Dermal LD50 Research Articles

Acute, pharmacokinetic, and subchronic toxicological studies of 2,4-dichlorophenoxyacetic acid

The single-dose oral LD 50 values in Fischer 344 rats for technical-grade 2,4-dichlorophenoxyacetic acid (2,4-D), esters, and salts ranged from 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylamine salt in males). The LD 50 values for the acid, esters, or salts, when expressed as acid equivalents, were consistent which suggests that the acute toxicity was due to 2,4-D per se. Acute dermal LD 50 values in rabbits for the acid, esters, and salts were greater than 2000 mg/kg. Overall, these results indicate that the acute oral and dermal toxicity of 2,4-D are low. Pharmacokinetics were evaluated in male Fischer 344 rats given single oral doses of 10, 25, 50, 100, or 150 mg 2,4-[ 14C ]D/kg. The amount of 2,4-D in the plasma, kidney, and urine 6 hr postdosing indicated that the urinary elimination of 2,4-D was saturated in male rats given oral doses in excess of 50 mg/kg. Subchronic dietary studies in male and female Fischer 344 rats used dose levels of 0, 15, 60, 100, or 150 mg/kg/day of purified or technical-grade 2,4-D acid for 13 weeks. Body weight gains were decreased for both sexes at the higher dose levels of purified and technical-grade 2,4-D acid. Kidney weights were increased in all treated male rats and in females given the higher three dose levels of purified 2,4-D. Treatment-related cytoplasmic alterations were present in the renal proximal tubules of most rats given 60 mg/kg/day and higher of purified or technical-grade 2,4-D; a few females given 15 mg/kg/day also had slight alterations in the cytoplasm of the proximal tubules. A dose-related degenerative change was identified in the descending proximal renal tubules of all male rats given the highest three dose levels of either test material and some given 15 mg/kg/day. Dose levels of 100 or 150 mg/kg/day of either compound for both sexes produced minimal swelling and increased staining homogeneity in the liver cells and were associated with a slight elevation of liver weight and serum glutamic pyruvic transaminase activity. Higher dose levels of technical-grade and purified 2,4-D decreased total serum tetraiodothyronine levels in female rats, however, the morphology of the thyroid gland was normal. The no-observed-effect level (NOEL) was less than 15 mg/kg/day for both purified and technical-grade 2,4-D acid.

4: Final Report on the Safety Assessment of n-Butyl Alcohol

n-BuOH is a primary aliphatic alcohol that is used in cosmetic nail products as a solvent at concentrations up to 10%. In vitro tissue permeability studies indicate that human epidermis and dermis were permeable to n-BuOH. The single oral dose LD50 of n-BuOH for rats ranged from 0.8 to 4 g/kg. The dermal LD50 has been reported as 4.2 g/kg. n-BuOH does not cause skin irritation in rabbits but is a severe rabbit eye irritant. Inhalation of n-BuOH vapors caused intoxication of laboratory animals; high concentrations were sometimes fatal. n-BuOH was not mutagenic in the Salmonella/mammalian-microsome mutagenicity test. The ingredient did not induce sister chromatid exchange or chromosome breakage in chick embryo cells or in Chinese hamster ovary cells and did not induce micronuclei formation in V79 Chinese hamster cells. Two nail formulations containing 3.0% n-BuOH were tested on 558 and 421 subjects, respectively; neither was considered an irritant or sensitizer. Clinically, n-BuOH produced edema in 4 of 105 dermatological patients. Additional clinical studies indicated that nail enamel products containing n-BuOH were neither irritants, sensitizers, nor photoallergens. Inhalation of n-BuOH can cause human nose, throat, and eye irritation. On the basis of the information in the report and only as it regards the use of n-BuOH in nail products, the ingredient is considered to be safe in the present practices of use and concentration.

