ABSTRACT
Autistic adults experience disparities in physical health and health care access. A major barrier to addressing these disparities is a lack of federal funding for research on this topic. In seeking funding from the National Institutes of Health (NIH), we discovered nodes that contribute to structural discrimination in physical health-related research for autistic adults. To examine this structural discrimination, we systematically searched funded research on all physical health-disparity conditions in autistic adults using NIH RePORTER. Among 61 unique studies, none focused on improving the relevant physical health condition through intervention, programs, or services for autistic adults. Thus, we need updated policies and procedures that support research on physical health disparities in populations with developmental or mental health conditions.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adult , United States , Humans , National Institutes of Health (U.S.) , Health Services AccessibilityABSTRACT
Published self-determination programs do not adequately address the needs of autistic adults. We designed a multi-component self-determination program, grounded in the neurodiversity paradigm, to help autistic adults achieve goals to improve their quality of life. The first phase involved 5 days of psychoeducation, practice, and social events; the second phase included 3 months of telecoaching; and the third phase included follow-up. Thirty-four university students coached 31 autistic adults on three evolving goals. On average, participants completed one goal per week. Most participants were satisfied with the program. We found that the program was appropriate, acceptable, and feasible. This program is a promising approach to helping autistic adults gain self-determination skills and improve their quality of life.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adult , Humans , Quality of Life , Feasibility Studies , Personal AutonomyABSTRACT
The prevalence of autism has increased dramatically over the last 60 years, and the cause of this increase is unclear. In this paradigm-shift paper, I propose an explanatory paradigm for the cause of autism and its increased prevalence in the general population. I also discuss how social and historical contexts may have influenced the evolution and manifestation of specific traits in the autism population. These traits expand the characterization of the broader autism phenotype to include a constellation of socially valued traits, termed Broader Autism Phenotype Constellations (BAPCO). The frequency of these traits may have increased due to assortative mating opportunities that occurred alongside social changes in education and occupational opportunities over the last 100 years. I propose that assortative mating can lead to both positive and negative developmental consequences affecting social and language development. I also propose that BAPCO traits, which are not intrinsically disabilities, could interact with co-occurring conditions in a new model called the BAPCO-Disability Matrix Paradigm (BAPCO-DMAP). In this paradigm, autism is located at the intersection of BAPCO traits and at least one co-occurring condition. These proposed models support the need to create a more comprehensive definition of autism that includes constellations of BAPCO traits. The BAPCO-DMAP paves the way to testable predictions of autism prevalence and provides a framework to better understand the foundational traits of autism. Finally, this paradigm radically redefines the broader autism phenotype with characteristics that can inform therapy and child development.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Child , Humans , Models, Theoretical , Phenotype , PrevalenceABSTRACT
BACKGROUND: A population segment of autistic adults are under-identified due, in part, to historic changes in criteria for diagnosing autism and diagnostic biases related to gender, socioeconomic status, and other individual characteristics such as intellectual functioning. Some of these individuals, described as the "lost generation", may choose to self-diagnose. Although little is known about this population, it is possible that they share similar self-conceptualizations or internalized stigma as their diagnosed counterparts. This study reports on the structural validity of the Autism Spectrum Identity Scale (ASIS) with individuals diagnosed and self-diagnosed with autism and compares the demographic characteristics, stigma, self-concept, and quality of life of these two groups. METHODS: Over 1000 adults diagnosed (n = 893) or self-diagnosed (n = 245) with autism were recruited through organizations serving the autism community to participate in a nationally distributed online survey that included demographic questions and measures for stigma, self-concept, quality of life, and wellbeing. The diagnosed dataset was randomly split with exploratory factor analysis performed on a training dataset. Split-half cross-validation was used to predict the factor structure of the holdout dataset. Then, the full diagnosed dataset structure was used to determine the generalizability of the factor structure to the self-diagnosed dataset. The diagnosed and self-diagnosed were also compared for differences in gender, age, employment status, diagnostic term preference, and factors of self-concept (autism identity and self-esteem), stigma, and quality of life. RESULTS: Factor analysis of diagnosed participants yielded a four-factor structure, consistent with previous research, with strong split-sample cross-validation and good internal consistency. Factor predictions of the self-diagnosed dataset from the diagnosed dataset ranged from .97 - 1.00 with similar internal consistency. Self-diagnosed participants were more likely to be older, women, or employed and less likely to be students or prefer the term "autism" than those with an autism diagnosis. The groups were remarkably similar in reported stigma, self-esteem, quality of life and in ASIS factors; both groups reported lower quality of life than the general population. CONCLUSIONS: The ASIS demonstrated the same internal structure with both the diagnosed and self-diagnosed. The profile of self-diagnosed participants matches the profile hypothesized for the "lost generation" and others at risk of being under-identified for autism. Both populations appear to be similarly struggling with employment, stigma, and quality of life. Future research should examine whether self-diagnosed individuals meet criteria for autism or could benefit from interventions, programs, or services serving autism communities.
