Table 2. Common Organic Solvents Encountered in a Chemical Laboratory with Corresponding CAS Number and Global Harmonization System Classification for Reproductive Toxicity and Adverse Reproductive Effects on Humans or Animals Based on Information from Toxicity Profiles in Online Databases17,18,38−41 and Other Literaturea.
| Solvent | CAS number | GHS cat.17,38 | Adverse effects | |
|---|---|---|---|---|
| Acetic acid | 64-19-7 | N | BO | No discernible effects on fetal survival (mice, 16–345 mg/kg-day, oral).17 |
| Low numbers of spontaneous abortions (mice, 1600 mg/kg-day, oral).17 | ||||
| No discernible effects on fetal survival (rats, 1600 mg/kg-day, oral).17 | ||||
| No discernible effects on fetal survival (rabbits, 16–1600 mg/kg-day, oral).17 | ||||
| F | No evidence of teratogenicity.17 | |||
| No significant abnormalities in either soft or skeletal tissues (mice, 15–345 mg/kg-day, oral).17 | ||||
| Slight reductions in ossification (mice, 1600 mg/kg-day, oral).17 | ||||
| No abnormalities (rats, 1600 mg/kg-day, oral).17 | ||||
| FR | No evidence of reproductive toxicity.17 | |||
| M | No discernible effects on maternal survival (mice, rats, and rabbits, 16–1600 mg/kg-day, oral).17 | |||
| Slightly reduced bodyweight gain (mice, 16–1600 mg/kg-day, oral).17 | ||||
| Dose-dependent decrease in maternal body weight attributable to bactericidal properties of acetic acid within the gastrointestinal tract of the rabbits (rabbits, > 74.3 mg/kg-day, oral).17 | ||||
| Acetone | 67-64-1 | 2 | BO | Slight increase in later resorptions (mice, 6600 ppm, inhalation).44 |
| F | No evidence of teratogenicity (chick embryos, 39 and 78 mg, yolk sac injection).39 | |||
| Decreased fetal body weight (mice, 6600 ppm, inhalation).44 | ||||
| Reduced fetal body weight and fetal malformations at high doses (rats, 11000 ppm, inhalation).44 | ||||
| N | Reduced postnatal pup survival (mice, 3500 mg/kg/day acetone on gestation days 6–10, oral).18 | |||
| FR | Increased number of abnormal sperm (human occupation exposure, 69.6–94.5 ppm of acetone and styrene, inhalation).45 | |||
| Premature menstrual periods in 3 of 4 women (human, 1000 ppm for 7.5 h, inhalation).39 | ||||
| No observed lesions in female reproductive organs (mice, 0.2 mL painted on skin, dermal).18 | ||||
| No effects on testes weight or testicular histopathology (rats, 5000 ppm, oral).46 | ||||
| Decreased epididymal weights, depressed sperm motility, and increased abnormal sperm (rats, 3400 mg/kg-day, oral).47 | ||||
| M | Significant decrease in maternal body weight (rats, 11000 ppm, inhalation).44 | |||
| Acetonitrile (ACN or MeCN) | 75-05-8 | N | BO | Increased resorptions and spontaneous abortions (rats, 1827 ppm, inhalation).40 |
| Increased spontaneous abortions and stillbirths (rabbits, 30 mg/kg, oral).40 | ||||
| F | Reduced fetal body weight and 5 out of 9 litters developed skeletal disorders (hamsters, 8000 ppm, inhalation).40 | |||
| Increase in malformed offspring with rib fusions being most common (hamsters, 300–400 mg/kg, oral).40 | ||||
| No effect on fetal weight and no significant difference in anomalies (rats, 1000–1827 ppm, inhalation).40 | ||||
| FR | No observed effects on fertility (rats, 100–1200 ppm, inhalation).40 | |||
| M | Reduced maternal body weight at lower doses and maternal mortality in 4 out of 12 dams at a higher dose (hamsters, 200–300 and 400 mg/kg respectively, oral).40 | |||
| Deaths in 2 out of 33 dams (rats, 1200 ppm, inhalation).40 | ||||
| Mortality in 8 out of 20 dams as well as reduced maternal body weight (rats, 1827 ppm, inhalation).40 | ||||
| Mortality in 2 dams, four emaciated dams out of 25 (rats, 275 mg/kg-day, oral).40 | ||||
| Mortality in 1 out of 5 dams exposed to high concentrations. (rabbits, 30 mg/kg, oral).40 | ||||
| Note: Acetonitrile can slowly convert to cyanide, and it is suspected that many of the dam deaths are attributable to cyanide release and not directly acetonitrile. | ||||
| Anisole (methoxybenzene) | 100-66-3 | N | BO | No effect on birth outcomes (rats, 50–800 mg/kg-day, oral).17 |
| F | Lower fetal body weights, discolored skin, and moderate subcutaneous edema (rats, 800 mg/kg-day, oral).17 | |||
| M | Reduced maternal body weight gain and pregnant uterus weight (rats, 800 mg/kg-day, oral).17 | |||
| Benzene | 71-43-2 | 2 | BO | Limited evidence of increased incidence of spontaneous abortion and intrauterine asphyxia of the fetus as compared to workers with no exposure or shorter exposure periods (chronic human occupational exposure, petroleum as the major source of benzene, inhalation).18 |
| Increase in abortions and resorptions (rabbits, 312 ppm, inhalation).18 | ||||
| No effect on resorptions (mice, 500 ppm, inhalation; inhalation rats, 2000 ppm, inhalation; rabbits, 500 ppm, inhalation). (18) | ||||
| F | Delayed bone formation and bone marrow damage (multiple animal studies, inhalation).41 | |||
| Decreased body weight and delayed ossification (mice, 500 ppm, inhalation).18 | ||||
| Reduced fetal weight and increased fetal anomalies (rabbits, 313 ppm, inhalation).18 | ||||
| Reduced fetal body weight (mice, 1300 mg/kg-day, oral).18 | ||||
| N | Low birth weight via maternal inhalation exposure (multiple animal studies, inhalation).41 | |||
| FR | Irregular menstrual periods and a decrease in ovary size (human occupational exposure, chronic exposure over months, inhalation).48 | |||
| Endometrial polyps and ovarian lesions in females and preputial gland lesions in males (mice, 600 mg/kg-day for 2 years, oral).18 | ||||
| Bilateral cysts, testicular atrophy, decreased sperm count, increase in abnormal sperm (mice, 300 ppm, inhalation).18 | ||||
| No adverse reproductive effects (rats, 1000 mg/kg-day, oral).18 | ||||
| N-butanol | 71-36-3 | N | BO | No effect on resorption or fetal viability (rats, 3500–8000 ppm, inhalation).40 |
| Pre- and postimplantation losses and spontaneous abortions, (rats, 1300 mg/kg-day, oral).40 | ||||
| F | Reduced crown-rump length and increased malformations (rats, 0.24–4%, oral).40 | |||
| Decreased fetal body weight (rats, 5654 mg/kg-day, oral).40 | ||||
