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Biomedical subjects

D K Gulati

Publications and source records attributed to D K Gulati.

At least 19 recordsLinked to original sources
PubMed1997

Reproductive toxicity of di-n-butylphthalate in a continuous breeding protocol in Sprague-Dawley rats.

The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its reproductive toxicity was tested in rats by the National Toxicology Program's Reproductive Assessment by Continuous Breeding protocol. Levels of 0.1, 0.5, and 1.0% DBP in the diet were selected, and this dosing design yielded average daily DBP intakes of 52, 256, and 509 mg/kg for males and 80, 385, and 794 mg/kg for females, respectively. DBP consumption by F0 rats reduced the total number of live pups per litter in all treated groups by 8-17% and live pup weights in the 0.5% and 1.0% dose groups by < 13%. In tests to determine the affected sex, the number of offspring was unchanged, but the weights of pups from treated females were significantly decreased and offspring from treated males were unchanged. At necropsy, high-dose F0 females had a 14% reduction in body weight, and both sexes had approximately 10-15% increased kidney and liver to body weight ratios compared to controls. Sperm parameters and estrous cyclicity were not affected. In the F1 mating trial, indices of mating, pregnancy, and fertility in the 1.0% dose group were all sharply decreased (one live litter was delivered out of 20 cohabited pairs), concomitant with a 13% decrease in dam body weight. Live F2 pup weights were 6-8% lower in all dose groups. F1 necropsy results revealed that epididymal sperm counts and testicular spermatid head counts were significantly decreased in the 1.0% dose group. Histopathologic investigation showed that 8 of 10 F1 males consuming 1.0% DBP had degenerated seminiferous tubules and 5 of 10 had underdeveloped or otherwise defective epididymides. No ovarian or uterine lesions were observed. In conclusion, this study showed that DBP is a reproductive/developmental toxicant in Sprague-Dawley rats exposed both as adults and during development; it also indicates that the adverse reproductive/developmental effects of DBP on the second generation were greater than on the first generation.

Abnormalities, Drug-Induced↗
PubMed1995

Assessment of the reproductive toxicity of a complex mixture of 25 groundwater contaminants in mice and rats.

The potential reproductive toxicity of a mixture of 25 chemicals (MIX) formulated to simulate contaminated groundwater supplies near hazardous waste dumps was evaluated in CD-1 Swiss mice and Sprague-Dawley rats using the reproductive assessment by continuous breeding protocol. Male and female mice and rats were exposed to MIX in the drinking water at concentrations of 1, 5, and 10% of a technically achievable stock solution. For mice, body weight and feed consumption were not affected by MIX but water consumption was decreased for both the 5 and 10% MIX groups in both F0 and F1 animals. For F0 mice, the number of live pups/litter was decreased at 10% MIX and the number of females/litter was decreased 10 and 17% at the mid and high MIX dose, respectively. Vaginal cytology was normal, as were testis weight and testicular spermatid head count. For F1 mice, fertility was unaffected, but there was a decreased number of female pups/litter (19%) and a decreased adjusted live pup weight at 10% MIX. At necropsy, cauda epididymal sperm concentration and spermatid head count were reduced (20%) in the presence of normal testis, epididymis, prostate, seminal vesicle, liver, and kidney/adrenal weight. Female estrous cyclicity was altered at 5 and 10% MIX with normal kidney/adrenal, uterus, and ovary/oviduct weight. For rats, F0 body weight and feed consumption were not affected by MIX but water consumption was decreased 10, 30, and 40% in the low-, medium-, and high-dose MIX groups, respectively, and 39% in the high-dose MIX F1 animals. Rat fertility was normal but there was a decreased number of male pups/litter (11%) and a decreased live pup weight (6%) at 10% MIX. Male and female (F1) pup weights were decreased on Postnatal Days 0, 4, 7, 14, and 21 (10% MIX) and remained lower through necropsy on Day 120 +/- 10. F1 fertility was normal but F2 pup weights were decreased (10% MIX). At necropsy, F1 (10% MIX) male body weight was decreased 16% and relative kidney, testis, epididymis, and prostate weights were increased in the presence of normal sperm concentration percentage motile sperm and percentage abnormal sperm. Estrous cyclicity was normal as were kidney/adrenal and ovary weight while female liver weight was reduced 14%. In summary, a "cocktail" of 25 chemicals commonly found in contaminated groundwater at or near hazardous waste sites was administered in drinking water at doses which resulted in severely decreased water consumption in both mice and rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Phenolphthalein: induction of micronucleated erythrocytes in mice.

