Salivary Glands - Adverse Effects
Fluorinated and Fluoride Pesticides
A little background on the Salivary Glands...
The tongue, cheeks, and palate (the hard and soft areas at the roof of the mouth) contain many glands that produce saliva. In saliva there are enzymes, or catalysts, that begin the breakdown (digestion) of food while it is still in the mouth. The glands are called salivary glands because of their function.
There are three big pairs of salivary glands in addition to many smaller ones. The parotid glands, submandibular glands and sublingual glands are the large, paired salivary glands. The parotids are located inside the cheeks, one below each ear. The submandibular glands are located on the floor of the mouth, with one on the inner side of each part of the lower jaw, or mandible. The sublingual glands are also in the floor of the mouth, but they are under the tongue.
Gland Feature Duct Glands Fat Lymphoid
Sebaceous Glands Nerve
Parotid Largest major salivary gland Stensen's duct Serous Yes Yes Yes Facial Nerve
Sub-mandibular gland Second largest major salivary gland Wharton's duct Mucous-Serous Yes None None None
Smallest of major salivary glands Bartholin's duct, Rivinus ducts Mucous-Serous Yes None None None
Small salivary glands Scattered throughout the tongue, palate and lip Small Mucous except for those in tongue


None None None

The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations

Note: This is not an exhaustive list.
When time allows more information will be added.

Chlorodifluoromethane - Insecticide, Fungicide, Propellant - CAS No. 75-45-6

-- Groups of 80 male and 80 female Alderley Park Wistar-derived rats (age unspecified) were exposed by inhalation to 0 (2 groups), 1000, 10,000 or 50,000 ppm (0, 3540, 35,400 or 177,000 mg/cu m) chlorodifluoromethane (CFC 22; purity >99.8%) for 5 hr/day, on 5 days/wk for up to 118 (females) or 131 (males) wk, by which time approx 80% of animals had died. Body-wt gain was reduced in high-dose males up to wk 80. Treatment did not affect number of animals with benign tumors. Among males, the proportions of animals with malignant tumors were higher in treated groups (controls, 16/80 & 18/80; low-dose, 27/80; mid-dose, 22/80; high-dose, 33/80), due primarily to increases in incidences of fibrosarcomas (controls, 5/80 & 7/80; low-dose, 8/80; mid-dose, 5/80; high-dose, 18/80). The numbers of animals in which such tumors involved the salivary glands were, 1, 0, 1, 0 & 7, respectively. The increase in the overall incidence of fibrosarcomas occurred between weeks 105 & 130. In addition, 4 high-dose males had Zymbal-gland tumors, whereas no such tumor was found in males of the other groups. No increased incidence of malignant tumors was observed in treated females. [IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).,p. V41 242 (1986)]
-- TSCA Test Submissions: Oncogenicity was evaluated in male and female Alderley Park rats (80/sex/group) exposed to chlorodifluoromethane via inhalation at 0 (2 groups), 1000, 10,000 and 50,000 ppm for 5 hrs/day, 5 days/week for 27-30 months. The only reported finding of significance was an increase in the incidence of malignant neoplasms, due mainly to fibrosarcoma of the salivary gland in both sexes at 50,000 ppm. The incidence of these tumors was significant only after 25 months. This preliminary report did not contain information concerning the histopathological results of the study. [ICI Americas, Inc.; Chlorofluorocarbon 22 (CFC 22 - chlorodifluoromethane). (1981), EPA Document No. FYI-OTS-0481-0111, Fiche No. 0111-0 ]
Ref: TOXNET profile from Hazardous Substances Data Base for Chlorodifluoromethane.