| Skeletal variations and thymic remnant in the neck (rats, 0.2–5.0%, oral).40 | ||||
| Reduced fetal body weight and increased abnormal skeletal and visceral malformations (rats, 6000–8000 ppm, inhalation).40 | ||||
| FR | No differences in estrous cycle and no changes in relative organ weights (rats, 0.24–4%, oral).40 | |||
| Decreased fertility (rats, 1300 mg/kg-day, oral).40 | ||||
| M | Decreased maternal body weight and food consumption (rats, 0.2–5.0%, oral).40 | |||
| Maternal fatalities in 2 out of 18 dams and lower food consumption (rats, 3500–8000 ppm, inhalation).40 | ||||
| Chloroform | 67-66-3 | 2 | BO | Fetal resorption and decreased conception rates (mice, 100 ppm, inhalation).18 |
| Spontaneous abortions (mice and rats, 30–300 ppm, inhalation).18 | ||||
| Increased fetal resorptions (rats, 30 ppm, inhalation).18 | ||||
| Spontaneous abortions (rabbits, 63 mg/kg-day, oral).18 | ||||
| F | 80% higher risk of intrauterine growth retardation at higher dose and 30% higher risk at lower doses as compared undetectable levels of chloroform (human study of 688 subjects exposed to chloroform in drinking water as a byproduct of chlorine treatment, ≥10 ug/L and 1–9 ug/L, oral).18 | |||
| Cleft palate, decreased ossifications, and decreased crown-rump length (mice, 100 ppm during organogenesis, inhalation).18 | ||||
| Delayed ossification and wavy ribs at 30 ppm, imperforate anus and missing ribs at 100 ppm, decreased fetal body weight and crown-rump length at 300 ppm (rats, 30–300 ppm, inhalation). | ||||
| N | 30% higher risk of low birth weight as compared to undetectable levels of chloroform (human study of 688 subjects exposed to chloroform in drinking water as a byproduct of chlorine treatment, ≥10 ug/L, oral).18 | |||
| Hepatocellular degradation (mice, 41 mg/kg while in utero, during lactation, and into adulthood, oral).49 | ||||
| FR | Abnormal sperm (mice, 400 ppm over 5 days, inhalation).18 | |||
| Gonadal atrophy (rats, 410 mg/kg/day, oral). (50) | ||||
| M | Decreased maternal body weight (rats, 150 mg/m3, inhalation).49 | |||
| Cyclohexane | 110-82-7 | N | BO | No evidence of effects on resorption frequency or pre- or postimplantation loss (rats, 100–1000 mg/kg-day, oral).51 |
| No adverse effects on viable fetuses or number of implantations (rats, 1000–10000 ppm, inhalation).51 | ||||
| F | No differences in fetal body weight (rats, 250–1000 mg/kg-day, oral).51 | |||
| No evidence of variations or malformations (rats, 100–1000 mg/kg-day, oral).51 | ||||
| No evidence of developmental toxicity (rats, 7000 ppm, inhalation).40 | ||||
| No observed developmental effects (rabbits, 500–7000 ppm cyclohexane, inhalation).17 | ||||
| N | Reduced pup weight through lactation period, gestational and lactation exposure (rats, 7000 ppm, inhalation).17 | |||
| FR | No observed effects on reproductive function (rats, 500–7000 ppm, inhalation).17 | |||
| M | No significant body weight changes and no changes in food consumption or uterine weights (rats, 100–1000 mg/kg-day, oral).51 | |||
| Decreased reaction to sound stimulus (rats, 2000 and 7000 ppm, inhalation).17,40 | ||||
| Reduced maternal weight gain (rats, 7000 ppm, inhalation).17,40 | ||||
| No maternal effects observed (rabbits, 500–7000 ppm, inhalation).17 | ||||
| Decane | 124-18-5 | N | – | No evidence of adverse outcomes, very limited amount of studies available.17,51 |
| 1,2-Dichloroethene (1,2-DCE) | 156-59-2 | N | BO | Resorption rates not statistically significant (rats, 6000 and 12000 ppm of trans-1,2-DCE, inhalation).18,39 |
| F | Reduced fetal mean weights due to reduced maternal food consumption rather than gestational exposure (rats, 12000 ppm of trans-1,2-DCE, inhalation).18 | |||
| FR | No lesions in mammary glands, clitoral glands, ovaries, uterus, seminal vesicles, prostate, testes or preputial glands (rats, 1900 mg/kg/day of cis-1,2-DCE, oral).18 | |||
| No histopathological lesions in reproductive organs (rats, trans-1,2-DCE).18 | ||||
| No organ weight changes or gross lesions in reproductive organs over the course of a 14-week exposure study (mice and rats, doses from 190–8065 mg/kg-day of trans-1,2-DCE, oral).40 | ||||
| M | Reduced maternal body weight (rats, 3134, 5778, and 6906 mg/kg-day of a 1,2-DCE isomer mixture, oral).40 | |||
| Dichloromethane (DCM) | 75-09-2 | 2 | BO | No adverse birth outcomes observed (rats, 1500 ppm for two generations, inhalation).18,40,52 |
| F | Abnormal ossification (mice and rats, 1250 ppm during gestation days 6–15, inhalation).40 | |||
| Decreased fetal body weight (rats, 4500 ppm, inhalation). | ||||
| N | No observed, statistically significant impacts on neonatal survival and some behavioral effects (rats, 4500 ppm, inhalation).40 | |||
| FR | No effects on male fertility index in 8 out of 9 studies (mice, 150 and 200 ppm, inhalation).40 | |||
| M | Increased percentage of hemoglobin in maternal blood indicating rupturing of red blood cells or CO poisoning (mice and rats, 1250 ppm, inhalation).40 | |||
| Diethyl ether | 60-29-7 | 2 | BO | Limited evidence that chronic exposure leads to spontaneous abortions, 18 out of 31 pregnancies ended in spontaneous abortion (human occupational exposure, anesthesiologists exposed to ethyl ether and other agents, 25 h a week, inhalation).53 |
| 96% of embryos died (chick embryos, 20 vol% of vaporized ethyl ether for 6 h for 3 days, in vivo).53 | ||||
| Increase in resorptions (mice, 65000–73000 ppm during organogenesis, inhalation).51 | ||||
| F | Decreased head growth and increased skeletal variations resulting (mice, 20 min increments during pregnancy).51 | |||
| N | No effects on cephalic diameter, body weight, or viability, no delay in cerebellar maturation of newborn pups (rats, 10 min increments during pregnancy, inhalation).51 | |||
| FR | No adverse effects have been observed on spermatozoa (mice, 49280 or 9856 mg/m3, inhalation).53 | |||
| Effects on male fertility including 30% reduction in adult, daily sperm production and germ cells in the testes (rats, neonatal exposure from soaked cotton pad, inhalation).51 | ||||
| Dimethoxymethane | 109-87-5 | N | BO | Increase in resorptions and postimplantation loss (rabbits, 300 and 1000 mg/kg-day, oral).17 |
