Table 1.

Experimental studies on oral candidiasis in animal models

Model, yr (reference)AuthorsNo. of animals/age/sex/avg wtaDietaOther conditionsaCandida strain, inoculum sizeaLength of studyCandidacarriageaRemarksa
 1971 (26)Budtz-Jörgensen6/adult/m and f/NRNRT onto acrylic plate weekly/biweeklyCA type A (Hasenclever)/SDA/48 h/37°C; inoculum, 100 mg (wet wt) of CA growth12 wkNRThe palatal candidal infection demonstrated features similar to changes observed inCandida-induced denture stomatitis. Treatment with T enhanced candidal growth and sustained an intense inflammatory reaction.
 1973 (27)Budtz-Jörgensen14/adult/m and f/NRNRAnimals were treated with AZACA type A; inoculum: 100 mg (wet wt) of CA growth8 moCandida blastospores and hyphae observedSpontaneous healing of the atropic type of candidal infection was observed in control animals. Animals immunosuppressed with azathioprine developed thrushlike candidal lesions in the palatal mucosa.
 1975 (28)Budtz-Jörgensen13/adult/m and f/2.5–5.4 kgNRAnimals were treated with TRICA type A (Hasenclever)/SDA/48 h/37°C; inoculum: 100 mg (wet wt) of CA growth5 moControl: mucosal smears showed Candida in small numbers; test: large numbers of Candida and hyphae were seen in mucosal smearsControl: an acute atrophic candidiasis developed in the group of non-steroid-treated monkeys, that healed in 2–5 wk; test: an acute pseudomembraneous candidiasis was induced in the steroid-treated monkeys, which healed slowly.
 1977 (133)Olsen and Haanaes10/NR/m and f/NRCMFOXY was given to suppress saliva flowCA type A (Hasenclever)/SDA/48 h/37°C; inoculum: 100 mg (wet wt) of CA growth14 wkControl: few yeasts were seen in palatal-smears; test: blastaspores and hyphae were abundantSustained depression of saliva flow with a higher dose of the drug caused larger thrush lesions. The lesions did not extend beyond the maxillary acrylic plates, showing the acrylic plate is a prerequisite for oral candidiasis.
Wistar rat
 1970 (78)Jones and Adams26/NR/m and f/350 gFood and water ad libitumHH injectedCA type A/SDA/48 h/37°C; inoculum: 0.25 ml of 108 cells/ml in saline10 daysCA found in the mouths of animals; hyoscine did not change the frequency of recovery of CA50% of rats had lesions that resembled oral candidiasis. Hysocine administration did not produce measurable change in the rate of infection.
 1971 (1)Adams and Jones42/NR/NR/NRNRCA type A/SDA/48 h/37°C; inoculum: 0.25 ml of 108 cells/ml in saline6 wkNR5 of 30 rats showed histologic evidence of candidal infection. The Wistar rat is a suitable animal model for the study of oral candidiasis.
 1978 (132)Olsen and Bondevik38/NR/m/NRSRP and T-waterCA from denture stomatitis patient/SDA/48 h/37°C; inoculum: 30 mg2 wkNRAnimals contracted a generalized, simple type of Candida infection of the palate.
 1981 (179)Shakir et al.77/NR/m/350 gFood and water ad libitumCA 3091/ serotype A/SDA/36 h/30°C; inoculum: 30 mg (wet wt) of CA suspension6 wkNRAnimals fitted with acrylic appliances and inoculated with CA showed infection and inflammation.
 1982 (54)Fisker et al.50/5–8 mo/m and f/200–370 gSRP and T-waterCA Hasenclever strain A/SDA/20 h/35°C; inoculum: 0.1 ml of 6 × 108 cells in saline6 wk100% of swabs were +ve for Candida, wk 1; 33% Ca +ve, wk 5 A correlation between the site ofCandida infection and the areas of the oral mucosa with a less densely keratinized surface was established.
 1983 (180)Shakir et al.35/NR/NR/NRFood and water ad libitumCA (serotypes A and B), CT, CG2 wkNRCA serotype A is more pathogenic than serotype B. Although CT and CG colonized the mucosa, both failed to induce pathological changes in the rat.
 1983 (97)Lamb and Martin10/NR/m/350 gFood and water ad libitumAutopolymerizing acrylic plates usedCA 309118 wkCandida was observed in animals fitted with acrylic plates unsupplemented with chlorhexidineA large number of yeasts and heavy infection were seen in rats infected with untreated Candida. No growth was observed in rats inoculated with yeasts but treated with chlorhexidine.
