Phenol, dodecyl-, branched, sulfurized

Endpoint summary

Description of key information

The toxicokinetics of phenol, dodecyl-, branched, sulfurized have not been directly studied. Oral studies conducted in structurally similar compounds indicate that these salts may be absorbed to a limited extent in the gastrointestinal tract resulting in further distribution and metabolism. Because of its high lipophilicity, they may accumulate to some degree in fatty tissues and be released slowly; however the finding of similar NOAELs in 28-day and 90-day studies using the same dose schedule indicates that elimination is occurring. The liver is expected to be the primary organ to receive and metabolize the substance, making it more soluble by oxidation and conjugation for eventual release into the bile and into the gastrointestinal tract for elimination. Phenol, dodecyl-, branched, sulfurized is above the size threshold expected to easily penetrate skin, and the degree of absorption through the skin or respiratory system is limited, but regardless of the route of exposure, there is no indication that systemically distributed phenol, dodecyl-, branched, sulphurised will bioaccumulate. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Phenol, dodecyl-,branched,sulfurized; CAS# 96152-43-1

Relevant Endpoints
Log Pow	9.5 (based on read-across from category members CAS #122384-86-5 & 68855-45-8)
Water Solubility	<0.206 mg/L (based on read-across from CAS #122384-86-5, 68515-93-5 & 26998-97-0)
MW	Variable; > 500
Vapour Pressure	0.0004 Pa
Viscosity	7465.5 cSt
Dissociation Constant	N/A based on UVCB
Boiling Point	>250° C
Protein Binding	Not predicted to bind to protein based on OECD Toolbox v1.1

 

There were no toxicokinetic studies that directly addressed absorption, distribution, metabolism, or excretion of phenol, dodecyl-,branched, sulfurized (the Registration material). However, information is available from structurally similar compounds with existing toxicology studies and physical chemical properties to infer potential toxicokinetic properties.

 

Significance of Route of Exposure

Dermal route:This is considered the principle route for occupational exposure.

Oral route:This is not considered a relevant route for occupational exposure or the general population. Slight exposure may occur via accidental hand-to-mouth contact, but this isn’t expected to contribute significantly to exposure.

Inhalation route:Under conditions of normal handling and use, the registered substance will not be aerosolized.

 

Absorption

Dermal route:According to ECETOC Monograph 20: Percutaneous Absorption, the physical chemical properties that influence dermal absorption are molecular weight, water and lipid solubility, and degree of ionization. The molecular weight of the substance is variable; however, it is expected to be larger than 500 g/mole, which is considered the limit for size exclusion by the skin.

 

Phenol, dodecyl-,branched, sulfurized is expected to be very lipophilic. The structurally similar compounds, phenol, tetrapropenyl-, sulfurized, carbonates, calcium salts (CAS # 122384-86-5) and phenol, tetrapropenyl-, sulfurized, calcium salts (CAS # 68855-45-8) have log Kow’s of 9.5 and 10.1, respectively. Maximum absorption is generally between log kow 1 and 2 and therefore the substance is expected to be too lipophilic to be readily absorbed. This is because the penetrant has to be lipophilic enough to cross the lipophilic portion of the membrane, but hydrophilic enough to pass the hydrophilic portion. The water solubility of this substance has not been measured; however, it can be expected to be <0.206 mg/L based on the measured value for a structurally similar compound. This indicates that the substance evaluated here is likely not to be soluble in water, thus further decreasing the potential for complete penetration.

 

Based on these physical chemical properties, this material is predicted to be absorbed very slowly and no significant systemic uptake is expected. This is supported by animal testing in structurally similar compounds in which no effects were observed following acute dermal exposure and minimal effects were observed in subacute testing. Two 4-week repeat dose dermal studies in rabbits indicated absorption and subsequent distribution based on decreased weight and pathology in male reproductive tissues and markers of liver toxicity (Biodynamics 1981, 1983). Another study by Korenga (1986), using a different formulation and removal after a daily 6-h exposure, did not find systemic toxicity at the same nominal dose (25%). This indicated that contact time is likely to be relevant to passage through the skin and is consistent with the physical chemical properties that suggest delayed absorption. These observations suggest poor percutaneous penetration and/or the substance has low inherent systemic toxicity. The registered substance will likely exhibit the same limited absorption profile following dermal exposure.