| FR | No adverse effects observed in male and female reproductive organs (rats, 0–9652 ppm, inhalation).54 | |||
| M | Symptoms of narcosis and reduced body weight (rats, 10068 ppm, inhalation).54 | |||
| Greater weight loss and lower food consumption (rabbits, 1000 mg/kg-day, oral).17 | ||||
| Dimethyl carbonate (DMC) | 616-38-6 | N | BO | Increased resorptions (mice, 3000 ppm, inhalation).55 |
| F | Reduced fetal body weight (mice, 3000 ppm, inhalation).55 | |||
| Cleft palate and malformations of skull and bones (mice, 3000 ppm, inhalation).55 | ||||
| No adverse developmental effects observed (rats, 500 mg/kg, oral).17 | ||||
| M | Reduced maternal body weight (mice, 3000 ppm, inhalation).55 | |||
| No maternal or fetal toxic effects (rabbits, 100–1000 mg/kg, oral).17 | ||||
| Dimethyl ether | 115-10-6 | N | F | Decreased fetal body weight and increased skeletal variation (rats, 40000 ppm, inhalation).17 |
| Excess ossification in the lumbar area (rats, 5000 ppm, inhalation).17 | ||||
| FR | No effect on male or female reproductive organs (rats, 0.2–2.5%, inhalation).17 | |||
| M | Reduced maternal weight gain and loss of hearing (rats, 40000 ppm, inhalation).17 | |||
| Dimethyl sulfoxide (DMSO) | 67-68-5 | N | F | Percentage of embryonic abnormalities increased with increased dose (88% of embryos were abnormal with a 4% concentration) (mice, 0.04%-4%, dermal).56 |
| Decreases in fetal body weight (rats, 5000 mg/kg-day, oral).17,56 | ||||
| Delayed ossification of the ribs (rats, 5000 mg/kg-day, oral).17,56 | ||||
| No teratogenic effects observed (rabbits, 5 g/kg of 50% DMSO, oral).17,56 | ||||
| M | Reduced weight gain and food consumption (rats, 5000 mg/kg-day, oral).17,56 | |||
| Dimethylformamide (DMF) | 68-12-2 | 1B | BO | Increased rate of spontaneous abortions (human occupational exposure, DMF mixed with other chemicals, inhalation).41 |
| Reduced implantation efficiency (rats, 32 ppm, inhalation).41 | ||||
| Spontaneous abortions in 12 out of 12 dams (rats, 500 mg/m3, inhalation).41 | ||||
| Reduced number of viable fetuses produced by exposed males and unexposed females (rats, 30 ppm, inhalation).49 | ||||
| F | Significantly reduced fetal weight (rats, 172 ppm, inhalation) | |||
| Fetotoxic effects at maternally toxic concentrations (rats, 100 mg/kg, gastrostomy feeding tube).49 | ||||
| Reduced fetal weight and increased malformations of live fetuses (rabbits, 188.9 mg/kg/day, oral).41 | ||||
| Fetal malformations (rabbits, 450 ppm, inhalation).49 | ||||
| N | Reduced live pup weight in second generation (mice, 1000–7000 mg/L, oral via drinking water).49 | |||
| FR | No effects on semen volume, sperm motility, count, and morphology (monkeys, 500 ppm, inhalation).49 | |||
| Reduced fertility and fecundity (mice, 4000 and 7000 mg/L, oral).49 | ||||
| No effects on sperm density, motility, or sperm count (mice and rats, < 800 ppm, inhalation).49 | ||||
| M | Maternal weight gain (rats, 300 ppm, inhalation).49 | |||
| 1,4-Dioxane | 123-91-1 | N | BO | Spontaneous abortions, premature births, and low birth weights (human occupational exposure, 1,4-dioxane mixed with other chemicals, inhalation).18 |
| F | One study observed reduced fetal weight and reduced sternum ossification (rats, 258–1033 mg, oral).18 | |||
| FR | No adverse effects observed in primary and secondary reproductive organs (rats, 3200 ppm for 13 weeks, 111 ppm for 2 years, and 1250 ppm for 2 years, inhalation).18 | |||
| No histological alterations in reproductive organs (mice and rats, 1614 and 2699 mg/kg-day for 13 weeks, 429 and 964 for 2 years, 1599 for 2 years, oral).18 | ||||
| Diphenyl ether | 101-84-8 | N | – | No studies on reproductive or developmental toxicity via pure diphenyl ether.51 Instead, Therminol VP-1, a heat transfer fluid that is a mixture of diphenyl ether and biphenyl, can be used as a reproductive and developmental toxicity indicator.51 |
| F | No observed malformations resulting from gestational exposure (rats, 50–500 mg/kg-day, Therminol VP-1, oral).17 | |||
| M | Reduced mean weight gain, alopecia, and fur staining (rats, 200 and 500 mg/kg-day, Therminol VP-1, oral).17 | |||
| Maternal fatality rate of 8.3% (rats, 500 mg/kg-day, Therminol VP-1, oral).17 | ||||
| Ethanethiol | 75-08-1 | N | F | No studies available on reproductive or developmental effects.18,57 Limited studies show evidence of adverse fetal effects of 2-methylpropane-2-thiol and butane-1-thiol, which can be used as reproductive and developmental toxicity indicators.17 |
| Ethanol | 64-17-5 | 2 | BO | Increased risk of spontaneous abortion (up to 5 times more likely) with consumption of 5+ alcoholic drinks per week (human study of 330 women in Denmark that had experienced spontaneous abortions, oral).58 |
| Increase in spontaneous abortion (monkeys, ≥1.8 g/kg, oral).59 | ||||
| Increased resorption of litters and fetal death (mice, 5 g/kg-day, oral; mice, 30% calories derived from ethanol, oral).17,60 | ||||
| No effect on pregnancy outcomes (rats, 16000 ppm, inhalation).61 | ||||
| Increased resorptions (rabbits, 15%, oral).62 | ||||
| F | The United States Surgeon General states, “No amount of alcohol consumption can be considered safe during pregnancy. Alcohol consumption during pregnancy increases the risks of fetal birth defects, growth deficiencies, facial abnormalities, and the impairment of the fetal nervous system”.63 | |||
| No incidences of external, visceral, or skeletal malformations (rats, 10000–20000 ppm, inhalation).59 | ||||
| Increased fetal malformations such as skeletal, neurological, urogenital, and cardiovascular anomalies (mice, 30% calories derived from ethanol, oral).60 | ||||
| Reduced fetal body weights (rats, 16000–20000 ppm, inhalation).60 | ||||
| N | Reduced birth weight (human study of 8448 pregnancies with continuous interviews to track alcohol consumption, > 120g/week, oral).59 | |||
| Cognitive issues and behavior problems in children (human meta-analysis of over 10000 children whose mothers drank alcohol moderately or binged, oral).63 | ||||
