity study carried out in mice. No variations of yGT were noted whatever the dosage used. However, an increase of the GSH S-transferase activity in females dosed at 400 and 800 mg/kg bw and in males dosed at 800 mg/kg bw showed that flllumequine induced detoxification phenomena, showing cells hepatotoxicity. However, this phenomena was not correlated with the number of tumours incidence. As the tumorigenicity is considered to be a consequence of hepatotoxiciity, it was concluded that the NOEL of 25 mg/kg bw/day covered both end-points.
Ref: Committee for Veterinary Medicinal Products. Flumequine. Summary Report. EMEA/MRL/104/96-FINAL. June 1996. Study performed by EMEA, London UK for the European Agency for the Evaluation of Medicinal Products. Veterinary Medicines Evaluation Unit.
http://www.fluoridealert.org/pesticides/Flumequine.Report.1996.pdf

Mitogenic (click on for all fluorinated pesticides)

PubMed Abstract: The influence of flumequine on mitogen induced lymphoid cell proliferation in European eels (Anguilla anguilla L., 1758) was studied. For this purpose an in vivo test, using peroral drug administration followed by successive intraperitoneal injections with concanavalin A (ConA) or bacterial lipopolysaccharides (LPS) and 5-bromo-2'-deoxyuridine, was applied. Direct counting of proliferated cells in blood smears revealed that flumequine possesses mitogenic properties. A synergistic and an antagonistic effect of the drug was observed after LPS and ConA stimulation, respectively. Flow cytometric analysis of peripheral blood lymphoid cells showed a significant reduction of the mean proportion surface immunoglobulin positive cells in the flumequine-treated animals. It is concluded that flumequine enhances proliferation of lymphoid cells (probably surface immunoglobulin negative cells) in eel under the present experimental conditions.
Ref: Vet Immunol Immunopathol 1995 Jul;47(1-2):143-52.
Influence of flumequine on in vivo mitogen responses of European eel (Anguilla anguilla L., 1758) lymphoid cells. van der Heijden MH et al.

Potent Photosensitizer (click on for all fluorinated pesticides)

-- PubMed abstract: An original physicochemical method is proposed for the evaluation of the photosensitizing activity of drugs in vitro. A Nuclear Magnetic Resonance (NMR) spectrum is recorded during light irradiation of drug solutions. The change in the intensity of the NMR lines under such conditions is termed the Photochemically Induced Dynamic Nuclear Polarization (Photo-CIDNP) effect. It is related to the formation of radical intermediates which may be involved in the in vivo photosensitization reactions (the so-called type-I photoreactions). Nine commercial quinolones were tested by this method: nalidixic, oxolinic, pipemidic and piromidic acids, rosoxacin, flumequine, enoxacin, pefloxacin and norfloxacin. Each quinolone was irradiated in alcoholic solutions in its UV absorption band (300-350 nm) in the absence or in the presence of a biological target chosen as a model: the amino-acid N-acetyltyrosine. The quinolones were classified in two groups in relation to the intensities of the observed CIDNP effects. Nalidixic and oxolinic acids, rosoxacin and flumequine are among the most potent photosensitizers.
Ref: J Pharm Belg 1990 Sep-Oct;45(5):299-305.
[Photophysical evaluation of photosensitization by various quinolones]. [Article in French]. G Vermeersch et al.

Definition: Photosensitizer (sensitizer) is an agent that absorbs light and subsequently initiates a photochemical or photophysical alteration in the system, the agent being not consumed therewith. In case of chemical alteration, the photosensitizer is usually identical to a photocatalyst. http://www.iupac.org/projects/posters01/parmon01.pdf

Teratogenic (click on for all fluorinated pesticides)

1999 PubMed Abstract:
(1) Follow-up studies of approximately 1,000 women exposed to quinolones during pregnancy show no increase in the risk of malformations, miscarriage, prematurity, intrauterine growth retardation or postnatal disorders, but there are not enough data to draw firm conclusions.
(2) Teratogenic effects have been observed in animals treated with the oldest quinolones (flumequine, nalidixic acid and pipemidic acid) and also with sparfloxacin, a fluoroquinolone.
(3) Cartilage damage after postnatal exposure to quinolones in animals and humans has been reported.
(4) Alternatives to quinolones can almost always be found for pregnant women.
(5) Accidental exposure to quinolones during pregnancy does not warrant termination.
Ref: Prescrire Int 1999 Feb;8(39):29-31.
Quinolones and pregnancy: worrying animal findings, few clinical data. [No authors listed]

