Toxicity-metabolism relationship of the photoisomers of cyclodiene insecticides in freshwater animals

Summary The onset of toxic symptoms of photoaldrin and photodieldrin is 3–5 times faster than aldrin and dieldrin in crayfish, bluegills and minnows and 1.3–2.2 times in other animals. Photoisodrin is 3–5 times slower than isodrin in its toxic action against other animals tested. The increased toxicity of photoaldrin and photodieldrin is apparently related to the rate ofin vivo formation of more toxic ketones as observed with photodieldrin.     

Toxicity-metabolism relationship of the photoisomers of certain chlorinated cyclodiene insecticide chemicals

Photoaldrin, photodieldrin, and photoheptachlor are more toxic than their corresponding parent compounds (aldrin, dieldrin, and heptachlor) to freshwater invertebrates and vertebrates, and to adult houseflies. The increase in toxicity is very significant in the case of the amphipod,Gammarus (1.5–12 times), bluegill fry (3.6–5.7 times), mosquito larvae,Aedas (2.3–6 times), minnow fry (2.5 times), and the isopid,Asellus (2 times). The greatest increases occur with photodieldrin which is 12 and 5 times more toxic than dieldrin, respectively, toGammarus, and to blue-gill fry, and with photoaldrin which is 6 and 4 times more toxic than aldrin, respectively, to mosquito larvae and bluegill fry. The toxicities of the photoisomers of isodrin and chlordene are generally less than those of their parent compounds to all the organisms tested. The basis of the differences in toxicities of the chlorinated cyclodiene photoisomers appears to be related to their chemical structure which possibly affects their action at the site(s) of toxic action and/or detoxication. The acidic proton present at the secondary chloride in photoaldrin, photodieldrin, and photoheptachlor possibly is responsible for the formation of charge-transfer complexes between components of the nerve and the mixed-function oxidase; the latter enzyme apparently dehydrochlorinates these photo products to their corresponding, more toxic ketones. The absence of such protons in photoisodrin and photochlordene renders them incapable of forming such ketones. The inhibition of these reactions by sesamex in house flies increases the stability of the chlorinated cyclodiene insecticides and, thus, significantly affects their toxicity. The conversion of photoaldrin, photodieldrin, and photoheptachlor to more-toxic and lipophilic ketones warrants additional studies of their accumulation and subsequent concentration by the food chain.     

Acute toxicity of 2-thiotriazone in rats

The acute toxicity of 2-thiotriazone (TTZ) was evaluated in adult and immature rats of both sexes. 2-Thiotriazone produced marked pulmonary toxicity in rats that was both age and sex dependent. TTZ was highly toxic to adult male rats when given as a single dose (oral LD₅₀ = 4.6 mg/kg and ip LD₅₀ =1.4 mg/kg) with 100% mortality being observed at 10 mg/kg orally and 5 mg/kg intraperitoneally (ip). Female rats were more resistant than males with only 40% mortality at concentrations of 10–100 mg/kg orally. Immature rats (30–40 days of age) of both sexes showed no response when TTZ was administered at concentrations of 10–1000 mg/kg either orally or ip. Gross and histological examination of lung tissue from rats affected by TTZ revealed severe pulmonary edema, effusion, and mottling of the lungs. Significant increases in lung weights were also observed. Studies with diethylmaleate (DEM) and TTZ indicated that DEM pretreatment potentiated the toxic effects of TTZ in adult male, adult female, and immature rats. Lung weights in DEM/TTZ-treated rats were twice that of animals treated with TTZ alone. The results of the present study indicate that TTZ is highly toxic to male rats with the lungs being particularly vulnerable to its effects and that TTZ toxicity is enhanced by DEM pretreatment.     

Structure-toxicity relationships for unsaturated alcohols to Tetrahymena pyriformis: C5 and C6 analogs and primary propargylic alcohols

In summary, the relative toxicity of selected unsaturated alcohols were evaluated in the static Tetrahymena pyriformis population growth assay. The alkyn-1-ols were found to be more toxic than alken-1-ols. Moreover, 2-position unsaturated derivatives were more toxic than other isomers. A linear log K_ow dependent relationship was generated (slope = 0.64; intercept = –0.61; r² = 0.974) for selected 2-alkyn-1-ols. However, the diols were observed to be more toxic than predicted.     

