500-ppm Group Research Articles

An in vitro Comparative Evaluation of Fluoride Uptake by Demineralized Enamel Exposed to Four Different Low Fluoride Dentifrices

Background: Topical fluoride application has an important role in caries prevention. The aim of the present study was to evaluate and compare fluoride uptake of tooth enamel after exposure to four commercially available low fluoridated toothpastes. Methods: The present in vitro study was conducted on 60 sound extracted premolar teeth. The teeth were covered with acid-resistance nail polish except at a 5×5 mm area on the buccal and lingual surface of each tooth (for experimental and control group respectively). After demineralization of the window area for 2 days, the teeth were immersed in toothpaste slurry containing: Sodium Fluoride 1000ppm (Group A), Soduim monofluorophosphate 1000ppm (Group B), Soduim monofluorophosphate 500ppm (Group C) and Sodium fluoride 500ppm (Group D). The pH of the dentifrices was measured. The acid biopsy technique and fluoride ion-specific electrode was used for fluoride ion estimation. Results: All of the applied toothpastes significantly increased fluoride content of the enamel compared with the control group (P <0.001). There was a significant difference among the four groups of toothpastes in the mean fluoride uptake and group A showed maximum uptake of fluoride (5.5920 ppm), followed by group B, C and D respectively. According to Pearson correlation analysis, there was not any significant relationship between the pH of the dentifrices and uptake of fluoride. Conclusion: There was a positive correlation between the fluoride concentration of dentifrices and the fluoride uptake on demineralized enamel. The toothpastes containing NaF are more effective than toothpastes containing NaMFP. Moreover, dentifrice pH had no influence on fluoride uptake by enamel.

Effect of rosemary essential oil as nitrite substitute on quality of sausage produced using chicken fed by thymus essential oil and rapeseed oil.

The objective was to determine the effect of rosemary essential oil (REO) as nitrite substitute on the physicochemical, microbiological and sensory quality of sausage from broilers fed different levels of thymus essential oil (TEO) and rapeseed oil (RO). Broiler chicks fed TEO (0, 300 and 500ppm) and RO (1, 3 and 5%) in a 3 × 3 factorial design. Sausages were made from meat of chicken fed TEO (0 and 500ppm) treated with REO (120ppm), REO:nitrite (60:60ppm), nitrite (120ppm) or without REO and nitrite in a 2 × 4 factorial design. Results showed that TEO increased water holding capacity and pH value and decreased malondialdehyde concentration. RO (1 and 3%) × TEO (500ppm) group had higher unsaturated to saturated fatty acids ratio in the meat. Results showed that treatments of REO (120ppm) decreased lipid oxidation and increased pH value of meat. Sausage produced by nitrite (120ppm) or REO:nitrite (60:60ppm) had lower total microbial count, lightness but higher redness and yellowness. Based on the results, TEO in chicken feed decreased lipid oxidation of sausages. Furthermore, substitution at least 60ppm nitrite with REO had more preserving effect on quality of produced sausages.

Toxic Impacts of Amorphous Silica Nanoparticles on Liver and Kidney of Male Adult Rats: an In Vivo Study.

The toxic effects of the amorphous silica nanoparticles have not been thoroughly studied. Moreover, the majority of the in vivo investigations were performed using an inhalation exposure method. The current study aimed to explore the potential toxic effects of silica nanoparticles (SiNPs) after the treatment of adult male rats with two different concentrations (500 and 1000 ppm) via drinking water for 28 days. The genotoxicity, antioxidant status, and liver and kidney functions were assessed. Besides, histopathological and immunohistochemical evaluations were performed. The results showed a significant elevation in the malondialdehyde (MDA) level concurrent with a reduction in total reduced glutathione (GSH) concentration and catalase activity in the 1000-ppm SiNP-exposed rats as well as increase in ALT and AST activity confirmed by various histopathological alterations detected in liver. Also, in the 1000-ppm SiNP-exposed animals, there was an elevation in urea and creatinine levels confirmed by histopathological alterations detected in kidneys. Immunohistochemical findings in both liver and kidneys indicated strong expression of caspase-3 in the 1000-ppm SiNP-treated rats compared with the control and 500-ppm SiNP-treated groups. Such findings indicated that the 1000-ppm SiNPs exerted severe hepato-renal toxic impacts when compared with the control and 500-ppm SiNP-exposed rats.

