Table 3. Common Heavy Metals Encountered in a Chemical Laboratory and Their Reproductive Effects Based on Information from Respective Toxicological Profiles from the Agency for Toxic Substances and Disease Registry18 and Other Literaturea.
| Metal | Adverse effects | |
|---|---|---|
| Aluminum | F | Limited evidence of adverse effects dependent on form of aluminum. No observed maternal toxicity, embryotoxicity, or teratogenicity of aluminum hydroxide (rats and mice, oral) while other forms induced developmental alterations (rats and mice, aluminum chloride, aluminum nitrate, and aluminum lactate, oral).27 |
| Fetal skeletal variations, particularly with bioavailable forms of aluminum (rats and mice, aluminum nitrate and citrate, oral).18 | ||
| N | Adverse neurobehavioral and immune system effects (mice and rats, oral).18,27 | |
| FR | No studies on reproductive effects in humans. | |
| No associations with adverse fertility effects (multiple studies, animals, oral). | ||
| No histological changes in reproductive tissues (rats and guinea pigs, 6.1 mg Al/m3 as aluminum chlorhydrate over 6 months, inhalation).18 | ||
| Antimony | BO | Limited evidence as studies are not high quality. |
| Increased incidence of spontaneous abortion (human occupational exposure, exposure scenario not clearly described, dust containing metallic antimony, antimony trioxide, and antimony pentasulfide, inhalation).18 | ||
| No associations with antimony levels in cord blood and adverse pregnancy outcomes (human epidemiology study).18 | ||
| F | No associations with neural tube defects or structural abnormalities (human epidemiology study, antimony in drinking water).18 | |
| N | No overt developmental effects observed for offspring (human occupational exposure, exposure scenario not clearly described, dust containing metallic antimony, antimony trioxide, and antimony pentasulfide, inhalation).18 | |
| Decreases in pup growth and alterations of the cardiovascular system (rats, 0.7 mg Sb/kg/day as antimony trichloride, antimony exposure.18 | ||
| FR | Increased incidence of menstrual disturbances (human occupational exposure, exposure scenario not clearly described, dust containing metallic antimony, antimony trioxide, and antimony pentasulfide, inhalation).18 | |
| Adverse effects on ability to conceive in females (rats, inhalation).18 | ||
| No alterations in sperm parameters (rats, antimony trioxide or antimony potassium tartrate, oral).18 | ||
| Arsenic | BO | Significant increased incidence of miscarriages, stillbirths, preterm births (human population study, inorganic arsenic, oral exposure from drinking water;18,94−96 human epidemiological studies, inorganic arsenic, inhalation).18 |
| Limited studies on increased risk of spontaneous abortion to occupational exposure of arsine gas (humans, inhalation).40 | ||
| F | Fetal malformations including congenital heart and neural tube defects (humans, inorganic arsenic).18,94,97 | |
| Fetal malformations including delayed ossification and irregular palatine rugae (mice, rats, and rabbits, methyl arsenates, oral).18 | ||
| N | Low birth weight (human population study, inorganic arsenic, oral exposure from drinking water; human epidemiological studies, inorganic arsenic, inhalation).18 | |
| FR | No histological damage to reproductive tissues (animals, methyl arsenates, oral).18 | |
| M | Increased risk of gestational diabetes (humans, oral drinking water).94 | |
| Barium | BO | Limited evidence as studies are not high quality. |
| Low birth weight (rodents, 180–200 mg barium/kg/day for 30 days of barium chloride, oral, not high quality study).18 | ||
| F | Lower risk of malformations with higher barium levels, (human statistical study, barium in drinking water, conclusions are limited as the exposure scenario was not clearly described).18 | |
| No adverse developmental effects (mice, up to highest dose of 200 mg barium/kg/day, oral).18 | ||
| FR | Adverse effects on male and female fertility with inhalation exposure (study of suspect quality), and following oral exposure studies are conflicting.18 | |
| No alterations in sperm parameters (rats and mice, barium in drinking water for 60 days, oral).18 | ||
| Beryllium | BO | Increased fetal mortality and stillbirths (rats and mice, beryllium nitrate, beryllium oxide, and beryllium chloride, injection).18 |
| N | No adverse developmental effects (dogs, beryllium sulfate in diet).18 | |
