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J R Hodgson

Publications and source records attributed to J R Hodgson.

At least 19 recordsLinked to original sources
PubMed1996

Prechronic toxicity studies on 2-ethylhexanol in F334 rats and B6C3F1 mice.

Data on the subchronic toxicity of 2-ethylhexanol (2EH) were required to establish the dose vehicle and dose levels for oncogenicity studies. In preliminary studies 2EH was given subacutely (11 days) to male and female Fischer 344 rats and B6C3F1 mice as an aqueous emulsion by oral gavage (0, 100, 330, 1000, and 1500 mg/kg/day). Clinical observations were made, body weights, food consumption, clinical chemistries, hematologies, and selected organ weights were measured, and gross and micropathologies were performed. Target organs were the central nervous system, liver, forestomach, spleen, thymus, and kidney in rats and the central nervous system, liver, and forestomach in mice. 2EH was then administered by oral gavage to male and female F344 rats and B6C3F1 mice as an aqueous emulsion (0, 25, 125, 250, and 500 mg/kg/day) for 13 weeks. At 500 mg/kg/day in the rat there was reduced body weight gain (6% male, 7% female), increased relative liver (29% male, 15% female), kidney (16% male, 6% female), stomach (11% male, 16% female), and testes (6%) weights, and moderate gross and microscopic changes in the liver and forestomach. There were no behavioral effects or effects on the spleen or thymus. A no-effect level for target organ effects in the rat was 125 mg of 2EH/kg/day. At 500 mg of 2EH/kg/day in the mouse the only effects were increased relative stomach weights in males (13%) and a low incidence of gross and microscopic findings in the forestomach (male and female) and liver (female). A no-effect level for target organ effects in the mouse was 125 mg of 2EH/kg/day. 2EH was a peroxisome proliferator in the rat but not in the mouse at subchronic dose levels of 500 mg/kg/day. Dose levels in oncogenicity studies were set at 50 mg/kg/day for the absence of treatment-related effects in rats and mice, and 500 and 750 mg/kg/day, respectively, in rats and mice as high doses producing minimal toxicity without altering the life span.

Administration, Oral↗
PubMed1996

Oncogenicity testing of 2-ethylhexanol in Fischer 344 rats and B6C3F1 mice.

2-Ethylhexanol (2EH) is a weak nongenotoxic hepatic peroxisome proliferator in the rat. It is a high-volume chemical intermediate in the preparation of the plasticizers bis-(2-ethylhexyl) adipate (DEHA), bis-(2-ethylhexyl) phthalate (DEHP), and tris-(2-ethylhexyl) phosphate (TEHP), which are weak hepatocellular tumorigens in female mice. In consequence, the oncogenic potential of 2EH was evaluated in male (M) and female (F) rats and mice (50 animals/sex/group). Oral gavage doses of 2EH in 0.005% aqueous Cremophor EL (polyoxyl-35 castor oil) were given five times a week to rats: 0 (water), 0 (vehicle), 50, 150, and 500 mg/kg for 24 months, and to mice: 0 (water), 0 (vehicle), 50, 200, and 750 mg/kg for 18 months. Statistical comparisons of data were made between vehicle controls and treatment groups. There were no differences of biological significance between data from vehicle and water control groups. In rats, there were no dose-related changes at 50 mg/kg. There was reduced body weight gain at 150 mg/kg (M, 16; F, 12%) and 500 mg/kg (M, 33; F, 31%) and an increased incidence of lethargy and unkemptness. There were dose-related increases in relative liver, stomach, brain, kidney, and testis weights at sacrifice. Female rat mortality was markedly increased at 500 mg/kg. There was marked aspiration-induced bronchopneumonia in rats at 500 mg/kg; hematologic, gross, and microscopic changes, including tumors, were otherwise comparable among all rat groups. In mice at 50 and 200 mg/kg there were no dose-related changes and essentially no time-dependent or time-independent adverse trends in liver tumor incidence at the 5% significance level. At 750 mg/kg mouse body weight gain was reduced (M, 26; F, 24%), and mortality increased (M and F, 30%) versus vehicle controls. At 750 mg/kg there was a slight increase in nonneoplastic focal hyperplasia in the forestomach of mice (M 5/50, F 4/50) versus vehicle controls (M 1/50, F 1/50). There were increases in mouse relative liver (F, 21%) and stomach (M, 13%; F, 19%) weights at 750 mg/kg. There was a 12% incidence of hepatic basophilic foci and an 18% incidence of hepatocellular carcinomas in male mice at 750 mg/kg, not statistically significant compared with either control by Fisher's exact test. There was a 12% incidence of hepatic basophilic foci and a 10% incidence of hepatocellular carcinomas in female mice at 750 mg/kg, statistically significant (p < 0.05) compared with vehicle but not with water controls by Fisher's exact test. There were no metastases. Time-dependent and -independent statistical analyses showed an adverse trend in the incidence of hepatocellular carcinomas in male and female mice, correlated with toxicity (expressed as mortality) at 750 mg/kg. The time-adjusted incidence of hepatocellular carcinomas in male mice (18.8%) was within the historical normal range at the testing facility (0-22%), but that in females (13.1%) lay outside the normal range (0-2%). Under the conditions of these studies 2EH was not oncogenic in rats, but there were weak adverse trends in hepatocellular carcinoma incidence in mice at high dose levels which may have been associated with toxicity. The major effects of chronic dosing were mortality in female rats at 500 mg/kg and in male and female mice at 750 mg/kg, accompanied by reductions in body weight gain in rats at 150 and 500 mg/kg and in mice at 750 mg/kg. Direct comparison of any tumorogenic effects of 2EH given alone to female mice with those due to 2EH formed in vivo from DEHA, DEHP, or TEHP is limited by the high mortality caused by 2ER in female mice at equivalent doses of 2EH. While 2EH may be a contributing factor in the hepatocellular carcinogenesis in female mice associated with the chronic administration of DEHA and DEHP, it is unlikely to be the entire proximate carcinogen.