ABSTRACT
The original version of this article contains an error in Results and Discussion sections and in Table 2. The corrected text and table are given below. Results: Participants' scores were higher for overall stigma and discrimination than those reported by King et al (2007). The pattern of descriptive statistics for the AAQOL was simialr to that reported by Brod et al. (2006). Discussion: Of note, participants in this study scored approximately 30 points lower than the non-ADHD scores on the AAQOL as reported by Brod and colleagues (2006). The distribution of scores in the current study more closely resembled the distribution of scores by those with ADHD than the non-ADHD control group. This is consistent with the widespread reports of decreased quality of life for adults on the autism spectrum (e.g., Howlin and Moss 2012; Taylor & Seltzer 2011). Further, and consistent with reports of increased stigma (e.g., Shtayermnan, 2009; Tyman, Salor, Saia, et al. 2010), participants in this study scored approximately 20 points higher for overall stigma, and ten points higher for discrimination, than participants with mental illness as reported by King and colleagues (2007).
ABSTRACT
Individuals on the autism spectrum face stigma that can influence identity development. Previous research on the 22-item Autism Spectrum Identity Scale (ASIS) reported a four-factor structure with strong split-sample cross-validation and good internal consistency. This study reports the discriminative and criterion validity of the ASIS with other measures. Adults (n = 1139) who have, or identify with, an autism spectrum diagnosis took a nationally distributed online survey that also included demographic questions and measures for stigma, self-esteem, and quality of life (QoL). All four ASIS factors discriminated from measures of stigma and self-esteem. The ASIS also showed good criterion validity with the factors of Positive Difference and Changeability demonstrating widespread relationships with subjective quality of life in the expected directions.
Subject(s)
Autism Spectrum Disorder/diagnosis , Quality of Life , Self Concept , Social Stigma , Surveys and Questionnaires/standards , Adult , Autism Spectrum Disorder/psychology , Female , Humans , Male , Middle Aged , Reproducibility of Results , Young AdultABSTRACT
This paper is a single case study involving a visit to a diagnostic clinic for autism spectrum disorder. A young boy finds a toy that he can hold with one hand and spin with another. In order to retrieve the toy and leave it in the clinic, the parents engage in a team effort. We describe this achievement in terms of two styles of practice or interactional routines with differing participation frameworks.We examine not only how the parents work as a team using these styles, but also how they improvise to extract the spinning toy from their son's grasp with minimal protest on his part.
Subject(s)
Autism Spectrum Disorder/psychology , Parent-Child Relations , Play and Playthings/psychology , Child, Preschool , Humans , MaleABSTRACT
This study examined the perceptions of adulthood among 31 high school students with autism spectrum disorder (ASD). We had two research aims: (1) to report students' postsecondary expectations in terms of school, work, friendships and living arrangement and (2) to describe how our sample defined adulthood. To better compare our sample's criteria of adulthood to the criteria traditionally endorsed in secondary schools, we used a directed content analysis approach. Data were derived from a semi-structured interview that questioned students about friendships, activities and the transition to adulthood. The majority of students expected to attain traditional markers of adulthood after high school; however, for some the pathways to achieving these outcomes were narrowly defined and perceived as a rigid, linear process. Independence, maturity and personal responsibility were the most highly endorsed characteristics of adulthood, followed by chronological age and traditional markers. Implications for transition planning and adult services are discussed.
