4-Tert-octylphenol

H315: Causes skin irritation [Warning Skin corrosion/irritation]

H318: Causes serious eye damage [Danger Serious eye damage/eye irritation]

H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P264, P264+P265, P273, P280, P302+P352, P305+P354+P338, P317, P321, P332+P317, P362+P364, P391, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 0.2% (3 of 1844) of reports.

H312 (45.7%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H314 (21.5%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]

H315 (78.4%): Causes skin irritation [Warning Skin corrosion/irritation]

H318 (78.4%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H400 (99.8%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

H410 (99.8%): Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P260, P264, P264+P265, P273, P280, P301+P330+P331, P302+P352, P302+P361+P354, P304+P340, P305+P354+P338, P316, P317, P321, P332+P317, P362+P364, P363, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 1844 reports by companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 3 of 1844 reports by companies.

There are 12 notifications provided by 1841 of 1844 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

P264+P265, P280, P305+P354+P338, and P317 (click each P-code to see the statement)

H312: Harmful in contact with skin [Warning Acute toxicity, dermal]

H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H373: May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P260, P264+P265, P273, P280, P302+P352, P305+P351+P338, P317, P318, P319, P321, P337+P317, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

H336: May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]

P203, P260, P261, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.

Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

For more Preventive Measures (Complete) data for 4-(1,1,3,3-Tetramethylbutyl)phenol (6 total), please visit the HSDB record page.

Keep container tightly closed in a dry and well-ventilated place.

0.5 [ppm]

Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Liquid; Other Solid; Liquid; Large Crystals

White solid; [HSDB] Fine white plates; [MSDSonline]

White solid

Density: 0.89 g/mL at 90 °C

0.03 [mmHg]

4.7X10-3 kPa at 74 °C /4.8X10-4 mm Hg at 25 °C/

Stable under recommended storage conditions.

When heated to decomposition it emits acrid smoke and irritating fumes.

157.1 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID9022360]

156.73 Ų [M-H]-

Liquid Molar Volume = 0.2232 cu m/kmol, determined at the triple point

Boiling point

Heat of sublimation

Vapor pressure

Other Classes -> Phenols

Semi-Volatile Organic Compound (SVOC) and(or) Waste-water effluent contaminant

Pharmaceuticals

Potential endocrine disrupting compound

Use unspecified -> FDA Substance added to food

Surfactant

Incompatible materials: Strong oxidizing agents, heavy metals.

IDENTIFICATION AND USE: 4-(1,1,3,3-Tetramethylbutyl)phenol (tOP) is a white solid. It is used in the synthesis of chemical surfactants. HUMAN STUDIES: tOP is a skin and eye irritant. An epidemiological study suggested significant negative associations between maternal urinary tOP concentrations and neonatal sizes at birth. ANIMAL STUDIES: tOP produced eye and skin irritation in rabbits. tOP was evaluated for subchronic dietary toxicity through administration to rats for 3 months. For all concentrations, food intake and death rates were not influenced by treatment. Toxic signs included decreased weight gain. Females had reduced hematocrit and thyroxin values. Neonatal exposure to a high-dose tOP enhanced uterine carcinogenesis in rats, and the type of uterine tumors was changed by the periods of neonatal exposure to tOP, suggesting that the mechanism of uterine tumor development is dependent upon neonatal exposure periods. A reproduction/developmental screening test was conducted in the rat. tOP was administered at dosages of 125, 250 or 500 mg/kg/day, once daily by gavage for two weeks prior to mating, throughout the two weeks mating period, and until litters reached day 4 post partum. Slight impairment of the mating performance and development of the conceptus, observed as a reduced conception and implantation rate, a prolonged duration of pregnancy and a developmental delay, only occured at 500 mg/kg/day. tOP interfered with uterine contractility in immature rats. tOP exposure caused dose-dependent maturation of oviducts in both male and female frogs. tOP has been shown to exert estrogenic effects on mammalian cells in culture. ECOTOXICITY STUDIES: tOP is a prevalent environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells. In male bank voles, treatment for 60 days adversely influenced weights and histological structure of the testes and seminal vesicles. In these tissues, expression of 3beta-hydroxysteroid dehydrogenase and androgen receptor and testosterone levels were reduced, whereas expression of aromatase and estrogen receptor a and estradiol levels were increased. Short-term exposure to the tOP and the natural estrogen 17beta-estradiol changed important sexual characteristics in the adult male guppy. Both compounds increased the number of sperm cells in the ejaculates, reduced the area and color intensity of the sexually attractive orange spots, and inhibited testis growth. The effect of various concentrations of tOP (0, 0.5, 1, 1.5, 2 and 3 mg/L) was studied in an aquatic plant, the submersed macrophyte Ceratophyllum demersum. The toxic effect caused by tOP inhibited the plant's growth rate, reduced total chlorophyll content and increased levels of the reactive oxygen species. tOP treatment significantly increased the activities of antioxidant enzymes including superoxide dismutase, guaiacol peroxidase, glutathione reductase and ascorbate peroxidase.

4-tert-Octylphenol

Semi-Volatile Organic Compound (SVOC) and(or) Waste-water effluent contaminant

Applies to alkylphenol ethoxylates and their metabolites; this compound is such a metabolite

Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

No indication of carcinogenicity to humans (not listed by IARC).

