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Article: Association of carcinoma yield with early papilloma development in SENCAR mice.

Bull, R J / Robinson, M / Laurie, R D

1986 Volume 68, Page(s) 11–17

Abstract: The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin ... ...

Abstract	The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin initiation/promotion protocols and to determine the extent to which early papilloma development can be used to predict the eventual development of malignant tumors. The chemicals were administered as initiators by four different routes: oral, intraperitoneal, subcutaneous, and topical. Following the initiating dose of carcinogen, the animals were subjected to topical applications of 1 microgram 12-O-tetradecanoylphorbol-13-acetate (TPA) 3 times per week for a period of 20 weeks. The yield of papillomas at 24 weeks was selected as a potential predictor of carcinoma yields at 52 weeks following the start of the promotion schedule. Positive responses were observed with only eight of the compounds tested. Where positive results were observed, there was some evidence that the response could depend both qualitatively and quantitatively on the route of administration. However, no route was clearly superior, i.e., different chemicals gave greater responses by different routes. Papilloma yield at 24 weeks following the start of the promotion schedule was clearly related to the development of carcinomas at 52 weeks. No simple linear relationship existed between papilloma yield and carcinoma development, since the number of malignant tumors per papilloma decreased with increasing papilloma yields. The relationship between papilloma and carcinoma yields appeared to be independent of the carcinogen used. These data indicate that there are some limitations in using mouse skin initiation/promotion experiments as the sole basis for identifying substances with carcinogenic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
MeSH term(s)	Animals ; Carcinogens ; Carcinoma/chemically induced ; Cocarcinogenesis ; Disease Models, Animal ; Drug Evaluation, Preclinical ; False Negative Reactions ; Female ; Mice ; Mice, Inbred Strains ; Papilloma/chemically induced ; Skin Neoplasms/chemically induced ; Tetradecanoylphorbol Acetate
Chemical Substances	Carcinogens ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	1986-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/ehp.866811
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Article: Subchronic toxicology of humic acid following chlorination in the rat.

Condie, L W / Laurie, R D / Bercz, J P

Journal of toxicology and environmental health

1985 Volume 15, Issue 2, Page(s) 305–314

Abstract: A subchronic 90-d study was conducted with chlorinated and nonchlorinated humic acids using male Sprague-Dawley rats. Body weight gain, terminal organ and body weights, food and fluid consumption, clinical chemistries, hematological parameters, and ... ...

Abstract	A subchronic 90-d study was conducted with chlorinated and nonchlorinated humic acids using male Sprague-Dawley rats. Body weight gain, terminal organ and body weights, food and fluid consumption, clinical chemistries, hematological parameters, and urinalyses were determined for all animals. Selected organs were examined microscopically. Significant findings were confined to those rats given the high dose of chlorinated humic acid (1.0 g/l total organic carbon). The terminal body weight and average weekly body weight gain were significantly lower (p less than 0.05) in the high-dose group as compared to the distilled-water control group. This difference can be partially explained by a 16% lower daily fluid consumption. The average weight of the kidneys was significantly higher in the 1.0-g/l chlorinated humic group as compared to distilled-water controls. Hematological parameters and clinical chemistry values were normal in all treatment groups. The most significant finding was the increased incidence and severity of hematuria in the 1.0-g/l chlorinated humic acid group. A thorough histopathological examination of the entire urinary tract indicated that the most likely cause of the more severe incidences of hematuria in the rats was caused by crystalline deposits in the renal pelvis.
MeSH term(s)	Administration, Oral ; Analysis of Variance ; Animals ; Body Weight/drug effects ; Hematuria/chemically induced ; Humic Substances/toxicity ; Hydrocarbons, Chlorinated/toxicity ; Kidney/drug effects ; Male ; Organ Size/drug effects ; Rats ; Rats, Inbred Strains
Chemical Substances	Humic Substances ; Hydrocarbons, Chlorinated
Language	English
Publishing date	1985
Publishing country	United States
Document type	Journal Article
ZDB-ID	197268-6
ISSN	1087-2620 ; 0098-4108 ; 0040-9014
ISSN (online)	1087-2620
ISSN	0098-4108 ; 0040-9014
DOI	10.1080/15287398509530656
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Article: Comparative renal and hepatotoxicity of halomethanes: bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride.

Condie, L W / Smallwood, C L / Laurie, R D

Drug and chemical toxicology

1983 Volume 6, Issue 6, Page(s) 563–578

Abstract: The renal and hepatotoxicities of five selected halomethanes, which are drinking water contaminants, were evaluated following a 14-day exposure. Bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride were administered at ...

