A urinary biomarker for monitoring exposures to 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate in rats. 2023

Toshiaki Yoshida
Department of Environmental Health, Osaka Institute of Public Health, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan. tsyosida@iph.osaka.jp.

2,2,4-Trimethyl-1,3-pentanediol monoisobutyrate (TMPD-MB) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TMPD-DB) are widely used primarily as surface stabilizers for water-based paints and plasticizers, respectively. Exposure to these compounds has been suspected as being associated with sick building syndrome and allergic diseases such as asthma in general populations. Therefore, it is very important to be able to know the amounts of these compounds absorbed into the body in order to evaluate its adverse effects on humans in living environments. In the present study, the urinary excretion kinetics of TMPD-MB and TMPD-DB were studied in animals to establish for urinary metabolites suitable as biomarkers for monitoring exposure. A single dose (48-750 mg/kg body weight) of TMPD-MB or TMPD-DB was administered intraperitoneally to male Sprague-Dawley rats, and their urine was collected periodically for a week. Two major metabolites, 2,2,4-trimethyl-1,3-pentanediol (TMPD) and 3-hydroxy-2,2,4-trimethylvaleric acid (HTMV), were measured in the urine samples. Their kinetics were evaluated by moment analysis of the urinary excretion rates of the metabolites versus time curves. The urinary excretion amounts of HTMV were suggested to be proportional to the absorption amounts over a wide exposure range of both TMPD-MB and TMPD-DB. The amounts of HTMV accounted for almost the same level, i.e., 4-5% of the dose at the lowest dosage, in rats tested for both TMPD-MB and TMPD-DB. Urinary HTMV was considered to be an optimal biomarker for monitoring exposure to mixtures of these compounds.

UI MeSH Term Description Entries
D008297 Male Males
D006018 Glycols A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015415 Biomarkers Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc. Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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