Comparative influences of dermal and inhalational routes of exposure on hazards of cleaning product ingredients among mammalian model organisms.

Health risks resulting from dermal or inhalational exposures are frequently assessed based on rodent oral toxicity information due to a lack of species- or route-specific toxicity data. Default uncertainty factors (UFs; e.g., 10-fold) are also applied during risk assessments to account for variability such as inter-species, intra-species, exposure duration, dose-response, and route-to-route extrapolations. However, whether rodent oral data and a default UF approach can provide adequate protection for other mammalian species under dermal or inhalational exposure scenarios remains understudied, particularly for cleaning product ingredients. Therefore, we collated and examined publicly available median lethal dose (LD50), no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values from different types of standard mammalian toxicity studies for rats (dermal and inhalational), mice, rabbits, guinea pigs, and dogs (oral, dermal and inhalational) using the Cleaning Product Ingredient Safety Initiative (CPISI) database. Probabilistic hazard assessments using chemical toxicity distributions (CTDs) were subsequently conducted, and threshold concentrations (TCs) and 95% confidence intervals (95% CIs) were derived to identify thresholds of toxicological concern (TTCs). Relative sensitivities among or between mammalian species, exposure routes, and chemical classes were also compared based on calculated TC5s and 95% CIs to support future toxicology studies and hazard and risk assessments. We then identified uncertainty factors (UFs) using both CTD comparisons and individual UF probability distributional approaches. Based on available rodent inhalational data, chemical category-specific UFs were derived for ethers. Additionally, we also determined whether default UFs of 10 or 100 would be protective for various distributions of cleaning product ingredients. Our novel observations among these routes of exposure and common mammalian model organisms appear particularly useful for read across and screening-level health hazard and risk assessments when limited data exists for specific chemicals.

Critical review and probabilistic health hazard assessment of cleaning product ingredients in all-purpose cleaners, dish care products, and laundry care products.

Though numerous chemical ingredients are used in cleaning products, empirical mammalian toxicology information is often limited for many substances. Such limited data inherently presents challenges to environmental health practitioners performing hazard and risk assessments. Probabilistic hazard assessment using chemical toxicity distributions (CTDs) is an alternative approach for assessments of chemicals when toxicity information is lacking. The CTD concept allows for derivation of thresholds of toxicological concern (TTCs) to predict adverse effect thresholds for mammalian species. Unfortunately, comparative health hazard assessment of cleaning product ingredients in common use categories such as all-purpose cleaners (APC), dish care products (DCP) and laundry care products (LCP) has not been well studied. However, APC, DCP, and LCP are used routinely for household and industrial applications, resulting in residential and industrial occupational exposures. Therefore, we reviewed and then examined hazard information (median lethal dose (LD50), lowest-observed-adverse-effect level (LOAEL), and no-observed-adverse-effect level (NOAEL)) from different types of standard mammalian toxicity studies for oral toxicity in the rat model from the unique Cleaning Product Ingredient Safety Initiative mammalian toxicology database. Probabilistic distributions (CTDs) were subsequently constructed using LD50, NOAEL and LOAEL data from a specific toxicity study type for all available ingredients in these three use categories. Based on data availability, product type-specific and chemical category-specific CTDs were also generated and compared. For each CTD, threshold concentrations (TCs) and their 95% confidence intervals (95% CIs) at 1st, 5th, 10th, 50th, 90th, 95th and 99th percentiles were calculated using the log-normal model. To test whether the common default uncertainty factor (UF) approach (e.g., 3, 10) in mammalian health risk assessment provides sufficient protection, UFs were also derived for LOAEL-to-NOAEL and exposure duration (e.g., subchronic-to-chronic) extrapolations. Relationships between CTDs of acute LD50s and sublethal LOAELs/NOAELs were also examined for acute-to-chronic ratio calculations, which may be useful in extreme circumstances. Results from our critical review and meta-analysis appear particularly useful for hazard and risk practitioners when identifying TTCs for ingredients in product use categories, and other chemical classes. This approach can also support development of regulatory data dossiers through read across, chemical substitutions and screening-level health risk assessments when limited or no empirical toxicity information exists for industrial chemicals.

Identification of novel uncertainty factors and thresholds of toxicological concern for health hazard and risk assessment: Application to cleaning product ingredients.