 1984 (111)Martin et al.24/NR/m/350 gFood and water ad libitumCA (GT +ve and −ve strains), CA 3091 serotype A/SDA/24 h/30°C; inoculum: 30 mg (wet wt) of CA suspension2 wkCA was recovered from all animalsGerm tube formation was necessary to induce palatal candidiasis in the rat.
 1985 (126)Norris et al.Expt 1, 26/NR/m/324 g; expt 2, 37/NR/m/315 gFood and water ad libitumAutopolymerizing acrylic resin was usedCA 3091/SDA/24 h/37°C; inoculum: 30 mg (wet wt) of CA suspensionExpt 1, 4 wk; expt 2, 8 wkSwabs taken from animals wearing MS-treated plates were −ve for CAExpt 1 (preventive effect): Rats fitted with an appliance supplemented with 10% (wt/wt) miconazole in the polymer powder did not develop palatal candidiasis. Expt 2 (curative effect): Previously infected animals could be cured by fitting miconazole supplemented appliances.
 1986 (181)Shakir et al.20/NR/NR/NRFood and water ad libitumCA 3091/serotype A; inoculum: 30 mg (wet wt) of CA suspension6 wkCA was recovered from inoculated animalsAnimals fitted with acrylic appliances and inoculated with CA showed infection and inflammation. Removal of the appliance resolved the infection completely. Refitting the appliance encouraged the change from commensal to pathogenic form.
 1986 (182)Shakir et al.35/NR/m/NRFood and water ad libitumThe rats were sequentially exposed to 12-h dark and 12-h light periods to stimulate diurnal variation CA 3091/ serotype A; inoculum: 30 mg (wet wt) of CA suspension4 wkNRInitial depression in thickness of epithelium and reduction in mitotic activity in rats may be due to loss of body weight. The palatal epithelium of animals inoculated with CA and fitted with appliances had a significant rise in the mitotic index and the thickness of nucleated epithelial layers than did that of normal control animals.
 1987 (110)Martin et al.34/NR/m/NR; expt 1, 18; expt 2, 16SERD and water ad libitumCA NCPF 3091 serotype A/SDA/48 h/37°C; inoculum: 30 mg (wet wt) of CA suspensionExpt 1, 10 wk; expt 2, 4 wkNRExpt 1: The palatal acrylic appliance and/or infection affected the selective permeability of the palatal epithelial barrier. Removal of the prosthesis results in healing of the oral epithelium. Expt 2: The presence of an oral appliance could affect the ultrastructural appearance of the epithelium.
 1987 (51)Dourov and Coremans-Pelseneer48/NR/m and f/300 gDiabetes mellitus was induced in ratsCA strain 4019; inoculum: 12 × 106 cells/ml in H2O10 moCandidal carriage was +ve for diabetic rats after mycotic infectionRats with streptozotocin-induced diabetes mellitus were highly susceptible to Candida infection and proved to be a favorable model for the study of long-term oral candidiasis.
 1989 (108)Martin224/NR/m/230–290 gNRFL and KE usedCA NCPF 3091/SDA/48 h/37°C; inoculum: 30 mg (wet wt) of CA suspension42 daysCandida was recovered from rats treated with >7.0 mg of KE kg−1 and >0.5 mg of FL kg−1Fluconazole is effective at a lower dose than ketoconazole in resolving rat palatal candidiasis.
 1993 (83)Jorge et al.20/NR/m/170– 200 gMajor salivary glands surgically removedCA/SDA/24 h/37°C; inoculum: 0.2 ml of 108 CFU/ml in saline32 wkCandida was observed in 40% of control animals and 100% of xerostomic animals70% of xerostomic rats developed oral candidiasis, whereas only 20% of normal rats showed candidal infection.
