Biomedical subjects

D W Herr

Publications and source records attributed to D W Herr.

24 records · Page 2Linked to original sources

PubMed1986

Pharmacological modification of DDT-induced tremor and hyperthermia in rats: distributional factors.

Pretreatment of rats with hydantoin (75 mg/kg, PO, an anticonvulsant), trihexyphenidyl (10 mg/kg, SC, a muscarinic cholinergic antagonist), or piperonyl butoxide (500 mg/kg, PO, a metabolic inhibitor) had no effect on the whole blood or brain tissue levels of orally administered DDT (75 mg/kg) or its metabolites DDD and DDE. Hydantoin and piperonyl butoxide decreased DDT-induced tremor and hyperthermia due to DDT when measured 12 h after DDT exposure, while trihexyphenidyl augmented some components of DDT-induced tremor. Additional experiments found that pretreatment with piperonyl butoxide increased tremor due to permethrin exposure (120 mg/kg, PO), while having no effect on tremor due to chlordecone administration (60 mg/kg, IP). Pretreatment with ellipticine (30 mg/kg, IP, a metabolic inhibitor) also decreased tremor 12 h after DDT exposure. The effects of piperonyl butoxide and ellipticine on DDT-induced tremor are postulated to occur through direct actions of these compounds on nerve or muscle tissue. Hydantoin-induced attenuation of DDT-induced neurotoxicity may be due to the ability of hydantoin to block repetitive firing of nerves by binding to the inactivation gates of sodium.

Animals↗

PubMed1985

DDT-induced tremor in rats: effects of pharmacological agents.

Rats given a tremorigenic dose of DDT (75 mg/kg, PO) were treated with pharmacological agents either 30 min prior to DDT or 1-2 h prior to testing at the time of peak effect (12 h postdosing). The administration of mephenesin (a centrally acting muscle relaxant) or Dilantin (an anticonvulsant) prior to DDT significantly attenuated tremor. Pretreatment with pizotifen (a serotonergic receptor antagonist) had no significant effect on tremor. Administration of the same agents 1-2 h prior to measurement had minimal effects. Trihexyphenidyl (a muscarinic cholinergic receptor antagonist) exacerbated the tremor produced by DDT. These data suggest that cholinergic neurotransmitter systems may be involved in DDT-induced tremor. That DDT-induced tremor was significantly attenuated by mephenesin and Dilantin is in accord with the conclusion that DDT-induced tremor is a manifestation of repetitive discharge due to interference with ionic conductance.

Analysis of Variance↗

PubMedDate not supplied

Alterations in flash evoked potentials (FEPs) in rats produced by 3,3'-iminodipropionitrile (IDPN).

3,3'-Iminodipropionitrile (IDPN) is a neurotoxicant that produces changes in flash evoked potentials (FEPs) 18 weeks after treatment. We examined dose- and time-related effects of IDPN on FEPs at earlier time points than previously studied (52). Adult male Long-Evans rats were given IDPN (0, 100, 200, 400 mg/kg/day x 3 days, i.p.) and FEPs were recorded 14 days later. IDPN (400 mg/kg/day) decreased the amplitudes of some of the "early" and "middle" FEP peaks (n30 and N56), and increased the latencies of some early peaks (P21 and P46). A separate group of rats was treated with IDPN (0 or 400 mg/kg/day x 3 days, i.p.) and FEPs were recorded 1, 3, 7, 14, and 35 days later. The latencies of of all portions of FEPs were increased by IDPN, with maximal changes occurring at 7 and/or 14 days. The amplitude of the middle portions of FEPs (peaks N56, P63, N70, P90) were altered as early as day 3, and some changes were observed up to day 14. In contrast, the "late" portion of FEPs (peak N160) was affected at later times (days 14 and 35). Corneal opacities were noted on days 3 and 7, but were largely reversible by day 14. In the time-course study, IDPN decreased colonic temperature on days 1, 3, 7, and 14. The present results suggest that IDPN alters both the early FEP peaks related to the initial afferent sensory volley, and cortical processing associated with the middle and later portions of FEPs.

Animals↗

PubMedDate not supplied

Flash-, somatosensory-, and peripheral nerve-evoked potentials in rats perinatally exposed to Aroclor 1254.