| Behavioral abnormalities from beryllium crossing placenta and reaching fetus (mice, injection).18 | ||
| FR | No adverse fertility effects (dogs, beryllium sulfate in diet; rats, beryllium sulfate in drinking water; rats, beryllium oxide, injection).18 | |
| Cadmium | BO | Embryonic death (rats, injection).27 |
| F | Malformations (mice, rats, and hamsters, injection).27 | |
| N | Low birth weight98,99 and birth length100,101 (humans). | |
| Retardation (mice and rats, injection).27 | ||
| FR | Endocrine disruptor and metalloestrogen causing female fertility effects (humans and rats, oral).18,102 | |
| Inconclusive evidence of effect on male fertility with some studies showing effects and others not observing effects (humans, animals).18 | ||
| Chromium | BO | Increased miscarriage (rats and mice, Cr6+, oral).18,103 |
| F | Abnormal skeleton and reproductive system development (mice, Cr6+ as potassium dichromate and Cr3+ as chromium chloride, injection).18,103 | |
| No developmental effects (rats, 1806 mg Cr3+/kg/day as chromium oxide for 60 days before mating and throughout the gestational period, oral).18 | ||
| FR | Limited human evidence: inverse correlation between blood Cr levels and sperm count (human occupational exposure, exposed to Cr6+ for 1–15 years in an electroplating factory).104 | |
| Inconclusive evidence in animal studies: adverse male fertility effects including reduced sperm mobility, sperm damage, and sperm death (mice, monkeys, rats, oral);18,104 adverse female fertility effects (mice, Cr3+ and Cr6+, oral); no adverse reproductive effects (mice, Cr3+ and Cr6+, oral).18 | ||
| M | Complications during pregnancy and childbirth (toxicosis and postnatal hemorrhage) (humans occupational exposure, dichromate manufacturing facility, Cr6+).18 | |
| Cobalt (stable) | BO | Maternal and fetal lethality at high doses, lower dose had significant increases in fetal mortality (rabbits, > 38 mg cobalt/kg/day cobalt; 7.6 mg cobalt/kg/day).18 |
| F | No developmental effects on human fetuses following treatment of pregnant women in third trimester (human, of 0.6 mg Co/kg/day of cobalt chloride for 90 days).18 | |
| Effects on fetal skeletal formation (mice fetuses, 5 mM cobalt chloride, injection).27 | ||
| No teratogenic effects (rats and mice, less than 38 mg cobalt/kg/day of cobalt sulfate; rats and mice, 24.8 mg cobalt/kg/day during gestation days 6–15 and 81.7 mg cobalt/kg/day during gestation days 8–12; mice, 5.4 or 21.8 mg cobalt/kg/day during gestation day 14 through postnatal lactation day 21).18 | ||
| N | Adverse effects on postnatal survival and development of pups, but was accompanied by overt maternal toxicity (rats, 5.4 or 21.8 mg cobalt/kg/day during gestation day 14 through postnatal lactation day 21, oral).27 | |
| FR | Testicular degeneration and atrophy (rats and mice, 13 mg cobalt/kg/day cobalt chloride, chronic ingestion).18 | |
| M | As an essential trace element, too low levels of Co in maternal blood were connected to pregnancy-induced hypertension and increased risk of preterm birth.88 | |
| Copper | BO | Some studies have suggested a link between copper levels in human maternal blood and spontaneous abortion, but others have not found such evidence.94 |
| F | Malformations (rats and mice, copper sulfate and copper acetate, ingestion).27 | |
| FR | Significantly reduced sperm motility (human in vitro studies, metallic copper and copper ions).18,27 | |
| Sexual impotence (human occupational exposure, male workers, 111–434 mg/m3 copper dust, study suspect in quality as there was no control group).18 | ||
| Effects on sperm (rats, copper chloride, inhalation)27 and negative effects on male sexual organs (rats, 0.95 or 1.4 mg Cu/kg/day for 26 days, injection).18 | ||
| No fertility effects (mink, 12 mg Cu/kg/day as copper sulfate in diet) or reproductive tissues (male and female mice and rats, 66 and 68 mg Cu/kg/day or 398 and 536 mg Cu/kg/day, respectively, oral).18 | ||
| M | Gestational diabetes and hypertension linked to higher levels of copper in maternal blood (human).94 | |
| Gallium | F | Reduced fetal weight, increased skeletal variations, and decreased number of viable implants at levels where maternal toxicity was observed (mice and hamsters, 12.5–100 mg/kg/d of gallium and gallium nitrate, injected).27 |