Activation of blood coagulation and fibrinolysis in vibration syndrome

Summary The pathophysiology of peripheral circulatory disturbance in patients presenting with vibration syndrome was studied from the viewpoint of blood coagulation. Plasma levels of fibronectin (FN), vitronectin (VN), thrombin-antithrombin III complex (TAT), and ₂-plasmin inhibitor-plasmin complex (PIC) were measured in 23 subjects who showed no evidence of vibration-induced white finger [VWF(–) group] and in 24 patients who presented with VWF [VWF(+) group]. In the VWF(–) group, plasma FN concentrations were elevated but plasma TAT and PIC levels were within the normal ranges. In the VWF(+) group, plasma FN concentrations were normal but plasma TAT and PIC levels were significantly elevated. In both groups, plasma VN concentrations were similar to those in normal controls. For purposes of comparison, 32 patients presenting with diabetes mellitus were also studied. They were divided into 2 groups, 13 subjects who showed no evidence of angiopathy [complication(–) group] and 19 patients who presented with angiopathy [complication(+) group]. In the complication(+) group, plasma TAT and PIC concentrations were significantly elevated, as in the VWF(+) group. These results suggest that in vibration syndrome, vibration, cold stimulus, or other factors first injure the vascular endothelium, resulting in a rise in plasma FN, and that in the VWF(+) group, augmentation of coagulation and fibrinolysis induces a state of compensated disseminated intravascular coagulation (DIC).     

PCB levels in egg yolks associated with embryonic mortality and deformity of hatched chicks

The effect of exposing White Leghorn hens for six weeks to 50 ppm of Aroclor 1254 in water was investigated. While egg production decreased temporarily, no significant effects were noted on egg weights or fertility. Incubation of eggs from exposed hens indicated that this polychlorinated biphenyl (PCB) did not interfere with gametogenesis and fertilization. As Aroclor 1254 accumulated in the yolk, however, embryonic development was arrested at progressively earlier developmental stages. When PCB was removed from the water there was an initial rapid decline in the PCB content of the yolk and a slow return of the normal developmental pattern of the embryo. Leg, toe, and neck deformities were present in many of the chicks hatched from eggs in which yolk PCB level was 10–15 ppm or more. The gross appearance of the liver and the presence of hemorrhages suggest that the liver and the vascular elements may be targets for PCB action.     

Effects of phenoxy acetic herbicides on growth,photosynthesis, and nitrogenase activity in cyanobacteria from rice fields

The effects of the phenoxy acetic herbicides 2,4-dichlorophenoxy acetic acid (2,4D) and methylchloro-phenoxy acetic acid (MCPA) on growth, photosynthesis, and nitrogenase activity of cyanobacteria has been investigated. Concentrations ranging from 10^–9 to 10^–3 M did not change significantly the parameters of Anabaena UAM 202. Concentrations higher than 10^–3 M of both herbicides were toxic. The primary toxic action of these herbicides in Anabaena UAM 202 was on photosynthesis.     

Impact of Parenteral Glutamine Supplement on Oncologic Outcomes in Patients with Nasopharyngeal Cancer Treated with Concurrent Chemoradiotherapy

Background: Oral mucositis (OM) is a common toxic side effect in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) that has a negative impact on treatment outcomes and patients’ survival. Our study aimed to evaluate the impact of parenteral glutamine supplement (dipeptiven) on oncologic outcomes in patients with NPC treated with CCRT. Methods: Patients who were diagnosed with pathologically proved NPC and treated with CCRT were enrolled into our study. Patients were classified as dipeptiven (+) and dipeptiven (–). Oncologic outcomes were measured, and multivariate regression analysis was performed. Grade 3–4 treatment related toxicities were also documented. Results: A total of 144 patients with NPC were recruited in this study to evaluate oncologic outcomes, with 41 dipeptiven (+) and 103 dipeptiven (–). CCRT interruption rate and severe adverse effect (SAE) rate were significant lower in the dipeptiven (+) group than in the dipeptiven (–) group. The median overall survival (OS) was not mature yet in the dipeptiven (+) group and 30 months in the dipeptiven (–) group (p < 0.01). Multivariate analysis demonstrated that dipeptiven supplementation and CCRT interruption were independent predictors associated with better survival. The OS was longest in patients with a dipeptiven supplement and patients who had CCRT interruption had significantly worst OS. As for safety profiles, grade 3 to 4 adverse effects were fewer in dipeptiven (+) than in dipeptiven (–). Conclusion: Dipeptiven supplementation is crucial in NPC patients treated with CCRT, which can ameliorate treatment-related toxicity and augment treatment efficacy. Further prospective clinical trials are warranted to validate our results.     