ABSTRACT
BACKGROUND: 'Ageing in place' is widely promoted as a response to global ageing and increased demand for services, but little evidence is available about what older people think they need in terms of services and supports to remain at home. AIM: To investigate older people's needs when ageing in place in order to provide evidence to inform policies and strategies promoting the option of ageing in place. METHODS: A total of 568 elderly persons in Hangzhou, China, were surveyed in 2009-2011 using a modified questionnaire validated in the USA and China. RESULTS: Overall, 88.9% of older adults were satisfied with the community in which they live; 97.2% were satisfied with life quality. Health problems and healthcare access difficulty increased with age. House repairs and housework were the most troubling. Respondents identified high need for social and health promotion services and this varied across age groups. LIMITATIONS: Cultural adaptation and validation of the questionnaire could have been influenced by differences in socioeconomic and cultural factors. The sample excluded older adults with disabilities, bed-ridden and/or unable to communicate thus limiting the scope of relevance. CONCLUSION: A majority of older adult respondents ageing at home lived a relatively healthy life; however, they required more comprehensive health insurance to cover costs of long-term health problems and access to home care support. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The needs of community-dwelling older Chinese people in the Xiacheng District are not being fully met and much remains be done to increase community and regional capacity before ageing in place can be promoted as a policy strategy. More generally, nursing and health policies geared to enhance the self-sufficiency of older people residing in their communities must draw upon evidence of assessed needs and client perspectives of their requirements before services can be designed and delivered.
Subject(s)
Geriatric Nursing/organization & administration , Health Promotion/organization & administration , Health Services Needs and Demand/organization & administration , Home Nursing/organization & administration , Homes for the Aged/organization & administration , Independent Living , Nursing Homes/organization & administration , Aged , Aged, 80 and over , China , Community Health Services/organization & administration , Cross-Sectional Studies , Female , Frail Elderly , Humans , Male , Middle Aged , Quality of LifeABSTRACT
PEGylation is the technology involving the covalent attachment of polyethylene glycol (PEG) to a protein-, peptide- or small-molecule drug to improve their pharmacokinetic, pharmacodynamic and immunological profiles, and thus, enhance the therapeutic effect. Today, PEGylation of proteins is a well-established technology and is being used in the treatment of a variety of clinical disorders. Several PEGylated coagulation proteins for haemophilia A and B are under development with the goal of prolonging the circulation half-life of factor VIII (FVIII) or factor IX. The prolongation of half-life, resulting in less frequent injections can provide significant benefits in improving the quality of life of subjects with haemophilia and improvement in adherence to treatment. A review of published literature on PEGylated therapeutic products currently approved for human use and a discussion of a PEGylated recombinant FVIII molecule (BAY 94-9027, Bayer HealthCare, Berkeley, CA, USA) currently being investigated in the pivotal clinical trial prior to registration is provided. Available safety information of PEGylated proteins containing high molecular weight PEG does not indicate any safety concerns to date, following long-term (chronic) use in animal models or patients. Chronic use of currently available PEGylated products has been shown to be safe, paving the way for chronic use of PEGylated coagulation products in persons with haemophilia.
Subject(s)
Factor IX/therapeutic use , Factor VIII/therapeutic use , Hemophilia A/drug therapy , Hemophilia B/drug therapy , Polyethylene Glycols/therapeutic use , Caregivers , Factor IX/pharmacokinetics , Factor VIII/pharmacokinetics , Humans , Polyethylene Glycols/pharmacokineticsABSTRACT
High background levels of phenol and hydroquinone are present in the blood and urine of virtually all individuals, but vary widely. Phenol and hydroquinone have been strongly implicated in producing leukemia associated with benzene exposure, because they reproduce the hematotoxicity of benzene, cause DNA and chromosomal damage found in leukemia, inhibit topoisomerase II, and alter hematopoiesis and clonal selection. The widely varying background levels of phenol and hydroquinone in control individuals stem mainly from direct dietary ingestion, catabolism of tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing foods, cigarette smoking, and the use of some over-the-counter medicines. We hypothesize that these background sources of phenol and hydroquinone and associated adducts play a causal role in producing some forms of de novo leukemia in the general population. This hypothesis is consistent with recent epidemiological findings associating leukemia with diets rich in meat and protein, the use of antibiotics (which change gastrointestinal flora make-up), lack of breastfeeding, and low activity of NAD(P)H quinone oxidoreductase which detoxifies quinones derived from phenol and hydroquinone and protects against benzene hematotoxicity. An attractive feature of our hypothesis is that it may explain why many people who have no known occupational exposures or significant smoking history develop leukemia. The hypothesis predicts that susceptibility to the disease would be related to diet, medicinal intake, genetics and gut-flora composition. The latter two of these are largely beyond our control, and thus dietary modification and reduced use of medicines that elevate phenol levels may be the best intervention strategies for lowering leukemia risk.