Inhalation exposure to 1,2-dichloropropane: Distribution of blood and tissue concentrations of 1,2-dichloropropane in rats during and after exposure

The present investigation was undertaken to determine the distribution and accumulation of 1,2-dichloropropane (DCP) in the blood, lung, liver, kidney, and abdominal fat of rats during and after inhalation exposure. Male rats were exposed to 80 or 500 ppm (v/v) DCP vapor for 360 min and the concentrations of DCP in the blood and tissues during the inhalation exposure period and after the end of the exposure period were measured. DCP accumulation in the abdominal fat was much greater than that in the blood and other tissues. Eighteen hours after the end of inhalation exposure, DCP could still be detected in the abdominal fat in the 80-ppm group, and in the blood, liver, kidney, and abdominal fat in the 500-ppm group. Our results are valuable data pertaining to the pharmacokinetics of DCP and to human health risk assessment of exposure to DCP vapor by inhalation.

Acute and subchronic toxicity of arprinocid in Sprague–Dawley rats

We subjected Sprague–Dawley rats to an acute and 13-week subchronic oral toxicity of arprinocid, a nucleoside analogue used as a coccidiostat, according to toxicological guidelines as part of its safety assessment. In the acute study, arprinocid was administered once by oral gavage to rats at doses ranging from 292.4 to 506.0mg/kgb.w. The calculated LD50 was 442.9mg/kgb.w. in males and 378.7mg/kgb.w. in females. In the subchronic study, male and female rats were fed with diets supplemented with 0, 25, 187.5 or 500ppm arprinocid for 13weeks. Significantly lower body weights were noted in the 500ppm group females. The mean body weights of the 500ppm group females were 12.9% lower than that of the controls. Significant differences in haematological and biochemical parameters as well as organ weights were detected between the 500 and 187.5ppm groups. Histopathological observations revealed that 500 and 187.5ppm arprinocid could induce hepatic steatosis and focal hepatocellular necrosis. Slight protein cast in some renal tubules and tubular regeneration were observed in the high dose group of both genders. The dietary no-observed-adverse-effect level (NOAEL) of arprinocid in rats for 13weeks is 25ppm (approximately 1.7mg/kgb.w./day).

Evaluation of the reproductive and developmental toxicity of aluminium ammonium sulfate in a two-generation study in rats

Aluminium ammonium sulfate (AAS) was tested for reproductive/developmental toxicity in a two-generation study. Male and female rats were continuously given AAS in drinking water at 0, 50, 500 or 5000ppm. Water consumption was decreased in all AAS-treated groups, and the body weight of parental animals transiently decreased in the 5000ppm group. In either generation, no compound-related changes were found in estrous cyclicity, sperm parameters, copulation, fertility and gestation index, number of implantations and live birth pups, sex ratios of pups or viability during the preweaning period. Male and female F1 pups in the 5000ppm group showed a lower body weight on postnatal day 21, while there were no differences in the birth weight of F1 and F2 pups between the control and AAS-treated groups. Preweaning body weight gain in F2 males and females indicated a similar decreasing tendency at 5000ppm. In F1 and F2 weanlings, the weight of the liver, spleen and thymus decreased at 5000ppm, but no histopathological changes were found in these organs. In F1 females in the 5000ppm group, vaginal opening was delayed slightly. There were no compound-related changes in male preputial separation or in other developmental landmarks. In behavioral tests conducted for F1 animals at 4–6weeks of age, no compound-related changes were found in spontaneous locomotor activity and performance in a water-filled multiple T-maze. In conclusion, the NOAEL of AAS for two-generation reproductive/developmental toxicity was considered to be 500ppm in rats. Considering the aluminium content in the basal diet, the total ingested dose of aluminium from drinking water and food in this 500ppm group was calculated to be 5.35mgAl/kgbw/day.