Cyfluthrin - Insecticide - CAS No. 68359-37-5

-- Cyfluthrin. 28-Day oral toxicity NOAEL = 15.0 (males & females) based on minimal decrease in blood glucose. LOAEL = 50 based on, gait abnormalities, salivation, nervousness, decrease in body weight, food consumption, changes in hematological, clinical chem. & urinalysis parameters, increases in selected organ wts., cytoplasmic swelling of glandular epithelium of submaxillary gland, minimal degrees of fiber degeneration in sciatic nerve (# not reported) which disappeared after recovery period.
Ref: Federal Register. September 27, 2002. Cyfluthrin; Pesticide Tolerance. Final Rule.
• Definition: [n] a salivary gland inside the lower jaw on either side that produces most of the nocturnal saliva; discharges saliva into the mouth under the tongue
Synonyms: mandibular gland, submandibular gland, submandibular salivary gland, submaxillary salivary gland

Cyhalothrin, lambda - Insecticide - CAS No. 91465-08-6

Gastrointestinal: Changes in structure or function of salivary glands.
Ref: The Registry of Toxic Effects of Chemical Substances. NIOSH.

PFOS - Insecticide, US EPA List 3 Inert

Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.

Sodium fluoride - Insecticide, Wood preservative, US EPA List 4B Inert - CAS No. 7681-49-4

1999 Material Safety Data Sheet:
Ref: Material Safety Data Sheet. Valid 08/1999 - 10/1999. Sigma Chemical Co. P.O. Box 14508 St. Louis, MO 63178 USA

1995 Abstract: Summary: The effect of various concentrations of NaF on human salivary amylase was studied. Sodium fluoride was found to inhibit the enzyme when the fluoride concentration was at and above 5 x 10-2 M.
Ref: Fluoride 1995; 28(2):71-74. Effect of fluoride on human salivary amylase activity, by K Hara and M-H Yu

1988 Abstract: The effect of NaF on cAMP accumulation, cAMP-dependent protein kinase activity (cAMP-dPK) ratios and [14C]-glucosamine-labelled mucin release from these isolated cells was investigated. NaF (0.01-5 mM) increased significantly the cellular cAMP concentration and cAMP-dPK activity ratios in a dose- and time-dependent manner. NaF (5.0 mM) increased [14C]-glucosamine-labelled mucin release in a time-dependent manner. Thus the stimulation of prelabelled mucin secretion by NaF is mediated by an increase in the cAMP concentration, which exerts its effect, at least partly, via the activation of cAMP-dPK activity.
Ref: Arch Oral Biol 1988;33(5):347-51. Stimulation of mucin release from rat submandibular salivary-gland cells by NaF.Shahed AR, Allmann DW.

1987 Paper: The effect of NaF on salivary gland function by Allmann DW, Shahed AR.
No abstract available. Dtsch Zahnarztl Z 1987 Oct;42(10 Suppl 1):S95-8

1984 Abstract: Summary: This study examined the effect of intakes of 25 or 50 ppm fluoride via drinking water for four weeks on the amylase activity of the parotid gland, isoproterenol-stimulated (1 mg/100 g b.w., i.p.) salivary flow and on the amylase activity in saliva fractions. A significant elevation of the tissue amylase activity was seen in the F25 and F50 groups compared to control. The volume of saliva collected for 30 min after isoproterenol injection was higher in the fluoride-treated groups; the amylase activity was also increased. In the glandular tissue cAMP level was augmented. It appears that fluoride may affect the parotid function; it may also influence the salivary amylase activity, presumably by acting on the adenyl cyclase activity.
Ref: Fluoride 1984; 17(4):217-223. Effect of F- on major salivary glands. The amylase activity, stimulated salivary flow response and cAMP levels in parotid gland of rats consuming F- via drinking water, by Boros I, Mozsik G, Keszler P

1982 Abstract: One to 10 ppm fluroide added to drinking water enchance the activity of carbonic anhydrase in the submandibular salivary gland of rats. With 25 ppm fluoride in drinking water, the fluoride content of the parotid gland increased considerably. It is concluded that fluoride affects the function of the salivary gland.
Ref: Acta Physiologica Academiae Scientiarum Hungaricae 1979; 53:155. Functional changes in the salivary glands of rats after sodium fluoride treatment, by Boros I, Keszler P, Zelles T. As cited in Fluoride 1982; 15(1):50

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