| FR | Limited evidence of male reproductive toxicity (rats and mice, gallium arsenide) but occupational exposures via inhalation of gallium arsenide are argued to not be primary contributors to male reproductive toxicity in humans.105 | |
| Indium | BO | Recommended in report by the Health Council of The Netherlands to classify indium (III) salts as presumed human reproductive toxicants based on animal studies.106 |
| Increased resorptions and stillbirths (mice and rats, and rabbits, indium trichloride, oral).106 | ||
| F | External malformations and skeletal malformations (mice and rats, and rabbits, indium trichloride, oral; mice and rats, hamsters, indium trichloride, indium nitrate, injection).106 | |
| No adverse developmental effects (mice and rats, up to 100 mg/m3 indium phosphide, inhalation).106 | ||
| FR | Recommended in report by the Health Council of The Netherlands to classify indium phosphide and indium arsenide as suspected human reproductive toxicants based on animal studies.106 | |
| Decrease in weight of male reproductive organs and atrophy of male and female reproductive organs (rats and mice, indium phosphide, inhalation; hamsters, indium phosphide, intratracheal instillation; rats and hamsters, indium arsenide, intratracheal instillation).106 | ||
| No effects on ovulation, fertilization, or male tissues or reproductive parameters (mice, up to 250 mg/kg/day indium trichloride, oral).106 | ||
| Lead | BO | Some evidence of higher risk of spontaneous abortion,27,102,107 miscarriage, stillbirth, preterm delivery85,93,108 (human epidemiological studies, ≤10 μg/dL Pb in blood).18 |
| F | Malformations in animal models (birds, fish, rodents) but not in humans.27,104 | |
| N | Low birth weight (human epidemiological studies, ≤10 μg/dL Pb in blood).18,85,93,108 | |
| Neurodevelopmental impairment, increased risk of developmental delay, reduced IQ, and behavioral problems later in life (humans, 5–10 μg/dL Pb in blood109).107,110,111 | ||
| FR | In males, reduced sperm count and sperm damage, reproductive hormonal alterations, and reduced fertility (humans – numerous epidemiological studies, | |
| ≤10 μg/dL Pb in blood) and more severe effects including decreased fertility and histopathological damage to testes (a few human epidemiological studies, > 10 μg/dL Pb in blood).18,93 | ||
| In females, inconsistent results, some reproductive hormonal alterations, decreased fertility, and early onset of menopause, others no adverse effects (human epidemiological studies, ≤10 μg/dL Pb in blood).18 | ||
| Manganese | F | No increases in birth defects observed (human occupational exposure, animals).18 |
| N | Adverse effects on neurological structures causing postnatal motor-, cognitive-, and behavioral impairments (human, airborne, drinking water, diet).18,112 | |
| Unusually high incidence of infant mortality (one human study, manganese in drinking water, unclear whether deaths directly attributable to manganese exposure).18 | ||
| Infant height and weight negatively correlated with blood maternal manganese levels.113 | ||
| FR | Loss of sex drive and low sperm count (human occupational exposure, inhalation).18 | |
| Sperm damage and adverse changes in male reproductive performance (animals, diet).18 | ||
| Little evidence of impairments in female fertility – decreased number of offspring (one rodent study, oral exposure before pregnancy).18 | ||
| Mercury | BO | Increased rate of spontaneous abortions or resportions (human, mercuric chloride; hamsters, inorganic mercury; rats, metallic mercury vapors, inhalation; mice and rats, guinea pigs, monkeys, organic mercury, oral).18 |
| F | Malformations (rats, metallic mercury vapors, inhalation).18 | |
| N | Neurological damage and adverse effects central nervous system (humans, methylmercury; mice and rats, hamsters, guinea pigs, organic mercury, oral).18 | |
| FR | No significant effect on male fertility (human occupational exposure, metallic mercury).18 | |
| Adverse effects on male fertility (animals, methylmercury, oral) and adverse effects on female fertility (rats and monkeys, methylmercury, oral).18 | ||
| Nickel | BO | Increased rate of spontaneous abortions (16% versus 8.5% in compared group of pregnant construction workers; human occupational exposure at nickel refining plant, 0.08–0.196 mg Ni/m3, primarily as nickel sulfate).18 |
| F | Increased rate of malformations (17% versus 6% in compared group of pregnant construction workers; human occupational exposure at nickel refining plant, 0.08–0.196 mg Ni/m3, primarily as nickel sulfate).18 | |