LC50 (rat) < 29,000 mg/m3/4h

LD50 Mouse ip 25 mg/kg

LD50 Rabbit dermal 1880 mg/kg

LD50 Rat inhalation </= 116 mg/L/ 24 hours /89% purity/

LD50 Rat oral >2000 mg/kg

LD50 Mouse oral 3210 mg/kg

The current study was carried out to elucidate the modulating effect of chicory (Cichorium intybus L.) fruit extract (CFR) against 4-tert-OP induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8 weeks as follow: group 1: normal control-treated (saline); group 2: chicory fruit extract-treated (100 mg/kg); group 3: 4-tert-OP treated; group 4: 4-tert-OP plus chicory fruit extract. The obtained results revealed that rats which received 4-tert-OP showed a significant increase in liver TBARS and bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. While a significant decrease in the levels of GSH, SOD, catalase recorded. On the other hand, CFR extract succeeded to modulate these observed abnormalities resulting from 4-tert-OP as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. Histopathological evidence, together with observed PCNA and DNA fragmentation, supported the detrimental effect of 4-tert-OP and the ameliorating effect of CFR extract on liver toxicity. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by 4-tert-OP compound.

The synergistic effect of numerous environmental endocrine disrupting chemicals (EDCs) has raised research concern among researchers. To extend previous studies, the measured additional potential interactions among bisphenol A (BPA), 4-nonylphenol (NP), 4-tert octylphenol (OP) and isobutylparaben (IBP) in mouse model were observed. Pregnant Swiss-albino mice were treated with binary combined chemicals (5, 50 or 500 mg/kg/bw/day) from gestation day (GD) 1 to 21. Interestingly, maternal exposure to these EDCs caused fluctuation in GD time, live ratio, female/male ratio, body and organ weights of mouse offspring at postnatal day (PND) 1, 21, and 41 days. At most doses early reduced 0.85 to 1.87 GD compared to controls. Besides females/males ratio showed a significant difference in BPA+ OP, BPA+IBP groups. Female body weight at PND 21 and 41, showed a significant reduction at all combined levels, whereas male offspring showed reduction in weight at dose 50 mg/kg/bw/day. The potential effects of synergic estrogenicity detected histopathological abnormities, such as ovary analysis revealed increase of corpora lutea, cystic follicles and an endometrial hypertrophy and morphometric changes in uteri measurement. Taken together, these results provided an additional insight into synergistic effects of EDCs toxicology on reproductive tracts.

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 mL saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/PREGNANCY AND HUMAN REPRODUCTION/ Exposure to 4-tert-octylphenol (tOP) has been linked with adverse health outcomes in animals and humans, while epidemiological studies about associations between prenatal exposure to tOP and fetal growth are extremely limited. We measured urinary tOP concentrations in 1100 pregnant women before their delivery, and examined whether tOP levels were associated with birth outcomes, including weight, length, head circumference and ponderal index at birth. tOP could be detected in all samples, and the median uncorrected and creatinine-corrected tOP concentrations were 0.90 ug/L (range from 0.25 to 20.05 ug/L) and 1.33 ug/g creatinine (range from 0.15 to 42.49 ug/g creatinine), respectively. Maternal urinary log-transformed tOP concentrations were significantly negatively associated with adjusted birth weight [beta (g) = -126; 95% confidence interval (CI): -197, -55], birth length [beta (cm) = -0.53; 95% CI:-0.93, -0.14], and head circumference [beta (cm) = -0.30; 95% CI: -0.54, -0.07], respectively. Additionally, considering sex difference, these significant negative associations were also found among male neonates, while only higher maternal tOP concentrations were associated with a significant decrease in birth weight among female neonates. This study suggested significant negative associations between maternal urinary tOP concentrations and neonatal sizes at birth, and they differed by neonatal sex. Further epidemiological studies are required to more fully elaborate the associations between prenatal tOP exposure and birth outcomes.

/ENDOCRINE MODULATION/ Endocrine disrupting chemicals (EDCs) are defined as environmental compounds that modulate steroid hormone receptor-dependent responses an abnormal manner, resulting in adverse health problems for humans such as cancer growth and metastasis. Cathepsins are proteases that have been implicated in cancer progression. However, there have been few studies about the association between cathepsins and estrogenic chemicals during the cancer progression. In this study, we examined the effect(s) of 4-tert-octylphenol (OP), a potent EDC, on the expression of cathepsins B and D in human MCF-7 breast cancer cells and a xenograft mouse model. Treatment with OP significantly induced the proliferation MCF-7 cells in an MTT assay. In addition, the expression of cathepsins B and D was markedly enhanced in MCF-7 cells at both the transcriptional and the translational levels following treatment with E2 or OP up to 48 hr. These results demonstrated the ability of OP to disrupt normal transcriptional regulation of cathepsins B and D in human breast cancer cells. However, the effects of OP on cell growth or overexpression of cathepsins by inhibiting ER-mediated signaling were abolished by an ER antagonist and siRNA specific for ERa. In conclusion, our findings suggest that OP at 10(-6)M, like E2, may accelerate breast cancer cell proliferation and the expression of cathepsins through an ER-mediated signaling pathway. In addition, the breast cancer cells exposed with OP to a xenograft mouse model were more aggressive according to our histological analysis and showed markedly increased expression of cathepsin B. These effects of mouse model resulted in an increased potential for metastasis in breast cancer. Taken together, we determined that OP can adversely affect human health by promoting cancer proliferation and metastasis through the amplification of cathepsins B and D via the ER-mediated signaling pathway.