2: Final Report on the Safety Assessment of Propylene Carbonate

Propylene Carbonate is a nonviscous, clear liquid that is used in cosmetic products at concentrations ranging from 0.1% to 5%. Undiluted Propylene Carbonate produced minimal to moderate ocular irritation and slight erythema in rabbits. The dermal LD50 in rabbits of the undiluted ingredient was >20 ml/kg. Undiluted Propylene Carbonate was nontoxic by inhalation to dogs and guinea pigs in a 21-day study. Propylene Carbonate was negative for mutagenicity in the Ames Assay, and negative for genotoxicity in the Rat He-patocyte Primary Culture/DNA Repair Test. In clinical studies, undiluted Propylene Carbonate caused moderate skin irritation, whereas 5 and 10% Propylene Carbonate in aqueous solution produced no skin irritation or sensitization. Cosmetic products containing up to 20% Propylene Carbonate were essentially nonsensitizing and, at most, moderately irritating to human skin, nonphototoxic, and nonphotosensitizing. It is concluded that Propylene Carbonate is safe as a cosmetic ingredient in the present practices of use and concentration.

Acute, Pharmacokinetic, and Subchronic Toxicological Sudies of 2,4-Dichlorophenoxyacetic Acid

The single-dose oral LD50 values in Fischer 344 rats for technical-grade 2,4-dichlorophenoxyacetic acid (2,4-D), es ters, and salts ranged from 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylamine salt in males). The LDH values for the acid, esters, or salts, when expressed as acid equivalents, were consistent which suggests that the acute toxicity was due to 2,4-D per se. Acute dermal LD50 values in rabbits for the acid, esters, and salts were greater than 2000 mg/kg. Overall, these results indicate that the acute oral and dermal toxicity of 2,4-D are low. Pharmacokinetics were evaluated in male Fischer 344 rats given single oral doses of 10, 25, 50, 100, or ISO mg 2,4- [14CJD/kg The amount of 2,4-D in the plasma, kidney, and urine 6 hr postdosing indicated that the urinary elimination of 2,4-D was saturated in male rats given oral doses in excess of 50 mg/ kg. Subchronic dietary studies in male and female Fischer 344 rats used dose levels of 0, 15, 60, 100, or 150 mg/kg/thy of purified or technical-grade 2,4-D acid for 13 weeks. Body weight gains were decreased for both sexes at the higher dose levels of purified and technical-grade 2,4-D acid. Kidney weights were increased in all treated male rats and in females given the higher three dose levels of purified 2,4-D. Treatment-related cytoplasmic alterations were present in the renal proximal tubules of most rats given 60mg/kg/thy and higher of purified or technical-grade 2,4- D; a few females given 15 mg/kg/thy also had slight alterations in the cytoplasm of the proximal tubules. A dose-related degenerative change was identified in the descending proximal renal tubules of all male rats given the highest three dose levels of either test material and some given 15 mg/kg/thy. Dose levels of 100 or 150 mg/kg/thy of either compound for both sexes produced minimal swelling and increased staining homogeneity in the liver cells and were associated with a slight elevation of liver weight and serum glutamic pyruvic transaminase activity. Higher dose levels of technical-grade and purified 2,4-D decreased total serum tetraiodothyronine levels in female rats, however, the morphology of the thyroid gland was normal. The no-observed-effect level (NOEL) was less than 15 mg/kg/day for both purified and technical-grade 2,4-D acid.

Short‐term toxicity studies of Sanguinarine and of two alkaloid extracts ofSanguinaria CanadensisL.

The short-term toxicity of sanguinarine, a benzophenanthridine alkaloid, and of two alkaloid extracts of Sanguinaria canadensis L. are presented. The acute oral LD50 in rats of sanguinarine was calculated to be 1658 mg/kg, and of the two alkaloid extracts, 1440 and 1250 mg/kg. The acute iv LD50 in rats of sanguinarine was found to be 29 mg/kg. No toxic effects were observed in rats fed up to 150 ppm sanguinarine in the diet for 14 d and in rats treated by gavage with up to 0.6 mg/kg body weight for 30 d. The acute dermal LD50 in rabbits was found to be greater than 200 mg/kg.