| Decreased mental development at 8 months postnatal (human, 60 g/day, oral).59 | ||||
| Facial dysmorphology and behavioral abnormalities (monkeys, ≥1.8 g/kg, oral).59 | ||||
| No significant effects on pup growth or survival (mice, 2.2–7.8 g/kg-day, oral).60 | ||||
| Reduced live pup weight (mice, 5–15%, oral).17 | ||||
| No effects on postnatal neuromotor coordination, activity levels, and learning ability (rats, 16000 ppm, inhalation).59 | ||||
| FR | Reduced sperm motility (mice, 16 g/kg-day, oral; mice, 5–15%, oral).17,60 | |||
| M | Maternal lethality (mice, 3600–7800 mg/kg-day, oral).17 | |||
| Severe maternal effects such as narcosis and decreased food consumption at high doses (rats, 20000 ppm, inhalation).60 | ||||
| Reduced liquid intake and maternal body weight (rabbits, 15%, oral).17 | ||||
| Ethyl acetate | 141-78-6 | N | – | No studies on developmental toxicity available and few studies on reproductive toxicity.51,61 The rapid hydrolysis of ethyl acetate to ethanol and acetic acid enables using those as developmental toxicity indicators.17 |
| FR | No effects on sperm counts, motility, or sperm concentration (rats, 350–6000 ppm chronic exposure to ethyl acetate, inhalation).17 | |||
| Adverse effects on plasma testosterone levels and sperm counts (rats, 16000 ppm for 5 min twice a day to ethyl acetate, inhalation).17 | ||||
| Ethylene glycol | 107-21-1 | 2 | BO | No observed effects on number of implantations, resorption sites, and fetal viability (mice, 750–3000 mg/kg-day, oral).49 |
| Reduction in live implantations observed (mice, 250–2500 mg/kg-day, oral).49 | ||||
| No effects observed on resorption frequency or preimplantation loss (rats, 1000 mg/kg-day, oral).49 | ||||
| F | Skeletal variations (mice, 2505 mg/m3, inhalation).49 | |||
| Decreased pup body weight (mice, ≥840 mg/kg-day, oral).49 | ||||
| Poorly ossified skull bone and unossified intermedia phalanges of the hindlimb (mice, 3500 mg/kg, dermal).49 | ||||
| Poorly ossified and unossified vertebral centra (rats, 1000 mg/kg-day, oral).41,49 | ||||
| Reduced fetal body weight, reduced skeletal ossification, malformations in skeleton (rats, > 1,000 mg/kg-day, oral).49 | ||||
| Skeletal, external, and visceral malformations (rats, 2500 mg/kg, oral).49 | ||||
| No observed developmental effects (rabbits, 100–2000 mg/kg-day, oral). | ||||
| More studies available.18 | ||||
| FR | No observed adverse effects on reproductive organs (mice, 250–2500 mg/kg-day, oral).49 | |||
| M | No evidence of maternal toxicity (rats, 1000 mg/kg-day).49 | |||
| Increase in kidney weight, indicating maternal toxicity, along with reduced food consumption and maternal body weight (rats, 2500 mg/kg-day, oral).49 | ||||
| Maternal mortality and degenerative changes in the kidney (rabbits, 2000 mg/kg-day, oral).49 | ||||
| Heptane | 142-82-5 | N | – | No studies regarding reproductive or developmental toxicity are available.17,51 |
| The European Chemicals Agency notes that hexane may be used as an indicator for the reproductive toxicity potential of heptane as it is structurally similar.17 | ||||
| Hexane | 110-54-3 | 2 | BO | Increased spontaneous abortions and increased resorptions (mice, rats, 200–5000 ppm, inhalation).18 |
| No effects on implantations or resorptions per litter (rats, 200–5000 ppm, inhalation).18 | ||||
| F | Reduced fetal weight, more extreme in males (mice, 200–5000 ppm, inhalation).18 | |||
| Adverse effects on ossification (mice, 9017 ppm, inhalation).18 | ||||
| At levels of maternal toxicity, fetal weight was reduced but no malformations occurred (mice, 7920 and 9900 mg/kg-day, oral).18 | ||||
| No significant adverse developmental effects including no observed differences in fetal body weight and malformation incidents (rats, 200–9017 ppm, inhalation).17,18 | ||||
| N | Reduced body weight in pups and delayed histogenesis of cerebellar cortex (rats, 500 ppm, inhalation).18 | |||
| FR | No changes in sperm morphology (mice, 5000 ppm, up to 5 days, inhalation).18 | |||
| No reproductive lesions and no adverse effects observed (mice, 1000 and 10000 ppm for 13 weeks, inhalation).18 | ||||
| Testicular damage and degeneration of male fertility indicators with adverse effects worsening with longer exposure time (rats, 5000 ppm, inhalation; rats, 5000 ppm up to 6 weeks, inhalation; rats, 1000 ppm for 28 or 61 days, inhalation).18,41 | ||||
| No reproductive effects (rats, 500 ppm for 6 months, inhalation).18 | ||||
| Reduced body and prostate weight in males (rats, 2000–1000 mg/kg-day oral).18 | ||||
| M | Decrease in maternal body weight and pregnant uterine weight (mice, 5000 ppm, inhalation).18 | |||
| Maternal fatalities in 5 out of 33 dams (mice, 9900 mg/kg-day, oral).18 | ||||
| No maternal fatalities, reduced weight gain at 5000 ppm (rats, 200–5000 ppm, inhalation).18 | ||||
| Reduced weight gain during exposure period (rats, 3025 and 9017 ppm, inhalation).17,18 | ||||
| Isobutanol | 78-83-1 | N | – | No studies available on reproductive or developmental toxicity. As an isomer of isobutanol, n-butanol can be used for reproductive and developmental toxicity indicators.64 |
| Isopropyl Acetate | 108-21-4 | N | – | No studies available on reproductive or developmental toxicity. The rapid hydrolysis of isopropyl acetate to isopropanol and acetic acid enables using those as reproductive and developmental toxicity indicators.17 |
| Isopropyl alcohol (IPA, isopropanol) | 67-63-0 | 2 | BO | Failure of implantation and increased resorption (rats, 7000 and 10000 ppm, inhalation).17 |
| No spontaneous abortions, implantation loss, resorption, or variable pregnancy duration (rabbits, 120–480 mg/kg-day, oral).17 | ||||
| F | No external, skeletal, or visceral malformations, gestational exposure (rabbits, 120–480 mg/kg-day, oral).17 | |||
| Reduced fetal body weight (rats, 7000 and 10000 ppm, inhalation; rats, 800 and 1200 mg/kg-day, oral; rats, 1242 and 1605 mg/kg-day, oral).17 | ||||
| Abnormal skeletal variations (rats, 1242 and 1605 mg/kg-day, oral).17 | ||||
| N | Evidence of increased pup mortality (rats, 1000 mg/kg-day, oral).17 | |||