/ALTERNATIVE and IN VITRO TESTS/ Environmental contamination has been one of the major drawbacks of the industrial revolution. Several man-made chemicals are constantly released into the environment during the manufacturing process and by leaching from the industrial products. As a result, human and animal populations are exposed to these synthetic chemicals on a regular basis. Many of these chemicals have adverse effects on the physiological functions, particularly on the hormone systems in human and animals and are called endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), 4-tert-octylphenol (OP), and 4-nonylphenol (NP) are three high volume production EDCs that are widely used for industrial purposes and are present ubiquitously in the environment. Bisphenol A is metabolized in the human body to a more potent compound (MBP: 4-Methyl-2, 4-bis (4-hydroxyphenyl) pent-1-ene). Epidemiological and experimental studies have shown the three EDCs to be associated with adverse effects on reproductive system in human and animals. Sex hormone-binding globulin (SHBG) is a circulatory protein that binds sex steroids and is a potential target for endocrine disruptors in the human body. The current study was done in order to understand the binding mechanism of OP, BPA, NP, and MBP with human SHBG using in silico approaches. All four compounds showed high binding affinity with SHBG, however, the binding affinity values were higher (more negative) for MBP and NP than for OP and BPA. The four ligands interacted with 19-23 residues of SHBG and a consistent overlapping of the interacting residues for the four ligands with the residues for the natural ligand, dihydrotestosterone (DHT; 82-91% commonality) was shown. The overlapping SHBG interacting residues among DHT and the four endocrine disruptors suggested that these compounds have potential for interference and disruption in the steroid binding function.

/ALTERNATIVE and IN VITRO TESTS/ Alkylphenols, considered to be endocrine disruptor chemicals and toxic environmental priority pollutants, pose great threats to humans with wide exposure from food and other potential sources. In this paper, to evaluate the toxicity of the alkylphenols at the protein level, the effects of 4-tert-octylphenol (OP) and 4-nonylphenol (NP) on human serum albumin (HSA) were characterized by molecular modeling, steady state and time-resolved fluorescence, ultraviolet-visible spectroscopy (UV-vis) and circular dichroism spectroscopy (CD). The enthalpy change (deltaH) and entropy change (deltaS) indicated that hydrophobic forces and hydrogen bonds were the dominant intermolecular forces in the binding of the alkylphenols to HSA. The binding constant of HSA-NP is much greater than that of HSA-OP, revealing that NP, which has a longer carbon chain, has a higher affinity than OP. The alterations of protein secondary structure in the presence of the alkylphenols were confirmed by UV-vis and CD spectroscopy. The time-resolved fluorescence study showed that the lifetimes of tryptophan (Trp) residue of HSA decreased after the addition of the alkylphenols, NP with longer carbon chain impact on the average lifetime of the Trp of HSA more than OP, which is consistent with the conclusion drawn from the fluorescence date.

/OTHER TOXICITY INFORMATION/ Exposure to toxic industrial chemicals that have capacity to disrupt the endocrine system, also known as endocrine disrupting chemicals (EDCs), has been increasingly associated with reproductive problems in human population. Bisphenol A (BPA; 4,4'-(propane-2,2-diyl)diphenol) and 4-tert-octylphenol (OP; 4-(1,1,3,3-tetramethylbutyl)phenol) are among the most common environmental contaminants possessing endocrine disruption properties and are present in plastics, epoxy resins, detergents and other commercial products of common personal and industrial use. A metabolite of BPA, 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is about 1000 times more biologically active compared to BPA. Epidemiological, clinical, and experimental studies have shown association of BPA and OP with adverse effects on male and female reproductive system in human and animals. The endocrine disruption activity can occur through multiple pathways including binding to steroid receptors. Androgen receptor (AR) and progesterone receptor (PR) are critical for reproductive tract growth and function. Structural binding characterization of BPA, MBP, and OP with AR and PR using molecular docking simulation approaches revealed novel interactions of BPA with PR, and MBP and OP with AR and PR. For BPA, MBP, and OP, five AR interacting residues Leu-701, Leu-704, Asn-705, Met-742, and Phe-764 overlapped with those of native AR ligand testosterone, and four PR interacting residues Leu-715, Leu-718, Met-756, and Met-759 overlapped with those of PR co-complex ligand, norethindrone. For both the receptors the binding strength of MBP was maximum among the three compounds. Thus, these compounds have the potential to block or interfere in the binding of the endogenous native AR and PR ligands and, hence, resulting in dysfunction. The knowledge of the key interactions and the important amino-acid residues also allows better prediction of potential of xenobiotic molecules for disrupting AR- and PR-mediated pathways, thus, helping in design of less potent alternatives for commercial use.

/LABORATORY ANIMALS: Acute Exposure/ Eye irritation: highly irritating 63.0 scores in 24 hours (rabbit)

/LABORATORY ANIMALS: Acute Exposure/ Skin irriatation: slightly irritating index 4.5/8 (rabbit)

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ p-tert-Octylphenol, purity 98.24% was administered to Crj:CD rats (6 male, 6 female/group) by oral gavage at dosages of 0, 15, 70, 300 mg/kg/day, daily for a period of 28 days. Salivation was observed on test substance administration in the medium- and high-dose females and males. Body weight gain was reduced in the high-dose males. Water intake was increased in males and females of the high dose group. No changes in food consumption and hematological parameters. NOEL: 15 mg/kg/day. LOEL: not available.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The test substance /octylphenol, purity 98.7%/ was administered at dosages of 15, 150 and 250 mg/kg/day, once daily for a period of 29 days. Target organs were liver and kidney. Kidney: In the kidneys of high dosage group rats, microscopic changes seen were basophilic epithelium with occasional mitotic figures in proximal tubules (males: 4 of 5, females 5 of 5; control: females: 1 of 5, males 0 of 5) and interstitial inflammation (males: 4 of 5, females 1 of 5, compared to control: males: 1 of 5, females: 2 of 5). Associated with these findings were increased kidney weights for females. For male rats of the intermediate dosage group, basophilic epithelium with occasional mitoses were also seen. Increased water consumption for rats of the high dosage group was considered to be related to the kidney effects. Liver: In the liver of high dosage group female rats, minimal centrilobular hepatocyte enlargement with associated increased liver weight. These findings were considerd to be adaptive and related to the metabolism of the test substance. The finding in the kidney at the high and intermediate dosages was considered to be an adverse effect. There were no treatment related effects on the low dosage of 15 mg/kg bw/day. Based on these findings, a LOAEL of 150 mg/kg bw/day and a NOEL of 15 mg/kg bw/day was derived. /Octylphenol/

