Toxicity acute oral

Acute oral toxicity is the study of adverse effects occurring shortly after oral administration of a single chemical dose or multiple doses given to an animal within 24 hours. In the evaluation of chemical safety, determination of acute oral toxicity becomes important, since it normally forms the first study step. Acute toxicity is important in establishing dose regimen for subchronic and other studies, and may provide initial information on the mode of chemical toxic action, as well as a basis of for classification and labeling. 

Groups of animals are exposed to the test chemical orally administered by gavage in one graduated dose per group. Subsequently, animals that die during 

Test System (Animal) Several mammalian species are used for acute toxicity studies, but the rat is the preferred rodent species. The body weight variation in test animals should not exceed 20% of the mean weight. At least 10 rodents (5 females, 5 males) should be used at each dose level, and females should be nulliparous and nonpregnant. 

The maximum volume of liquid that can be administered orally at one time depends on the size of the test animal. For instance, in rodents, the volume should not exceed 1 mL/100 g body weight. In cases of aqueous solutions, the concentration must be adjusted to ensure a constant volume at all dose levels. If a dose of at least 5,000 mg/kg body weight using the above procedure produces no chemical or drug-related mortality, a full study using three dose levels may not be necessary. 

After the administration of the test chemical, observations are recorded systematically. Individual data sheets should be maintained for each animal. The 

Environmental Protection Agency, Toxic Substances Control Act (EPA-TSCA) 44 FR 44066-7 (7/26/79) 

Consumer Product Safety Commission (CPSC)—16 CFR part 1500 

CPSC does not provide a detailed guideline for oral studies. Their definitions regarding toxicity are as follows  

Interagency Regulatory Liaison Group (IRLG)—Testing Standard 1981 

Studies should be conducted according to good laboratory practice regulations (e.g.. Noncllnical Laboratory Studies. Good Laboratory Practice Regulations. 43 FR 59986, 22 December 1978.  

LDso Values for Various Glycols Single Doses to Rats 

Itargest dose suivived by a(l rats tested 10.0 gm/kg resutted in the death of an 

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Butynediol is a primary skin irritant and sensitizer, requiring appropriate precautions. Acute oral toxicity is relatively high LD q is 0.06 g/kg for white... 

All of the propylene glycols display a low acute oral toxicity in laboratory rats as shown in Table 7 (30). Information for sucrose is shown for comparison. 

Table 7. Acute Oral Toxicity of Propylene Glycols ...

Sahcylaldehyde has a moderate acute oral toxicity the LD q for rats is 0.3-2.0 g/kg of body weight. Hydroxybenzaldehyde has a low acute oral toxicity the LD q for rats is 4.0 g/kg of body weight. Neither material is likely to present a problem from ingestion incidental to its handling and industrial use. It should be recognized, however, that serious effects may result if substantial amounts are swallowed. 

Toxicology. The nitroparaffins have minimal effects by way of actual contact. There were neither systemic effects nor irritation in dermal studies in rabbits. Human exposure of a prolonged or often-repeated nature has led to low grade irritation attributable to removal of oil from the skin, an effect produced by most organic solvents. Eye irritation potential of all four nitroparaffins has been deterrnined in rabbits. Other than a transient slight redness and some lachrymation, no effects were noted. The average Draize score was 0.0. The acute oral toxicity, LD q, of all four nitroparaffins has been deterrnined in the rat (Table 8). 

Health and Safety Factors. Terephthahc acid has a low order of toxicity. Inhalation by rats for 6 h/d, 5 d/wk for 4 wk produced no fatahties at a dust exposure level of 25 mg/m. The mean acute oral toxicity for rats is over 18 g/kg (86), and for mice over 6 g/kg (87). When terephthahc acid was fed as 3% of the diet to rats, urinary calcuh formed in 90 d, some of which led to cancer. High doses of terephthahc acid lead to formation of calcium terephthalate at levels exceeding its solubihty in urine. This insoluble material leads to the calcuh and provides a threshold below which cancer is not observed (88). Normal precautions used in handling industrial chemicals should be observed with terephthahc acid. If ventilation is inadequate, a toxic-dust respirator should be used to avoid prolonged exposure. 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. Eor example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD q, 4000 mg/kg, whereas the acute oral toxicity is LD q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have PDA approval for reuse food apphcations. 

Oral Toxicity. Alkan olamines generally have low acute oral toxicity, but swallowing substantial quantities could have serious toxic effects, including injury to mouth, throat, and digestive tract. 