Pregnant Long-Evans rats were exposed to 0, 1 or 6 mg/kg/day of Aroclor 1254 (A1254; Lot no. 124-191), a commercial mixture of polychlorinated biphenyls (PCBs), from gestation day (GD) 6 through postnatal day (PND) 21. At 128-140 days of age, male and female offspring were tested for visual-, somatosensory- and peripheral nerve-evoked potentials. The evoked responses increased in amplitude with larger stimulus intensities, and gender differences were detected for some endpoints. In contrast, developmental exposure to A1254 failed to significantly affect the electrophysiological measures. A subset of the animals were tested for low-frequency hearing dysfunction using reflex modification audiometry (RMA). An elevated threshold for a 1-kHz tone was observed, replicating previous findings of A1254-induced auditory deficits [Hear. Res. 144 (2000) 196; Toxicol. Sci. 45(1) (1998) 94; Toxicol. Appl. Pharmacol. 135(1) (1995) 77.]. These findings indicate no statistically significant changes in visual-, somatosensory- or peripheral nerve-evoked potentials following developmental exposure to doses of A1254 that produce behavioral hearing deficits. However, subtle changes in the function of the visual or somatosensory systems cannot be disproved.

Administration, Oral↗

PubMedDate not supplied

Brain distribution and fate of tris(2-chloroethyl) phosphate in Fischer 344 rats.

Tris(2-chloroethyl) phosphate (TRCP) is a flame retardant that has a wide variety of industrial applications. In subchronic studies, oral administration of TRCP to rats and mice has been reported to produce dose-, sex-, and species-dependent lesions in the hippocampal brain region. The present investigation has examined the metabolism, elimination, and regional brain distribution of [14C]TRCP in male and female rats. [14C]TRCP was administered by gavage (0, 175, 350, or 700 mg/kg) and urine, feces, exhaled volatiles, CO2, and selected tissues were collected. Regional brain distribution of 14C was determined 2 hr following single doses of TRCP to male and female rats, and 24 hr after a single dose and the last of 14 daily doses of TRCP to female rats. Results of these studies indicate that TRCP is readily absorbed from the gastrointestinal tract, distributed to all brain regions, and that metabolism and excretion are nearly complete in 72 hr. Most of the TRCP-derived radioactivity was excreted in urine (up to 85%), with feces, volatiles, and CO2 combined accounting for less than 10% of the dose. Predominant signs of toxicity associated with TRCP administration (350 and 700 mg/kg) were seizures within 2 hr of treatment, when most of the TRCP-derived radioactivity present in brain tissue was in the form of the parent compound. Traces of inextractable 14C were detected at later times, but this material was not concentrated in brain relative to other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Metabolism of tris(2-chloroethyl) phosphate in rats and mice.

Tris(2-chloroethyl) phosphate (TRCP), a flame retardant, produces a dose-, sex-, and species-dependent lesion in the hippocampal region of the brain following subchronic oral administration. This lesion is more common and more severe in female F344 rats than in male F344 rats, and is not observed in B6C3F1 mice. The present investigation of the metabolism of TRCP was designed to detect sex and species variations that might account for differences in toxicity. Elimination of TRCP-derived radioactivity was more rapid in mice, which excreted greater than 70% of an oral dose of 175 mg/kg in urine in 8 hr vs. approximately 40% for male or female rats. However, the metabolic profile of TRCP-derived radioactivity in urine was similar for both species. The major metabolite in female rat urine was identified as bis(2-chloroethyl) carboxymethyl phosphate. This metabolite co-chromatographed with the major metabolite found in both male rat and mouse urine. Two additional metabolites identified in female rat urine were bis(2-chloroethyl) hydrogen phosphate and the glucuronide of bis(2-chloroethyl) 2-hydroxyethyl phosphate. These metabolites also cochromatographed with metabolites found in male rat and mouse urine. TRCP metabolism in rats was not induced or inhibited by nine daily 175 mg/kg doses. Toxicity, as evidenced by seizures, was potentiated in male rats pretreated with inhibitors of aldehyde dehydrogenase.

Animals↗