Subject(s)
Hydroquinones/toxicity , Leukemia/etiology , Mutagens/toxicity , Phenols/toxicity , Diet/adverse effects , Digestive System/metabolism , Humans , Hydroquinones/metabolism , Leukemia/metabolism , Mutagens/metabolism , Phenols/metabolismABSTRACT
Abnormal repetitive behaviors such as stereotypies are associated with neurodevelopmental disorders and are often observed under conditions of environmental restriction, particularly early in development. Few studies, however, have systematically assessed the effects of environmental enrichment and almost no information is available as to whether a sensitive period exists for such enrichment effects. We hypothesized that spontaneous stereotypies exhibited by deer mice housed under standard laboratory conditions were the result of environmental restriction and that a sensitive period exists for the development/prevention of stereotypies. Exposure to a more complex environment early in the post-weaning period resulted in substantially less stereotypy in the complex environment. Importantly, this outcome was maintained even after mice were housed in standard cages for an identical period of time. Later exposure to the more complex environment also resulted in significantly lower levels of stereotypy compared to controls. These effects were observed in the experimental housing condition as well as in a standard test context. The effects of early and late enrichment support the importance of environmental restriction in the genesis of stereotype and provide support for the efficacy of early and late enrichment in the prevention of stereotypies.
Subject(s)
Behavior, Animal/physiology , Environment , Peromyscus/psychology , Stereotyped Behavior/physiology , Age Factors , Animals , Animals, Newborn/psychology , Female , Male , MiceABSTRACT
Levels of the polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, appear to be rising rapidly in human tissues, as evidenced by studies of human breast milk. The case of the PBDEs illustrates the value of breast-milk monitoring programs in identifying important emerging pollutants, and highlights why such monitoring programs are needed in the United States. A review of the use, occurrence, and toxicity of PBDEs indicates many parallels between some PBDEs, PCBs, and other polyhalogenated persistent organic pollutants, and suggests that the PBDEs may be a significant environmental challenge in the future.
Subject(s)
Milk, Human/chemistry , Phenyl Ethers/analysis , Polybrominated Biphenyls/analysis , Animals , Endocrine Glands/drug effects , Environmental Health , Environmental Monitoring , Environmental Pollutants/analysis , Environmental Pollutants/toxicity , Female , Flame Retardants/analysis , Flame Retardants/toxicity , Humans , Nervous System/drug effects , Nervous System/embryology , Nervous System/growth & development , Phenyl Ethers/toxicity , Polybrominated Biphenyls/toxicity , Receptors, Aryl Hydrocarbon/drug effects , United StatesABSTRACT
This study examines the initial activation of benzene, exploring key aspects of its metabolism by measurement of benzene oxide (BO) and BO-protein adducts in vitro and in vivo. To assess the potential influence of various factors on the production of BO, microsomes were prepared from tissues that were either targets of benzene toxicity, i.e. the bone marrow and Zymbal glands, or not targets, i.e. liver and kidneys, of control and acetone-treated F344 rats. No BO or phenol was detected in microsomal preparations of bone marrow or Zymbal glands (less than 0.007 nmol BO/mg protein and 0.7 nmol phenol/mg protein). On the other hand, BO and phenol were readily detected in preparations of liver and kidney microsomes and acetone pretreatment resulted in a 2-fold (kidney) increase or 3.7-fold (liver) increase in production of these metabolites. Initial rates of BO production in the liver isolates were 30 (control) to 50 (acetone-treated) times higher than in the corresponding kidney tissues. The estimated half-life of BO in bone marrow homogenates was 6.0 min and the second-order reaction rate constant was estimated to be 1.35 x 10(-3) l (g bone marrow)(-1) (h)(-1). These kinetic constants were used with measurements of BO-bone marrow adducts in F344 rats, receiving a single gavage dosage of 50-400 mg benzene (kg body weight)(-1) (McDonald, T.M., et al. (1994), Cancer Res. 54, 4907-4914), to predict the bone marrow dose of BO. Among the rats receiving 400 mg (kg body weight) (-1), a BO dose of 1.13 x 10(3) nM BO-h was estimated for the bone marrow, or roughly 40% of the corresponding blood dose predicted from BO-albumin adducts. Together these data suggest that, although BO is not produced at detectable levels in the bone marrow or Zymbal glands of F344 rats, BO is rapidly distributed via the bloodstream to these tissues where it may play a role in toxicity.
