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Zinc Chloride - Toxicological Information

LC50 (rat)
 : 467
NOTE: This value cannot be reliably converted to a 4-hour LC50, because the exposure duration is too short.
LD50 (oral, male rat)

LD50 (oral, mouse)
LD50 (oral, rat)
LD50 (oral, rat)
LD50 (oral, guinea pig)
LD50 (oral, male rat)
LD50 (oral, male mouse)
 : greater than 1000 mg/kg (1/3 died at 1000 mg/kg; 2/3 died at    1500 mg/kg) (66)
 : 329 mg/kg (1)*
 : 511 mg/kg (1)*
 : 350 mg/kg (67, unconfirmed)
 : 200 mg/kg (67, unconfirmed)
 : mg/kg (buffered with sodium carbonate) (65)
 : 1250 mg/kg (buffered with sodium carbonate) (65)
NOTE: The methods and materials used in this study are poorly described. Therefore, the validity of these values is questionable.
Eye Irritation
Solutions are expected to be corrosive, based on their corrosivity to skin. Solutions have caused moderate irritation to corrosive injury in rabbit eyes.
Application of 0.1 mL of a 10% solution (carrier not specified) caused moderate irritation in rabbits. The effects were described as penetrating corneal opacity and mild conjunctivitis, which reversed in 7-14 days.(5) In a study, which is not available in English, opacity of the cornea, clouding of the lens and other harmful effects were observed in a rabbit following repeated application of a 50% solution. Harmful effects were still observed 6 days later.(2, unconfirmed)
Skin Irritation
Solutions have caused corrosive effects (necrosis and ulceration) following prolonged exposure.
Corrosive effects (necrotic erythema and severe edema) were observed in rabbits following application of 0.5 mL of a 10% zinc chloride solution (carrier not specified), under a closed patch, for 24 hours.(5) Severe irritation including ulceration was observed in rabbits and mice following application of 0.5 mL of a 1% solution in water for 5 days (using both open and closed patch for rabbits and using open patch for mice). Moderate irritation was seen in guinea pigs (open patch).(4) This exposure time is longer than what is normally accepted for this type of test.
Effects of Short-Term (Acute) Exposure:
Inhalation
Rats were exposed for 10 minutes to 1200-3900 mg/m3 zinc chloride, as an aerosol (median diameter 2 microm) generated from 3.7 and 10.3 M zinc chloride solutions. Irritation was not observed during or shortly after exposure, but signs of respiratory distress (e.g. shortness of breath and difficulty breathing) gradually developed. Deaths were observed at 1880 mg/m3 and above. Autopsy showed signs of severe lung injury (pulmonary edema and bleeding).(3)
Skin Contact
Evidence of absorption through the skin (metallothionein enzyme induction) was observed in rats and guinea pigs following daily application of 5% zinc chloride in liquid paraffin for 2 or 3 days. Some skin irritation was also observed after 2 or 3 applications, but not after a single application.(8) Application of 0.4 mL of an oil preparation containing 7500 ppm zinc chloride to the skin of zinc-deficient female rats for 8-24 hours resulted in sufficient absorption to increase plasma zinc levels to normal concentrations. (43)
Ingestion
Rats receiving 0.12 mg/mL zinc chloride in their drinking water for 4 weeks had a significant decrease in hemoglobin and in red blood cell counts in both sexes and a significant increase in leukocytes in males. (The approximate dose was 12 mg/kg/day as zinc; or 25 mg/kg/day, as zinc chloride).(9)
Effects of Long-Term (Chronic) Exposure:
Ingestion
In a reproductive toxicity study, rats were given zinc chloride orally at doses of 0, 7.5, 15, or 30 mg/kg/day for 98 days for males and 140 days for females. (Doses were 0, 3.6, 7.2, or 14.3 mg/kg/day, as zinc). Males had a dose-dependent decrease in body weight gain, which was significant at all doses. There were no significant decreases in body weight in females. Harmful effects on the spleen, lesions in the digestive system and a smaller than usual pancreas were seen in both sexes at 15 and 30 mg/kg/day and in the thymus at all doses (statistical evaluation not reported).(21)
Carcinogenicity
No conclusion can be drawn based on the limited information available. Zinc chloride did not promote tumour development in the liver, stomach, kidneys, or pancreas of rats or hamsters or on the skin of mice following administration with known carcinogens.(11) No conclusions can be drawn from a study, which is not available in English, involving a 3-year, 5-generation exposure of tumour-resistant and tumour-susceptible strains of mice. The cancer frequency was reported to be higher in animals receiving 10 or 20 mg/kg/day zinc, as zinc chloride, in the drinking water.(6, unconfirmed) No statistical analysis or information on individual tumour types was provided and there was a lack of dose response with the tumour-resistant strain.