Animals↗
PubMed1992

The developmental toxicity of 2-ethylhexanol applied dermally to pregnant Fischer 344 rats.

Undiluted 2-ethylhexanol (2-EH) was administered by occluded dermal application for 6 hr per day on Gestation Days 6 through 15 to pregnant Fischer 344 rats, in range-finding (R) and main (M) studies. The dermal route is considered to be the most relevant for human exposure. Treatment levels were (R) 0.0, 0.5, 1.0, 2.0, and 3.0 ml/kg/day (equivalent to 0, 420, 840, 1680, and 2520 mg/kg/day) and (M) 0.0, 0.3, 1.0, and 3.0 ml/kg/day (equivalent to 0, 252, 840, and 2520 mg/kg/day). Controls (0.0 ml/kg/day, sham controls) received deionized water at 3.0 ml/kg/day. Dermal-positive control groups received undiluted 2-methoxyethanol (2-ME) at (R) 0.5 and 1.5 ml/kg/day and (M) 1.0 ml/kg/day as a reference compound in a similar regimen. An oral reference compound, valproic acid, was administered by gavage in the range-finding study on Gestation Days 6 through 15 at 400 mg/kg/day. The range-finding study employed an untreated (naive) control group. Numbers of plug-positive females per group were (R) 8 and (M) 25. Maternal weight gain was reduced for 2-EH at 1680 (R) and 2520 (R and M studies) mg/kg/day. Exfoliation and encrustation were seen at the application site in both studies at 840, 1680, and 2520 mg/kg. Maternal liver, kidney, thymus, spleen, adrenal, and uterine weights, and gestational and fetal parameters were unaffected by treatment with 2-EH. There were no treatment-related increases in the incidence of individual or pooled external, visceral, and skeletal malformations or variations following the application of 2-EH. The NOAELs for the maternal toxicity of 2-EH were 252 mg/kg/day based on skin irritation and 840 mg/kg/day based on systemic toxicity. The developmental toxicity NOAEL was at least 2520 mg/kg/day, with no teratogenicity. Administration of 2-ME at 840 mg/kg/day resulted in reduced maternal weight gain and food consumption, increased postimplantation loss, reduced numbers of live fetuses per litter, and reduced fetal body weights per litter. The incidence of fetal malformations and variations was increased. Oral administration of VPA produced maternal toxicity, developmental toxicity, and teratogenicity. The Fischer 344 rat is thus susceptible to known rodent teratogens by both the dermal and oral routes. It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity.