Subject(s)
Benzene/metabolism , Bone Marrow/metabolism , Cyclohexanes/metabolism , Animals , Phenol/metabolism , Rats , Rats, Inbred F344ABSTRACT
Little is known about the formation and disposition of benzene oxide (BO), the initial metabolite arising from oxidation of benzene by cytochrome P450. In this study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated in blood from B6C3F1 mice, F344 rats, and humans in vitro. The estimated half-lives of BO in blood were 6.6 min (mice), 7.9 min (rats), and 7.2 min (humans). The following second-order rate constants were estimated for reactions between BO and cysteinyl residues of Hb and Alb [in units of L (g of Hb- or Alb-h)-1]: mouse Hb = 1.16 x 10(-)4, rat Hb = 15.4 x 10(-)4, human Hb = 0.177 x 10(-)4, mouse Alb = 2.68 x 10(-)4, rat Alb = 4.96 x 10(-)4, and human Alb = 5.19 x 10(-)4. These rate constants were used with BO-adduct measurements to assess the systemic doses of BO arising from benzene in vivo in published animal and human studies. Among rats receiving a single gavage dose of 400 mg of benzene/kg of body weight, the BO dose of 2.62 x 10(3) nM BO-h, predicted from Alb adducts, was quite similar to the reported AUC0-infinity = 1.09 x 10(3) nM BO-h of BO in blood. Interestingly, assays of Hb adducts in the same rats predicted a much higher dose of 14.7 x 10(3) nM BO-h, suggesting possible in situ generation of adducts within the erythrocyte. Doses of BO predicted from Alb adducts were similar in workers exposed to benzene [13.3 nM BO-h (mg of benzene/kg of body weight)-1] and in rats following a single gavage dose of benzene [8. 42 nM BO-h (mg of benzene/kg of body weight)-1]. Additional experiments indicated that crude isolates of Hb and Alb had significantly higher levels of BO adducts than dialyzed proteins, suggesting that conjugates of low-molecular-weight species were abundant in these isolates.
Subject(s)
Cyclohexanes/metabolism , Hemoglobins/metabolism , Serum Albumin/metabolism , Animals , Cyclohexanes/blood , Humans , Male , Mice , Rats , Rats, Inbred F344ABSTRACT
Benzene is metabolized to a number of electrophilic species that are capable of binding to both DNA and proteins. We used adducts of hemoglobin (Hb) and bone marrow proteins to study the disposition of three benzene and metabolites (benzene oxide [BO], 1,2-benzoquinone [1,2-BQ], and 1,4-benzoquinone [1,4-BQ]) in F344 rats and B6C3F1 mice following a single oral dosage of [13C6]benzene and/or [14C]benzene. Our assays focused upon cysteine adducts that accounted for 38 to 45% of protein binding to Hb and 63 to 81% of protein binding to bone marrow. Although both mice and rats showed dose-related increases in Hb and bone marrow protein adducts of BO and of the two benzoquinones, large intertissue and interspecies differences were noted, suggesting different preferences in metabolic pathways. The highest levels of adducts in mice were of 1,4-BQ (10-27% of all cysteine adducts), while in rats, BO adducts predominated in Hb (73% of all cysteine adducts) and 1,2-BQ adducts predominated in the bone marrow (14% of all cysteine adducts). High background levels of 1,2-BQ and 1,4-BQ adducts were also detected in both species, indicating that the toxic effects of quinone metabolites may only be important at high levels of benzene exposure.
Subject(s)
Benzene/metabolism , Benzene/toxicity , Proteins/drug effects , Proteins/metabolism , Animals , Benzoquinones/metabolism , Biomarkers , Bone Marrow/drug effects , Bone Marrow/metabolism , Cyclohexanes/metabolism , Hemoglobins/drug effects , Hemoglobins/metabolism , Male , Mice , Rats , Rats, Inbred F344 , Species SpecificityABSTRACT
A method is reported for measuring cysteinyl adducts of the benzene metabolite benzene oxide (BO) with hemoglobin (Hb) in blood from humans or rodents exposed to benzene. After reacting the purified, dried protein with trifluoroacetic anhydride and methanesulfonic acid, the resulting phenyltrifluorothioacetate is extracted, washed, and detected by GC-MS in the negative-ion chemical ionization mode. The analysis of Hb adducts of BO from rats dosed with 50-400 mg/kg [13C6]benzene via this method resulted in values which were generally consistent, though slightly lower, than those obtained using an established method. However, while 3 weeks were required to process the samples by the former method, only 2 days were needed with the new procedure. This new method should, therefore, prove to be reliable and convenient for the rapid quantitation of cysteine-bound Hb adducts of BO.