 

Oral Route:The same physical chemical factors that affect dermal absorption also affect absorption from the gastrointestinal (GI) tract. The difference being that log kow between 0 and 4 are optimal for GI absorption. The expected high lipophilicity, low water solubility, and large molecular weight of the registered substance are not favorable for GI absorption. Transport across cell membranes by forming a complex with carrier protein(s) is unlikely to occur because the material is not expected to bind to protein (OECD ToolBox version 1.1). Therefore, the overall absorption rate is estimated to be slow and inefficient. This argument is supported by the results obtained from animal toxicity tests conducted in structurally similar compounds in which acute toxicity was not observed (i.e., LD50s were greater than 5000 mg/kg) and a low order of toxicity (i.e., minimal effects at 1000 mg/kg/day) was observed in subacute and chronic toxicity studies. In those studies, Lamb (1993) showed increased adrenal weight after an oral 28-day repeat dose toxicity/ neurotoxicity study with recovery phase. There was similar evidence of systemic toxicity to both parental and F1 generation animals in two 2-generation reproductive studies with exposure durations of more than 90 days (Nemec 1995, Lamb 1993). Taken together, the physical chemical properties and the relatively low toxicity observed in the animal studies suggest that either low levels of the test substance were absorbed, and/or the test material has low inherent toxicity. The registered substance will most likely exhibit the same limited absorption profile following oral exposure.

 

Distribution

Some of the factors that affect absorption will also affect the distribution of chemicals within the body. In general, the more lipophilic the substance, the more readily it will move into the tissues and the more highly perfused tissues such as heart, liver and kidney will receive the bulk of the absorbed chemical. Plasma protein binding can influence the movement of chemicals from blood to tissue, however, this substance is not expected to bind protein. The tissue effects observed in Schroeder (1998) and Nemec (1994) were minimal, but do suggest that either small levels of the test substance are distributed, and/or the substance has low inherent toxicity.

Bioaccumulation:A bioaccumulation study has not been conducted on the registered substance, however test data from a structurally similar compound are available that indicate the substance is not expected to significantly concentrate in tissue. In those studies, both a 28-day and a 2-generation study by Lamb set a NOAEL at 200 mg/kg using the same dose schedule. If a lipophilic compound were to bioaccumulate, the likelihood is that a long term study would determine a lower NOAEL; therefore, while not definitive, it is hypothesized that the test compound is eliminated from the body rather than bioaccumulating to an effects level detectable by these studies. Additional tangential evidence that compound does not bioaccumulate can be observed in the lack of a fatty liver, a tissue effect indicative of lipophilic compounds which bioaccumulate. Supporting the expectation for a lack of bioaccumulation is that the structurally similar compound was not found to bioconcentrate in aquatic organisms (Rausina 1996). It is unclear whether the lack of bioaccumulation is due to low absorption potential leading to limited distribution or whether the substance has a low potential for bioconcentration or cumulative effects. The registered substance is expected to exhibit this same distribution profile with a lack of significant bioaccumulation potential.

 

Metabolism

Acute and repeated-dose toxicity studies with structurally similar compounds suggest the parent compound(s) are not transformed to toxic metabolites based on the low order of toxicity observed. Additionally, the cytotoxic concentrations from in vitro genetic toxicity tests were the same with or without metabolic activation. For those compounds, OECD Toolbox v1.1 predicted metabolites with functional groups suitable for conjugation reaction with phase II enzymes. The registered test substance has the potential to be subject to similar hydroxylation, oxidation and reduction reactions mediated by liver enzymes or enzymes from intestinal microflora and will likely exhibit the same metabolic profile as the structurally similar compounds.

 

Excretion

The metabolic assessment indicates that this substance has the potential to undergo biotransformation and form breakdown products. If these metabolites were not assimilated into normal cellular metabolic pathways, they were expected to readily undergo routine renal and/or biliary excretion based on the predicted structures.

 

Summary

The toxicokinetics of phenol, dodecyl-, branched, sulfurized have not been directly studied. Oral studies conducted in structurally similar compounds indicate that these salts may be absorbed to a limited extent in the gastrointestinal tract resulting in further distribution and metabolism. Because of its high lipophilicity, they may accumulate to some degree in fatty tissues and be released slowly; however the finding of similar NOAELs in 28-day and 90-day studies using the same dose schedule indicates that elimination is occurring. The liver is expected to be the primary organ to receive and metabolize the substance, making it more soluble by oxidation and conjugation for eventual release into the bile and into the gastrointestinal tract for elimination. Phenol, dodecyl-, branched, sulfurized is above the size threshold expected to easily penetrate skin, and the degree of absorption through the skin or respiratory system is limited, but regardless of the route of exposure, there is no indication that systemically distributed phenol, dodecyl-, branched, sulphurised will bioaccumulate.