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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 486
CCOHS Chemical Name: Zinc sulfate

Synonyms:
White copperas
White vitriol
Zinc sulfate heptahydrate
Zinc sulfate monohydrate
Zinc sulphate
Zinc vitriol
Sulfuric acid, zinc salt (1:1)
Zinc sulfate (1:1)
Zinc sulfate anhydrous
Zinc sulfate hexahydrate

Chemical Name French: Sulfate de zinc
Chemical Name Spanish: Sulfato de cinc

Trade Name(s):
Bonazen
Bufopto
Op-thal-zin
Optraex
Zincomed
Zinkosite
Verazinc
Solvezink
Medizinc

CAS Registry Number: 7733-02-0
Other CAS Registry Number(s): 7446-19-7 7446-20-0 13986-24-8
RTECS Number(s): ZH5260000 ZH5300000
EU EINECS/ELINCS Number: 231-793-3
Chemical Family: Zinc and compounds / inorganic zinc compound / zinc salt / sulfate
Molecular Formula: O4-S-Zn
Structural Formula: Zn.SO4

SECTION 2. DESCRIPTION

Appearance and Odour:
Colourless, odourless crystals or granular, crystalline powder.(13) Anhydrous zinc sulfate is hygroscopic (absorbs moisture from the air).(17,24)

Odour Threshold:
Odourless

Warning Properties:
Insufficient information for evaluation.

Composition/Purity:
Zinc sulfate exists as the anhydrous salt (ZnSO4; CAS 7733-02-0), and as three stable hydrates, the monohydrate (ZnSO4.H2O; CAS 7446-19-7), hexahydrate (ZnSO4.6H2O; CAS 13986-24-8) and heptahydrate (ZnSO4.7H20 (orthorhombic); CAS 7446-20-0). Three unstable hydrates also exist, tetrahydrate (ZnSO4.4H20; CAS 33309-49-8), dihydrate (ZnSO4; CAS 80867-26-1) and heptahydrate (ZnSO4.7H20 (monoclinic); CAS 7446-40-0).(25) The main commercial preparation of zinc sulfate is the monohydrate, but it is sometimes sold as the heptahydrate.(25,26) It is also available in solution.

Uses and Occurrences:
Zinc sulfate is used as a micronutrient in fertilizers; as a trace element and disease-control agent in animal feeds; as a component of spinning bath in the manufacture of rayon; as a froth flotation agent; as the starting material for the manufacture of lithopone (a pigment), carbamate fungicides (e.g. zineb), zinc metal, and many other zinc chemicals; in textile dyeing and printing; in electrogalvanizing for zinc plating; in paper bleaching; as a water treatment chemical; as a plaster-accelerating agent in dental impression materials; in the manufacture of glue; as a preservative for wood and hides; and as a fireproofing agent.(17,25,26) It is also used in the electroplating of magnesium (27) and in sewage against animal pathogenic bacteria (17).
Zinc sulfate was formerly used in some pesticide products.(17)
The heptahydrate occurs naturally in a few small deposits, as the mineral goslarite.(25)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Colourless, odourless crystals or granular, crystalline powder. Anhydrous zinc sulfate is hygroscopic (absorbs moisture from the air). Will not burn or support combustion. During a fire, corrosive and toxic sulfur trioxide gas and zinc oxide fume may be generated by thermal decomposition or combustion. May be harmful if swallowed, based on unconfirmed animal information.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Zinc sulfate is unlikely to be inhaled because it readily absorbs moisture from the air forming a wet, pasty solid. Exposure to any dust that is generated or to mists from dilute solutions may be irritating, but is not expected to cause significant harmful effects, based on limited animal information and physical properties. There is no human information available.

Skin Contact:
Zinc sulfate and its solutions are not expected to be irritating to the skin, based on limited animal information and the pH of solutions.
Harmful effects are not expected by skin absorption.