Abstract	The renal and hepatotoxicities of five selected halomethanes, which are drinking water contaminants, were evaluated following a 14-day exposure. Bromodichloromethane, bromoform, chloroform, dibromochloromethane and methylene chloride were administered at three dose levels. Toxicity was evaluated by measuring changes in total body weight, uptake of p-aminohippurate into renal cortical slices, blood urea nitrogen, serum creatinine, and serum glutamate-pyruvate transaminase levels and by performing a histopathologic examination of liver and kidney tissues. Dose-related effects on the liver and kidney were detected with the uptake of p-aminohippurate into kidney slices and with the histopathologic evaluation of tissues. Treatment-related effects seen in the methylene chloride exposed mice were less pronounced as compared to the other halomethane treatment groups. In general, histopathological changes were the most sensitive indicators of both liver and kidney damage.
MeSH term(s)	Animals ; Body Weight/drug effects ; Chloroform/toxicity ; Hydrocarbons, Brominated/toxicity ; Hydrocarbons, Halogenated/toxicity ; Kidney/drug effects ; Kidney Cortex/drug effects ; Liver/drug effects ; Male ; Methylene Chloride/toxicity ; Mice ; Mice, Inbred Strains ; Trihalomethanes
Chemical Substances	Hydrocarbons, Brominated ; Hydrocarbons, Halogenated ; Trihalomethanes ; Methylene Chloride (588X2YUY0A) ; bromodichloromethane (7LN464CH2O) ; Chloroform (7V31YC746X) ; bromoform (TUT9J99IMU)
Language	English
Publishing date	1983
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	548368-2
ISSN	1525-6014 ; 0148-0545
ISSN (online)	1525-6014
ISSN	0148-0545
DOI	10.3109/01480548309017810
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Article: Carcinogenic effects in A/J mice of particulate of a coal tar paint used in potable water systems.

Robinson, M / Laurie, R D / Bull, R J / Stober, J A

Cancer letters

1987 Volume 34, Issue 1, Page(s) 49–54

Abstract: Coal tar paints are among the products used as inside coatings for water pipes and storage tanks to retard corrosion in potable water supply systems. Four different formulations of these paints were tested in earlier work by this laboratory in the Ames ... ...

Abstract	Coal tar paints are among the products used as inside coatings for water pipes and storage tanks to retard corrosion in potable water supply systems. Four different formulations of these paints were tested in earlier work by this laboratory in the Ames mutagenesis and the mouse skin carcinogenesis bioassays. The paint most active in these assays were then tested in a particulate form in the lung adenoma assay with A/J mice. The paint was applied to clean glass plates, cured, collected and homogenized in 2% Emulphor. Doses of this coal tar suspension were administered by gavage at 1.0, 10.0 and 55.0 mg in 0.2 ml per mouse 3X weekly for 8 weeks. The total doses of coal tar paint were 24, 240, and 1320 mg/mouse. Benzo[a]pyrene (BaP), administered in a parallel schedule to a total dose of 6 mg/mouse, served as positive control. A negative control group received an equivalent volume of 2% Emulphor. Animals were killed at 9 months of age (8 months after first dose) and lung adenomas counted. A dose-related response, in the average number of lung tumors per mouse, was observed with the coal tar particulate. There were also squamous cell tumors of the forestomach in 42% of the mice receiving 55.0 mg coal tar paint per application.
MeSH term(s)	Animals ; Coal Tar/toxicity ; Female ; Lung Neoplasms/chemically induced ; Mice ; Neoplasms, Experimental/etiology ; Paint/analysis ; Paint/toxicity ; Stomach Neoplasms/chemically induced ; Water Supply/analysis
Chemical Substances	Coal Tar (8007-45-2)
Language	English
Publishing date	1987-01
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/0304-3835(87)90072-3
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Article: Studies of the toxic interactions of disinfection by-products.

Laurie, R D / Bercz, J P / Wessendarp, T K / Condie, L W

Environmental health perspectives

1986 Volume 69, Page(s) 203–207

Abstract: A large number and variety of compounds are formed in the process of chlorinating drinking water. The classes of compounds formed include trihalomethanes, haloacetic acids, haloacetonitriles, halophenols, and halopropanones. Many of the compounds have ... ...