For more Non-Human Toxicity Excerpts (Complete) data for 4-(1,1,3,3-Tetramethylbutyl)phenol (27 total), please visit the HSDB record page.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of November 16, 2017: http://actor.epa.gov/dashboard/]

The acute toxicity of p-(1,1,3,3-tetramethylbutyl)phenol to Selenastrum capricornutum printz was tested in a static algal assay. The test exposure was to 1.0, 1.8, 3.2, 5.6, and 10 ppm for 96 hours at pH 7.5 and 24-25 degC. The 96-hour EC-50 (95% C.I.) was 1.9 (1.0-2.7) mg/l and a 96-hour, no observed effect concentration of <1.0 mg/l was determined by one-way analysis of variance (ANOVA). All test concentrations were significantly different than the controls (a=0.05)

P-(1,1,3,3-tetramethylbutyl)phenol (CAS # 140-66-9) was evaluated for subchronic dietary toxicity. The test substance was administered to rats (20/sex/group) at concentrations of 30, 300, and 3000 ppm for 3 months. For all concentrations, food intake and death rates were not influenced by treatment. At 300 ppm and above, toxic signs included decreased weight gain. At 3,000 ppm, females had reduced hematocrit and thyroxin values.

P-(1,1,3,3-tetramethylbutyl)phenol (CAS # 140-66-9) was evaluated for subchronic dietary toxicity. The test substance was administered in the diets of albino rats (15/sex/group) at a concentration of 5%. No treatment-related effects on growth, mortality, food consumption, urinary excretion of sugar and protein, hematologic values, or organ to body weight ratios, and no pathologic lesions were observed.

EC50; Species: Microcystis aeruginosa (Blue-Green Algae) 200000 cells/mL; Conditions: freshwater, static, 23 °C; Concentration: 328 nM for 10 days (95% confidence interval: 313-343 nM); Effect: decreased population growth rate /> or =90% purity/

LC50; Species: Tigriopus japonicus (Harpacticoid Copepod) age 2 wk adult, length 0.8-1.2 mm length; Conditions: saltwater, renewal, 20 °C, pH 7.9; Concentration: 300 ug/L for 96 hr (95% confidence interval: 160-740 ug/L) /99.9% purity/

LC50; Species: Daphnia magna (Water Flea) age <24 hr neonate; Conditions: freshwater, static, 19-21 °C, pH 7.0-7.2; Concentration: 90 ug/L for 48 hr (95% confidence interval: 70-120 ug/L) /formulation/

LC50; Species: Daphnia magna (Water Flea); Conditions: freshwater, static, 25 °C, pH 7.8, hardness 170 mg/L CaCO3, alkalinity 110 mg/L CaCO3; Concentration: 11 ug/L for 48 hr /99% purity/

For more Ecotoxicity Values (Complete) data for 4-(1,1,3,3-Tetramethylbutyl)phenol (16 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ The present study was designed to evaluate the effects of 4-tert-octylphenol (OP) on male testes and seminal vesicles of bank vole. Adult males kept under long or short photoperiod were orally administered OP (200 mg/kg bw) for 30 or 60 days. Treatment for 30 days had no discernible effect on the parameters examined. Treatment for 60 days adversely influenced weights and histological structure of the testes and seminal vesicles. In these tissues, expression of 3beta-hydroxysteroid dehydrogenase and androgen receptor and testosterone levels were reduced, whereas expression of aromatase and estrogen receptor a and estradiol levels were increased. The alterations were more evident in voles kept in long photoperiod. Taken together, it is suggested that adverse changes in bank vole reproductive tissues induced by long-term OP-exposure result from disturbed androgen and estrogen synthesis and action. Moreover, there might be a subtle difference in the sensitivity to OP between voles kept in different light conditions.

/AQUATIC SPECIES/ Many studies have considered recent increases in ultraviolet B radiation (UVBR) and endocrine disrupting chemicals polluting the environment as possible contributing factors to the reduction in amphibian populations. It has been demonstrated that exposure of amphibians to estrogenic chemicals or UVBR can affect the timing of larval development and metamorphosis. However, amphibians in the wild are exposed to multiple environmental stressors simultaneously. Therefore, our study examines the effects of UVBR and the estrogenic chemical 4-tert-octylphenol (OP), alone and in combination, on the thyroid system of Rana pipiens tadpoles, which is the main regulator of amphibian metamorphosis. Results demonstrate that thyroid gland histomorphology measurements in Gosner stage 31 tadpoles continuously exposed to UVBR (0.21 W/m(2)) were not different than those measured in animals from the control group. In a separate experiment, tadpoles exposed to environmentally relevant levels of UVBR (0.22 W/m(2)) and/or OP (0.01nM or 10nM) exhibited significantly delayed development starting from Gosner stage 29, given that fewer tadpoles developed past stage 29 in these groups. In addition, significantly fewer UVBR-treated tadpoles developed past stage 34 and metamorphosed. Samples were collected from stages 29 and 34 tadpoles for gene expression analysis in tail tissue and measurements of T3 (triiodothyronine) whole body levels (minus tail). UVBR and/or OP exposure did not affect T3 levels in stages 29 and 34 tadpoles. However, a decrease in deiodinase type 2 (D2) or increase in deiodinase type 3 (D3) mRNA levels was observed in groups of tadpoles with slowed developmental rates at those developmental stages. Given that D2 activates and D3 inactivates thyroid hormones (TH), UVBR/OP mediated disruptions in development are likely caused by dysfunctions in the localized metabolism of THs through alterations in the expression of these enzymes in peripheral tissues. This is the first study to our knowledge reporting a potential thyroid-based mechanism of action for the developmental delays in amphibians exposed to UVBR and/or OP.