Uncertainty factors (UFs) are commonly used during hazard and risk assessments to address uncertainties, including extrapolations among mammals and experimental durations. In risk assessment, default values are routinely used for interspecies extrapolation and interindividual variability. Whether default UFs are sufficient for various chemical uses or specific chemical classes remains understudied, particularly for ingredients in cleaning products. Therefore, we examined publicly available acute median lethal dose (LD50), and reproductive and developmental no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values for the rat model (oral). We employed probabilistic chemical toxicity distributions to identify likelihoods of encountering acute, subacute, subchronic and chronic toxicity thresholds for specific chemical categories and ingredients in cleaning products. We subsequently identified thresholds of toxicological concern (TTC) and then various UFs for: 1) acute (LD50s)-to-chronic (reproductive/developmental NOAELs) ratios (ACRs), 2) exposure duration extrapolations (e.g., subchronic-to-chronic; reproductive/developmental), and 3) LOAEL-to-NOAEL ratios considering subacute/acute developmental responses. These ratios (95% CIs) were calculated from pairwise threshold levels using Monte Carlo simulations to identify UFs for all ingredients in cleaning products. Based on data availability, chemical category-specific UFs were also identified for aliphatic acids and salts, aliphatic alcohols, inorganic acids and salts, and alkyl sulfates. In a number of cases, derived UFs were smaller than default values (e.g., 10) employed by regulatory agencies; however, larger UFs were occasionally identified. Such UFs could be used by assessors instead of relying on default values. These approaches for identifying mammalian TTCs and diverse UFs represent robust alternatives to application of default values for ingredients in cleaning products and other chemical classes. Findings can also support chemical substitutions during alternatives assessment, and data dossier development (e.g., read across), identification of TTCs, and screening-level hazard and risk assessment when toxicity data is unavailable for specific chemicals.

Relationships between benthic macroinvertebrate community structure and geospatial habitat, in-stream water chemistry, and surfactants in the effluent-dominated Trinity River, Texas, USA.

Over the past 20 years, benthic macroinvertebrate community structure studies have been conducted on the upper Trinity River, Texas, USA, which is dominated by municipal wastewater treatment plant (WWTP) and industrial effluents. The Trinity River is located in the Dallas-Fort Worth metropolitan area, and is the most highly populated and industrialized watershed in Texas. As such, the Trinity River represents a near-worst-case scenario to examine the environmental effects of domestic-municipal and industrial effluents on aquatic life. A 1987 to 1988 study concluded that many stretches of the river supported a diverse benthic community structure; however, a decline in taxa richness occurred immediately downstream of WWTPs. A 2005 study designed to parallel the 1987 to 1988 efforts evaluated how changes in water quality, habitat, and increased urbanization impacted benthic community structure. Physicochemical measurements, habitat quality, geospatial variables, and benthic macroinvertebrates were collected from 10 sites. Surfactants were measured and toxic units (TUs) were calculated for surface water and pore water as indicators of domestic/household use of cleaning products. Total TUs indicated a low potential for biological impacts. Toxic unit distribution was not dependent on WWTP location and did not correlate with any benthic variable. Eight environmental parameters were determined to be useful for predicting changes in benthic macroinvertebrate community structure: surfactant surface water TUs (SWTU), in-stream habitat cover, and surface water total organic carbon were the top three parameters. Abundance, taxa richness, and taxa similarity in 2005 had increased since the earlier study throughout the immediate vicinity of the metropolitan area.

Occurrence and weight-of-evidence risk assessment of alkyl sulfates, alkyl ethoxysulfates, and linear alkylbenzene sulfonates (LAS) in river water and sediments.

Alkyl sulfates (AS), alkyl ethoxysulfates (AES) and linear alkyl benzene sulfonates (LAS) are all High Production Volume (HPV) and 'down-the-drain' chemicals used globally in detergent and personal care products, resulting in low levels ultimately released to the environment via wastewater effluent. Due to their surfactant properties, they preferentially sorb to sediments. Hence, assessment of their levels and potential perturbations on benthos are of interest. The relative levels of AS/AES decreased with distance from the wastewater treatment plant outfall. However, this was not evident for LAS. Short chained AES and especially AS dominated the homologue distribution for AES. There were no evident patterns in LAS homologue distribution. The overall mean margin of exposure (MoE) for AS/AES and LAS is approximately 40 (range: 3 to 100) suggesting no noteworthy perturbation on biota. The findings in this study are in concordance with previous preliminary hazard screening. Comparative sediment contamination analyses principally based on Chapman and Anderson [Chapman PM, Anderson, J. A decision-making framework for sediment contamination. Integr Environ Assess Mana. 2005; 1: 163-173.] and the U.S. Environmental Protection Agency RAPID assessment methods [USEPA. Rapid bioassessment protocols for use in wadeable streams and rivers: Periphyton, benthic, macroinvertebrates, and fish. 1999. Second Edition. U.S. Environmental Protection Agency Office of Water, Washington, D.C. EPA 841-B-99-002.] did not reveal significant correlations between the surfactant concentrations and ecological status of the sampling locations. Several Lines of Evidence (LoE) of the Weight-of-Evidence (WoE) lead to the conclusion of low aquatic risk associated to the monitored compounds.