Administration, Cutaneous↗
PubMed1987

Results of peroxisome induction studies on tri(2-ethylhexyl)trimellitate and 2-ethylhexanol.

The results of these studies demonstrate that Tri(2-ethylhexyl)trimellitate (TOTM) produces the sam spectrum of morphological and biochemical changes in the rat liver as di(2-ethylhexyl)phthalate (DEHP). TOTM, however, was much less potent in its action, with a dietary level of 2.0%, causing less peroxisome proliferation and enzyme induction than 0.67% DEHP. Also, these studies show that the level of peroxisome induction in rats given TOTM is less than in those receiving a metabolically equivalent dose of 2-ethylhexanol (2-EH). Furthermore, on a molar basis, effects were lower than with DEHP. A "monoester effect" of the kind attributed to MEHP, a metabolite of DEHP, was not seen with TOTM.

Animals↗
PubMed1983

Cytogenetic evaluation of di-(2-ethylhexyl)phthalate and its major metabolites in Fischer 344 rats.

Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were evaluated for their ability to induce chromosomal damage in male Fischer 344 rats after oral administration. Dose levels, the highest of which represents one-tenth of the five-day LD50, were based on a preliminary five-day dose-finding study for each test material. The dose levels selected were 5.0, 1.7, and 0.5 ml/kg/day for DEHP; 0.14, 0.05 and 0.01 ml/kg/day for MEHP; and 0.21, 0.07 and 0.02 ml/kg/day for EH. All test materials and vehicle control (corn oil) were administered by gavage for five consecutive days. A triethylenemelamine (TEM)-positive control group received a single intraperitoneal injection of 0.5 mg/kg TEM one day prior to sacrifice. Of the 50 metaphase bone marrow cells examined from each animal, no significant increase in chromatid and chromosome breaks or structural rearrangements were noted for DEHP, MEHP, and EH. In addition, the mitotic index, determined from 100 cells per animal, was unaffected by DEHP, MEHP, or EH. The results of this investigation indicate that DEHP, MEHP, and EH, at these dose levels, did not induce detectable chromosomal aberrations after oral administration.

Animals↗
PubMed1983

Evaluation of di-(2-ethylhexyl)phthalate and its major metabolites in the Ames test and L5178Y mouse lymphoma mutagenicity assay.

Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were tested for genetic activity in both the Salmonella/mammalian microsome mutagenicity (Ames) assay and the L5178Y TK+/- mouse lymphoma cell mutagenicity assay. All chemicals were tested in both the presence and absence of Aroclor-induced liver microsomes prepared from male Sprague-Dawley rats. Dose levels for both assays were selected from preliminary toxicity studies for each chemical. Neither DEHP, MEHP, nor EH exhibited any significant mutagenic activity in strains TA-98, TA-100, TA-1535, TA-1537, and TA-1538 in the Ames test or when tested in the L5178Y TK+/- mouse lymphoma cell mutagenicity assay.

Animals↗
PubMed1977

Absence of mutagenicity of coralyne and related antileukemic agents: structural comparison with the potent carcinogen 7,12-dimethylbenz[a]anthracene.

The structural similarity between antileukemic alkaloid coralyne and the carcinogenic and antineoplastic hydrocarbon 7, 12-dimethylbenz[a]anthracene, as well as the similarity between the antileukemic alkaloid nitidine and the carcinogenic hydrocarbon 5-methylchrysene, prompted a mutagenicity evaluation of coralyne sulfoacetate, nitidine chloride, the 8-ethyl homolog of coralyne, nitidine methosulfate, and the tetramethoxy analog of nitidine by the Ames method against the histidine-auxotroph strains of Salmonella typhimurium TA-1537, TA-1538, TA-98, and TA-100; 7,12-dimethylbenz[a]anthracene was used as a reference standard. The mutagenicity of these antileukemic compounds was either completely eliminated or drastically reduced, but the mutagenic response was generally high for 7,12-dimethylbenz[a]anthracene. The results suggest that the presence of a quaternary nitrogen atom and alkoxy groups could be important in alleviating the mutagenicity of the parent mutagenic and carcinogenic hydrocarbons.

9,10-Dimethyl-1,2-benzanthracene↗