Eye Contact:
Solid zinc sulfate can cause mechanical irritation as it is rinsed from the eye by tears. Zinc sulfate solutions may cause slight to moderate irritation, based on limited animal information and pH. Eye contact with solutions of greater than 1% may cause the appearance of white flecks on the lens of the eye, according to human information.
A 20% zinc sulfate solution was used historically to treat several medical conditions. An effect on the lens of the eye (appearance of white flecks), which appears to have been observed after a single application, has been reported in more than one case and this use has been discontinued. There is no specific information given about whether this effect cleared over time. More dilute solutions (up to 1%) have not caused harmful effects when applied therapeutically.(14)

Ingestion:
Zinc sulfate may be toxic if ingested, based on unconfirmed animal information. For zinc compounds, including zinc sulfate, ingestion of large doses can cause anemia and stomach symptoms with nausea, vomiting, abdominal pain, diarrhea and, in severe cases, vomiting of blood, based on human and animal information.(8,19,21) Zinc sulfate has been used therapeutically to induce vomiting.(15)
Zinc is an essential nutrient for humans and animals. Both zinc deficiency and overexposure to zinc by ingestion have been associated with harmful effects.(8) Ingestion is not a typical route of occupational exposure.

Effects of Long-Term (Chronic) Exposure

In general, zinc is considered to be a low toxicity metal. Zinc is a very important trace element for humans. It is an important component of many enzymes and other proteins and has an essential role in many processes of normal growth and development. For zinc compounds, including zinc sulfate, a number of reversible harmful effects (red and white blood cell deficiencies (anemia and leukopenia), headache, stomach symptoms, and copper deficiency) can result from long-term ingestion, based on non-occupational human reports and animal information.(8,20,21)

Respiratory Sensitization:
There is insufficient information available to conclude that zinc sulfate is an occupational sensitizer.
A 47-year-old man, who worked at a company that galvanized metal, developed shortness of breath, chest tightness and wheezing. He did not experience symptoms when he was away from work. He was a smoker and had no family or personal history of allergies. His work consisted of processing metals, first in basins containing sulfuric acid and then in basins containing hot zinc. A positive skin prick test was obtained with zinc sulfate. Inhalation challenge testing with zinc sulfate showed a positive response.(53)
A small number of cases (five) of asthma, increased bronchial responsiveness or a generalized allergic reaction have been associated with zinc exposure following occupational exposure to fumes generated by soldering or welding galvanized metal. For a discussion of these cases, refer to the CHEMINFO review of zinc oxide.

Skin Sensitization:
Zinc sulfate is not an occupational skin sensitizer.
In a study, which is not available in English, a test with an ointment containing 0.5% zinc, as zinc sulfate, in 200 patients caused no allergic skin reactions.(46, unconfirmed) Zinc salts are used regularly in skin medications without allergic reactions.(47)

Digestive System:
Abdominal cramps, vomiting and nausea were experienced by 26/47 healthy volunteers that received 2.0 mg/kg/day as zinc, (dose administered as anhydrous zinc sulfate, 5 mg/kg/day) for 6 weeks.(8,unconfirmed)

Blood/Blood Forming System:
In one case report, ingestion of 520-740 mg/day of zinc sulfate (130-185 mg/ day of zinc) for 10 months by a 35-year old woman resulted in anemia caused by copper deficiency.(16)

Immune System:
Conclusions can be drawn from one small-scale human study in which a possible effect on the immune system was observed. Impaired lymphocyte and polymorphonuclear leukocyte functions were observed in 11 male volunteers following oral administration of 150 mg/day zinc (as zinc sulfate, form not specified) twice/day for 6 weeks.(48)

Carcinogenicity:

Zinc and its compounds are not known to be carcinogenic. There is no human information available for zinc sulfate. Firm conclusions cannot be drawn from a limited animal study with zinc sulfate that did not show carcinogenic effects.

The International Agency for Research on Cancer (IARC) has not evaluated the carcinogenicity of this chemical.

The American Conference of Governmental Industrial Hygienists (ACGIH) has no listing for this chemical.

The US National Toxicology Program (NTP) has not listed this chemical in its report on carcinogens.

Teratogenicity and Embryotoxicity:
No harmful effects were observed in two human studies following low-level ingestion. There are insufficient details available to evaluate the other human studies located. No conclusions can be drawn from two limited animal studies that showed harmful effects on the embryo, because it is not clear that the effects were observed in the absence of harmful effects on mothers.
In humans, no harmful effects in the children were observed in studies where the 104 mothers ingested 45 mg/day zinc as zinc sulfate (form unspecified) in different trimesters of pregnancy (49), or where 250 mothers ingested 20 mg/day zinc (66 mg/day zinc sulfate (form unspecified, but likely dihydrate)) from week 20 until delivery (50). Insufficient details are available to evaluate a report of harmful effects (3 premature births and 1 stillbirth) in four women following oral administration of 100 mg/day zinc sulfate (form unspecified) during the last trimester of pregnancy.(10, unconfirmed) The total number of women involved in the study was not reported and there was not comparison made to an unexposed control group. No conclusions can be drawn from a study, which is not available in English, where women who were 9 weeks pregnant ingested a very large amount (20000 mg) of zinc sulfate and had miscarriages on day 12.(26, unconfirmed) There are inadequate details available for evaluation.