Phenolphthalein was tested for the induction of micronucleated erythrocytes in mice. Results of an initial investigation revealed significant, dose-related increases in micronucleated polychromatic erythrocytes (MN-PCE) and normochromatic erythrocytes (MN-NCE) in peripheral blood samples of male and female mice exposed to 0.6% to 5% phenolphthalein (approximately 1100 to 10,000 mg/kg/day) in feed for 90 days (Dietz et al., 1992). Results from a second long-term feed study with Swiss CD-1 mice confirmed this effect. However, administration of comparable doses of phenolphthalein by corn oil gavage on two consecutive days gave negative results in a mouse bone marrow micronucleus test. Subsequent tests were performed to clarify the conflicting results seen in the chronic exposure, dosed-feed, peripheral blood studies and the acute, corn oil gavage, bone marrow studies. Phenolphthalein was administered to male B6C3F1 mice in feed (3%) for 14 days. Peripheral blood samples taken at 4, 7, and 14 days all showed significant increases in micronucleated PCE; bone marrow samples taken on days 7 and 14 also were clearly positive for micronucleus induction. Therefore, comparable results were obtainable from both bone marrow and peripheral blood analyses. Because of the negative results in the two-exposure gavage test, additional tests were then designed to investigate the effects of bolus vs continuous dosing, feeding vs gavage administration, and corn oil vs feed as a carrier for phenolphthalein. Results of these tests indicated that the rate of exposure to phenolphthalein affects the frequency of induced MN-PCE and that micronucleated erythrocytes can be induced by phenolphthalein either by feeding or by corn oil gavage administration. In all the acute exposure studies, relatively high doses of phenolphthalein (2000-6000 mg/kg/day for at least 2 days) were required to induce micronuclei. The positive results obtained with phenolphthalein in vivo were consistent with the results of an in vitro chromosomal aberration test in Chinese hamster ovary cells, where dose-related increases in aberrations were noted only in cells treated in the presence of induced rat liver S9.

Animals↗
PubMed1994

Assessment of the reproductive and developmental toxicity of pesticide/fertilizer mixtures based on confirmed pesticide contamination in California and Iowa groundwater.

Pesticides and fertilizers, as used in modern agriculture, contribute to the overall low-level contamination of groundwater sources. In order to determine the potential of pesticide and fertilizer mixtures to produce reproductive or developmental toxicity at concentrations up to 100 x the median level found in groundwater, we prepared and studied two mixtures of pesticides and a fertilizer (ammonium nitrate). One mixture containing aldicarb, atrazine, dibromochloropropane, 1,2-dichloropropane, ethylene dibromide, and simazine plus ammonium nitrate was considered to be a representative of groundwater contamination in California (CAL). The other, containing alachlor, atrazine, cyanazine, metolachlor, metribuzin, and ammonium nitrate, simulated groundwater contamination in Iowa (IOWA). Each mixture was administered in the drinking water of either Swiss CD-1 mice during a Reproductive Assessment by Continuous Breeding study or pregnant Sprague-Dawley rats (gd 6-20) at three dose levels (1x, 10x, and 100x) where 1x was the median concentration of each pesticide component as determined in the groundwater surveys in California or Iowa. Unlike conventional toxicology studies, the purpose of this study was to evaluate the health effects of realistic human concentrations. Thus, the testing concentrations are probably well below the maximally tolerated dose. Propylene glycol was used as the solubilizer for the pesticides in drinking water formulations in both studies. In the reproductive study, neither mixture caused any clinical signs of toxicity, changes in food or water consumption, or body weight in either F0 or F1 mice at doses up to 100x the median groundwater concentrations. There were no treatment-related effects on fertility or any measures of reproductive performance of either the F0 or the F1 generation mice exposed to either CAL or IOWA at up to 100x. Similarly, measures of spermatogenesis, epididymal sperm concentration, percentage motile sperm, percentage abnormal sperm, and testicular and epididymal histology were normal. In the developmental study, CAL- or IOWA-exposed females did not exhibit any significant treatment-related clinical signs of toxicity. No adverse effects of CAL or IOWA were observed for measures of embryo/fetal toxicity, including resorptions per litter, live litter size, or fetal body weight. CAL or IOWA did not cause an increased incidence of fetal malformations or variations. In summary, administration of these pesticide/fertilizer mixtures at levels up to 100-fold greater than the median concentrations in groundwater supplies in California or Iowa did not cause any detectable reproductive (mice), general, or developmental toxicity (rats).