/AQUATIC SPECIES/ Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring of endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17beta-estradiol (E2; 10(-9)M) or 4-tert-octylphenol (OP; 10(-9)M, 10(-8)M, and 10(-7)M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10(-7)M OP increased testicular transcript levels. Treatment with 10(-9) and 10(-8)M OP, but not 10(-7)M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed within the environment influence the levels of gonadal mRNA encoding key proteins involved in gonadal differentiation.

EC50; Species: Microcystis aeruginosa (Blue-Green Algae) 200000 cells/mL; Conditions: freshwater, static, 23 °C; Concentration: 328 nM for 10 days (95% confidence interval: 313-343 nM); Effect: decreased population growth rate /> or =90% purity/

LC50; Species: Tigriopus japonicus (Harpacticoid Copepod) age 2 wk adult, length 0.8-1.2 mm length; Conditions: saltwater, renewal, 20 °C, pH 7.9; Concentration: 300 ug/L for 96 hr (95% confidence interval: 160-740 ug/L) /99.9% purity/

LC50; Species: Daphnia magna (Water Flea) age <24 hr neonate; Conditions: freshwater, static, 19-21 °C, pH 7.0-7.2; Concentration: 90 ug/L for 48 hr (95% confidence interval: 70-120 ug/L) /formulation/

LC50; Species: Daphnia magna (Water Flea); Conditions: freshwater, static, 25 °C, pH 7.8, hardness 170 mg/L CaCO3, alkalinity 110 mg/L CaCO3; Concentration: 11 ug/L for 48 hr /99% purity/

For more Ecotoxicity Values (Complete) data for 4-(1,1,3,3-Tetramethylbutyl)phenol (16 total), please visit the HSDB record page.

/BIRDS and MAMMALS/ The present study was designed to evaluate the effects of 4-tert-octylphenol (OP) on male testes and seminal vesicles of bank vole. Adult males kept under long or short photoperiod were orally administered OP (200 mg/kg bw) for 30 or 60 days. Treatment for 30 days had no discernible effect on the parameters examined. Treatment for 60 days adversely influenced weights and histological structure of the testes and seminal vesicles. In these tissues, expression of 3beta-hydroxysteroid dehydrogenase and androgen receptor and testosterone levels were reduced, whereas expression of aromatase and estrogen receptor a and estradiol levels were increased. The alterations were more evident in voles kept in long photoperiod. Taken together, it is suggested that adverse changes in bank vole reproductive tissues induced by long-term OP-exposure result from disturbed androgen and estrogen synthesis and action. Moreover, there might be a subtle difference in the sensitivity to OP between voles kept in different light conditions.

/AQUATIC SPECIES/ Many studies have considered recent increases in ultraviolet B radiation (UVBR) and endocrine disrupting chemicals polluting the environment as possible contributing factors to the reduction in amphibian populations. It has been demonstrated that exposure of amphibians to estrogenic chemicals or UVBR can affect the timing of larval development and metamorphosis. However, amphibians in the wild are exposed to multiple environmental stressors simultaneously. Therefore, our study examines the effects of UVBR and the estrogenic chemical 4-tert-octylphenol (OP), alone and in combination, on the thyroid system of Rana pipiens tadpoles, which is the main regulator of amphibian metamorphosis. Results demonstrate that thyroid gland histomorphology measurements in Gosner stage 31 tadpoles continuously exposed to UVBR (0.21 W/m(2)) were not different than those measured in animals from the control group. In a separate experiment, tadpoles exposed to environmentally relevant levels of UVBR (0.22 W/m(2)) and/or OP (0.01nM or 10nM) exhibited significantly delayed development starting from Gosner stage 29, given that fewer tadpoles developed past stage 29 in these groups. In addition, significantly fewer UVBR-treated tadpoles developed past stage 34 and metamorphosed. Samples were collected from stages 29 and 34 tadpoles for gene expression analysis in tail tissue and measurements of T3 (triiodothyronine) whole body levels (minus tail). UVBR and/or OP exposure did not affect T3 levels in stages 29 and 34 tadpoles. However, a decrease in deiodinase type 2 (D2) or increase in deiodinase type 3 (D3) mRNA levels was observed in groups of tadpoles with slowed developmental rates at those developmental stages. Given that D2 activates and D3 inactivates thyroid hormones (TH), UVBR/OP mediated disruptions in development are likely caused by dysfunctions in the localized metabolism of THs through alterations in the expression of these enzymes in peripheral tissues. This is the first study to our knowledge reporting a potential thyroid-based mechanism of action for the developmental delays in amphibians exposed to UVBR and/or OP.