Abstract	A large number and variety of compounds are formed in the process of chlorinating drinking water. The classes of compounds formed include trihalomethanes, haloacetic acids, haloacetonitriles, halophenols, and halopropanones. Many of the compounds have been shown to be toxic and are currently being further evaluated by the U.S. Environmental Protection Agency (EPA). One group of the halopropanones found in chlorinated drinking water is the dichloropropanones. The toxicological properties of this group have not been well characterized. In addition, a number of investigators have shown that ketones potentiate the hepatotoxicity of haloalkanes. We conducted a series of studies to explore both the toxicity of the dichloropropanones and their potential interactions with a well-characterized haloalkane, carbon tetrachloride. A variety of toxicological and biochemical endpoints were used to evaluate the toxicity of the dichloropropanones and their interaction with CCl4, including cytochrome P-450 concentration, reduced glutathione levels, pentane generation, serum enzyme activities, and histopathology. Administration of 1,1-dichloropropanone (DCP) resulted in elevated serum enzymes associated with periportal necrosis. Glutathione levels were reduced by the administration of 1,1-DCP; pentane generation was not increased. When 1,1-DCP was given prior to CCl4, the data were consistent with additivity. Administration of 1,3-DCP did not result in elevated serum enzymes, nor was there histopathologic evidence of necrosis. Glutathione levels and pentane generation in the 1,3-DCP-treated groups were the same as those of controls. Inhibition of the toxicologic effects of CCl4 in a dose-related manner was observed when 1,3-DCP was administered prior to CCl4.
MeSH term(s)	Acetone/analogs & derivatives ; Acetone/toxicity ; Animals ; Chloroform/toxicity ; Cytochrome P-450 Enzyme System/metabolism ; Disinfectants/toxicity ; Enzymes/blood ; Glutathione/metabolism ; Lethal Dose 50 ; Liver/drug effects ; Liver/metabolism ; Liver/pathology ; Mice ; Necrosis ; Pentanes/metabolism ; Water Supply/analysis
Chemical Substances	Disinfectants ; Enzymes ; Pentanes ; Acetone (1364PS73AF) ; Chloroform (7V31YC746X) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Glutathione (GAN16C9B8O) ; 1,1-dichloroacetone (MCU87D3FRT) ; 1,3-dichloroacetone (UFH8559WS5)
Language	English
Publishing date	1986-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/ehp.8669203
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Article: Effects of chlorine dioxide on thyroid function in neonatal rats.

Orme, J / Taylor, D H / Laurie, R D / Bull, R J

Journal of toxicology and environmental health

1985 Volume 15, Issue 2, Page(s) 315–322

Abstract: Chlorine dioxide (ClO2), an alternative to chlorine for drinking water disinfection, has been implicated as a potential antithyroid agent (Bercz et al., 1982). Because antithyroid compounds are known to alter neurobehavioral development, the present ... ...

Abstract	Chlorine dioxide (ClO2), an alternative to chlorine for drinking water disinfection, has been implicated as a potential antithyroid agent (Bercz et al., 1982). Because antithyroid compounds are known to alter neurobehavioral development, the present study was designed to determine if perinatal exposure to ClO2 affects behavioral activity in rat pups. The activity cage system was designed to monitor the development of locomotor activity of a litter of pups between ages 14-21 d. Pups were exposed to ClO2 either directly, by gavaging 14 mg/kg . from age 5 to 20 d, or indirectly via their dams' drinking water in concentrations of 2, 20, or 100 mg/l from gestation to weaning (21 d postpartum). Although the activity of the indirectly exposed group was not different from controls, the gavaged group showed significantly depressed activity for d 18 and 19 postpartum. The T4 levels of the 21-d-old pups was significantly depressed in the 100-mg/l ClO2 group. The gavaged pups showed an even greater T4 depression, which correlates with their activity levels. These data support the hypothesis that ClO2 affects thyroid function and suggests that a slight depression in T4 can result in developmental delays.
MeSH term(s)	Administration, Oral ; Analysis of Variance ; Animals ; Animals, Newborn ; Chlorine/toxicity ; Chlorine Compounds ; Female ; Male ; Maternal-Fetal Exchange ; Motor Activity/drug effects ; Oxides/toxicity ; Pregnancy ; Radioimmunoassay ; Rats ; Rats, Inbred Strains ; Thyroid Gland/drug effects ; Thyroxine/blood ; Triiodothyronine/blood
Chemical Substances	Chlorine Compounds ; Oxides ; Triiodothyronine (06LU7C9H1V) ; Chlorine (4R7X1O2820) ; chlorine dioxide (8061YMS4RM) ; Thyroxine (Q51BO43MG4)
Language	English
Publishing date	1985
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	197268-6
ISSN	1087-2620 ; 0098-4108 ; 0040-9014
ISSN (online)	1087-2620
ISSN	0098-4108 ; 0040-9014
DOI	10.1080/15287398509530657
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Article: Subacute and subchronic toxicity of ethylene glycol administered in drinking water to Sprague-Dawley rats.