| High number of offspring deaths in second generation after parental exposure, possibly due to underdeveloped metabolism in young (rats, 1000 mg/kg-day isopropanol, oral).17 | ||||
| FR | No reproductive toxicity (rats, < 1000 mg/kg, oral).17 | |||
| M | Parental toxicity indicated by body, liver and kidney weight effects (rats, 1000 mg/kg-day, oral).17 | |||
| Reduced food and water intake, reduced body weight gain, increase in organ weights (rats, 0.5–2.0%, oral).17 | ||||
| Small increase in maternal mortality and reduced weight gain (rats, 400–1200 mg/kg-day, oral).17 | ||||
| Narcotic effects, reduced body weight gain, and reduced food intake (rats, 7000 and 10000 ppm, inhalation).17 | ||||
| Reduced weight gain, clinical signs of intoxication, mortality at highest dose (rabbits, 120–480 mg/kg-day, oral).17 | ||||
| Lactonitrile | 78-97-7 | 2 | BO | No adverse effects on fetal viability or survival (rats, 1.2–30 mg/kg, oral).17,51 |
| F | No effects on fetal body weight and no abnormalities (rats, 1.2–30 mg/kg, oral).17,51 | |||
| FR | No effects on mating, fertility, and estrus cycle but some mating behavioral alterations observed at high doses (rats, 1.2–30 mg/kg, oral).17,51 | |||
| Mesitylene (1,3,5-trimethylbenzene) | 108-67-8 | N | – | Limited information (one study) for isolated mesitylene. The C9 distillation fraction from petroleum processing contains mesitylene and other trimethylbenzene isomers (TMBs in C9 fraction) which can be used as reproductive and developmental toxicity indicators. (40) |
| BO | Increase in fetal death, postimplantation loss (mice, 4059 mg/m3 TMBs in C9 fraction, inhalation).40 | |||
| Decreased live births and decreased litter sizes in second generation (rats, 271–4059 mg/m3 TMBs in C9 fraction, inhalation).40 | ||||
| F | No adverse effects on fetal viability, skeletal, visceral, or external morphology (rats, 5904 mg/m3, inhalation).40 | |||
| Decreased fetal body weight (rats, 492–5904 mg/m3, inhalation).40 | ||||
| Cleft palate and unossified sternebrae and reduced fetal body weights (mice, 1353–4059 mg/m3 TMBs in C9 fraction, inhalation).40 | ||||
| Decreases in postnatal body weights occurred at lower doses each generation (rats, 271–4059 mg/m3 TMBs in C9 fraction, inhalation).40 | ||||
| N | Decreased pup survival (rats, 4059 mg/m3 TMBs in C9 fraction,, inhalation).40 | |||
| FR | No lesions in reproductive organs and no alteration in fertility (rats, 271–4059 mg/m3 TMBs in C9 fraction, inhalation).40 | |||
| Decreased male fertility in second generation (rats, 271–4059 mg/m3 TMBs in C9 fraction, inhalation).40 | ||||
| M | Decreased maternal body weight gain (rats, 492–5904 mg/m3, inhalation).40 | |||
| Reduced body weight gain and decreased food consumption (rats, ≥1476 mg/m3 and 2952 mg/m3, inhalation).40 | ||||
| Maternal fatality of 44% of dams and decreased body weight gain (mice, 4059 mg/m3 TMBs in C9 fraction, inhalation).40 | ||||
| Methanol | 67-56-1 | 2 | BO | Decrease in number of live pups at lower dose and increase in fully resorbed litters at higher dose (mice, ≥7500 ppm and ≥10000 ppm, inhalation).65 |
| Increased late resorptions and reduced live fetuses (rats, 5000 ppm, inhalation).65 | ||||
| F | No observed developmental effects (human case study, a pregnant woman ingested 250–500 mL in 38th week of pregnancy).65 | |||
| Skeletal and visceral malformations (mice, 2000 ppm, inhalation). (65) | ||||
| Reduced fetal body weights, delayed ossification, skeletal anomalies, and cleft palate exencephaly (mice, 5000–15000 ppm, inhalation).65 | ||||
| Reduction in fetal weight (rats, 10000 and 20000 ppm, inhalation).65 | ||||
| Skeletal or visceral malformations (rats, 20000 ppm, inhalation).65 | ||||
| N | Decreased organ weight (rats, 5000 ppm, inhalation).65 | |||
| Additional studies on postnatal development are available.65 | ||||
| FR | No effects on menstrual cycles or conception (primates, 200–1800 ppm).65,66 | |||
| No adverse reproductive effects (rats, 800 ppm, inhalation).65 | ||||
| M | Reduced body weight and reduced food and water intake (rats, 5000 ppm, inhalation).65 | |||
| 2-Methoxyethanol | 109-86-4 | 1B | BO | Spontaneous abortion in 8 out of 8 pregnancies (macaques, 36 mg/kg-day, oral).51 |
| Decreases in live pups, pup viability, and pup body weights (rats, 0.03% by volume, orally in drinking water).51 | ||||
| Significant number of fetuses resorbed (rats, 0.006–0.5% volume, oral).51 | ||||
| All fetuses resorbed (rats, 30–300 ppm, inhalation).51 | ||||
| No live pups born (mice, 1000 mg/kg-day, oral).51 | ||||
| F | Organ malformations and dysmorphogensis (mice, 125–250 mg/kg-day, gestational).51 | |||
| Reduced fetal body weights (rats, 16–620 mg/kg-day, diet).51 | ||||
| Cardiovascular malformations (rats, 50 mg/kg-day, oral).51 | ||||
| Limb-bud dysmorphogensis (rats, 50–250 mg/kg-day, oral).51 | ||||
| Reduced fetal body weight, cardiac malformations, skeletal malformations (rats, 50–100 ppm, inhalation).51 | ||||
| Delayed ossification of vertebral centra and lumbar spurs (rats, 50 ppm, gestational inhalation).51 | ||||
| Shortened or missing digits and other malformations (rabbits, 50 ppm, inhalation).51 | ||||
| N | Limited neonatal data due to high embryo lethality.51 | |||
| FR | Reduction in testes weights and the degeneration of sperm (rats, 500 and ≥100 mg/kg-day respectively, oral).51 | |||
| Decreased sperm concentrations, sperm motility, increased abnormal sperm (rats, 0.1% concentration in drinking water, oral).51 | ||||
| Decreased testicular size and atrophy of the seminiferous tubules (rats, 300 ppm, inhalation).51 | ||||
| M | Anorexia and maternal body-weight loss, severe loss of appetite (macaques, 12–36 mg/kg-day, oral).51 | |||
| Methyl acetate | 79-20-9 | N | – | No studies on reproductive or developmental toxicity available.51,67 The rapid hydrolysis of methyl acetate to methanol and acetic acid enables using those as reproductive and developmental toxicity indicators.17 |
| Methyl tert-butyl ether (TBME, MTBE) | 1634-04-04 | N | BO | Increased number of nonviable implantations and late resorptions (mice, 8000 ppm, inhalation).18 |