 1993 (84)Jorge et al.12/NR/m/170– 200 gFood and T-water ad libitumT reduced to 0.001 mg/mlCA isolated from patient with chronic oral candidiasis; inoculum: 0.2 ml of 108 CFU/ml in saline18 wkNumbers of CA isolates were significantly larger in sialoadenectomized rats (P < 0.05) than in normal controlsNR
Sprague-Dawley rat
 1973 (154)Russell and JonesExpt 1, 60; Expt 2, 20CRD, SMP, and waterMycelial and yeast forms were usedCA; inoculum: 0.1 ml of 6 × 108 cells/ml in salineExpt 1, 36 days; expt 2, 39 daysExpt 1: candidal carriage was greater in the group given CRDExpt 1: Infection was greater in CRD animals but not significant. Expt 2: Similar results to expt 1. This expt did not permit a comparison between the pathogenicity of yeast and mycelial phases of CA.
 1973 (155)Russell and Jones60/NR/m and f/200gCRD, SMP, and T-waterCA isolated from human carrier/SDA/35°C/48 h; inoculum: 0.1 ml of 6 × 108cells/ml in saline34 daysNSD between normal and CRD or yeast/hyphal phase CA cellsMycelial penetration of tongue in 26 of 30 rats given normal diet and 19 of 30 given CRD (but P > 0.05 ).
 1973 (79)Jones and Russell36/12 days/NR/NR/NRMycelial and yeast forms were usedCA; inoculum: 0.1 ml of 108 cells/ml in saline15 daysRats harbored the mycelial form when CA was inoculatedSome rats demonstrated histologic evidence of infection when the mycelial form of CA was inoculated.
 1975 (156)Russell and Jones60/NR/m and f/NRSRD and T-waterCA; inoculum: 0.1 ml of 6 × 107 cells/ml in saline12 moMuch variation in candidal carriage; the rat seems to become adapted to the presence of the yeastSignificant changes in the tongue surface and the superficial layers of the lingual muscle was seen. Epithelial atypia noted, but there was no progress to carcinoma.
 1975 (157)Russell et al.120/NR/m and f/200 gSRD and T-waterCA; inoculum: 0.1 ml of 5 × 107 cells/ml in saline22 wkInitial short-term or long-term T treatment did not affect colonization by CATreatment with T (short or long term) did not affect histologic changes of the rat tongue due to CA infection.
 1976 (82)Jones et al.Expt 1, 80/NR/NR/80–100 g; Expt 2, 39/NR/NR/NROxoid irradiated diet, vitamin K with or without T-waterCA; inoculum: 0.1 ml of 6 × 108 cells/ml in salineExpt 1, 9 wk; expt 2, 27 wkAntibiotics and GF state favored oral candidal carriageThe GF state favored infectivity to a significant level (P < 0.05) in comparison to conventional rats, T treated or nontreated.
 1982 (6)Allen et al.10/NR/f/200 gSLC and T-waterCA/mycological agar; inoculum: 0.1 ml of 5 × 107 cells/ml in saline40 wkVariation in candidal carriage was evident within rats in a particular week and in successive cultures from a particular ratThe lesions induced in the rat tongue resembled histologic features of human median rhomboid glossitis.
 1982 (55)Fisker et al.104/6 wk/m and f/120–150 gSRP and T-waterSPF ratsCA-Hasenclever strain A; inoculum: 0.1 ml of 6 × 108 cells/ml in saline34 wk50% of animals were +ve for Candida during 34 wk 25% of animals showed hyphal penetration15 of 60 rats demonstrated candidal infection. Topographical distributions of infective foci were similar to results obtained in an earlier investigation (50).
 1983 (3)Allen and Beck50/NR/f/200 gSLC and T-waterFour strains of CA from clinical lesions; inoculum: 0.1 ml of 5 × 107 cells/ml in saline25 wkThree of the four CA strains were recovered on culture of swabsTwo strains produced candidal lesions, while the other two were unable to induce infection. Strain-related differences in mucosal pathogenicity for the lingual mucosa of the rat were proposed.
 1983 (147)Rennie et al.62/NR/m/NRNormal rat diet and TFe-free vitamin-rich dietCA MRL 3153/SDA/48 h/37°C; inoculum: 0.2 ml of 107–108 CFU/ml in saline14 wkT was effective in reducing oral candidal carriageCandidal infection was promoted in rats receiving both CRD and T compared to animals receiving the diet or drug alone.
 1985 (66)Hassan et al.120/35 days/m and f/100–110 gSRP and T-water; CRD and T-waterCA isolated from human carrier/SDA/35°C/48 h; inoculum: 0.1 ml of 6 × 108 cells/ml in saline14 wkT and CRD enhanced candidal carriage regardless of being inoculated once or on several occasionsCandidal infection in more sites in rats treated with T and CRD than in rats given T or CRD alone.