| N | Decreased birth weight (rats, 1.6 mg Ni/m3 as nickel oxide 23.6 h/day on gestation days 1–21), although no effect at 0.8 mg Ni/m3.18 | |
| FR | Limited evidence for male fertility effects including histological alterations, decreases in sperm concentration, motility, and abnormalities, and decreases in fertility (mice and rats, nickel subsulfide, nickel sulfate, nickel chloride, nickel nitrate, oral).18 | |
| Palladium | F | Not enough good evidence on fetal effects.114 |
| No apparent teratogenicity in one low quality study (chicken embryos, 20 mg/egg of palladium(II) chloride, injection).114 | ||
| FR | Limited evidence of adverse effects on testes and sperm in low quality studies (mice and rats, 0.02 mmol palladium(II) chloride, injected).114 | |
| BO | Increased fetal mortality (rats, 13 mg/kg of cisplatin: Pt(NH3)2Cl2, drug for cancer treatment).115,116 | |
| Platinum | F | No fetotoxic effects observed (rats, platinum metal, PtCl2, PtCl4 in diet).115 |
| N | Reduced birth weight (rats, 200 mg Pt/kg Pt(SO4)2 in diet; rats, Na2PtCl3).115 | |
| Developmental toxicity (500 mg/kg/d of Pt-siloxane, Karstedt catalyst).115 | ||
| FR | Adverse effects on male fertility, known effect with cisplatin; limited data for other platinum compounds (rats, 9–18 mg/kg platinum chloride injection; rats, 1000 μM hexachloroplatinate or tetraammineplatinum(II) chloride, injection).115,116 | |
| No adverse effects on male fertility (rats, up to 1000 μM hydrogen hexachloroplatinate; human sperm, metallic platinum).115,116 | ||
| Selenium | BO | No change in pregnancy outcomes (ewes, 24 ppm selenium as sodium selenate in diet).18 |
| F | Excess selenium is a demonstrated teratogen in birds, effects include reduced hatchability, grossly deformed embryos lacking eyes and beaks, deformed wings and feet (chick, coot, duck, stilt, and grebe embryos, selenium as sodium selenite or sodium selenate in diet or injection).18 | |
| No clear evidence linking selenium exposures to teratogenic effects in mammals.18 | ||
| May interfere with normal fetal development and result in malformations (sheep and cattle, high seleniferous diets).18 | ||
| Silver | N | No studies on developmental effect from exposure via inhalation, oral, and dermal exist in humans.18 |
| Silver in drinking water linked to reduced volume of certain well defined brain regions (neonatal rats).18 | ||
| FR | No evidence to support reproductive effects in humans from exposure via inhalation, oral, and dermal.18 | |
| Temporary histopathological damage to testicular tissue and effects on sperm morphology (male rats, silver nitrate, injection,).18 | ||
| Termination of pregnancy (monkeys, silver nitrate, injection).18 | ||
| Strontium | BO | No teratogenic effects (rats, 82 mg strontium/kg/day as strontium nitrate, injection).18 |
| Increased incidences of adverse pregnancy outcomes (mortality from developmental anomalies, chromosomal anomalies, labor complications, and other unspecified perinatal conditions; humans, radioactive strontium-90).18 | ||
| F | Teratogenic effects (skeletal abnormalities) on the fetus from exposure to high doses during gestation (mice and rats, radioactive strontium-90, injection).18 | |
| N | Impaired bone development (rickets) at high doses in young children (human, stable strontium, oral, no information available on gestational or neonatal exposure effects).18 | |
| FR | Limited evidence on the reproductive toxicity of stable strontium in humans; not directly harmful to human sperm (human sperm, strontium chloride, in vitro).18 | |
| Adverse reproductive effect from injected radioactive strontium.18 | ||
| Increase rate of fetal death and evidence of selective accumulation in the testis (male mice, radioactive strontium-90, injection).18 | ||
| Reduced number of oocytes, reduced reproductive capacity of offspring (female pregnant mice, radioactive strontium-90, injection).18 | ||
| Tellurium | F | Recommended in report by the Health Council of The Netherlands to be classified as a presumed human reproductive toxicant based on animal studies.117 |
| Increased incidence of hydrocephalus and malformations (rats, rabbits, tellurium in diet).117 | ||
| Thallium | F | Increased embryo lethality, dose-related growth retardation and growth inhibition (cultured rat embryos, 10–100 μg/mL thallium).18 |