Reproductive Toxicity:
There is no human information available. No conclusions can be drawn from a limited study using male rats where exposure to zinc sulfate resulted in significant decreases in sperm motility and conception rate. The study used a single, relatively high dose and it is not clear if the effects were observed in the absence of other significant toxic effects.

Mutagenicity:
There is no human information available. There is insufficient animal information available to conclude that zinc sulfate is mutagenic. A positive result was obtained in a study using live mice. However, the test used (the Comet Assay) is relatively new and has not been validated in an interlaboratory comparison study.
A positive result in cultured mammalian cells, a negative result in bacteria, a weak positive result in yeast and an inconclusive result in fruit flies (Drosophila) were also obtained.

Toxicologically Synergistic Materials:
When zinc is absorbed into the body, it interacts with other trace elements, especially copper. It also competes with other metals, such as lead or mercury, which may sometimes reduce the harmful effects of these metals.

Potential for Accumulation:
Zinc can accumulate in the body. Intestinal absorption of zinc can vary widely following oral administration (in animals ranges of less than 10 to over 90% are reported) and is influenced by age and a number of dietary factors. Zinc is stored mainly in the muscle and bone, and also in the prostate, liver, gastrointestinal tract, kidneys, skin, lung, brain, heart and pancreas.(51,52) In humans ingesting normal amounts of zinc, the reported half-lives were from 100-500 days.(52) The body regulates the amount of zinc stored by decreasing absorption and increasing excretion when intake is increased.(21) It is excreted mainly in the feces.(52)


SECTION 4. FIRST AID MEASURES

Inhalation:
If symptoms are experienced, remove source of contamination or move victim to fresh air. Obtain medical advice.

Skin Contact:
Remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts). Flush with lukewarm, gently flowing water for at least 5 minutes. Obtain medical advice. Completely decontaminate clothing, shoes and leather goods before re-use or discard.

Eye Contact:
SOLID: DO NOT allow victim to rub eye(s). Let the eye(s) water naturally for a few minutes. Have victim look right and left, and then up and down. If particle/dust does not dislodge, flush with lukewarm, gently flowing water for 5 minutes or until particle/dust is removed, while holding the eyelid(s) open. If irritation persists, obtain medical attention. DO NOT attempt to manually remove anything stuck to the eye(s). SOLUTIONS: Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 5 minutes, while holding the eyelid(s) open. If irritation persists, repeat flushing and obtain medical advice.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, or is unconscious or convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 60 to 240 mL (2 to 8 oz) of water. If vomiting occurs naturally, have victim rinse mouth with water again. Immediately obtain medical attention. NOTE: Zinc sulfate is an emetic (can cause vomiting).

First Aid Comments:
Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin contact.
All first aid procedures should be periodically reviewed by a doctor familiar with the material and its conditions of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Not applicable (does not burn).

Lower Flammable (Explosive) Limit (LFL/LEL):
Not applicable

Upper Flammable (Explosive) Limit (UFL/UEL):
Not applicable

Autoignition (Ignition) Temperature:
Not applicable

Sensitivity to Mechanical Impact:
Probably not sensitive. Stable material.

Sensitivity to Static Charge:
Zinc sulfate is unlikely to accumulate static charge. Since it does not burn, it will not be ignited by a static discharge.

Electrical Conductivity:
Not available

Minimum Ignition Energy:
Not applicable

Combustion and Thermal Decomposition Products:
Sulfur oxides and zinc oxides are formed if zinc sulfate is involved in a fire. Sulfur trioxide is formed at about 680 deg C and zinc oxide fume above 930 deg C.(25)

Fire Hazard Summary:
Zinc sulfate does not burn or support combustion. During a fire, corrosive and toxic sulfur trioxide gas may be generated by thermal decomposition or combustion. Closed containers may rupture violently when exposed to fire or excessive heat for sufficient time.