Toxicity of inorganic contaminants, individually and in environmental mixtures, to three endangered fishes (Colorado squawfish, bonytail, and razorback sucker)

Two life stages of three federally-listed endangered fishes, Colorado squawfish (Ptychocheilus lucius), bonytail (Gila elegans), and razorback sucker (Xyrauchen texanus) were exposed to copper, selenate, selenite, and zinc individually, and to mixtures of nine inorganics in a reconstituted water that simulated the water quality of the middle Green River, Utah. The mixtures simulated environmental ratios of arsenate, boron, copper, molybdenum, selenate, selenite, uranium, vanadium, and zinc in two tributaries, Ashley Creek and Stewart Lake outlet, of the middle Green River. The rank order of toxicity of the individual inorganics, from most to least toxic, was: copper > zinc > selenite > selenate. Colorado squawfish larvae were more sensitive to all four inorganics and the two mixtures than the juveniles, whereas there was no consistent response between the two life stages for the other two species. There was no consistent difference in sensitivity to the inorganics among the three endangered fishes. Both mixtures exhibited either additive or greater than additive toxicity to these fishes. The primary toxic components in the mixtures, based on toxic units, were copper and zinc. Acute toxicity values were compared to measured environmental concentrations in the two tributaries to derive margins of uncertainty. Margins of uncertainty were low for both mixtures (9–22 for the Stewart Lake outlet mixture, and 12–32 for the Ashley Creek mixture), indicating that mixtures of inorganics derived from irrigation activities may pose a hazard to endangered fishes in the Green River.     

Acute toxicity of several organophosphorous insecticides and protection by cholinergic antagonists and 2-PAM on Artemia salina larvae

The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methyl-parathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methyl-parathion = parathion < methyl-chlorpyrifos < chlorpyrifos.The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino) methyl)-1-piperidinylacetyl)-5,11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10^–5 M) and atropine (10^–4 M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC₈₄ of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC₅₀) of Artemia salina against mortality by LC₈₄ of the OPI selected at concentrations in the range of 6.62×10^–7–1.6×10^–6 M, 2.38×10^–4–2.05×10^–3 M, 8.91×10^–7–1.24×10^–6 M, 9.66×10^–8–1.34×10^–7 M, and 1.95×10^–8–2.73×10^–8 M, respectively.Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10^–5 M) in combination with 2-PAM (10^–7 M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10^–6 M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than each antagonist alone (about 14 and 46%, respectively).     

Autonomic and peripheral nervous system dysfunction in workers exposed to hand-arm vibration: a study of R-R interval variability and distribution of nerve conduction velocities

Summary To assess the effects of vibrating-tool operation on the autonomic and peripheral nervous system, we measured the variability in the electrocardiographic R-R interval (CV_RR) and the distribution of nerve conduction velocities (DCV) in 24 men who were vibrating-tool operators and in 17 healthy adult men (control group). Of the 24 tool operators, 13 had a history of vibration-induced white finger [VWF(+) group] and 11 had no such history [VWF(–) group]. Two components of CV_RR, i.e. C-CV_RSA and C-CV_MWSA, which have been considered to reflect parasympathetic and sympathetic activities, respectively, were also examined. Both the CV_RR and the C-CV_RSA in the VWF(+) group and the CV_RR in the VWF(–) group were found to be significantly depressed as compared with the control values; moreover, a significant difference in the C-CV_RSA was observed between the VWF(+) group and the VWF(–) group. The faster DCVs and the sensory median nerve conduction velocity were significantly slowed in the VWF (+) and VWF(–) groups. The C-CV_MWSA was significantly correlated with most of the DCV parameters and with the median nerve conduction velocities in all 24 vibrating-tool operators. These data suggest that operation of vibrating tools, which involves exposure to combined stressors of local vibration, heavy work, climate, and noise, affects both the faster myelinated nerve-fiber activity and the parasympathetic activity; the sympathetic activity at rest in workers exposed to hand-arm vibration may be related to depression of peripheral nerve conduction.     