Subject(s)
Cyclohexanes/metabolism , Hemoglobins/metabolism , Animals , Benzene/metabolism , Gas Chromatography-Mass Spectrometry , Male , Rats , Rats, Inbred F344ABSTRACT
Protein binding of hemoglobin (Hb) and bone marrow was used to compare in vivo reactions of 3 electrophilic metabolites of benzene, i.e., benzene oxide and 1,2- and 1,4-benzoquinone (1, 2-BQ and 1, 4-BQ), in F344 rats and B6C3F1 mice. Following a single p.o. administration of a mixture of [14C]- and [13C6]benzene between 50 and 400 mg/kg body weight, cysteine adducts of benzene oxide, 1,2-BQ, and 1,4-BQ were assayed, and the proportions of cysteine-bound adducts to total protein binding were estimated. Although dose-related production of each adduct was seen, large differences were observed between species and tissues. With rat Hb, benzene oxide adducts represented 27% of the total Hb binding and 73% of the cysteinyl binding, whereas quinone adducts represented relatively small proportions. However, with mouse Hb, the 1,4-BQ adducts accounted for 5.5% of the total Hb binding and 12.2% of the cysteinyl binding, while 1,2-BQ and benzene oxide each accounted for less than 3% of the total. In the bone marrow of both rats and mice, BQ adducts were more abundant than those of benzene oxide. However, adducts of 1,2-BQ predominated in rat marrow (9% of binding), whereas adducts of 1,4-BQ were more abundant in the mouse (21% of binding). The average blood concentrations of 1,4-BQ were estimated from the adduct levels and reaction-rate constants to be 2-5-fold higher in the mouse than in the rat. This work suggests that BQ binding is favored over that of benzene oxide in the bone marrow; however, high background levels of BQ adducts, observed with Hb and bone marrow proteins, suggest that any toxic effects of the quinones should only arise from high exposures to benzene.
Subject(s)
Benzoquinones/metabolism , Bone Marrow/chemistry , Cyclohexanes/metabolism , Hemoglobin A/metabolism , Proteins/metabolism , Animals , Cysteine/metabolism , Electrophoresis, Polyacrylamide Gel , Male , Mice , Proteins/isolation & purification , Rats , Rats, Inbred F344 , Species SpecificityABSTRACT
Tetrachloro-1,4-benzoquinone (Cl4BQ), a metabolite of pentachlorophenol (PCP), is believed to play a role in the genotoxicity of PCP. We have developed a method to measure the adducts of Cl4BQ with cysteine residues of hemoglobin (Hb) and albumin (Alb). This method employs the use of Raney nickel to selectively cleave the sulfur-bound adducts. Adducts of Hb and Alb with Cl4BQ were measured following modification of rat blood with Cl4BQ (0-90 microM) in vitro. The formation of both Hb and Alb adducts was linear over the entire range with second-order rate constants of 6.89 and 167 L mol-1 h-1, respectively. The proportions of the concentrations of these Hb and Alb adducts to those of all covalently-bound products were estimated to be 0.053 and 0.178, respectively, at initial Cl4BQ concentrations between 3 and 90 microM. The overall rate of reaction of Cl4BQ in rat blood (in vitro) was pseudo-first-order with an estimated half-time of 4.35 h. Hb and Alb adducts of Cl4BQ were also measured in vivo following oral administration of PCP to rats (0-20 mg/kg body wt). Linear production of Hb and Alb adducts was observed over the entire range of dosages, with slopes of 0.09 and 8.22 pmol of adduct (g of protein)-1 [(mg of PCP)/(kg body wt)]-1, respectively. On the basis of production of Hb adducts in vitro and in vivo, it is estimated that 2.7 x 10(-7) mol of Cl4BQ was released to the blood of rats per mole of PCP administered.(ABSTRACT TRUNCATED AT 250 WORDS)