Environmental (click on for all fluorinated pesticides)

-- Coyne et al. (1994) investigated the concentration of OTC in the sediment of two cages at a fish farm site, and found half-lives of 16 and 13 days. Oxytetracycline, oxolinic acid, flumequine and sarafloxacine were all found to be very persistent in sediments (Hektonen et al. 1995). In the deeper layer of the sediment hardly any degradation had occurred after 180 days and a calculated half-life of more than 300 days was estimated. The residues in the top layer of the sediment disappeared more rapidly. The removal of these substances from the sediment is most probably due to leaching and redistribution rather than degradation.
-- Samuelsen et al. (1994) showed that the toxicity of OTC to bacteria declined rapidly in sediments, although no degradation occurred. Binding to ions (Ca2+, Mg2+) and other substances were mentioned as possible explanation for the inactivation of oxytetracycline., The same study found that both oxolinic acid and flumequine sustained their antimicrobial activity over a six month period in sediment material.
Ref: Environmental Project no. 659, 2002. Environmental Assessment of Veterinary Medicinal Products in Denmark. 3. Environmental fate and occurrence of Veterinary Medicinal Products. Danish Environmental Protection Agency.
http://www.mst.dk/udgiv/publications/2002/87-7944-971-9/html/kap03_eng.htm


Environmental Spatio-temporal monitoring of the contamination of a coast river in oxolinic acid, flumequine and oxytetracycline

by Raphael Delepee, Herve Pouliquen, Herve Le Bris

Unite mixte de recherche INTRA/ENVN 1035 Chimiotherapie Aquacole et Environment, Ecole Nationale Veterinaire de Nantes Atlanpole - Le Chantrerie - BP 40706 Nantes Cedex 03, France

ABSTRACT:
Oxytetracycline, oxolinic acid and flumequine are antibacterial agents commonly used in fish farming, especially because of their broad spectrum of activity. About 80 % of these drugs reached the environment because of their administration as medicated pelleted feed and their low oral bioavailability. Under these conditions, there is a clear need in studying the impact of these treatments on the freshwater environment.

A spatio-temporol study was then realised to estimate the concentration of oxolinic acid, flumequine and oxytetracycline in water, sediments and bryophytes all along a coast river. The 25 sampling points were chosen around 6 study stations. Each of these points were sampled once per season over one year.

Concentrations in water were under limit of detection. The 900 analysis showed that concentrations were greater in the bryophytes • than in the sediments. The greatest environmental concentrations were 120 ppb, 2000 ppb, 1500 ppb for oxolinic acid flumequine and oxytetracycline respectively. Multivariate statistical analysis were performed on the data.

This study showed a real contamination of the environment by flumequine and oxytetracycline, and to a lesser extent by oxolinic acid. No seasonal difference in concentrations was noticed. The analysis of the results showed the relevance of the use of bryophytes instead of sediments in the freshwater environmental monitoring. The fine study of the results seemed to reveal a real impact of the study stations on the environment. These observations should be confirmed by more specific studies, by using moss bags for example.
Ref: Abstract (Poster 7) from: Aquaculture and Environment Symposium, September 18, 2002. 7th Bordeaux Aquaculture. September 18 - 20, 2002. Bordeau

• Definition for bryophyte:
-- Any primitive plant in the division Bryophyta, includes liverworts, mosses, and hornworts.
-- Plants in which the gametophyte generation is the larger, persistent phase; they generally lack conducting tissues. Bryophytes include the Hepaticophyta (liverworts), Anthocerotophyta (hornworts), and Bryophyta (mosses). Ref: UCMP Glossary: Botany
-- any plant of the phylum Bryophyta, having stems and leaves but lacking true vascular tissue and roots and reproducing by spores: includes the mosses and liverworts. [ETYMOLOGY: 19th Century: New Latin, from Greek bruon moss + -phyte] bryophytic adjective. Ref: WordReference.com

 
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