Robinson, M / Pond, C L / Laurie, R D / Bercz, J P / Henningsen, G / Condie, L W

Drug and chemical toxicology

1990 Volume 13, Issue 1, Page(s) 43–70

Abstract: Subacute (10-day) and subchronic (90-day) toxicity studies of ethylene glycol (EG) were conducted in male and female Sprague-Dawley rats to provide the U.S. Environmental Protection Agency's (EPA) Office of Drinking Water with toxicity data for final ... ...

Abstract	Subacute (10-day) and subchronic (90-day) toxicity studies of ethylene glycol (EG) were conducted in male and female Sprague-Dawley rats to provide the U.S. Environmental Protection Agency's (EPA) Office of Drinking Water with toxicity data for final preparation of a Health Advisory for the chemical. Ethylene glycol was administered in drinking water at concentrations of 0.5, 1.0, 2.0, and 4.0% for both sexes in the 10-day study. Based on a projected consumption rate of 100 ml/kg/day, the respective doses on a mg/kg/day basis would be 554, 1108, 2216, and 4432. These dose levels were also used in the 90-day study for females, but dose levels for the males in the 90-day study were 0.25, 0.5, 1.0, and 2.0% (227, 554, 1108, and 2216 mg/kg/day). At time of sacrifice necropsies were performed and tissues were prepared for histological evaluation. Blood samples were taken for hematology and clinical chemistry determinations. Body weights were measured weekly. Water and food consumption were determined three times weekly. No mortality occurred in the 10-day study. In the 90-day study 8/10 females and 2/10 males in the high dose group died prior to sacrifice. Body weights were suppressed in a dose response fashion for males and females. Hemoglobin, hematocrit, erythrocytes, and leukocytes were all significantly decreased in female rats receiving 4% EG for 10 days. The most significant histopathological findings, seen predominantly in males, were kidney lesions which included calcium oxalate crystals in tubules and pelvic epithelium; tubular dilation and degeneration; intratubular proteinaceous material; and inflammation in tubules and pelvic epithelium. At the same dose of ethylene glycol, males had more kidney lesions and much higher incidence and severity of lesions than the females.
MeSH term(s)	Administration, Oral ; Animals ; Blood Cell Count ; Blood Chemical Analysis ; Body Weight/drug effects ; Calcium Oxalate/analysis ; Ethylene Glycols/blood ; Ethylene Glycols/toxicity ; Female ; Kidney Diseases/chemically induced ; Kidney Diseases/pathology ; Male ; Organ Size/drug effects ; Rats ; Rats, Inbred Strains ; Sex Factors ; Water
Chemical Substances	Ethylene Glycols ; Water (059QF0KO0R) ; Calcium Oxalate (2612HC57YE)
Language	English
Publishing date	1990
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	548368-2
ISSN	1525-6014 ; 0148-0545
ISSN (online)	1525-6014
ISSN	0148-0545
DOI	10.3109/01480549009011069
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Article: Effect of gavage vehicle on hepatotoxicity of carbon tetrachloride in CD-1 mice: corn oil versus Tween-60 aqueous emulsion

Condie, L.W / Laurie, R.D / Mills, T / Robinson, M / Bercz, J.P

Fundamental and applied toxicology. Aug 1986. v. 7 (2)

1986

Keywords	mice ; fumigants ; toxicity ; liver ; carbon tetrachloride ; corn oil ; emulsions ; drinking water ; food contamination
Language	English
Dates of publication	1986-08
Size	p. 199-206.
Document type	Article
ZDB-ID	604594-7
ISSN	0272-0590
ISSN	0272-0590
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Article: Studies of the toxic interactions of disinfection by-products

Laurie, R.D / Bercz, J.P / Wessendarp, T.K / Condie, L.W

E H P Environmental health perspectives. Nov 1986. v. 69

1986

Keywords	drinking water ; disinfection ; byproducts ; toxicity
Language	English
Dates of publication	1986-11
Size	p. 203-207.
Document type	Article
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
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Article: Effects of chlorine dioxide on thyroid function in neonatal rats

Orme, J / Taylor, D.H / Laurie, R.D / Bull, R.J

Journal of toxicology and environmental health. 1985. v. 15 (2)

1985

Keywords	rats ; chlorine ; drinking water ; thyroid gland ; animal behavior ; neonates
Language	English
Size	p. 315-322.
Document type	Article
ZDB-ID	197268-6
ISSN	1087-2620 ; 0098-4108 ; 0040-9014
ISSN (online)	1087-2620
ISSN	0098-4108 ; 0040-9014
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