 1985 (5)Allen et al.40/NR/f/200 gSLC; group 1, T-water; group 2, DDDHCA/SDA/23°C/72 h; inoculum: 0.1 ml of 5 × 107 cells/ml in saline20 wkNo difference in candidal carriage between the 2 groupsNo significant difference was noted in the number of lesions between the 2 groups. However, the size of the lesional area does seem to be influenced by T in drinking water.
 1986 (abstract)Walrath and Blozis107/NR/f/NRLRF and T-waterFood pellets soaked in an ethanol/ clotrimazole solution and driedCA8 moHyperkeratosis produced by CA can be resolved by incorporating clotrimazole into the laboratory food. However, different strains of CA may respond differently.
 1987 (4)Allen and Beck320/NR/f/150– 175 gSLC and T-waterCA isolates were from different patients16 isolates of CA/SDA/23°C/72 h; inoculum: 0.1 ml of 5 × 107 cells/ml in saline16 wkVariable recovery rates were noted for the 16 isolatesA wide variety of clinical behaviors were demonstrated for the 16 isolates with respect to their ability to induce mucosal lesions.
 1987 (199)Van Wyk et al.46/ 5–8 wk/NR/NRCA/BHI broth/37°C/96 h; inoculum: above suspension in 250 ml of drinking water (106 CFU/ml)36 daysCandida organisms appeared in the oral epithelium after 48 h and colonization became extensive after 3–7 days; yeasts were eliminated after 8 daysGF rats developed candidiasis from 48 h onwards. The lesions were pronounced from 72 h to 6 days and then resolved after day 15. The development and the extent of lesions varied among the rats.
 1988 (8)Allen et al.60/NR/f/200 gSLC and waterInoculated rats were treated with KECA; inoculum: 0.1 ml of 5 × 107CFU/ml27 wkEight animals (100%) showed clinical resolution in the antimycotic-treated group, and 2 of 9 (22%) showed clinical resolution in the untreated group. Thus mucosal lesions induced by CA could be spontaneously eliminated, and the epithelial changes produced were reversible in some animals.
 1989 (7)Allen et al.210/NR/f/175 gSLC and tap waterSEM was conductedCA/SDA/25°C/48 h; inoculum: 0.1 ml of 3 × 108 yeasts/ml20 wkNRHistologic evaluation, SEM & clinical photographs demonstrated that a single oral inoculation with a virulent CA strain was sufficient to produce the classic epithelial changes. Most changes occured during 2-3 wks of infection. After 18 wks animals appeared to develop resistance to candidal infection.
 1990 (145)Reed et al.80/NR/m/150– 250 gRRDCA was grown in chemically defined mediumCA/SDA/37°C/24 h; inoculum: 5- and 23-h CA culture supernatants31 hNRCandidaculture supernatants which contain unknown factors may induce epithelial proliferation.
 1990 (119)Meitner et al.Expt 1, 18/27 days/NR/NR; expt 2, 40/26 days/NR/NR; expt 3, 40/26 days/NR/NRDiet 2000 (56% sucrose) and sucrose in waterPSG ligated; SM and SL glands surgically removedCA strains 613 and 623-ml (a colony morphology mutant)3–4 wkCA carriage of HSR were 30 fold more than normal ratsCandidal infection was induced with a small challenge inoculum. Mucosal lesions developed in oral cavities in HSR much faster than in the intact recipient animals. Infection from one desalivated animal to another desalivated animal occurred rapidly. In contrast, the morphological mutant took longer to transmit oral infection to uninoculated cagemates.
 1993 (131)O'Grady and Reade63/NR/f/NRSRD and T-waterTrauma was induced by applying heat on the tongueCA/SDA; inoculum: 0.1 ml of 6 × 108 yeasts/ml35 daysNRThe degree of infection was far greater in rats subjected to trauma and inoculation of CA than in the control rats (trauma without inoculation).
 1994 (9)Allen et al.79/NR/f/200 gSLC and waterCyclosporin was given to some ratsTwo isolates of CA (lesion-inducing and non-lesion-inducing isolates); inoculum: 0.1 ml of 108 yeasts/ml8 wkThe non-lesion-inducing isolate showed no significant increase in its ability to produce mucosal infection in the setting of reduced host immune status, in contrast to the lesion-inducing isolate, which demonstrated a significant increase in its ability to produce lesions.