| Decrease number of viable implantations and increase in late resorptions (mice, 8000 ppm, inhalation).41 | ||||
| No effects on the number of uterine implantations, resorption, or live fetuses (mice and rats, ≤ 2500 ppm, inhalation).18 | ||||
| No effects on resorption percentage or fetal viability (rats, ≤ 2500 ppm, inhalation).18 | ||||
| No effects on early or late resorption or stillbirths (rabbits, ≤ 8000 ppm, inhalation).18 | ||||
| F | Skeletal malformations (mice, 8000 ppm, inhalation).41 | |||
| No effects on crown-rump distances, external malformations, or soft-tissue malformations (mice, 250–2500 ppm, inhalation).18 | ||||
| Slight increase in fused sternebrae (mice, 250–2500 ppm, inhalation).18 | ||||
| Reduced skeletal ossification and reduced body weight (mice, 4000 ppm, inhalation). | ||||
| Reduced fetal body weight, increase in cleft palate and skeletal malformations, reduction in partial fetal atelectasis(mice, 8000 ppm, inhalation).18 | ||||
| N | Reduced pup viability and reduced pup body weight gain (rats, 1240 ppm and 2980 ppm, inhalation).41 | |||
| Reduced body weight (rats, 3000 ppm and 8000 ppm, inhalation).41 | ||||
| FR | No gross lesions in the reproductive organs, no changes in testicular weight (mice and rabbits, ≤ 8000 ppm, inhalation).18 | |||
| No histological changes in the reproductive system (rats, ≤ 3000 ppm, inhalation).18 | ||||
| No structural effects on reproductive systems or performance (rats, 250–2500 ppm, inhalation).18 | ||||
| No treatment-related lesions (rats, 400–8000, inhalation).18 | ||||
| No effects on testicular or ovarian weights, no evidence of lesions (rats, 357–1428 mg/kg-day, oral).18 | ||||
| No effects on germ cell frequency in testes and ovaries (rats, ≤ 1000 mg/kg-day, oral).18 | ||||
| No lesions of the prostate, uterus, gonads but slight increase in testicular tumors in high-dose males (rats, 250 or 1000 mg/kg-day, 104 week exposure, oral). (18) | ||||
| M | Reduced body weight gain, reduced food consumption, and clinical signs of central nervous system depression (mice, 8000 ppm, inhalation).18 | |||
| Decrease in uterine weights (mice and rabbits, ≤ 8000 ppm, inhalation).18 | ||||
| 2-Methyltetrahydrofuran (2-MeTHF) | 96-47-9 | N | BO | Insufficient studies available on reproductive and developmental toxicity.64,68 |
| Acute embryo toxicity (zebrafish, 2980 mg/L, in vivo).68 | ||||
| N-Methyl-2-pyrrolidone (NMP) | 872-50-4 | 1B | BO | Preimplantation loss (rats, 0.68 mg/L, inhalation).69 |
| Increased resorptions (rats, ≥750 mg/kg, dermal).69 | ||||
| Large number of resorptions including 24 out of 29 dams showed complete resorption (rats, 997 mg/kg-day, oral).70 | ||||
| F | Decreased fetal body weight (rats, 0.478 mg/L, inhalation).69 | |||
| Delayed ossification (rats, 0.68 mg/L, inhalation).69 | ||||
| Decreased body weight, incomplete closing of the skull, reduced or incomplete hyoid bone, and incomplete ossification of vertebrae (rats, ≥750 mg/kg, dermal).69 | ||||
| Decreased fetal weight and increase in fetal stunted growth (rats, 400 mg/kg, oral).69 | ||||
| No teratogenicity during postimplantation phase (rats, 124–494 mg/m3, inhalation).70 | ||||
| N | Decrease in pup survival (rats, 500 mg/kg-day, oral).70 | |||
| Decrease in pups surviving lactation and low body weights in second generation offspring (rats, mg/kg-day, oral).70 | ||||
| Neurobehavioral effects in pups including latency, impairment in operant behavior with delayed spatial alteration (rats, 0.622 mg/L, inhalation).69 | ||||
| FR | Testicular effects observed (rats, 2060 mg/kg-day or 3 mg/L for 13 weeks, oral and inhalation).69 | |||
| No testicular effects (rats, 0.618 mg/L for 90 days, inhalation; rats, 0.04–0.478 mg/L, inhalation).69 | ||||
| Significant decreases in the male fertility index and female fecundity index (rats, 50–500 mg/kg-day, oral).70 | ||||
| M | Depressed body weight gain (rats, 400 mg/kg, oral).70 | |||
| Reduced maternal body and placental weights (rats, 997 mg/kg-day, oral).70 | ||||
| Prolonged clotting time and increased liver weight (rabbits, 1000 and 2000 mg/m3, inhalation).70 | ||||
| Decreased food intake and weight gain (rabbits, 175 and 540 mg/kg-day, oral).70 | ||||
| Xylenes | 1330-20-7 | 2 | – | Xylene is often present as a mix of isomers (mixed xylenes) including m-xylene, o-xylene, and p-xylene. |
| BO | Increase in spontaneous abortions in early pregnancy (human occupational exposure of 37 women exposed to xylenes and formalin in pathology and histology laboratories).18 | |||
| Increased resorptions (rats, 775 ppm, mixed xylenes, inhalation).18 | ||||
| Postimplantation loss (rats, 4500 mg o-xylene, inhalation).18 | ||||
| F | Skeletal variations, delayed ossification, organ hemorrhages, decreased fetal weight (mice, rats, and rabbits, mixed xylenes, inhalation).18 | |||
| Increased incidences of cleft palate and decreased fetal body weight (mice, 2060 mg/kg/day mixed xylenes, oral).18 | ||||
| Decreased fetal weight gain (rats, 3000 mg/m3, m-xylene, inhalation).18 | ||||
| Significant increase in delayed ossification, skeletal variation (rats, 2000 ppm m-xylene, inhalation).18 | ||||
| Decreased fetal weight, skeletal retardation via gestational exposure (rats, 4500 mg o-xylene, inhalation).18 | ||||
| Significant reduction in fetal body weight, gestational exposure (rats, 500 ppm o-xylene, inhalation).18 | ||||
| Skeletal variations, incomplete ossification (rats, 2000 ppm o-xylene, inhalation).18 | ||||
| significant increase in delayed ossification, skeletal variation (rats, 2000 ppm p-xylene, inhalation).18 | ||||
| N | Decreased neuromuscular coordination (rats, 200 ppm mixed xylenes, inhalation).18 | |||
| Reductions in absolute brain weight and neurobehavioral effects (rats, 500 ppm mixed xylenes, inhalation).18 | ||||
| FR | No adverse effects on the prostate, testes, ovaries, uterus, or mammary glands (mice, 2000 mg/kg mixed xylenes, oral; rats, 1000 mg/kg mixed xylenes, oral).18 | |||
| No adverse reproductive effects after chronic exposure (mice, 1000 mg/kg mixed xylenes, oral; rats, 5000 mg/kg mixed xylenes, oral).18 | ||||
| No adverse effects (rats, >500 ppm mixed xylenes, inhalation).18 | ||||