Animals↗
PubMed1994

Cytogenetic studies of sodium fluoride in mice.

The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks. Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined.

Anaphase↗
PubMed1993

The effects of feed restriction on reproductive function in Swiss CD-1 mice.

Many test compounds used in toxicity studies produce a "systemic" toxicity manifested as reduced body weight gain. While it is known that reduced weight gain during juvenile growth reduces or delays reproductive competence, the effects of adult-onset feed restriction (FR) and inhibited weight gain on the reproductive system of mice are poorly known. To gain some information on the effects of graded body weight reduction, or reduced body weight gain, on commonly used reproductive endpoints, the studies reported below were conducted at two laboratories, using adult mice that were maintained at 90, 80, and 70% of concurrent control body weight (CBW) for up to 21 weeks. Estrous cyclicity and fertility in the females were significantly affected. While male fertility was variably affected, there was a significant decrease in the number of epididymal sperm and in the number of testicular spermatids in the 70% CBW groups. Testis weight was conserved in both studies; relative testis weight increased in all FR groups. These data can improve the interpretation of future studies by helping to separate chemically induced changes from those produced by reduced body weight gain.

Animals↗
PubMed1993

The effects of feed restriction on reproductive function in Sprague-Dawley rats.

Although it is known that severe feed restriction (FR) and weight reduction (to 50-60% of control values) will sharply impair rat reproduction, few data exist on the effects of less severe body weight reduction. In the present studies, adult Sprague-Dawley rats were feed restricted and maintained at 90, 80, and 70% of control body weight (CBW) for up to 17 weeks. In females, this treatment had no effect on fertility or total number of implants per dam, but transiently increased the length of the estrous cycle and decreased by 20% the number of corpora lutea in the 70% CBW females. Ovary weight at necropsy was decreased only in the 70% CBW group. Liver and kidney weights varied with body weight. In males, fertility was not affected when they were mated to nonrestricted females. While prostate and seminal vesicles weight varied with body weight, testis and epididymis weights were unchanged by any degree of FR, as were the number of sperm in the cauda epididymis and the number of homogenization-resistant spermatids in the testis. The percentage motile sperm was slightly decreased at all levels of FR. These data show that the Sprague-Dawley rat is largely resistant to adverse reproductive changes caused by feed restriction to 70% CBW. These data should be of use in interpreting changes seen in toxicity studies that produce weight-reduce Sprague-Dawley rats.

Animals↗
PubMed1993

Are mouse strains differentially susceptible to the reproductive toxicity of ethylene glycol monomethyl ether? A study of three strains.

Most rodent reproductive toxicology studies utilize strains of high fecundity. These studies were conducted to examine the possibility that mouse strains of differing fecundity would respond differently to a known reproductive toxicant. Thirty pairs each of Swiss CD-1, C57B1, and C3H mice were cohabited for 14 weeks while consuming 0, 0.03, 0.10, or 0.30% EGME in the drinking water. Litter data were collected during cohabitation. Body and organ weights, and various sperm data, were collected at necropsy, and second-generation fertility was evaluated. The data show that the most fecund strain (Swiss) was affected the least by exposure to EGME, while the least fecund strain (C3H) suffered the greatest declines in fertility. These differences might alter interspecies extrapolation factors, or the permissible exposure levels for humans.

Animals↗
PubMed1992

Biologic markers in hospital workers exposed to low levels of ethylene oxide.