Epoxiconazole causes changes in testicular histology and sperm production in the Japanese quail (Coturnix coturnix japonica)

The fungicide epoxiconazole (Epox), a triazole, belongs to the group of azole compounds that are extensively used as fungicides in various fruit crops. The frequent use of agricultural lands for wintering by migrating birds can be the source of their increased dietary intake of agricultural pesticides. We investigated whether exposure to Epox causes effects on avian fertility and reproduction, using the Japanese quail (Coturnix coturnix japonica) as a model species for the assessment of reproductive effects of pesticides in wild birds. Epox was administered to adult Japanese quail for three weeks at dietary levels of 10, 50, and 500 ppm, and possible effects on reproduction were investigated. Epox administration resulted in a significantly decreased number of spermatids in the 50- and 500-ppm dose groups. Histopathology showed a reduced number of testicular canaliculi with visible germ cells and a reduction in spermatid number. However, testis weight was not affected up to the highest dose level. No impact was observed on hormone levels, fertility, and reproductive outcome, as laying rate and percentage of fertile eggs were not altered. Likewise, treatment had no influence on the egg or chick parameters evaluated. A time- and dose-related transfer of Epox into the eggs was determined in all treatment groups. We conclude that dietary treatment of Japanese quail with 50 and 500 ppm of the triazole fungicide Epox resulted in a clear impact on the testis. The evaluation of the additional endpoints spermatid count and testicular histology have proven useful and are recommended for future studies on avian reproduction.

Two generation reproduction study of styrene by inhalation in Crl‐CD rats

This study was conducted to evaluate the potential adverse effects of styrene on reproductive capability from whole-body inhalation exposure of F0 and F1 parental animals. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F0 and F1 generations, and F1 generation offspring growth and development. Four groups of male and female Crl:CD(SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through gestation day 20. Inhalation exposure of the F0 and F1 females was suspended from gestation day 21 through lactation day 4. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). These oral dosages were calculated to provide similar maternal blood peak concentrations as provided by the inhalation exposures. Inhalation exposure of the F0 and F1 females was re-initiated on lactation day 5. Styrene exposure did not affect survival or clinical observations. Rats in the 150- and 500-ppm groups in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts and corpora lutea counts for the F1 females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F0 and F1 generations. A previously characterized pattern of degeneration of the olfactory epithelium that lines the dorsal septum and dorsal and medial aspects of the nasal turbinates occurred in the F0 and F1 generation animals from the 500-ppm group. In the 500-ppm group, F2 birthweights were reduced compared to the control and F2 offspring from both the 150- and 500-ppm exposure groups gained weight more slowly than the controls. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for F0 and F1 parental systemic toxicity; the NOAEL for F0 and F1 reproductive toxicity was 500 ppm or greater.

Developmental neurotoxicity study of styrene by inhalation in Crl‐CD rats

This study was conducted to assess potential adverse functional and/or morphological effects of styrene on the neurological system in the F2 offspring following F0 and F1 generation whole-body inhalation exposures. Four groups of male and female Crl:CD (SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure continued for the F0 and F1 females throughout mating and through gestation day 20. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). Inhalation exposure of the F0 and F1 females was re-initiated on lactation day 5 and continued through weaning of the F1 or F2 pups on postnatal day (PND) 21. Developmental landmarks were assessed in F1 and F2 offspring. The neurological development of randomly selected pups from the F2 generation was assessed by functional observational battery, locomotor activity, acoustic startle response, learning and memory evaluations, brain weights and dimension measurements, and brain morphometric and histologic evaluation. Styrene exposure did not affect survival or the clinical condition of the animals. As expected from previous studies, slight body weight and histopathologic effects on the nasal olfactory epithelium were found in F0 and F1 rats exposed to 500 ppm and, to a lesser extent, 150 ppm. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. There were exposure-related reductions in mean body weights of the F1 and F2 offspring from the mid and high-exposure groups and an overall pattern of slightly delayed development evident in the F2 offspring only from the 500-ppm group. This developmental delay included reduced body weight (which continued through day 70) and slightly delayed acquisition of some physical landmarks of development. Styrene exposure of the F0 and F1 animals had no effect on survival, the clinical condition or necropsy findings of the F2 animals. Functional observational battery evaluations conducted for all F1 dams during the gestation and lactation periods and for the F2 offspring were unaffected by styrene exposure. Swimming ability as determined by straight channel escape times measured on PND 24 were increased, and reduced grip strength values were evident for both sexes on PND 45 and 60 in the 500-ppm group compared to controls. There were no other parental exposure-related findings in the F2 pre-weaning and post-weaning functional observational battery assessments, the PND 20 and PND 60 auditory startle habituation parameters, in endpoints of learning and memory performance (escape times and errors) in the Biel water maze task at either testing age, or in activity levels measured on PND 61 in the 500-ppm group. Taken together, the exposure-related developmental and neuromotor changes identified in F2 pups from dams exposed to 500 ppm occurred in endpoints known to be both age- and weight-sensitive parameters, and were observed in the absence of any other remarkable indicators of neurobehavioral toxicity. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for growth of F2 offspring; an exposure level of 500 ppm was considered to be the NOAEL for F2 developmental neurotoxicity.