Extinguishing Media:
Zinc sulfate is not combustible (does not burn). Use extinguishing media suitable for surrounding fire.(17)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products.
Closed containers may rupture violently when exposed to the heat of the fire. If possible, isolate materials not yet involved in the fire, and move containers from the fire area if this can be done without risk, and protect personnel. Otherwise, fire-exposed containers, tanks or car/trailer loads should be cooled by application of hose streams. Application should begin as soon as possible (within the first several minutes) and should concentrate on any unwetted portions of the container. Apply water from the side and from a safe distance until well after the fire is out. Cooling should continue until well after the fire is out. If this is not possible, use unmanned monitor nozzles and immediately evacuate the area.
Withdraw immediately in case of rising sound from venting safety device or any discolouration of tank. ALWAYS stay away from the ends of tanks, but be aware that flying material (shrapnel) from ruptured tanks may travel in any direction. Tanks or drums should not be approached directly after they have been involved in a fire, until they have been completely cooled down.

Protection of Fire Fighters:
The decomposition products of zinc sulfate are corrosive and hazardous to health. Do not enter without wearing specialized protective equipment suitable for the situation. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. Chemical resistant clothing (e.g. chemical splash suit) and positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 161.45 (anhydrous); 179.47 (monohydrate); 287.56 (heptahydrate)

Conversion Factor:
Not applicable

Physical State: Solid
Melting Point: Decomposes at 680 deg C (1256 deg F) (25,28)
Boiling Point: Does not boil. Decomposes at 680 deg C (1256 deg F) (25,28)
Relative Density (Specific Gravity): 3.8 at 25 deg C (anhydrous) (28,29); 1.957 at 25 deg C (heptahydrate) (13) (water = 1)
Solubility in Water: Very soluble (167 g/100 mL (heptahydrate); 53.8 g/100 mL at 20 deg C(monohydrate)) (28,30)
Solubility in Other Liquids: Very soluble in glycerol (40 g/100 mL); soluble in dilute mineral acids; insoluble in ethanol and methanol (heptahydrate).(17,28,30) The monohydrate is practically insoluble in ethanol.(30)
Coefficient of Oil/Water Distribution (Partition Coefficient): Log P(oct) = -0.07 (estimated) (31)
pH Value: 4.5 (saturated solution) (30)
Acidity: Water solutions are weakly acidic.(30)
Viscosity-Dynamic: Not applicable
Surface Tension: Not applicable
Vapour Density: Not applicable
Vapour Pressure: Practically zero
Saturation Vapour Concentration: Not applicable
Evaporation Rate: Not applicable
Henry's Law Constant: Not available

Other Physical Properties:
The monohydrate loses water above 238 deg C (460.4 deg F), while the heptahydrate loses all water at 280 deg C (536 deg F) to form anhydrous zinc sulfate.(13,25,30)


SECTION 10. STABILITY AND REACTIVITY

Stability:
Normally stable.

Hazardous Polymerization:
Will not occur.

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


STRONG BASES (e.g. alkali hydroxides) - react vigorously or violently, with the evolution of heat.(32)

Hazardous Decomposition Products:
None reported at normal temperatures.

Conditions to Avoid:
High temperatures

Corrosivity to Metals:
Zinc sulfate solutions (10% to saturation) are reported, in one source, to corrode carbon steel (such as types 1010 and 1020) and aluminum (types 3003, Cast and B-356) at a rate greater than 1.27 mm/year at 21 deg C.(33) According to other sources, zinc sulfate solutions corrode steel and aluminum at rates less than 1.27 mm/year.(34,35) Zinc sulfate solutions (10% to saturation) are also reported to corrode gray and ductile cast iron, brass (unspecified) and admiralty brass at rates greater than 1.27 mm/year at 21 deg C.(33,34) Zinc sulfate solutions (5% to saturation) corrode stainless steels (such as types 300 series, 440 and 20 Cb 3), nickel, nickel-base alloys, such as Hastelloy and Incoloy, high silicon cast iron, copper, and its alloys, such as naval and aluminum bronze and bronze (unspecified), tantalum, titanium and zirconium at rates less than 0.5 mm/year at temperatures up to 21 deg C.(33,34,35)