Operators of hospital sterilizers that use ethylene oxide were studied to determine if there was a relationship between exposure and a battery of biological markers. A total of 73 workers from nine hospitals in the United States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide exposure during four months prior to collection of peripheral blood. The frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S. subjects when controlling by regression analysis for various confounding factors, including cigarette smoking. Hemoglobin adducts, but not SCEs, were also increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no consistent relationship with exposure. The U.S. study participants were classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide exposure. The group with an exposure of greater than 32 ppm-h had an increased frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA) exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was 0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for SCEs. The latter finding may have been due to longer shipping times for the specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/- 0.08 ppm. This study is the third to suggest that exposures less than the U.S. OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is not known whether these changes may be indicative of increased risk of disease; however, they do appear to reflect exposure to relatively low levels of ethylene oxide. The exact meaning of these changes is unknown.

Adult↗
PubMed1991

Reproductive toxicity assessment by continuous breeding in Sprague-Dawley rats: a comparison of two study designs.

The protocol for Reproductive Assessment by Continuous Breeding (RACB) studies was originally designed to use mice as the test species. However, rats are commonly used for reproductive toxicity research and could be used in the basic RACB design. One of the studies reported below evaluated a standard murine RACB design using rats, which rears the fifth litter to test second generation fertility. The second design tested the logistics and feasibility of rearing the second litter for second generation fertility testing. The standard fifth litter design (L5) was modified slightly for rats by increasing the time allowed for gestation and delivery. Compared to rats rearing their second litter (L2), rats in this L5 design had more litters per pair during continuous breeding and maintained this fertility better over time, as evidenced by producing more pups per litter during the crossover mating segment. Both L2 and L5 rats gave sufficient pups to conduct the second generation fertility evaluation. In addition, the L5 design was easier to conduct and produced pups from gametes exposed to chemical throughout spermatogenesis, making it the preferred design for using rats in Continuous Breeding studies.

Animals↗
PubMed1990

Chromosome aberration and sister chromatid exchange test results with 42 chemicals.

Forty-two chemicals were tested for their ability to induce cytogenetic change in Chinese hamster ovary cells using assays for chromosome aberrations (ABS) and sister chromatid exchanges (SCE). These chemicals were included in the National Toxicology Program's evaluation of the ability of four in vitro short-term genetic toxicity assays to distinguish between rodent carcinogens and noncarcinogens. The conclusions of this comparison are presented in Zeiger et al. [Zeiger E, Haseman JK, Shelby MD, Margolin BH, Tennant RW (1990): [Environ Molec Mutagen 16(Suppl 18): 1-14]. The in vitro cytogenetic testing was conducted at four laboratories, each using a standard protocol to evaluate coded chemicals with and without exogenous metabolic activation. Most chemicals were tested in a single laboratory; however, two chemicals, tribromomethane and p-chloroaniline, were tested at two laboratories as part of an interlaboratory comparison. Four chemicals (C.I. basic red 9 HCl, 2-mercaptobenzothiazole, oxytetracycline HCl, and rotenone) were tested for SCE in one laboratory and in a different laboratory for ABS. Tetrakis(hydroxymethyl)phosphonium sulfate was tested at one laboratory and the chloride form was tested at a different laboratory. Twenty-five of the 42 chemicals tested induced SCE. Sixteen of these also induced ABS; all chemicals that induced ABS also induced SCE. There was approximately 79% reproducibility of results in repeat tests, thus, we conclude that this protocol is effective and reproducible in detecting ABS and SCE.

Animals↗
PubMed1990

Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures.