Teratogenicity, Embryotoxicity and/or Fetotoxicity
No conclusions can be drawn from the only study located, since the route of exposure used (intraperitoneal injection) is not relevant to occupational settings.
Reproductive Toxicity
It is not possible to conclude that zinc chloride is a reproductive toxin, based on the available animal information. The available studies are limited by the small animal numbers or provide inadequate details for evaluation. In one study, which was limited by small animal numbers, ingestion of zinc chloride caused reduced fertility in rats at doses that caused significant other harmful effects.
Rats were given zinc chloride orally at doses of 0, 7.5, 15, or 30 mg/kg/day (0, 3.6, 7.2, or 14.3 mg/kg/day, as zinc) for 77 days before mating and a 21-day mating period. Dosing of females was continued throughout pregnancy and lactation. Males had a dose-dependent decrease in body weight gain, which was significant at all doses. There were no significant decreases in body weight in females. The fertility index was significantly lower than the control for all doses and there was a significant decrease in live pups/litter at 15 and 30 mg/kg/day. Detailed examination of the tissues indicated atrophy of the prostate in 7/10 rats at 15 and 30 mg/kg/day compared to 0/10 for control and 7.5 mg/kg/day groups.(21) This study is limited by small animal numbers (5-9 reproducing pairs). As part of the same study, reported by abstract, 2 offspring/dose group were analyzed for zinc accumulation after weaning. Zinc was found to accumulate to a greater extent in the ovary and thymus.(20, unconfirmed) In a related study, also reported by abstract, mice were given zinc, as zinc chloride, orally at doses of 0, 1.56, 3.13, or 6.25 mg/kg/day for males and 0, 3.13, 6.25 or 12.5 mg/kg/day for females starting 49 days before mating and through a 21 day mating period. (Doses were 0, 3.3, 6.5, or 13 mg/kg/day for males and 0, 6.5, 13, or 26 mg/kg/day for females, as zinc chloride). Dosing of females was continued throughout pregnancy and lactation. Significant decreases in fertility index, litter size and body weight of offspring were found for all doses of zinc chloride.(26, unconfirmed) There are insufficient details available to evaluate this study. Male weanling rats were fed zinc, as zinc chloride, in the diet at concentrations of 4, 12 (normal dietary amount) or 500 mg/kg for 8 weeks. (Approximate doses were 0.24, 0.72 or 30 mg/kg/day, as zinc; or 0.50, 1.5, or 63 mg/kg/day, as zinc chloride). At the high dose, there were no effects on testicular development. A significant negative effect on testicular cells was observed for the diet deficient in zinc (0.50 mg/kg/day, as zinc chloride).(44) In a study, which is limited by small animal numbers (5/group), mice were given 800 ppm zinc, as zinc chloride, in their drinking water for 12 weeks. (The approximate dose was 160 mg/kg/day as zinc; or 335 mg/kg/day, as zinc chloride). There was a significant decrease in body weight gain and testes weight and a non-significant decrease in the epididymal sperm numbers in treated animals. Detailed examination of the testes did not indicate any harmful effects.(12) In a study, reported by abstract, mice were given zinc chloride orally at doses of 0, 0.78, 1.56, or 3.125 mg/kg/day (0, 0.37, 0.75, 1.50 mg/kg/day, as zinc). Males were killed after mating and females after lactation. No significant effects were noted on body weight gain or food consumption. Reported effects were dose-dependent decreases in implantation efficiency and litter size, and at 1.56 and 3.125 mg/kg/day, a decrease in the number of live births.(45, unconfirmed) No statistical evaluation was reported and there are insufficient details available to evaluate this study.
Mutagenicity
It is not possible to conclude that zinc chloride is mutagenic, based on the available information. A negative result was obtained in a test using live mice exposed to zinc chloride orally. Other in vivo tests have not used relevant routes of exposure. A negative result (chromosomal aberrations in bone marrow) was observed in a test involving oral administration to mice for 30 days in the diet. When the diet was deficient in calcium, a positive result was obtained.(7,46) Other in vivo tests have used routes of exposure which are not relevant to occupational situations.(10,13,18-unconfirmed) Positive results (chromosome aberrations) have been obtained in tests with cultured human lymphocytes.(7,47,48,49) Another positive result (DNA damage) was obtained in a test using cultured human cells, in the absence of metabolic activation.(50) A negative result (gene mutation) was obtained in a test with mammalian cells, without metabolic activation.(51) Negative results (gene mutation, DNA repair) were obtained in tests using bacteria, with and without metabolic activation.(52,53,54,55)
A positive result (gene mutation) was obtained in a test using fruit flies (Drosophila).(56)