4: Final Report on the Safety Assessment of Hydroquinone and Pyrocatechol

Hydroquinone and Pyrocatechol, two benzenediol isomers, are used as couplers in oxidative hair dyes at concentrations of less than 1.0%. Both compounds are absorbed from the gastrointestinal tract; Pyrocatechol is also readily absorbed through the skin. Both compounds are excreted in the urine, mainly as the ethereal sulfate. In acute oral studies Hydroquinone is practically nontoxic to moderately toxic; the data from subchronic feeding studies of Hydroquinone indicated that it was not toxic at 1% but was at higher concentrations. Pyrocatechol was moderately toxic in acute studies. Subchronic oral studies of Pyrocatechol at 0.25% produced hepatic cell hyperplasia in rats. Hydroquinone was a weak depigmenter but not an irritant when tested at 1.0%. Theingredient was a sensitizer when injected at 2.0%. The acute dermal LD50 of Pyrocatechol was 0.8 g/kg. Pyrocatechol did not depigment rabbit skin at 1.0% but did at 3.0%; skin irritation was observed at 5.0%. Guinea pigs were sensitized when Pyrocatechol was injected at concentrations above 0.2 μM. Undiluted product formulation containing 2.0% Hydroquinone produced mild conjunctivitis in 3 of 6 animals; undiluted Pyrocatechol is an extreme ocular irritant. Hydroquinone was not teratogenic in three separate studies. The results of mutagenesis assays of Hydroquinone varies with the assay system used. In four Salmonella typhimurium strains, both with and without activation, the mutagenesis assay was negative. Hydroquinone produced positive results both with and without activation in the HeLa DNA synthesis test but was not considered mutagenic in assays using Chinese hamster cells. Hydroquinone induced SCE and delayed cell-turnover time in human lymphocyte studies. Oral doses of Hydroquinone did not inhibit testicular DNA synthesis in male mice, and was nonmutagenic in the mouse sperm-head abnormality test. In multigeneration studies with rats, topically applied hair dyes containing 0.2% Hydroquinone had no effect on reproduction; the dye was neither embryotoxic or teratogenic. Dermally applied hair dyes containing Hydroquinone were not carcinogenic. Hydroquinone when applied topically was neither a tumor promoter nor a cocarcinogen in mice. The mutagenicity of Pyrocatechol also varies with the test system used. In most studies, Pyrocatechol was nonmutagenic, both with and without metabolic activation, in the Ames' assay. The compound was negative in the Escherichia coli DNA polymerase assay, but was positive in the yeast, Saccharomyces cerevisiae. Pyrocatechol was negative in the HeLa DNA synthesis test and with Chinese Hamster V79 cells. The compound increased the numbers of chromatid breaks and exchanges in Chinese hamster ovary cells and induced SCE and delayed cell turnover time in human lymphocyte cultures. The compound given by intraperitoneal injection to mice was negative in the sperm-head abnormality test but was positive in the bone marrow assay. In three studies in mice, topically applied Pyrocatechol was not a tumor promotor. However, topically applied Pyrocatechol was a cocarcinogen for mouse skin in two other studies. Positive sensitization reactions to Hydroquinone were reported in 8.9% of 536 dermatologic patients. Two of 38 patients treated with an ointment containing 5.4% Hydroquinone became sensitized. A cosmetic formulation containing 2% Hydroquinone produced one or more mild irritation reactions in 69 of 90 subjects in the induction phase of a sensitization test; 22 of the 69 subjects were mildly sensitized when challenged. The use of ointments containing 2, 3, and 5% Hydroquinone produced at least minimal depigmentation in white but not black subjects. It is concluded that Hydroquinone and Pyrocatechol are safe for cosmetic use at concentrations of ≤ 1.0% in formulations that are designed for discontinuous, brief use followed by rinsing from the skin and hair.