DDE thins eggshells and lowers reproductive success of captive black ducks

Summary Eggs of captive black ducks fed diets containing DDE at 10 and 30 ppm (dry weight) experienced significant shell thinning and an increase in shell cracking when compared to eggs of untreated black ducks. Eggshells from dosed ducks were: 18–24 percent thinner at the equator than shells from undosed ducks; 28–31 percent thinner at the cap; and 29–38 percent thinner at the apex. Shell cracking averaged 21 percent among eggs from the 30 ppm DDE dosage and 10 percent among eggs from the 10 ppm dosage. Only 2 percent of the eggs from untreated black ducks were cracked. Survival of ducklings from dosed parents in terms of percentage of 21-day ducklings of embryonated eggs was 40–76 percent lower than survival of ducklings from undosed parents. Average DDE residues (wet weight) in eggs from hens fed 10 and 30 ppm DDE were 46 ppm and 144 ppm, respectively.     

Carpal tunnel syndrome. A new feature in the natural history of TOS?

Objective: To ascertain whether carpal tunnel syndrome (CTS) in patients affected with toxic oil syndrome (TOS) is associated with conditions and diseases considered risk factors for CTS in the general population and/or with certain clinical manifestations of TOS. Methods: We conducted a case–control study to compare 89 TOS patients residing in Madrid diagnosed with CTS from 1981 through July 2001 (cases) against 638 TOS patients not affected with CTS (controls). Risk factors for CTS and clinical manifestations of TOS were analyzed. Results: Multivariate logistic regression analysis yielded the following odds ratios (95% confidence interval): 3.32 (1.47–7.50) for TOS-related neuropathy; 2.85 (1.14–7.13) for TOS-related thromboembolic events; 2.63 (1.36–5.06) for female gender; 0.43 (0.24–0.80) for TOS-related scleroderma; 0.26 (0.12–0.59) for smoking; and, in women, 2.53 (1.06–5.70) for fibrositis and 1.84 (1.04–3.20) for miscarriages. Conclusion: Our study findings support the hypothesis that CTS in TOS patients is more linked to certain clinical manifestations of TOS, mainly neuropathy, than to conditions and diseases considered risk factors for CTS in the general population.     

Eggshell thinning and residues in mallards one year after dde exposure

A group of 16 mallard hens (Anas platyrhynchos), that had been given feed containing 40 ppm ofp,p'-DDE for 96 days, laid eggs with shells averaging about 15%–20% thinner than those of ten control birds during and up to 42 days after treatment. In eight of the treated birds killed at that time, whole-body DDE residues averaged 33.1 ppm (wet weight). The other eight treated birds and ten controls were kept through the winter with no additional DDE exposure and penned separately five days for individual egg collection about three weeks after laying began in spring. At that time (nearly 11 months after DDE feeding had stopped), the treated birds laid eggs with shells averaging 7.4% thinner than control eggshells (significant at P0.05) and their whole-body DDE residues averaged 9.6 ppm (wet weight). Variations in eggshell thickness and DDE residues were considerable among treated birds. However, regression analysis showed moderate negative correlations (r=–0.51 to –0.62) between eggshell thickness and DDE residues in whole bodies and eggs, and strong positive correlations (r=0.73 and 0.91) between DDE residues in whole bodies and in eggs.     