 1998 (172)Samaranayake et al.15/4 wk/m/200 gCRD, SRP, and T-waterRats were given CYCA/2 CK isolates/SDA/37°C/24 h; inoculum: 0.1 ml of 108 yeast/ml29 wkCA demonstrated a higher oral carriage rate in comparison to the 2 CK isolatesUnder normal conditions, all CA and CK isolates failed to induce lingual infection. However, under immunosuppressed conditions, CA produced 100% infection while two CK isolates produced 25 and 50% lingual infection.
 1982 (185)Sofaer et al.150/NR/m/NRNRCA/MB/37°C/48 h; Inoculum: expt 1, a drop of a 108-CFU/ml yeast suspension; expt 2, 5 × 104 CFU/ml added to drinking water23 daysExpt 1: approximate comparison of CFU was made; expt 2: greater numbers of Candida were observedExpt 1: No histologic evidence of Candida infection was observed in any of the rats. Expt 2: Two types of Candida infection were observed: (i) large numbers of Candida hyphae penetrated the epithelium, and no associated inflammatory reaction was noted; (ii) few yeasts and hyphae in keratinized tissue lesions, and a dense neutrophil leukocyte infiltrate.
 1983 (72)Holbrook et al.80/NR/NR/NRNRVirulent strain 19321 and attenuated strain 22114; inoculum: 104 CFU/ml added to drinking water3 wkApproximate colony counts were takenThe virulent strain colonized and caused more disruption of the keratin and also demonstrated a higher inflammatory response than the attenuated strain.
 1984 (15)Balish et al.NR/NR/NR/NRNRCA B311 (type A) SDA/37°C/24 h; inoculum: 105 cells/ml in drinking water for 2–24 hGF mice were colonized with CAWhen CA monoassociated mice (nu/nu or +/nu) were infected with CA, extensive mucosal infection on the tongue and cheeks was observed.
 1989 (92)Krause and SchaffnerNR/NR/NR/NRRat pellets and acidified water ad libitumCyclosporin A was givenCA #1; inoculum: 106cells in saline15 daysNRMacroscopic thrushlike lesions developed within 4–6 days of infection.
 1990 (16)Balish et al.NR/6–8 wk/NR/NRNRCA B311 type A/SDA/37°C/24 h; inoculum: dipping a swab into an inoculum, 106cells/ml in water24 wkCA invaded the dorsal tongues of both nu/nu and nu/+ mice; infection persisted for 24 wk in nu/nu mice but resolved innu/+ mice by 10 wkThe nu/nu andnu/+ murine models of candidiasis described here mimic mucosal candidiasis observed in patients with defects in T-cell-mediated immunity.
 1990 (96)Lacassse et al.NR/17–23 wk/m/NRNRCA/Lee's medium/25°C/18 h; inoculum size: 50 μl (108 cells/ml in PBS) 13 daysCandida recovered during 1–7 days postinoculation from oral mucosa and saliva samplesProgressive candidal infection was observed in early stages up to 48 h. During the latter stages (7–13 days), the oral mucosa returned to normal.
 1991 (32)Cantoma and BalishNR/NR/NR/NRNRCA B311 type A/SDA/37°C/24 h; inoculum: 105 cells/ml mixed in drinking water20 wkYeasts and hyphae was observed on the tongue surfacebg/bg nu/nu mice were extremely susceptible to oral candidiasis 1–4 wk after colonization, which persisted throughout a 20-wk period, but the infection diminished over time. The oral cavities of bg/bg nu/+ mice becameCandida infected mainly in wk 1, but the infection was quickly cleared.
 1993 (95)Lacasse et al.NR/17–23 wk/m/NRNRCA/Lee's medium/25°C/18 h; inoculum: 108 cells/ml in saline33–92 daysFollowing primary inoculation, Candida showed peak CFU on days 3–4; these counts declined after a second inoculationThe primary infection resolved under 8 days of stimulating cellular immunity in the animals. A second challenge inoculum of Candida 30 days after primary challenge failed to produce a strong reaction in the oral mucosa.
 1993 (17)Balish et al.NR/NR/NR/NRNRCY givenCA B311 type A/SDA/37°C/24 h; inoculum: 105 cells/ml mixed in drinking water16 wkNRCY enhanced the tongue candidiasis in SCID mice.