Dermal toxicity of ammonium perfluorooctanoate

Ammonium perfluorooctanoate (CAS Registry No. 3825-26-2) is used commercially in the aqueous polymerization of fluorinated monomers. Because the chemical exists as a fine white powder which can come in contact with skin, its dermal toxicology was studied in rabbits and rats. Dermal applications of 0.5 g for 24 hr produced mild irritation to rabbit skin. The dermal LD50 was 4300 mg/kg for rabbits, 7000 mg/kg for male rats, and greater than 7500 mg/kg for female rats. Rat skin showed less irritation than rabbit skin and the general effects were more pronounced for the male (compared to the female) rat. Subchronic dermal treatment (10 applications, 5 doses, 2 rest days, 5 doses) with either 0, 20, 200, or 2000 mg/kg resulted in no, no, mild, or marked decreases in body weights, respectively. Increases in serum enzyme activities indicating hepatic effects occurred in treated rats. Liver weights were increased and necrosis and enlargement of hepatocytes were microscopically observed. Rats in the 2000-mg/kg-dose group also had epidermal necrosis at the application site. Blood organofluorine amounts were increased in a dose-related manner. All of the treatment-related toxicity findings resolved during a 42-day recovery period although prior exposure was evident by the presence of organofluorine in the blood.

Acute toxicity, subchronic dermal toxicity, and delayed contact sensitization evaluations of dicyclopentenyloxyethyl methacrylate in rabbits and guinea pigs

The subchronic dermal toxicity of dicyclopentenyloxethyl methacrylate (DPOMA) was evaluated in young adult New Zealand White rabbits, and its potential to produce delayed contact sensitization was evaluated in Harley guinea pigs by a modified Buehler's closed patch technique. In addition, studies were conducted to evaluate the acute systemic toxicity of DPOMA in rats (oral) and rabbits (dermal), and its eye and skin irritancy in rabbits. In the subchronic dermal toxicity study, 4 groups of rabbits were treated percutaneously with DPOMA at 0 (acetone), 10, 107, and 1067 (undiluted) mg/kg X day in a volume of 1 ml/kg, over a 4-wk period. The application sites were unoccluded. No deaths occurred, and no signs of systemic toxicity were observed. No treatment-related effects were seen on body weights, hematology, clinical chemistry, urinalysis, organ weights, or histopathology (except the treated skin). The only treatment-related effect was slight to moderate skin irritation in the mid- and high-dose groups. The severity of skin irritaton was dependent on the number of applications and the concentration of DPOMA. Maximal skin irritation occurred after 1 wk. No skin irritation was seen in the control and low-dose group. In the DCS study, guinea pigs received 6 induction doses of 0.5 ml 100% DPOMA and were challenged with 0.5 ml of 50% (w/v) DPOMA in acetone 2 wk after the last induction treatment. No erythema or edema was observed in any of the challenged guinea pigs in either the treated and control groups. These acute toxicity studies indicate that DPOMA is practically nontoxic by a single exposure via both oral and dermal routes (the oral LD50 in rat and dermal LD50 in rabbits were greater than 5.0 g/kg body weight), slightly irritating to the skin, and inconsequentially irritating to the eyes. The no-observed-effect level (NOEL) for systemic toxicity of DPOMA applied repeatedly to rabbits skin is at least 1067 mg/kg X d. DPOMA is not a strong or moderate skin sensitizer in guinea pigs.

Toxicity of organophosphorus esters to laying hens after oral and dermal administration.

Fourteen organophosphorus esters (OPs) were evaluated for their potential to cause organophosphorus ester induced delayed neurotoxicity (OPIDN) when administered dermally and/or orally to white leghorn hens. The compounds were chlorpyrifos, DEF, dichlorvos, dimethoate, EPN, ethoprop, fenthion, isofenphos, leptophos, merphos, ronnel, tetrachlorvinphos, terbufos, and trichlorfon. DEF induced ataxia if given dermally or orally at over 21 mg/kg/day for up to 90 days. Hens treated with EPN developed irreversible ataxia after repeated exposure to as little as 1.3 mg/kg dermally or 5 mg/kg/day orally, while leptophos was neurotoxic at doses of 6-7 mg/kg/day dermally and 10 mg/kg/day orally. Multiple treatments of chlorpyrifos, terbufos, dichlorvos and dimethoate caused death after varying periods of increasing debility; although birds had difficulty walking, they did not display typical symptoms of OPIDN. Fenthion and isofenphos induced drastic weight loss in hens at low levels of treatment; Isofenphos treated hens developed OPIDN, but died soon afterwards. Dichlorvos given at greater than 6 mg/kg/day po or dermally at 1 mg/kg/day produced cholinergic symptoms and most hens died before the end of the treatment period. At lower levels, dichlorvos did not induce overt ataxia. None of the other compounds in this series induced consistent ataxia whether administered orally or dermally. Ethoprop, with an acute oral LD50 near 5 mg/kg and an acute dermal LD50 of approximately 3 mg/kg, was the most toxic compound tested and could not be fully evaluated for its potential to cause OPIDN.