Exposure of professional pesticide applicators to carbaryl

Dermal and respiratory exposure, and erythrocyte and serum acetylcholinesterase activity were monitored on two groups of professional pesticide applicators spraying trees with carbaryl. The mean dermal exposure to the first group was 128 mg hr^–1 of carbaryl and the mean respiratory exposure was 0.1 mg hr^–1. The maximum percent (%) toxic dose received by the applicators was 0.12% hr^–1. The mean exposure to the second group of applicators was 59.4 mg hr^–1 dermal and 0.1 mg hr^–1 respiratory, for a total of 0.02% toxic dose per hr. It was estimated that 86.9% of the dermal exposure was to the forearms and hands. The rate of exposure to pads placed under the applicators clothing was approximately 1/20 that of pads on the outside of the clothing. Of the body areas monitored, the back received the least rate of exposure. It was determined,in vitro, that 10^–3 M carbaryl would inhibit human serum (pseudocholinesterase) and erythrocyte acetylcholinesterase for at least 72 hr. There was no overall inhibition of acetylcholinesterase activity in the applicators.Published with the permission of the Director of the Nebraska Agric. Exp. Stn. as Journal Article No. 6000. This research was funded as Grant No. 85-288-042-01 & 02 from the North Central Regional Pesticide Impact Assessment Program, USDA/SEA-CR.     

Comorbidity of hospital-treated psychiatric and physical disorders with special reference to schizophrenia: a 28 year follow-up of the 1966 Northern Finland general population birth cohort

We studied the comorbidity of psychiatric and physical disorders in a sample (n = 11017) from the unselected, general population, Northern Finland 1966 Birth Cohort. During the period 1982–1994, hospital-treated psychiatric patients were more likely than people without psychiatric diagnoses to have been treated for physical disease in hospital wards, 298 out of 387 (77.0%) vs 6687 out of 10 630 (62.9%) (OR = 2.0, 95% CI = 1.6−2.5). Injuries, poisonings and indefinite symptoms were a more common reason for hospital treatment in people with schizophrenia or other psychiatric disorder as compared with people without a psychiatric disorder. Men with psychiatric disorder had more than a 50-fold risk for poisoning by psychotropic drugs (OR = 52.6, 95% CI = 27.7−99.8), women with psychiatric disorder a 20-fold risk (OR = 19.0, 95% CI = 9.5–38.1) and schizophrenics more than a 30-fold risk (OR = 37.5, 95% CI = 19.1–73.8). Men with psychiatric disorders were more commonly hospitalised for a variety of gastrointestinal disorders and circulatory diseases (OR = 2.3, 95% CI = 1.2–4.4), as compared with men with no psychiatric disorder. Respiratory diseases (OR = 2.2, 95% CI = 1.2–4.2), vertebral column disorders (OR = 4.2, 95% CI = 1.8–9.9), gynaecological disorders (OR = 2.1, 95% CI = 1.2–3.6) and induced abortions (OR = 1.8, 95% CI = 1.2–2.7) were more prevalent in women with psychiatric disorder than in other women. Epilepsy was strongly associated with schizophrenia (OR = 11.1, 95% CI = 4.0–31.6). Nervous and sensory organ diseases in general (OR = 2.5, 95% CI = 1.1–5.8) and inflammatory diseases of the bowel (OR = 12.8, 95% CI = 3.8–42.7) were also overrepresented in schizophrenia when compared with people without a psychiatric disorder. Our results indicate that physicians must be alert for psychiatric disorder, and mental health professionals must be aware of the considerable physical morbidity in their patients.     

A comparison of contraceptive services for adolescents at school‐based versus community health centers in Oregon

ObjectiveTo compare Oregon school‐based health centers (SBHCs) with community health centers (CHCs) as sources of adolescent contraceptive services.Data sourcesOregon electronic health record data, 2012–2016.Study designWe compared clinic‐level counseling rates and long‐acting reversible contraception (LARC) provision, adolescent populations served, and visit‐level LARC provision time trends. We evaluated adjusted associations between LARC provision and Title X participation by clinic type.Data collection/extraction methodsWe used diagnosis and procedure codes to identify contraceptive counseling and provision visits, excluding visits for adolescents not at risk of pregnancy.Principal findingsCHCs were more likely to provide LARC on‐site than SBHCs (67.2% vs. 36.4%, respectively). LARC provision increased more at SBHCs (5.8‐fold) than CHCs (2‐fold) over time. SBHCs provided more counseling visits per clinic (255 vs. 142) and served more young and non‐White adolescents than CHCs. The adjusted probability of LARC provision at Title X SBHCs was higher than non‐Title X SBHCs (4.4% [3.9–4.9] vs. 1.7% [1.4–2.0]), but there was no significant association at CHCs.ConclusionsIn Oregon, CHCs and SBHCs are both important sources of adolescent contraceptive services, and Title X plays a crucial role in SBHCs. Compared with CHCs, SBHCs provided more counseling, showed a larger increase in LARC provision over time, and served more younger and non‐White adolescents.     