| Reduced fertility (rats, 775 ppm mixed xylenes, inhalation).18 | ||||
| No alterations in testes, glands, or male hormone levels (rats, 1000 ppm mixed xylenes, inhalation).18 | ||||
| No effects on testicular weights (rats, 100 ppm m-xylene, inhalation).18 | ||||
| M | 31.5% mortality in dams (rats, 3100 mg/kg/day mixed xylenes, oral).18 | |||
| Maternal growth inhibition and maternal mortality (rats, 3000 mg/m3m-xylene, inhalation).18 | ||||
| Decreased weight gain (rats, 3500–7000 mg/m3p-xylene, inhalation).18 | ||||
| Pentane | 109-66-0 | 2 | – | No studies on reproductive or developmental toxicity available.17 According to the European Chemicals Agency, cyclohexane is oxidized to cyclohexanol, whose excretion and conjugation is identical to n-pentane so studies on cyclohexane can be used as reproductive and developmental toxicity indicators.17 |
| Phenol | 108-95-2 | N | – | No adverse reproductive, developmental, or fertility effects seen in either human or animal studies of sufficient quality as determined by the Agency for Toxic Substances and Disease Registry, except at doses toxic to the mother.18 |
| No significant increase in the rate of miscarriage was found in a group of 576 women exposed to organic solvents relative to 576 unexposed pregnancies. Specific mention of phenol was reported in only five cases, all of which were normal deliveries (human occupational exposure in university laboratory, inhalation). | ||||
| 1-Propanol | 71-23-8 | N | F | Insufficient studies to establish teratogenicity. |
| Reduced fetal body weight (rats, 7000–10000 ppm for 7 h per day, inhalation).71 | ||||
| N | Biochemical changes in the brain (neonatal rats, oral).71 | |||
| FR | Impaired male reproductive performance (rats, 15220 mg/m3, inhalation).71 | |||
| Decrease in absolute weight of testes (rats, 100 ppm for 6 h a day for 5 days a week for 4 weeks, inhalation).72 | ||||
| Propylene glycol | 57-55-6 | N | BO | No effects on the number of resorptions, still births, or preimplantation losses (mice, 0.5–10.0 mL/kg-day, oral).73 |
| No effect on fetal survival (hamsters, 1550 mg/kg, oral; mice and rats, 1600 mg/kg, oral; rabbits, 1230 mg/kg, oral).73 | ||||
| F | No significant change in number of abnormalities (hamsters, 1,550 mg/kg, oral; mice and rats, 1,600 mg/kg, oral; rabbits, 1,230 mg/kg, oral).73 | |||
| No effect on pup survival or body weight gain in pups (mice, 1–5%, oral).73 | ||||
| No significant differences in malformation or fetal body weight (mice, 0.5–10.0 mL/kg-day, oral).73 | ||||
| Further animal studies and in vitro studies are available.51,73 | ||||
| FR | No effects on number of litters, live pups, gestational period, and maternal weight at delivery (mice, 1–5% weight per volume, oral in drinking water).73 | |||
| No significant changes in male sex organs or sperm motility and count or female estrual cycle (mice, 1–5% weight per volume, oral in drinking water).73 | ||||
| M | No effects on body weight, gravid uterine weight, and absolute liver and kidney weights (mice, 0.5–10.0 mL/kg-day, oral).73 | |||
| Pyridine | 110-86-1 | N | F | No human studies or quality animal studies (as determined by the Agency for Toxic Substances and Disease Registry) available on reproductive effects of pyridine.18 |
| Very limited evidence of malformations and abnormal development at high doses (chicks, 10–20 mg pyridine/egg, injection).18 | ||||
| FR | Limited evidence of adverse effects on male and female fertility that is dose dependent (mice, male effects at 250, 500, and 1000 ppm, no female effects, oral in drinking water; rats, male and female effects at 1000 ppm, no effect at 0, 250, or 500 ppm, oral in drinking water).74 | |||
| Styrene | 100-42-5 | 2 | BO | Increase incidence of spontaneous abortions (human occupational exposure, pregnant Finnish chemical workers employed in styrene production; human occupational exposure, polystyrene plastics processing).18 |
| No increased risk of spontaneous abortions (human occupational exposure, processing polymerized plastics or heated plastics made of styrene).18 | ||||
| No increase in stillbirths or fetal viability (human occupational exposure, case-control studies of pregnant plastics workers in Sweden and Norway).18 | ||||
| Significant increase in stillbirths and resorbed fetuses (hamsters, 1000 ppm, inhalation).18 | ||||
| No significant changes in fetal viability or resorption numbers (mice, 250 ppm, inhalation).18 | ||||
| F | No fetal malformation or low birth weights (human occupational exposure, case-control studies of pregnant plastics workers in Sweden and Norway).18 | |||
| No significant increase in congenital malformations (human occupational exposure, pregnant reinforced plastics workers).18 | ||||
| No significant developmental effects observed (rats, 300 and 600 ppm, inhalation; rats, 300 mg/kg, oral; rabbits, 600 ppm, inhalation).18 | ||||
| N | Increase in neonatal deaths in offspring (rats, 300 ppm, inhalation).18 | |||
| Delays in righting reflex and incisor eruption (rats, second generation offspring, 500 ppm, inhalation).18 | ||||
| FR | No menstrual disturbances or significant fertility effects (human occupational exposure, pregnant reinforced plastics workers, direct exposure of 52 ppm, indirect exposure of 13 ppm, inhalation).18 | |||
| Significant decrease in sperm concentration, sperm count, normal sperm, and nonvital sperm in 23 male workers but no significant alterations in female workers’ fertility (human occupation exposure, 6 months of working at a styrene manufacturing facility).18 | ||||
| No significant changes in frequency of abnormal sperm heads (mice, 300 ppm, inhalation).18 | ||||
| No alteration in reproductive performance, estrous cycle, spermatogenic parameters (rats, 500 ppm, inhalation).18 | ||||
| Degeneration of seminiferous tubules and decreased spermatozoa and decrease in markers of testicular function (rats, 400 mg/kg, oral).18 | ||||
| tert-Butanol | 75-65-0 | N | BO | Increased in stillborn pups (mice, 1% of calories consumed, diet).75 |
| Increase in resorptions and stillborn pups (mice, 1556 mg/kg-day, oral).76 | ||||