Observations on side effects of endosulfan used to control tsetse in a settlement area in connection with a campaign against human sleeping sickness in Ivory Coast

Abstract Two villages and their environs in the Bouaflé area of Ivory Coast were monitored for side effects following a spraying campaign to control Glossina spp. in 1978–79. Residual applications of endosulfan at 267 g a.i./ha and 150 μm vmd were made on surrounding vegetation and non‐residual applications at 10 g a.i./ha and 50 μm vmd were made over the villages themselves. Residue analysis of α‐cellulose pads worn by human volunteers showed very low (0.007–0.27% of rat dermal LD50) insecticide deposits. The spraying had no measurable effect on hatchability of chicken eggs, which contained less than 0.01 ppm of insecticide. No measurable changes in lizard (Agama agama L.) populations were observed, and residues in the livers of sampled lizards ranged from 0.01–0.02 ppm. However, all the fish in pools were killed, and populations of non‐target insects were reduced repeatedly but recovered after each residual application. No effects were apparent two years after the spraying.

Today's requirements in food, drug and chemical control.

Abstract The acute toxicity tests which generate LD50's or LC 50's have been used for several decades to detect potential acute hazards to humans who are exposed to toxic substances. Several federal regulatory agencies use the results of these tests in regulating chemicals such as food additives, drugs, products found in homes such as pesticides and household cleaners, chemicals produced in industrial environments and chemicals which are transported in interstate commerce.Acute toxicity data are used by these federal agencies in many different ways depending upon their regulatory missions and the regulations that these agencies utilize to accomplish their missions. For instance, the Federal Hazardous Substances Act regulations used by the Consumer Product Safety Commission address the specific labeling of consumer products dependent upon the calculated oral or dermal LD50. In some instances, a consumer product can be banned from commerce as an imminent hazard dependent upon the peculiar toxicity of the product.However, the Food and Drug Administration with the authority contained in the Federal Food, Drug and Cosmetic Act uses acute toxicity data in determining the approvability of intentional food additives and indirect food additives contained in food packaging. In addition, such data are used to provide guidance for the design of longer term studies in man and animal needed to obtain food and drug approvals.Since many federal regulatory agencies require acute toxicity tests in some phase of their regulatory activities, it was decided to develop common guidelines for these tests. As a result, the Interagency Regulatory Liaison Group (IRLG) was established in 1977, in part to develop guidelines to resolve existing test protocols and to design tests to be used by all IRLG agencies for chemical testing.In mid 1979, a draft acute oral toxicity protocol for rodents was released for general public comment. As a result of this action, the guidelines were modified to incorporate some of the expressed public ideas. One modification provided for the use of a limit test involving 10 rats dosed at a level of 5g/kg which could preclude the use of further numbers of animals. If no compound related mortality was observed at this dose, the compound would be considered as non‐toxic. The acute toxicity guidelines were finalized and published in January, 1981.Although the IRLG recognizes that at present the acute toxicity rodent test is the most reliable method to determine potential acute hazards to man, it also recognizes that alternatives such as in vitro tests may prove useful once further research and development refine them to the point of regulatory utility.

Application of a dermal self-exposure model to worker reentry.