Dental pulp infarction in female rats following inhalation exposure to 2-butoxyethanol.

Female Fischer 344 (F344)/N rats (10 per exposure group) were exposed to 2-butoxyethanol (BE) vapors (0, 31, 62.5, 125, 250, or 500 ppm 6 h/d, 5 d/wk, for 13 weeks) to characterize its prechronic toxicity. Dental lesions consisting of bilateral multifocal dental pulp thrombosis, pulp infarction, and odontoblast infarction were noted in the maxillary incisors of 3 of 4 rats from the 500-ppm group that were sacrificed when moribund during the first week of exposure. In addition, 1 rat from the 500-ppm group that was sacrificed on day 32 had similar unilateral incisor lesions but with additional findings consistent with a unilateral maxillary incisor fracture. In contrast, rats sacrificed after 13 weeks of exposure lacked dental lesions. In conclusion, BE has the potential to cause pulp thrombosis and odontoblast infarction in female rats. The apparent variability in response to BE noted in moribund sacrificed vs terminally sacrificed rats was attributed to development of tolerance to BE-induced hemolysis and subsequent incisor regeneration.

Chronic dietary toxicity and oncogenicity evaluation of MCPA (4-chloro-2-methylphenoxyacetic acid) in rodents.

The chronic toxicity and oncogenicity of 4-chloro-2-methylphenoxyacetic acid (MCPA) were evaluated in Wistar rats at target doses of 20, 80, and 320 ppm for 2 years. Chronic effects were noted in male and/or female rats in the 80- and 320-ppm dose groups, namely elevations in triglycerides and serum glutamic transaminase levels. Nephrotoxicity was confined to male rats in the 320-ppm dose group. The systemic NOEL was determined to be 20 ppm for male and female rats. No oncogenic potential was observed. Doses in the 2-year oncogenicity study in mice were 20, 100, and 500 ppm. Kidney weight changes with corresponding minor histopathological findings in the kidney were evident in females in the 500-ppm dose group. MCPA was determined to have no oncogenic potential in B6C3F1 mice. In summary, there is no evidence of any oncogenic potential after dietary exposure of MCPA in rats or mice even at doses where limited chronic toxicity is seen.

A two-generation reproduction study in rats with methyl bromide-fumigated diets

Crj: CD(SD) rats were fed basal (control) diet or methyl bromide-fumigated diet containing 80, 200 or 500 ppm total bromine for two successive generations (18 wk for each generation). Compared with controls, food consumption was significantly lower in F 1 parental females of the 500-ppm group during the second half of the dosing period, and F 2 female pups of the 500-ppm group showed lower body weights throughout the lactation period. No other treatment-related changes were found at any dietary level of total bromine in either parental animals (F 0, F 1) or their offspring (F 1, F 2) for any of the parameters studied (i.e. clinical signs, oestrous cycle, sperm count and morphology, mating, fertility, gestation, parturition, litter size, pup viability, organ weights, and gross or histopathological examination). It was concluded that residues of 200 and 500 ppm total bromine in diets fumigated with methyl bromide are the no-observed-effect level and the minimum toxic level, respectively, for both parental rats and their offspring, and that bromine residues do not affect reproductive performance at dietary levels of up to 500 ppm.