Azodicarbonamide (ADA), a compound used in the baking and plastics industries, has been reported to cause pulmonary sensitization and dermatitis in people. Two-week repeated and 13-week subchronic inhalation exposures of F344/N rats and B6C3F1 mice to ADA were conducted to determine the toxicity of inhaled ADA. The mean air concentrations of ADA in the 2-week studies were 207, 102, 52, 9.4, or 2.0 mg/m3. No exposure-related mortality nor abnormal clinical signs were observed in rats or mice during or after exposure. The terminal body weights were slightly depressed in the highest exposure group. Liver weights were lower in male rats exposed to 200 mg ADA/m3. No significant lesions were noted on either gross or histologic evaluation of rats or mice. In the 13-week subchronic study, the mean air concentrations of ADA were 204, 100, or 50 mg/m3. No mortality or clinical signs related to exposure were observed. The terminal body weights of exposed rats were not significantly different from those of control rats but were significantly depressed in mice exposed to 100 or 200 mg ADA/m3. No histopathological lesions were noted in mice. Lung weights were increased and enlarged mediastinal and/or tracheobronchial lymph nodes were noted in rats exposed to 50 mg ADA/m3. No exposure-related lesions were observed microscopically in rats exposed to 100 or 200 mg ADA/m3. All rats in the 50 mg ADA/m3 exposure group only had lung lesions that consisted of perivascular cuffing with lymphocytes and a multifocal type II cell hyperplasia, suggesting a possible immune reaction to an antigen in the lung. Viral titers for rats exposed to 50 mg ADA/m3 were negative for Sendai virus and pneumonia virus of mice, which produce similar lesions. The possibility of an unknown viral antigen causing this lesion cannot be eliminated. Lung tissue from male rats was analyzed for ADA and biurea, the major metabolite of ADA. No ADA was detected. The amount of biurea in the lungs increased nonlinearly with increasing exposure concentration, suggesting that clearance was somewhat impaired with repeated exposures. However, even at the highest exposure concentration, this amount of biurea was less than 1% of the estimated total ADA deposited over the exposure period. In summary, ADA is rapidly cleared from the lungs, even when inhaled at concentrations up to 200 mg/m3. Exposure to ADA for up to 13 weeks did not appear to be toxic to rodents.

Administration, Inhalation↗
PubMed1990

Assessment of ethylene glycol monobutyl and monophenyl ether reproductive toxicity using a continuous breeding protocol in Swiss CD-1 mice.

A continuous breeding reproduction study design was utilized to examine the reproductive toxicity of ethylene glycol monobutyl ether (EGBE) and ethylene glycol monophenyl ether (EGPE). Swiss CD-1 mice were administered EGBE in drinking water (0, 0.5, 1.0, and 2.0%, i.e., 0.7, 1.3, and 2.1 g/kg body wt/day) and EGPE was administered via the feed (0, 0.25, 1.25, and 2.5%, i.e., 0, 0.4, 2.0, and 4 g/kg body wt/day). Both male and female mice were dosed for 7 days prior to and during a 98-day cohabitation period. EGBE was toxic at the high (2%) and mid dose (1%) to adult F0 female mice: 13 out of 22 females at the high dose and 6 out of 20 at the mid dose died during the cohabitation period. Both the high- and mid-dose animals produced fewer litters/pair, fewer pups/litter, with decreased pup weight. These effects occurred in the presence of decreased body weight, decreased water consumption, and increased kidney weight. A crossover mating trial indicated that the reproductive effects could be attributed primarily to an effect on the female. This was substantiated at necropsy where testes and epididymis weights were normal as were sperm number and motility. Fertility of the offspring of the 0.5% group was normal in the presence of increased liver weights. With respect to EGPE, there was no change in the ability to produce five litters during the continuous breeding period. There was, however, a significant but small (10-15%) decrease in the number of pups/litter and in pup weight in the high-dose group. A crossover mating trial suggested a female component of the reproductive toxicity of EGPE. While fertility was only minimally compromised, severe neonatal toxicity was observed. By Day 21 there were only 8 out of 40 litters in the mid- and high-dose groups which had at least one male and female/litter. Second generation reproductive performance of the mid-dose group (1.25%) was unaffected except for a small decrease in live pup weight. In summary the reproductive toxicity of EGBE and EGPE was only evident in the female and occurred at doses which elicited general toxicity. EGBE was particularly toxic to adult female mice while EGPE was particularly toxic to immature mice of both sexes.

Animals↗
PubMed1990

Evaluation of the mutagenicity of the anti-inflammatory drug salicylazosulfapyridine (SASP).