| Reduced fetal weight, hydronephrosis, and absence of vertebral bodies (pregnant rats, injection of 2 mg thallium/kg/day as thallium sulfate).18 | ||
| FR | No human data but animal data suggests susceptibility of male reproductive system to thallium.18 | |
| Decreased sperm motility, inhibition of β-glucuronidase activity and histopathological alterations of testes (rats, 0.74 mg thallium/kg/day as thallium sulfate administered in drinking water).18 | ||
| N | Crosses human placenta but data is limited regarding developmental effects. Existing data suggests it might be a potential developmental neurotoxicant. | |
| Causes alterations in the functional competence of the nervous system, impairment of learning observed after prenatal exposure (rats, 0.08 mg thallium/kg/day thallium sulfate).18 | ||
| Tin | BO | Embryonic and fetal death at maternal toxic doses (rats, organotin compounds such as triphenyltin, dibutyltin, dioctyltin- S,S’-bis[isooctylmercaptoacetate].104 |
| F | Decreased fetal growth, reduced fetal ossification and other malformations at doses nontoxic to the mother and fetal growth suppression and cleft palate at maternal toxic doses (rats, organotin compounds such as triphenyltin and dibutyltin).104 | |
| FR | Testicular degeneration (rats, tin(II) chloride 10 g/kg for 13 weeks in diet).118 | |
| Abnormalities in the testes and ovaries (rats, triphenyltin hydroxide, oral).118 | ||
| Titanium | Fr | No reproductive effects in humans reported from inhalation, oral or dermal exposure to titanium tetrachloride.18 |
| No histopathological alterations in the testis and epididymis (male rats, up to 40 mg/m3 titanium tetrachloride).18 | ||
| N | No studies on developmental effects in humans or animals from inhalation, oral or dermal exposure to titanium tetrachloride.18 | |
| Uranium | BO | Decrease in litter size, increased late resorptions and decreased live fetuses, increased neonatal death per litter, decreased day 21 viability index, reduced pup’s weight (mice and rats, uranyl nitrate or uranyl acetate, oral).18 |
| N | Reduced body weight and length, increases incidences of malformation and developmental variation (mice, uranyl acetate dihydrate, oral).27 | |
| Delayed hyperactivity, decreased spatial working memory (rats, enriched uranyl nitrate, oral).18 | ||
| FR | Testicular degeneration linked to high oral doses (male rats, 331 mg U/kg/day as uranyl nitrate hexahydrate for 2 years in diet).18 | |
| 3-fold increase in plasma testosterone, reduced pregnancy rate, disturbance in ovarian folliculogenesis, increased proportion of morphologically abnormal oocytes, increased oocyte dysmorphism and micronuclei in cumulus cells (mice and rats, 1.9–11.2 mg U/kg/day as uranyl nitrate or uranyl acetate, oral). (18) | ||
| Vanadium | BO | Reduced pup weight and length, decreased viability, increased gross, skeletal and visceral anomalies, decreased pup body weight (mice and rats, sodium metavanadate, ammonium metavanadate, vanadyl sulfate).18 |
| F | Embryotoxicity and fetotoxicity (mice and rats, and hamsters, ingestion).119 | |
| FR | Decreased fertility, sperm count, and motility (mice and rats, 31 mg V/kg/day vanadyl sulfate ammonium metavanadate, 25 mg V/kg/day sodium metavanadate).18 | |
| Zinc | BO | One adverse effect reported from oral consumption of 0.6 mg zinc/kg/day as zinc sulfate during third trimester (4 women study: 3 premature births, 1 still birth). |
| Increased fetal resorption, reduced fetal weight, altered tissue concentration of fetal iron and copper, reduced growth in offspring, and still births (rats, dams, mice, zinc oxide, zinc carbonate, >200 mg zinc/kg/day in diet).18 | ||
| N | No studies on developmental effects in humans or animals after inhalation exposure to zinc exist.18 | |
| FR | No reproductive effects in humans after inhalation, oral (0.3 mg/kg/day).18 | |
| No adverse effect on mammary glands, ovaries, fallopian tubes, or uteri (mice and rats, and guinea pigs exposed to 119.3 or 121.7 mg zinc/m3 as zinc chloride smoke for 20 weeks).18 | ||
| Altered sperm chromatin structure, decreased live pups per litter in all groups of treated rats, increased preimplantation loss, no reproduction in females (rats, 7–25 mg zinc/kg/day zinc chloride, 200 mg zinc/kg/day zinc sulfate, 250 mg zinc/kg/day zinc carbonate oral).18 | ||
a
Adverse effects: BO: Birth outcome; F: Fetal effects; N: Neonatal and beyond effects; FR: Fertility effect; M: Maternal effects.