/AQUATIC SPECIES/ Wildlife and human populations are exposed to anthropogenic mixtures of chemicals in the environment that may adversely influence normal reproductive function and development. We determined the effects of exposure to estrogenic chemicals and wastewater effluent (WWE) on developing gonads of the American bullfrog, Rana (Lithobates) catesbeiana, a species whose widespread distribution make it an ideal model for environmental monitoring of endocrine effects of chemical contaminants. Premetamorphic bullfrog tadpoles were exposed to treatment vehicle, 17beta-estradiol (E2; 10(-9)M) or 4-tert-octylphenol (OP; 10(-9)M, 10(-8)M, and 10(-7)M). Additionally, gonadal differentiation was evaluated in bullfrog tadpoles from a WWE-containing site versus those from a reference location receiving no WWE. In both studies, phenotypic sex, steroidogenic factor-1 (nr5a1), and aromatase (cyp19a1) mRNA levels using quantitative real-time PCR were determined. Exposure to E2 or OP did not alter sex ratios. In controls, both nr5a1 and cyp19a1 transcript levels exhibited sexual dimorphism, with males demonstrating higher levels of nr5a1 and females greater abundance of cyp19a1. However, E2 exposure increased cyp19a1 mRNA abundance in testes and decreased levels in ovaries, eliminating the sexual dimorphism observed in controls. E2-exposed males exhibited increased nr5a1 transcript levels in the testes compared to controls, while females demonstrated no E2 effect. OP treatment had no effect on female cyp19a1 mRNA abundance, but exposure to 10(-7)M OP increased testicular transcript levels. Treatment with 10(-9) and 10(-8)M OP, but not 10(-7)M, resulted in decreased abundance of nr5a1 transcript in both ovaries and testes. Animals from the field had sexually dimorphic gonadal levels of cyp19a1, but both sexes from the WWE site exhibited elevated cyp19a1 transcript abundance compared to the reference location. Individual chemical compounds and anthropogenic wastewater effluent dispersed within the environment influence the levels of gonadal mRNA encoding key proteins involved in gonadal differentiation.

/AQUATIC SPECIES/ Estrogenic chemicals are often detected in the aquatic environment and can negatively affect animal development and reproduction. In teleost fishes, the hormonal regulation during a critical period of larval development has a strong influence on gonadal sex differentiation; thus this process may be affected by the exposure to environmental estrogens. In this study, we first assessed the lethal acute toxicity of the natural estrogen 17beta-estradiol (E2) and the weaker estrogen mimics 4-tert-octylphenol (OP) and 4-nonylphenol (NP) on larval stages of the South American cichlid fish Cichlasoma dimerus. In a further experiment, we analyzed the effects of chronic waterborne exposure to E2 and OP on gonad development and sex differentiation. Exposure to high concentrations of E2 had a pronounced feminizing effect directing sex differentiation towards ovarian development, while testis development was inhibited at a lower, environmentally relevant concentration. Among OP-exposed fish, 15-38.5% of the males exhibited testicular oocytes (TOs), a commonly reported biomarker of estrogenic exposure. However, since TOs were also recorded in control males and the proportion of males with TOs was not significantly higher in OP treatments, their occurrence could not be attributed to OP exposure. In addition, TOs did not seem to impair male gonad development and functionality since normal spermatogenesis was observed in testes of OP-treated fish. These results indicate that E2 occurring in the South American aquatic environment may affect male reproductive development and pose a risk for wild C. dimerus, especially under prolonged exposure, while the effects of weaker xenoestrogens such as OP would be negligible for gonad development in this species. As illustrated by this study, the natural occurrence of TOs indicates that conclusions concerning the causes of this phenomenon must be drawn with care.

For more Ecotoxicity Excerpts (Complete) data for 4-(1,1,3,3-Tetramethylbutyl)phenol (11 total), please visit the HSDB record page.

4-(1,1,3,3-Tetramethylbutyl)phenol's production and use in nonionic surfactants, plasticizers, antioxidants, fuel oil stabilizer, intermediate for resins, fungicides, bactericides, dyestuffs, adhesives and rubber chemicals may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 4.78X10-4 mm Hg at 25 °C indicates p-(1,1,3,3-tetramethylbutyl)phenol will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase p-(1,1,3,3-tetramethylbutyl)phenol will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 9 hrs. Particulate-phase p-(1,1,3,3-tetramethylbutyl)phenol will be removed from the atmosphere by wet and dry deposition. p-(1,1,3,3-Tetramethylbutyl)phenol does not contain chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, p-(1,1,3,3-tetramethylbutyl)phenol is expected to have low mobility based upon an estimated Koc of 1000. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 6.9X10-6 atm-cu m/mole. p-(1,1,3,3-Tetramethylbutyl)phenol is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Utilizing the Japanese MITI test, 0% of the Theoretical BOD was reached in 2 weeks indicating that biodegradation is not an important environmental fate process in soil or water. If released into water, p-(1,1,3,3-tetramethylbutyl)phenol is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 7 and 61 days, respectively. BCF values of 261 and 90 suggest that bioconcentration in aquatic organisms is high. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to p-(1,1,3,3-tetramethylbutyl)phenol may occur through inhalation and dermal contact with this compound at workplaces where p-(1,1,3,3-tetramethylbutyl)phenol is produced or used. Monitoring data indicate that the general population may be exposed to p-(1,1,3,3-tetramethylbutyl)phenol via dermal contact with contaminated water. (SRC)

4-(1,1,3,3-Tetramethylbutyl)phenol's production and use in nonionic surfactants, plasticizers, antioxidants, fuel oil stabilizer, intermediate for resins, fungicides, bactericides, dyestuffs, adhesives and rubber chemicals(1) may result in its release to the environment through various waste streams(SRC). 4-(1,1,3,3-Tetramethylbutyl)phenol may be formed as a degradation product of alkylphenol surfactants in wastewater. Concentrations of 4-(1,1,3,3-tetramethylbutyl)phenol increased with time in primary wastewater containing such compounds(2,3).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1000(SRC), determined from a structure estimation method(2), indicates that p-(1,1,3,3-tetramethylbutyl)phenol is expected to have low mobility in soil(SRC). Volatilization of p-(1,1,3,3-tetramethylbutyl)phenol from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.9X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(2). p-(1,1,3,3-Tetramethylbutyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 4.78X10-4 mm Hg at 25 °C(3). A 0% of theoretical BOD using activated sludge in the Japanese MITI test(4) suggests that biodegradation is not an important environmental fate process in soil(SRC).