Salicylazosulfapyridine, commonly known as sulfasalazine or SASP, is an anti-inflammatory drug that is widely used in the treatment of diseases such as ulcerative colitis and Crohn's disease. Increases in sister chromatid exchanges (SCE) and micronuclei (MN) frequencies have been reported in lymphocytes of patients maintained on SASP therapy for up to 21 months. We have tested SASP for its ability to induce chromosome aberrations (ABS) and SCE in cultured Chinese hamster ovary (CHO) cells, ABS in mouse bone marrow cells, and MN in erythrocytes from both bone marrow and peripheral blood of mice. In vitro assays for ABS and SCE were negative. In vivo, SASP administered by single gavage at doses up to 1000 mg/kg did not increase ABS in bone marrow cells of male B6C3F1 mice; however, increases in MN were observed in the peripheral blood erythrocytes of male and female B6C3F1 mice administered 675, 1350 or 2700 mg/kg SASP by gavage for 90 days. Weak but significant dose-related increases in MN were also observed in the bone marrow cells of male B6C3F1 mice administered 500, 1000 and 2000 mg/kg SASP for 3 days. These positive findings in mice support the role of SASP in the induction of MN and SCE in humans, and suggest the need for further evaluation of possible adverse human health effects associated with SASP therapy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. III. Results with 27 chemicals.

Twenty-seven chemicals previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations (ABS) and sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Seventeen of the chemicals tested were carcinogens; only two of these were negative for both ABS and SCE. Of the eight noncarcinogens tested, four were negative for both endpoints (ABS and SCE) and four gave a positive response for at least one endpoint. Of the remaining two chemicals, one, diallyl phthalate, gave an equivocal response in the bioassay and a positive response in these CHO cell cytogenetics tests. The other chemical, 2,4-toluene diisocyanate, was tested for carcinogenicity as a mixture with the 2,6-isomer; the mixture was carcinogenic, but the cytogenetic test results for the 2,4-isomer were negative. Only six of the 27 chemicals tested produced an effect in one endpoint alone; the other 21 were either positive or negative for both ABS and SCE. Only one of the 27 chemicals tested required S9 for a positive response in the SCE test; two chemicals required S9 for a positive result in the ABS test. Experiments with unsynchronized CHO cells demonstrated that mean SCE frequency increased with increasing culture time, and this may have been a factor in the positive results obtained for five chemicals in the SCE test under conditions of delayed harvest.

Animals↗
PubMed1989

Results of tests for micronuclei and chromosomal aberrations in mouse bone marrow cells with the human carcinogens 4-aminobiphenyl, treosulphan, and melphalan.

Three human carcinogens, 4-aminobiphenyl, treosulphan, and melphalan, were tested for the induction of micronuclei or chromosomal aberrations in the bone marrow cells of male B6C3F1 mice. These studies were conducted to provide further information on the in vivo genetic toxicity of compounds known to cause cancer in humans. All three compounds gave positive results in the mouse bone marrow micronucleus test, and melphalan, the only compound tested for aberration induction, was positive in this assay. These results extend the evidence that nearly all known human carcinogens are detected in relatively simple and widely employed short-term in vivo tests.

Aminobiphenyl Compounds↗
PubMed1989

Reproductive toxicity of three phthalic acid esters in a continuous breeding protocol.

A continuous breeding protocol was utilized to examine the reproductive toxicity of three phthalate esters. CD-1 mice were given diets with either di-n-propyl phthalate (DPrP: 0.0, 1.25, 2.5, or 5.0%), di-n-pentyl phthalate (DPP: 0.0, 0.5, 1.25, or 2.5%), or di-n-octyl phthalate (DOP: 0.0, 1.25, 2.5, or 5.0%). Both male and female mice (20 pairs per treatment group, 40 pairs of control animals) were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring number of litters per pair, live pups per litter, and pup weight. There was no apparent effect on reproductive function in the animals exposed to DOP at dose levels sufficient to cause a significant increase in liver weight. Both DPP and DPrP were toxic to the reproductive system as evidenced by a complete inhibition of fertility at 1.25 and 2.5% DPP or 5.0% DPrP, and reduced fertility (litters/pair and live pups/litter, 0.5% DPP; live pups/litter, 2.5% DPrP). Toxicity of DPP had a strong male component and female component, whereas DPrP was more toxic to the female than the male reproductive system. DPP and DPrP treatment was associated with decreased body weight, increased liver weight, decreased testis and epididymis weights, decreased epididymal sperm concentration, and elevated seminiferous tubule atrophy. A comparison of seven phthalate esters tested using this continuous breeding protocol indicates the relative order of reproductive toxicity as diethylhexyl, dihexyl, dipentyl, dibutyl, dipropyl; diethyl and dioctyl are nontoxic.

Animals↗