| Increase in stillborn pups (rats, 1000 mg/kg-day, oral).76 | ||||
| F | Depressed fetal weight skeletal variations (rats, 2000–5000 ppm, inhalation).75 | |||
| N | Decline in pup survival and male pup weight (rats, 1000 mg/kg-day, oral).76 | |||
| FR | No reduction in fertilizing capacity of spermatozoa (mice, 1000–4000 mg/L).77 | |||
| Increased estrous cycle length (mice, 11620 mg/kg-day, oral).76 | ||||
| Slight decrease in sperm motility (rats, 1000 mg/kg-day, oral).76 | ||||
| No adverse effects on reproductive performance or sperm parameters (rats, 100–1600 ppm, inhalation).76 | ||||
| M | Depressed maternal weight gain and food consumption (rats, 5000 ppm, inhalation).75 | |||
| Reduced weight gain and consumption (mice, 1% of calories, diet).75 | ||||
| Severe signs of neurotoxicity and decreased consumption and body weight gain (rats, 1000 mg/kg-day, oral).76 | ||||
| Tetrahydrofuran (THF) | 109-99-9 | 2 | BO | No effect on implantations but reduced percentage of live fetuses (mice, 600–5000 ppm, inhalation).17 |
| No effect on the number of live fetuses per litter (rats, 600–5000 ppm, inhalation).17 | ||||
| F | No effect on fetal weight (mice, 1800 and 5000 ppm, inhalation).17 | |||
| Low incidences of cleft palate, edema, ectopic ovaries, undescended testes, increased incidence of reduced ossifications (mice, 1800 ppm, inhalation).17 | ||||
| Reduced body weight in first generation and second generation pups and delayed auditory canal opening and eye opening in second generation pups (rats, 1000–9000 ppm, oral).17,40 | ||||
| Reduced fetal body weight at highest dose and no significant fetal malformations (rats, 600–5000 ppm, inhalation).17 | ||||
| Reduced body weights and reduced ossification (rats, 5000 ppm, inhalation).17 | ||||
| FR | No adverse effects in reproductive function (rats, 4000–12000 ppm, oral).17 | |||
| M | Reduced body weight and increased lethargy during gestation and lactation (rats, 1000–9000 ppm, oral).17 | |||
| Toluene | 108-88-3 | 2 | BO | Increased risk of spontaneous abortion and preterm birth (human occupational exposure meta-analysis, mixed solvents including toluene, inhalation).18,78 |
| F | Increased risk of malformations (human occupational exposure meta-analysis, mixed solvents including toluene, inhalation).18,78 | |||
| Limited evidence of increased central nervous system anomalies and neural tube closure defects (human occupational exposure meta-analysis, small study of 14 women, mixed solvents including toluene, inhalation).18 | ||||
| Malformations including microcephaly, central nervous system dysfunction, growth deficiency, craniofacial and limb abnormalities, and reversible renal tubular acidosis (human, toluene abuse study, inhalation).18 | ||||
| N | Inconclusive evidence of neurobehavioral deficits at high doses—no effects at 200 or 400 ppm, adverse effects at 2000 ppm (mice, 200–2000 ppm for 60 min exposures 3 times a day during gestational days 12–17, inhalation), and no effects (rats, same exposure as mice).18 | |||
| FR | Inconclusive studies on male and female fertility effects, some showing effects, others no effects (rats, ≤ 2000 ppm, inhalation).18 | |||
| Triethylamine | 121-44-8 | N | BO | Early embryonal deaths (chicken embryos, 1.0–4.0 μmol, injection).17 |
| F | Insufficient studies on the teratogenic effects of triethylamine.41,79 | |||
| Fetal malformations (chicken embryos, 0.5–4.0 μmol, injection).17 | ||||
| FR | Insufficient studies on the reproductive effects of triethylamine.41,79 | |||
| No adverse reproductive effects observed (rats, 25–247 ppm, inhalation).17 | ||||
| Disruption of ova development into normal blastocysts (rabbits, 10–20 mg/kg, oral).79 | ||||
| Trifluoroacetic acid (TFA) | 76-05-1 | N | BO | Note: Studies have been carried with structurally similar salts (sodium trifluoroacetate, potassium trifluoroacetate (TFAK) and potassium trifluoromethanesulphinate (TFSK)) to prevent corrosive effects resulting from TFA.17 |
| Slightly low live birth index—the ratio of surviging number of offspirng after one day over total number of offspring—(rats, 8400 ppm of sodium trifluoroacetate, oral). | ||||
| F | No teratogenic effects (rats, 1400 ppm and 3400 ppm of sodium trifluoroacetate, oral).17 | |||
| No adverse effects on litters (rats, 100–1000 mg/kg-day TFAK and TFSK, oral).17 | ||||
| No observed fetal abnormalities or variations and no effects on fetal body weight or ossification parameters (rats, 150 mg/kg-day TFA during organogenesis, oral).17 | ||||
| Note: an extended, one-generation study on rats is ongoing, will be finalized October 2021.17 | ||||
| N | Low body weight gain after birth (rats, 3400 ppm and 8400 ppm sodium trifluoroacetate, oral).17 | |||
| FR | No adverse effects on reproductive performance or reproductive organs (rats, 100–1000 mg/kg-day TFAK/TFSK, oral).17 | |||
| M | Low food consumption and body weight gain (rats, 8400 ppm gestation of sodium trifluoroacetate, oral).17 | |||
| No observed effects on consumption, body weight gain, placental weight, or uterine weight (rats, 150 mg/kg-day TFA, oral).17 | ||||
| Undecane | 1120-21-4 | N | BO | No effects on number of live pups delivered (rats, 300 and 1000 mg/kg, oral).17 |
| FR | No effects on female sex cycle, conception, reproductive organ weights (rats, 300 and 1000 mg/kg, oral).17 | |||
| No adverse reproductive effects (rats, 25–1000 mg/kg-day, oral).17 | ||||
| No adverse reproductive effects (rats, 100–1000 mg/kg).17 | ||||
| M | Body weight increase during lactation period (rats, 1000 mg/kg, oral).17 | |||
a
Exposures described in adverse effects are maternal exposures unless otherwise noted. GHS classifications: 1A: Known human reproductive toxicant (based on human studies); 1B: Presumed human reproductive toxicant (based on mostly animal studies); 2: Suspected human reproductive toxicant (limited evidence in either human or animal studies); along with N: Not a GHS listed reproductive hazard (not enough information for classification). Adverse effects: BO: Birth outcome; F: Fetal effects; N: Neonatal and beyond effects; FR: Fertility effect; M: Maternal effects.