Effect of pH on Arsenate and Arsenite Toxicity to Luminescent Bacteria (<Emphasis Type="Italic">Vibrio fischeri</Emphasis>)

Arsenic is an abundant metalloid and a dangerous pollutant when in solution under the arsenate or arsenite forms—As(V) and As(III), respectively. Since its biological effects are expected to depend on the oxidation state and on speciation, effect of pH on either As(V) or As(III) speciation and resulting toxicity was investigated using the Microtox bioassay based on change in light emission by the luminescent bacteria Vibrio fischeri. Within a 5.0–8.0 pH range, EC50 values for As(V) were found to decrease as pH became basic, reflecting an increase in toxicity; whereas in the case of As(III), EC50 values were almost unchanged within a 6.0–8.0 pH range and lowered only at pH 9.0. HAsO₄^2– and H₂AsO₃^– were found to be the most toxic species. A statistical approach based on testing the null hypothesis of additive toxicity revealed an antagonistic effect between the arsenate chemical species. At low concentrations, As(V) was regularly found to be more toxic than As(III), independent of the pH value. Conversely, at high concentrations, the toxicity of both As(III) and As(V) was found to chiefly depend on pH, as a consequence of the strong influence of this parameter on the chemical speciation.     

Acute toxicity of permethrin to four size classes of red swamp crayfish (Procambarus clarkii) and observations of post-exposure effects

The mean static acute 96-h LC₅₀ of permethrin [(3-phenoxybenzyl (+)cis, trans, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate)] to red swamp crayfish (Procambarus clarkii) 8–12 mm (0.017 g), 25–35 mm (0.64 g), 45–55 mm (2.45 g), and 65–75 mm total length (8.98 g) was 0.44,0.85, 1.30, and 0.81 g/L, respectively. Permethrin toxicity did not differ among immature or mature male and femaleP. clarkii. Crayfish surviving permethrin exposures exhibited no differences in post-exposure growth, survival, onset of sexual maturity, or the reproduction of viable young when compared to non-exposed controls. Teratogenisis was not observed in third-instar crayfish produced from permethrin-exposed parents.Approved for publication by the Director of the Louisiana Agricultural Experiment Station.     

Comparative developmental toxicity of n-butyl benzyl phthalate and di-n-butyl phthalate in rats

n-Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) were evaluated and compared for their developmental toxic potential. Pregnant rats were given either BBP or DBP by gastric intubation at a dose of 0.75, 1.0 and 1.25 g/kg on days 7–9, days 10–12 and days 13–15 of pregnancy. Regardless of the days of treatment, a significantly increased incidence of postimplantation loss was found at all doses of BBP and DBP. While treatment with BBP and DBP at doses of 0.75 g/kg and above on days 7–9 or days 13–15 resulted in a significant increase in the incidence of fetuses with malformations, no increase in the incidence of malformed fetuses was found after treatment with BBP and DBP on days 10–12. The incidences of postimplantation loss and malformed fetuses increased as the doses of BBP and DBP were increased. Deformity of the vertebral column and ribs commonly occurred after treatment with BBP and DBP on days 7–9. Cleft palate and fusion of the sternebrae were predominantly observed after treatment with BBP and DBP on days 13–15. The similarity in dependence of gestational days of treatment on the manifestation of developmental toxicity and on the spectrum of fetal malformations caused by BBP and DBP suggests that they may act by the same mechanism, possibly via a common metabolite of these two parent compounds.