The dermal toxicity of five commonly used organophosphate insecticides was investigated with a mouse intermittent self-exposure model. Blood cholinesterases were monitored on d -3 and -1 before exposure and for 4--6 d during exposure to foliar residues. Responses were much greater in unmuzzled than in muzzled animals due to oral contamination. After two 10-h exposures, muzzled mice showed log-linear cholinesterase responses across a wide range of foliar pesticide concentrations. Foliar pesticide levels that caused 50% depression in plasma or red blood cell cholinesterase were determined with log-probit dose-response analysis. The greatest cholinesterase responses for both emulsifiable concentrate and encapsulated formulations were found with diazinon, followed by parathion and methyl parathion. Azinphos-methyl and mevinphos produced no significant responses in muzzled mice at maximal foliar concentrations. Symptomatology, food consumption, and body weight provided less sensitive indicators of response than cholinesterases. No consistent relation existed between the mouse intermittent self-exposure toxicities and mouse dermal LD50 values. Use of data from acutely exposed animals to predict the hazard of intermittent foliar exposure appears inadvisable.

Acute dermal toxicities of various organophosphate insecticides in mice.

Dermal LD50 values for five organophosphate insecticides were determined in mice by application of solutions to hind feet. Values were simultaneously generated for the ED50 (milligrams per kilogram) for both cholinesterase and acetylcholinesterase. Lethality was greatest with mevinphos, followed by parathion, methyl parathion, diazinon, and azinphosmethyl. LD50 values were higher than reported values for mice treated on shaved back skin. Cholinesterase ED50 values roughly agreed with LD50 values for mevinphos, parathion, methyl parathion, and azinphos-methyl, but diazinon appeared much more inhibitory of blood than neuronal cholinesterase. Red blood cell and plasma cholinesterase activities were equally sensitive for all but mevinphos and diazinon.

Exposure of urban applicators to carbaryl.

Thirty-eight urban volunteers from the Lincoln and Omaha, Nebraska areas were monitored for carbaryl exposure during the summer of 1979. All volunteers were involved in the application of carbaryl incidental to their employment or leisure activities. The investigators made no attempt to affect the method of carbaryl application. The mean rates of carbaryl exposure were 3.85 and 0.26 microgram cm-2 hr-1, respectively, for the outside of the clothing and the skin beneath the clothing; clothing apparently provided an effective barrier to carbaryl penetration. The rate of carbaryl exposure to the hands of applicators was 2.36 and 24.96 micrograms cm-21 hr-1, respectively, for applicators with and without gloves. The maximum dermal exposure recorded in this study was 2.86 mg kg-1 hr-1 which is significantly less than the stimated dermal LD50 value for carbaryl (4000 mg kg-1). The maximum air concentration of carbaryl was 0.28 microgram L-1. Only a small mean decrease was found in the applicators serum (-1.01%) or erythrocyte (-1.39%) acetylcholinesterase activity. Although some applicators had decreases in either serum or erythrocyte acetylcholinesterase activity greater than 20%, an equal number had increases of the same magnitude. The mean total carbaryl exposure to the applicators, expressed as a percent of toxic dose per hr, was 0.01%, with a maximum estimated exposure of 0.08%.

Acute dermal toxicity of two quarternay organophosphonium salts in the rabbit

Tetrabutyl phosphonium chloride and tetrabutyl phosphonium bromide were evaluated for their potential to cause primary dermal irritation and acute dermal toxicity in rabbits. Both chemicals were found to not only be severely irritating to skin, but the pure hygroscopic chemicals caused death in more than half the number of rabbits used in the primary dermal irritation tests. Further investigations revealed the single-application dermal LD 50 of tetrabutyl phosphonium chloride (Bu 4PCl) (using an ethylene carbonate (EC) vehicle) was 600 mg/kg for male rabbits and 500 mg/kg for female rabbits. The single-application dermal LD 50 of tetrabutyl phosphonium bromide (Bu 4PBr) (using the EC vehicle) was 700 mg/kg for male rabbits and 850 mg/kg for female rabbits. The dermal LD 50 of pure undiluted Bu 4PCl was 225 mg/kg for male rabbits. These data indicate that Bu 4PCl and Bu 4PBr represent a substantial acute dermal toxicity hazard.

Worker exposure to ethion in Florida citrus.