FIELD: p-(1,1,3,3-Tetramethylbutyl)phenol, present at 7.0 and 27 ug/kg, exhibited field dissipation half-lives of 231 and 75 days in two anaerobically-digested biosolids that were centrifuged dried and lagoon solar dried, respectively, applied to soil under field conditions in South Australia in May 2008. From day 224 through the end of the study (day 336) there was no relevant change in the concentration(1).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1000(SRC), determined from a structure estimation method(2), indicates that p-(1,1,3,3-tetramethylbutyl)phenol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 6.9X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 7 and 61 days, respectively(SRC). According to a classification scheme(4), BCF values of 251 and 90(5) suggests bioconcentration in aquatic organisms is high(SRC). A 0% of theoretical BOD using activated sludge in the Japanese MITI test(5) suggests that biodegradation is not an important environmental fate process in water(SRC).

AQUATIC FATE: Multiphase partitioning of endocrine-disrupting chemicals (EDCs) in the Pearl River (China) were investigated. The colloidal concentrations for 4-tert-octylphenol, 4-nonylphenol, bisphenol A (BPA), and estrone (E1) were in the ranges of 0.2 ng/L to 0.8 ng/L, 23.2 ng/L to 108 ng/L, 2.3 ng/L to 97.6 ng/L, and not detectable (nd) to 0.32 ng/L, respectively; for truly dissolved concentrations, the ranges were 0.5 ng/L to 5.4 ng/L, 39 ng/L to 319 ng/L, 13.7 ng/L to 91.2 ng/L, and nd to 1.2 ng/L, respectively. Positive correlations of EDCs with colloidal organic carbon (COC) were observed. The in situ COC normalized partitioning coefficients (log KCOC) for 4-tert-octylphenol (5.35+ or -0.42), 4-nonylphenol (5.69+ or -0.50), and BPA (5.51+ or -0.77) were within the ranges reported by other studies, whereas they were 1 to 2 orders of magnitude higher than their particulate/truly dissolved phase partition coefficients (log math formula), revealing much strong sorption of EDCs by aquatic colloids. Moreover, colloid-bound percentages of 4-tert-octylphenol, 4-nonylphenol, and BPA ranged, respectively, from 6.9% to 36.4%, from 16.7% to 63.1%, and from 3.6% to 52.4%; their estimated mass fractions were 0.29+ or -0.21, 0.38+ or -0.26, and 0.39+ or -0.33, respectively. Obviously the colloid-bound fractions are significant. Furthermore, a medium risk of estrogenic effects was estimated from the truly dissolved concentrations of EDCs in the Pearl River, which was lower than the estimated high risk according to the conventionally dissolved concentrations. It is suggested that the presence of colloids be incorporated into future water quality prediction and ecological risk assessment.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), p-(1,1,3,3-tetramethylbutyl)phenol, which has a vapor pressure of 4.78X10-4 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase p-(1,1,3,3-tetramethylbutyl)phenol is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 9 hours(SRC), calculated from its rate constant of 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) (that was derived using a structure estimation method(3). Particulate-phase p-(1,1,3,3-tetramethylbutyl)phenol may be removed from the air by wet and dry deposition(SRC). p-(1,1,3,3-Tetramethylbutyl)phenol does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

AEROBIC: p-(1,1,3,3-Tetramethylbutyl)phenol, present at 100 mg/L, reached 0% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). In experiments with a soil column, concentrations of 4-(1,1,3,3-tetramethylbutyl)phenol were about two orders of magnitude lower in the column effluent than in the feed(2). Soil from this column, which had undergone 3 inundation cycles with 4-(1,1,3,3-tetramethylbutyl)phenol at 10 ug/l, required 16 hours to convert 7% of this compound to CO2. Microbial adaptation was noted for this compound, as indicated by increased removal efficiencies during successive inundation cycles (6 day flooding, 16 day drying cycle) at varying concentrations. Column effluent concentrations of 4-(1,1,3,3-tetramethylbutyl)phenol were independent of input concentrations during the final stage of the test(2). Following three aerobic flooding cycles, anaerobic conditions were introduced(3). Fractional breakthrough profiles for 4-(1,1,3,3-tetramethylbutyl)phenol did not change (from those obtained during aerobic test conditions) although the degree of breakthrough increased for this compound; this indicates that the inhibition in compound removal mediated by anaerobic conditions is not due solely to cessation of mineralization activity(3).