Corrosivity to Non-Metals:
Saturated zinc sulfate solutions attack elastomers, such as polyacrylate, polysulfide and chlorinated polyethylene at 21 deg C.(36) Zinc sulfate solutions (5% to saturation) do not attack most plastics, such as chlorinated polyvinyl chloride (CPVC), fluorocarbons, such as Teflon, nylon, polyesters, polyethylene and polyvinyl chloride (PVC); elastomers, such as butyl rubber, chloroprene, fluorocarbons, such as Viton A, hard and soft rubbers, natural rubber, isoprene, neoprene and Nitrile Buna-N (NBR), and coatings, such as epoxy chemical resistant and vinyls.(35,36,37)


SECTION 11. TOXICOLOGICAL INFORMATION

LD50 (oral, mouse): 245 mg/kg (zinc sulfate, anhydrous) (11, unconfirmed)
LD50 (oral, mouse): 200 mg/kg (zinc sulfate heptahydrate) (41, unconfirmed)
LD50 (oral, male mouse): 926 mg/kg (zinc sulfate, dihydrate; buffered with sodium carbonate) (2)
LD50 (oral, male rat): 1710 mg/kg (zinc sulfate, dihydrate; buffered with sodium carbonate) (2)
LD50 (oral, mouse): 422 mg/kg (zinc sulfate, form not specified) (40)*
LD50 (oral, rat): 1710 mg/kg (zinc sulfate, form not specified) (40)*
*Note: The methods and materials used in this study are poorly described. Therefore, the validity of these values is questionable.

Eye Irritation:

No conclusions can be drawn from a study that reported moderate irritation from zinc sulfate solutions in rabbits, because the test procedures are not those commonly used to assess irritation.

Buffered, stabilized solutions containing 0.009M zinc sulfate produced slight irritation in rabbits when administered as five 10-minute instillations. Unbuffered, non-stabilized solutions of 0.026M and 0.032M caused moderate irritation.(23)

Skin Irritation:

Dilute solutions of zinc sulfate are either not irritating or slightly irritating, based on a limited animal study.

Slight irritation was observed in rabbits, mice and guinea pigs following application of 0.5 mL of a 1% solution in water for 5 days (using open and closed patches for rabbits and open patches for mice and guinea pigs).(3) This is a longer exposure time than normal for this type of test.

Effects of Short-Term (Acute) Exposure:

Inhalation:
Increased pulmonary resistance was observed in male guinea pigs exposed for 1 hour to 0.91 mg/m3 of an aerosolized zinc sulfate solution.(54) No harmful effects on lung function were observed in anesthetized dogs exposed to very fine mists of 0.1-1.0% zinc sulfate solutions. The airborne concentrations were up to 15.8 mg/m3 for 7.5 minutes and 8.3 mg/m3 for 4 hours.(1) A dose-related, significant increase in mortality from a bacterial (Streptococcus-pyogenes) infection was observed in mice after they were exposed for 3 hours to a mist of 0.5-3.0% zinc sulfate solution at concentrations of greater than 1.3 mg/m3 (approximately 90% of particles less than or equal to 3 micrometres in diameter).(6)

Ingestion:
Rats were given oral doses of 1, 10, or 100 mg/kg/day (cited as 0.1, 1.0, or 10 mg/100g/day) of zinc sulfate (form unspecified) for 3 days or a single dose of 100 mg/kg. All doses for 3 days and 100 mg/kg for 1 day caused significant decreases in calcium levels in the blood and in the bone.(7)

Effects of Long-Term (Chronic) Exposure:

Ingestion of zinc sulfate has resulted in harmful effects in the pancreas, and adrenal and pituitary glands of mice exposed to as low as 100 mg/kg/day zinc for 3 months. Harmful effects in the pancreas were also observed in rats orally exposed to 339-407 mg/kg/day zinc for 13 weeks. Anemia was reported following ingestion of 407 mg/kg/day zinc in male rats and 814 mg/kg/day zinc in mice for 13 weeks. Increased mortality, harmful effects on the kidneys and digestive tract were noted in mice exposed to 814 mg/kg/day zinc.