Two-year oral chronic toxicity and carcinogenicity study in rats of diets fumigated with methyl bromide

A chronic toxicity and carcinogenicity study was conducted by feeding diets containing 80, 200 or 500 ppm total bromine following fumigation with methyl bromide, a diet containing 500 ppm potassium bromide, or a basal diet alone to groups of 60 male and 60 female Fischer (F344) rats for up to 2 yr. Ten males and ten females from each group were killed after wk 52 and 104 for urinalysis, haematology, blood biochemistry and pathology. Rats that were killed in extremis or found dead during the study and all rats that survived to the end of the study were also subjected to pathological examinations. In rats fed the diets fumigated with methyl bromide there were no marked toxic changes, except for a slight depression of body-weight gain from wk 60 onwards in males of the 500-ppm group, and tumour incidence was unaffected. Rats given a diet containing potassium bromide did not show any treatment-related changes. It was concluded that residues of up to 500 ppm total bromine in diets fumigated with methyl bromide are not carcinogenic in F344 rats of either sex and that the maximum no-effect level is 200 ppm (6.77 mg total bromine/kg body weight/day) in males. The maximum no-effect level could not be determined in females.

Primary brain tumours in Fischer 344 rats chronically exposed to acrylonitrile in their drinking-water

Acrylonitrile (ACN) has been tested for carcinogenicity by various routes in a number of rat strains. At relatively high levels of administration (e.g. 500 ppm in the drinking-water) there were statistically significant increases in microscopically detectable primary brain tumours, which were difficult to classify. In a further study of ACN-induced brain tumours, ACN was administered to groups of 50 male and 50 female F-344 rats from 6 wk of age at levels of 0, 100 and 500 ppm in the drinking-water. A fourth group of 300 rats (147 males, 153 females), was also given 500 ppm ACN. Neurological signs were observed in 0, 4, 16 and 29, respectively, of the rats in these four groups within 12–18 months. Among the treated animals, females died slightly earlier than males. Few controls of either sex had died by month 18, but, apart from those killed for tumour donation, a high proportion of the rats in the 500-ppm groups had died by that time. Of the 49 brain tumours found in rats exposed to 500 ppm ACN, 11 were only detectable microscopically, 28 were 1–5 mm in diameter and 10 were greater than 5 mm. Despite this variation in size, all the tumours were similar in cellular and architectural features. They were densely cellular, with occasional areas of focal necrosis, and were infiltrative at the margins. They were negative for glial fibrillary acidic protein (GFAP). Ultrastructurally, the tumour cells showed intermingling cytoplasmic processes but no glial filaments and no neurosecretory granules or specialized cell contacts. Samples of tumour tissue were successfully grown in culture, but transplantation of samples from these cultures (observed for up to 12 wk) was unsuccessful. However, a direct intracerebral transplantation from a large tumour was successful.

Effects of feeding stannous chloride on different parts of the gastrointestinal tract of the rat

The effects of feeding inorganic tin on the gastrointestinal tract were examined in rats. Three groups of male weanling Wistar rats were fed a diet to which 0, 250, or 500 ppm Sn 2+ had been added as SnCl 2. A fourth group was subjected to feed restriction by pair feeding with the 500-ppm group. Comparison of the data from the tin-fed groups with both the control and the reduced diet groups allowed discrimination between effects of reduced feed intake and Sn 2+ effects. Independent of the reduced feed intake, Sn 2+ affected hemoglobin concentration in the blood and several small intestine parameters. Total length of the small intestine, as well as absolute and relative weights, was increased. An increase was also observed in the migration of epithelial cells along the villus, as revealed by [ 3H]thymidine incorporation and autoradiography in rats fed 900 ppm Sn 2+ for 4 weeks. Stereo-light microscopy and scanning electron microscopy revealed the formation of ridge-like villi due to Sn 2+ feeding and a decreased number of villi per unit surface. These data suggest that an increase in cell turnover in the small intestine, due to Sn 2+, was responsible for these changes.