The rate constant for the vapor-phase reaction of p-(1,1,3,3-tetramethylbutyl)phenol with photochemically-produced hydroxyl radicals has been estimated as 4.2X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 9 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). p-(1,1,3,3-Tetramethylbutyl)phenol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). p-(1,1,3,3-Tetramethylbutyl)phenol does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Measured BCF values of 251 and 90 were reported in fish for p-(1,1,3,3-tetramethylbutyl)phenol at concentrations of 70 and 6.3 ppb (w/v), respectively, using carp (Cyprinus carpio) which were exposed over an 8-week period(1). According to a classification scheme(2), these BCF values suggest the potential for bioconcentration in aquatic organisms is high(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of p-(1,1,3,3-tetramethylbutyl)phenol can be estimated to be 1000(SRC). According to a classification scheme(2), this estimated Koc value suggests that p-(1,1,3,3-tetramethylbutyl)phenol is expected to have low mobility in soil(SRC). The compound was measured in wells down gradient from the flooding basins (0.17 ug/L) during rapid infiltration of primary sewage (containing 4-(1,1,3,3-tetramethylbutyl)phenol at 0.79 ug/L) at a kame site(4). Sorption processes did not appear to completely control the movement of this compound through soil(3). This compound was again present in wells down gradient from the initial site(at 0.01-0.017 ug/L) at another rapid infiltration site in Arizona (4-(1,1,3,3-tetramethylbutyl)phenol initially present at 0.757 ug/L); here, removal of 4-(1,1,3,3-tetramethylbutyl)phenol was attributed mainly to sorption processes as the sewage had been through secondary treatment(4).

The Henry's Law constant for p-(1,1,3,3-tetramethylbutyl)phenol is estimated as 6.9X10-6 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that p-(1,1,3,3-tetramethylbutyl)phenol is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 7 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 61 days(SRC). p-(1,1,3,3-Tetramethylbutyl)phenol is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 4.78X10-4 mm Hg(3).

GROUNDWATER: 4-(1,1,3,3-Tetramethylbutyl)phenol was present in two wells, down gradient from a rapid infiltration plant in Massachusetts, at 0.62 and 2.5 ug/L(1). 4-(1,1,3,3-Tetramethylbutyl)phenol was present in two wells, down gradient from a rapid infiltration basin (Arizona) at concentrations ranging from 0.01-0.017 ug/L(2). 4-(1,1,3,3-Tetramethylbutyl)phenol was present at 0.53 ug/L in ground water down gradient from a land application site in Boulder, CO(3).

DRINKING WATER: 4-(1,1,3,3-Tetramethylbutyl)phenol was tenatively identified in drinking water from Seattle, WA in November 1976(1). p-(1,1,3,3-Tetramethylbutyl)phenol was tested for but not detected in finished water samples from a US drinking water treatment facility in a heavily populated, highly urbanized drainage basin; reporting level = 1 ug/L(2). The compound was found in 10 German tap water samples at a mean concentration of 2.0 ng/L(3).

SURFACE WATER: Water samples from the Delaware River between Marcus Hook, PA and Trenton, NJ contained 4-(1,1,3,3-tetramethylbutyl)phenol at 1-2 ppb in the winter (March 1977) and 0.2-2 ppb in the summer (August 1976)(1). In a study of three treatment plants in southern Germany, the compound was present in surface water samples collected from the Danube, Blau and Nau Rivers at a mean concentration of 7.3 ng/L (detection limit = 0.5 ng/L); sampling was conducted from June to October 2000(6).

4-(1,1,3,3-Tetramethylbutyl)phenol was positively identified in advanced waste treatment water from Lake Tahoe, CA in October 1974 and from Pomona, CA in September 1974(1). 4-(1,1,3,3-Tetramethylbutyl)phenol was detected at unreported concentrations in final effluent grab samples from 3 POTWs in Illinois(2). 4-(1,1,3,3-Tetramethylbutyl)phenol was detected in the primary sewage(0.79 ug/L)(3) and secondary sewage (0.757 ug/L)(4) of waste treatment plants in Massachusetts and Arizona, respectively. p-(1,1,3,3-Tetramethylbutyl)phenol was detected not quantified in 8% of 12 stream and raw water samples from a US drinking water treatment facility in a heavily populated, highly urbanized drainage basin. More than 50 sewage treatment plants discharge treated effluent into the stream that provides raw water to the drinking water plant; reporting level = 1 ug/L(5). In a study of three treatment plants in southern Germany, the compound was present in all 16 effluent samples at a mean concentration of 22 ng/L (detection limit = 0.5 ng/L); sampling was conducted from June to October 2000(6).

4-(1,1,3,3-Tetramethylbutyl)phenol was detected on fruits sampled in Taiwan after washing with a food detergent containing this compound(1).[Table#5393]

4-(1,1,3,3-Tetramethylbutyl)phenol was detected in the Lake Ontario basin at an unreported location and concentration(1). The compound was reported in household food detergents (surfactant, non-ionic surfactant, anionic surfactant, others) sampled in Taiwan at a range of not detected to 1.71X10-5 mg/g(2).

According to the 2016 TSCA Inventory Update Reporting data, 5 reporting facilities estimate the number of persons reasonably likely to be exposed during the manufacturing, processing, or use of 4-(1,1,3,3-tetramethylbutyl)phenol in the United States may be as low as 10 workers and as high as 10,000 workers per plant; the data may be greatly underestimated due to confidential business information (CBI) or unknown values(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 15,351 workers (736 of these are female) were potentially exposed to 4-(1,1,3,3-tetramethylbutyl)phenol(1). Occupational exposure to p-(1,1,3,3-tetramethylbutyl)phenol may occur through inhalation and dermal contact with this compound at workplaces where p-(1,1,3,3-tetramethylbutyl)phenol is produced or used. Monitoring data indicate that the general population may be exposed to p-(1,1,3,3-tetramethylbutyl)phenol via dermal contact with contaminated water(SRC).

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material; Contaminated packaging: Dispose of as unused product.