Ingestion:
Mice and rats were fed 0, 300, 3000 or 30000 ppm zinc sulfate heptahydrate for 13 weeks. (Approximate doses were 0, 8, 80 or 815 mg/kg/day in mice as zinc, 0, 3-4, 35-40, or 340-410 mg/kg/day in rats as zinc; or 0, 36, 360 or 3600 mg/kg/day in mice as zinc sulfate heptahydrate and 0, 15-18, 150-180 or 1500-1800 mg/kg/day in rats as zinc sulfate heptahydrate). At 30000 ppm, there was significantly decreased body weight for male and female mice and for male rats. Increased mortality, anemia, and harmful effects on the digestive system, pancreas and kidneys were noted in mice of both sexes. In rats, harmful effects were noted in the pancreas and anemia was noted in males. No significant toxic effects were observed at lower concentrations (300 or 3000 ppm).(4) Mice were given 0.5 g/L of zinc as zinc sulfate (form unspecified) for 5-14 months. (Approximate dose was 100 mg/kg/day as zinc). There were no effects on mortality, body weight or general health. Detailed tissue examination indicated harmful effects on the pancreas, adrenal gland and pituitary gland after 3 months of exposure.(42) In a study, which is limited by small animal numbers (8/group), rats were fed 100, 500 or 1000 ppm zinc sulfate heptahydrate in their diet for 21 months. (Approximate doses were 1.1-1.4, 5.7-6.8, or 11-14 mg/kg/day as zinc; or 5-6, 25-30 or 50-60 mg/kg/day as zinc sulfate heptahydrate). No overall changes in food intake, body weights, hemoglobin levels or blood cell counts were noted, although there were temporary effects on the blood during the study. The kidneys of male rats exposed to 500 and 1000 ppm were larger. However, no statistical analysis of the data was reported. Vomiting and anemia was observed in 6 dogs fed various doses between 50-200 mg/kg/day (11-45 mg/kg/day zinc) for a total of 64 weeks.(9)

Skin Sensitization:
Zinc sulfate heptahydrate produced negative results in the mouse local lymph node assay.(43)

Carcinogenicity:
No conclusions can be drawn from a limited study in which mice (number/group not reported) were given zinc sulfate heptahydrate in their drinking water at zinc concentrations of 1000 or 5000 ppm for 1 year. (Approximate doses were 200 or 1000 mg/kg/day as zinc, or 885 or 4420 mg/kg/day as zinc sulfate heptahydrate). There were no effects on body weight or growth and no increase in tumour incidence.(5)

Teratogenicity, Embryotoxicity and/or Fetotoxicity:
There is insufficient information available to conclude that zinc sulfate causes developmental toxicity. Two limited studies suggest that oral administration of zinc sulfate may cause a significant increase in preimplantation loss or embryo resorption in rats. However, it is not clear if the effects were observed in the absence of harmful effects on mothers and both studies only used a single dose.
Female rats were fed diets with 4000 ppm zinc, as zinc sulfate anhydrous, from days 0-18 of pregnancy. (Approximate doses were 200 mg/kg/day as zinc; or 497 mg/kg/day as zinc sulfate anhydrous). A significant increase in preimplantation loss was observed. This phase of the study is limited by the relatively small number of animals/group (12/group). In the same study, exposure to the zinc sulfate for 21-26 days before mating and throughout the pregnancy did not affect implantation and was interpreted to indicate an adaptation to the zinc feeding. No stillborn or malformed fetuses were observed for either feeding regime.(44) There was no evaluation of maternal toxicity reported. The study is limited by having using only a single dose. Pregnant rats fed a diet with 150 ppm zinc, as zinc sulfate (form not specified), in addition to 30 ppm as part of the basal diet (approximate total dose 9 mg/kg/day as zinc) throughout pregnancy had a statistically significant increase in embryo resorptions from 2/101 in controls to 11/116 in treated animals.(10) There was no report of maternal toxicity, however it would not be expected at this dose based on other studies. This study is limited by the small animal numbers (12-13/group) and by having used only a single dose.

Reproductive Toxicity:
There is insufficient information available to conclude that zinc sulfate causes reproductive toxicity. In a limited study, zinc sulfate caused significant decreases in sperm motility and fertility in male rats. It is not clear if the effects were observed in the absence of other toxic effects.
Male rats fed 4000 ppm zinc, as anhydrous zinc sulfate, in their diet for 32 days had a significant decrease in sperm motility and a significant decrease in the number of females (untreated) who conceived (11/18 females conceived when mated with treated males compared to 15/15 mated with control males). (The approximate dose was 240 mg/kg/day as zinc, or 596 mg/kg/day as zinc sulfate, anhydrous).(12) There was no evaluation of toxicity in the male rats reported and this study is limited by having used only a single dose. No harmful effects on the testes or ovaries were observed in mice or rats fed 30000 ppm for 13 weeks. (Approximate doses were 815 mg/kg/day for mice, 340-410 mg/kg/day for rats as zinc; or 3600 mg/kg/day for mice, 1500-1800 mg/kg/day for rats as zinc sulfate, heptahydrate).(4) Reproductive outcome was not evaluated in this study. Generalized toxic effects were noted at these doses.