 1994 (37)Chakir et al.NR/8–10 wk/m/NRC. albicans (LAM-1)/IMDA; inoculum: 108 cells/ml in saline25 daysAt 5 h postinoculation, CA was seen in digested mucosal tissue of both BALB/c and DBA/2 mice; a carrier state of the yeast was maintained following resolution of candial infection; statistical analysis indicated that the viable Candida carrier pattern for DBA/2 was significantly different from the BALB/c pattern on days 3–6.TheCandida carrier state is associated with the persistence of intraepithelial CD4+ T cells. The clearance of viableCandida from mucosal tissue is associated with the differential recruitment of γδ T cells. There is evidence that the different kinetics of Candida clearance may involve the differential priming of T-cell subsets in the two strains of mice that are not associated with the histocompatibility complex.
 1995 (47)Deslauriers et al.75/8–10 wk/m/NRNRTopical application of corticosteroidCA (LAM-1) IMDM/27°C/48 h; inoculum: 108 cells/ml in salineCandida carrier state was established within 10 days and persisted for at least 3 moNR
 1997 (46)Deslauriers et al.6/adult/f/3–4 wkNRMice were injected with the Du5H(G6T2) virus mixture of murine leukemia viruses to induce MAIDSC. albicans (LAM-1); inoculum: 108 cells/ml in saline210 daysCandida carrier state was established in control mice in <10 days and remained stable at <100 CFU for more than 6 mo; similar colonization patterns was seen for 70% of retrovirus-infected mice on day 10 after C. albicansinoculation; the carrier state fluctuated in 30% of infected mice from day 100 postinoculation, with high levels of Candidaproliferation for 2–3-wk episodes, separated by transient recoveries to the carrier stateMAIDS syndrome shows many similarities to human AIDS, although the depletion of CD4+ cells is not observed in this disease. It has been viewed as a model for the early stages of AIDS.
 1985 (116)McMillan and Cowell64/NR/NR/NRNRCA (ATCC 10261), CA (UOI), CT (3100)/MEA; inoculum: 1 ml of 107cells/ml in water6 wkNo hyphal invasion of the superficial epitheliumAll animals treated with CA (UOI) exhibited visual changes in some or all levels of the cheek pouch epithelium. Only half of animals treated with CA (ATCC 10261) or CT (3100) showed changes in some areas of the cheek pouch.
 1986 (58)Franklin and Martin35/4–6 wk/m/NRFood and water ad libitumEpithelial hyperplasia induced with TLP50CA NCPF 3091 serotype A/SDA/36 h/37°C; inoculum: 60 mg of aqueous suspension of CA20 wk6 animals retained CA for 3 wkCA caused changes to hyperplastic epithelium which resembled those seen in Candidaleukoplakia.
 1992 (117)McMillan and Cowell80/adult/m/NRNRCA (ATCC 10261), CA (UOI)/MEA; inoculum: 1 ml of 107 cells in waterCA in the yeast form was seen scattered on the entire mucosa; no epithelial invasion by CA was foundAreas of hyperorthokeratosis or hyperparakeratosis was seen associated with microabscesses. The affected areas varied in size and appeared to correspond to “white” plaques seen grossly.
  • a Abbreviations: aw, average weight; AZA, azathioprine; BHI, brain heart infusion; CA, Candida albicans; CG, Candida glabrata; CK, Candida krusei; CT, Candida tropicalis; CMF, commercial monkey fodder; CY, cyclophosphamide; DDDH, double-distilled demineralized water; ERC, Epol rat cubes; f, female; FL, fluconazole; GF, germ free; GT, germ tubes; HH, hyoscine hydrobromide; HSR, hyposalivatory rats; IC, immunocompetent mice; IMDM, Iscove's modified Dulbecco's medium; KE, ketoconazole; LRF, laboratory rat food; m, male; MB, malt broth; MS, miconazole supplemented; NR, not recorded; NSD, no significant difference; OXY, oxyphecyclimine; RRD, routine rat diet; SDA, Sabouraud's dextrose agar; SERD; Sprotts expanded rodent diet, SG, salivary glands; SL, sublingual; SLC, standard laboratory chow; SM, submandibular; SMP, standard mouse pellets; SPF, specific pathogen free; SRD, standard rat diet; SRP, standard rat pellets; T, tetracycline; TRI, triamcinalone acetonide; TSB, tryptic soy broth; TLP50, 50% turpentine and liquid paraffin.