Review of recent toxicology studies on p-dichlorobenzene

Results from recent long-term inhalation, mutagenicity, embryotoxicity and metabolism studies on p-dichlorobenzene(p-DCB) are reviewed. Groups of male and female rats and female mice were exposed for 5 hr/day on 5 days/wk to p-DCB at concentrations of 0, 75 or 500 ppm for a total period of c. 76 wk (rats) or 57 wk (female mice) followed by 36 wk (rats) or 19 wk (female mice) without p-DCB exposure. No overt signs of toxicity were apparent at any exposure level nor were there treatment-related effects on the biochemical determinations, urine analyses or haematological parameters. Slightly elevated urinary coproporphyrin excretion and increased liver and kidney weights were regarded as treatment-related effects in the 500-ppm exposure group of the rats. The non-tumour and tumour pathology did not indicate any treatment-related effect in any group of either species. An embryotoxicity and teratology study on rats exposed to 0, 75, 200 or 500 ppm p-DCB vapour in air during the period of organogenesis did not demonstrate any signs of embryo- or foetotoxicity or teratogenicity at any exposure level. In a series of mutagenicity tests including the Salmonella typhimurium, dominant lethal and cytogenetic assays, p-DCB did not produce a mutagenic response. Studies using oral or inhalation routes of exposure demonstrated rapid metabolic transformation of p-DCB and excretion of the products, even after long-term exposure.

Structural teratogenicity evaluation of methyl chloride in rats and mice after inhalation exposure

One hundred bred Fischer-344 female rats were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 25 females per exposure concentration, from gestation day (gd) 7 through gd 19. On gd 20, the females were sacrificed for evaluation of maternal reproductive and fetal parameters. Maternal and fetal toxicity was apparent at the highest exposure concentration. There were no methyl chloride-induced external, skeletal, or visceral abnormalities seen in the fetuses. One hundred thirty-two C57BL/6 female mice bred to C3H males to produce B6C3F1 offspring were exposed daily for 6 hours to atmospheres containing 0, 100, 500, or 1,500 ppm methyl chloride, 33 females per exposure concentration, from gd 6 through gd 17. Exposure to the entire 1,500-ppm group was terminated on gd 10-14, with the animals killed in extremis. Selective necrosis of neurons in the internal granular layer of the cerebellum, ranging from individual cell involvement to focal areas comprising large numbers of neurons, was found in all females. On gd 18, the females from the other treatment groups, all of which survived, were killed for evaluation of maternal reproductive and fetal parameters. No evidence was seen of maternal or fetal toxicity in these exposure groups. There were no significant alterations in external appearance in fetuses from any of the exposure groups. Visceral examination of mouse fetuses revealed a small, but statistically significant, incidence of heart defects in litters of the 500-ppm group. The anomaly, a reduction or absence of the atrioventricular valve, chordae tendineae, and papillary muscle, was observed on the left side (bicuspid valve) in three fetuses and the right side (tricuspid valve) in six fetuses: three males and six females. It is concluded that methyl chloride inhalation exposure in pregnant rats, during critical periods of embryo and fetal development, is not teratogenic at concentrations which elicit maternal and fetal toxicity. In pregnant mice, methyl chloride was severely toxic to dams following 4 days or more of exposure to 1,500 ppm in air. Methyl chloride, at 500, but not 100 ppm, was teratogenic in mice, leading to a malformation in the heart. No embryo-fetal toxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 100 ppm of ethyl chloride.

Subacute toxicity of O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate (Sumithion) in the rat

To observe the subacute toxicity of Sumithion, 6 groups of male Wistar rats were fed for 90 days with control food and food containing 32, 63, 125, 250, and 500 ppm of the compound. Rats in the 500-ppm group showed significant inhibition of growth and various cholinergic signs for the first 2 or 3 weeks. Thereafter, they showed a clear recovery in growth and appearance. However, there were significant differences in mean body weight and food intake between the control and 500-ppm groups even at the end of 90 days. The testis- and brain-body weight ratios were higher in this group than in control groups at the end of 11, 30, 60, and 90 days. Rats in groups dosed with 250 ppm or less showed almost no changes by these measures. The decrease of cholinesterase activity in the kidney, liver, red blood cells, and plasma was dependent on the concentration of Sumithion in the diet, was somewhat delayed in its time course compared with the appearance of cholinergic signs or inhibition of growth, and showed a tendency to recover after the 30th to 60th day of feeding. The decrease in activity of the brain cortex enzyme was much less and was earlier in its appearance than in the case of the other tissues. Histopathologic observation revealed almost no significant differences between the control and each of the Sumithion-dosed groups. Sumithion had no effects on the excretion of urinary sugar and protein. There were no significant differences in the content of norepinephrine and 3-hydroxy-tyramine in the liver, spleen, and brain stem between the control and 500-ppm groups.