Mutagenicity:
There is insufficient information available to determine if zinc sulfate is mutagenic. A positive result was obtained with anhydrous zinc sulfate in a study using live mice. However, the test used (the Comet Assay) is relatively new and has not yet been validated in an interlaboratory comparison study.
A positive result (DNA damage) was observed in male mice orally exposed to 5.70, 8.55, 11.4, 14.25, 17.10 or 19.95 mg/kg anhydrous zinc sulfate. A significant, dose-dependent increase in single-strand DNA breaks (as represented by comet tail-lengths) was observed in leukocytes at all exposure levels at 24 hours post-treatment. A gradual decrease in tail-lengths from 48 hours post-treatment on was observed, indicating a time dependent decrease in DNA damage, likely indicating DNA repair. At the end of the first week post-treatment, the mean comet tail-lengths of DNA at all dose levels approached those of the controls.(39) The Comet Assay is a relatively new test and has not yet been validated in an interlaboratory comparison study. A negative result (bone marrow micronucleus) was obtained in mice receiving 2 doses of up to 57.4 mg/kg.(22) The route of exposure (intraperitoneal) used in this study is not relevant to occupational situations.
A dose-dependent, positive result (chromosome aberrations) was obtained in a test using cultured human lymphocytes.(18) A negative result (gene mutation) was obtained in a test using bacteria, with and without metabolic activation.(22) A weak positive result (gene mutation) was obtained in a test using yeast.(45)
An inconclusive result (sex-linked recessive lethals) was obtained in a test using fruit flies (Drosophila).(22)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Sackner, M.A., et al. Effects of brief and intermediate exposures to sulfate submicron aerosols and sulfate injections on cardiopulmonary function of dogs and tracheal mucous velocity of sheep. Journal of Toxicology and Environmental Health. Vol. 7, no. 6 (1981). p. 951-972
(2) Domingo, J.L., et al. Acute zinc intoxication: comparison of the antidotal efficacy of several chelating agents. Veterinary and Human Toxicology. Vol. 30, no. 3 (June 1988). p. 224-228
(3) Lansdown, A.B.G. Interspecies variations in response to topical application of selected zinc compounds. Food and Chemical Toxicology. Vol. 29, no. 1 (1991). p. 57-64
(4) Maita, K., et al. Subacute toxicity studies with zinc sulfate in mice and rats. Journal of Pesticide Science. Vol. 6, no. 3 (Aug. 1981). p. 327-336
(5) Walters, M., et al. A study of the effects of zinc and tin administered orally to mice over a prolonged period. Food and Cosmetics Toxicology. Vol. 3 (1965). p. 271-276
(6) Ehrlich, R., et al. Susceptibility to bacterial pneumonia of animals exposed to sulfates. Toxicology Letters. Vol. 1 (1978). p. 325-330
(7) Yamaguchi, M., et al. Zinc-induced hypocalcemia and bone resorption in rats. Toxicology and Applied Pharmacology. Vol. 67, no. 2 (1983). p. 224-228
(8) Agency for Toxic Substances and Disease Registry. Toxicological profile for zinc (Update). TP-93/15. Public Health Service, US Department of Health and Human Services, May 1994
(9) Hagan, E.C., et al. Blood and bone marrow effects of feeding zinc sulfate to rats and dogs. Journal of the American Pharmaceutical Association. Vol. 42, no. 11 (Nov. 1953). p. 700-702
(10) Kumar, S. Effect of zinc supplementation on rats during pregnancy. Nutrition Reports International. Vol. 13, no. 1 (Jan. 1976). p. 33-36
(11) MDL Information Systems, Inc. Zinc sulfate (1:1). Last updated: 1999-09. In: Registry of Toxic Effects of Chemical Substances (RTECS(R)). [CD-ROM]. Canadian Centre for Occupational Health and Safety (CCOHS). Also available at: <ccinfoweb.ccohs.ca/rtecs/search.html> {Subscription required}
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Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 2005-11-30

Revision Indicators:
Bibliography 2004-11-29
EU classification 2004-11-29
EU risks 2004-11-29
EU safety 2004-11-29
Passive Sampling Devices 2005-02-01



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