Dermal and respiratory exposure to ethion was determined for 17 men in eight spray crews in Florida citrus spray operations. Respiratory exposure was less than 1% of the total exposure. Hands represented 42% of the total body exposure for applicators and 76% for suppliers. At one location, suppliers exhibited a larger decrease in ChE activity than applicators. This difference appeared related to the higher mean dermal ethion exposure to suppliers. Acute symptoms of organophosphorous poisoning were not observed. The total percent/hr of the probable human dermal LD50 was very low in all cases. These data indicate a relatively low potential acute hazard to workers applying ethion with air blast equipment under the conditions of this study.

The U.S. oil shale industry: a health perspective.

The United States holds the world's largest and richest deposits of oil shale. If this resource is to have a role in meeting future energy needs, it must be developed in accordance with the nation's health and environmental objectives. Previous oil shale operations in Scotland and Estonia are reviewed, along with the limited United States experience. A possible carcinogenesis hazard is suggested, based upon occurrence of skin cancers in Scottish workers. The API supported toxicologic studies to define potential health hazards related to oil shale. Analysis of crude retort oils revealed the presence of carcinogens in the polyaromatic hydrocarbon fraction. Bacterial screening tests for mutagenic activity were positive following enzymatic activation, and cancers were produced by painting the oils on the skin of mice. Tests for acute toxicity showed an oral LD50 of 8–10 g/kg, and a dermal LD50 of 20 g/kg for the crude retort oils which produced liver damage. Further processing of the retort oils by hydrogenation will reduce these toxic effects. Controls to prevent inhalation of raw and spent shale dusts (which contain SIO2) and contact with retort oils are indicated. Comparisons between oil shale and petroleum industries are useful in evaluating health risks.

Acute and subacute toxicology and safety evaluation of hexahydro-1,3,5-triethyl-S-triazine.

Acute and subacute toxicology and safety evaluation was determined for hexahydro-1,3,5-triethyl-s-triazine (Vancide-TH), a bacteriostatic and fungiastatic agent proposed for industrial use by R. T. Vanderbilt and Co., Inc. Single dose oral toxicity, subacute 14 day dermal toxicity and eye irritation studies were conducted on either the rat or the rabbit. The data obtained indicate that Vancide-TH should be classified as a "toxic, corrosive and an eye-irritating" substance as defined under the "Regulations" of the Federal Hazardous Substances Act. Since the acute dermal LD50 closely approximated the acute oral LD50 in rats, this route might constitute the most serious hazard involved with V-TH and special precautions should be exercised when handling or using this substance. Because of the severe eye-irritating action, precautions should be taken to protect the eyes when handling or using the compound; the ocular damage produced may be irreversible. The "in use" concentrations (1,000 to 10,000 ppm) produced a much lesser toxocity in animals and could be without hazard if precautions are taken.

DC 51762, a New Carbamate Insecticide

UC 51762, O-[[N-[N'-(methylthioethylidcneiminoxy-carbonyl)-N'-methylaminosulfenyl]-N-methylcarbamoyl]]-S-methylacetothiohydroximate, a new broad spectrum carbamate insecticide, was particularly effective in laboratory and field tests for control of lepidopterous larvae that attack several economically important crops. Residues of UC 51762 on plant foliage remained toxic to insects forextended periods of time but its soil-life is short. Available evidence suggests that UC 51762 is primarily a stomach poison with only modest contact toxicity. The compound does not appear to be a practical systemic insecticide. No injury was observed either in laboratory or field trials when UC 51762 was applied to a number of vegetable and field crops, including cotton, soybean, and corn. The peroral LD50 of UC 51762 to rats was 160 mg/kg. The rat dermal LD50 was greater than 1600mg/kg, and the compound was relatively safe by inhalation.

Acute toxicity studies with insect attractants

Eight insect attractants and one inhibitor of a sex attractant were tested for acute oral and aerosol inhalation toxicity in rats, for acute dermal toxicity, eye irritation, and primary skin irritation on rabbits, and for toxicity to rainbow trout and bluegill sunfish. Except for phenethyl propionate + eugenol, 7:3 (acute dermal LD50, 1220 mg/kg), none of the test materials was classified as more than slightly toxic. ( Z)-7-Dodecen-1-ol acted as a primary skin irritant, since it caused superficial chemical burns.