Health and Safety Factors. Results of acute oral toxicity studies of 2-pyrrohdinone on white rats and guinea pigs show the LD q to be 6.5 ml,/kg. Skin patch tests on 200 human subjects indicate that 2-pyrrohdinone is a skin kritant, but there is no indication of sensitising action. It is a mild eye irritant (79). 

Toxicity. Sugar alcohols are classified as relatively harmless. Acute oral toxicity values in mice for mannitol and sorbitol (5) are given in Table 4. The acute oral LD q value for xyUtol in mice is 25.7 g/kg (205). Ingestion of 10 g/d of either mannitol or sorbitol by a normal human subject for one month resulted in no untoward effects (206). XyUtol given to healthy humans for 21 d in increasing doses up to 75 g/d produced no adverse effects (207). The limiting dose of xyUtol for production of diarrhea in humans is 20—30 g (4), but tolerance usually develops on continued adrninistration (207). 

Health and Safety Factors. MSA is a strong toxic acid and is corrosive to skin. The acute oral toxicity of the sodium salt in mice LD q is 6.2 g/kg. The 1976 edition of the NIOSH Registry of Toxic Effects of Chemical Substances Hsts certain reaction products of MSA as having suspected mutagenic, teratogenic, and carcinogenic activity (410). 

Table 2. Acute Oral Toxicity of Selected Inorganic Tin Compounds...

Table 10. Acute Oral Toxicities of Triorganotin Compounds...

Poly(methyl vinyl ether-i o-maleic anhydride) and their monoalkyl ester derivatives have been shown on rabbits to be neither primary irritants nor primary sensiti2ers to skin and eyes. The acute oral toxicities on white rats of the two copolymers are, respectively, 29 g/kg and 25 g/kg body weight. 

The data from some single-dosage oral toxicity tests, expressed as LD q, are reported in Table 4. The values reported on the order of 1 g/kg or greater indicate a low acute oral toxicity. In animals, continued ingestion of chlorobenzenes over a long time can cause kidney and Hver damage. 

The acute oral toxicity and the primary skin and acute eye irritative potentials of dimer acids, distilled dimer acids, trimer acids, and monomer acids have been evaluated based on the techniques specified ia the Code of Eederal Regulatioas (CER) (81). The results of this evaluatioa are showa ia Table 7. Based oa these results, monomer acids, distilled dimer acids, dimer acids, and trimer acids are classified as nontoxic by ingestion, are not primary skin irritants or corrosive materials, and are not eye irritants as these terms are defined ia the Eederal regulatioas. 

Syltheiin XLT (Dow Corning Coiporation). A sihcone polymer (Dimethyl Polysiloxane) recommended temperature range —70°C to 250°C odorless low in acute oral toxicity noncorrosive toward metals and alloys commonly found in heat transfer systems,... 

Acute oral toxicity (rat)3 Ames mutagenicity screening test (Salmonella typhimurium)... 

Sulfosuccinates have a history of safety as their use in consumers products in the past years has proven. However, few toxicity data can be found in the literature, mostly in connection with the evaluation of other surfactants. As the figures show, all sulfosuccinates and sulfosuccinamates described in this chapter have an acute oral toxicity (LD50) of >2000 mg/kg. Results are listed in Table 20. 

Stein and Baumann [14] studied the hydrolytic stability of MES and found the hydrolysis rate to be very slow in the pH range of 3-9.5 even at a temperature of 80°C. MES possesses good washing, foaming, and lime soap dispersing properties as well as ready biodegradability and a low acute oral toxicity. 

The acute oral toxicity (mice), skin and eye irritation (rabbits), sensitization (rabbits), and toxicity to fish were determined for the three detergent formulations and were found to be no more severe than those obtained for LAS [46] and phosphate-containing commercial detergents. 

Cannon Laboratories (1979) Acute oral toxicity of 1185-13 (dioctyltin dichloride), 28G082, 28H047, 1185-114, 1219-21 (dimethyltin dichloride), 1185-150, 1185-119 and 1185-138 in weanling Sprague-Dawley rats. Reading, PA, Cannon Laboratories Inc., 21 March. 

Following acute oral toxicity from dosages ranging from 14 to 80 mg/kg, laboratory rats had earlier recovery of brain acetylcholinesterase levels than did feral cotton rats. Similar results were seen in a comparison of laboratory mice to feral mice (Roberts et al. 1988). 

Golbs S, Fuchs V, Leipner E, et al. 1978a. [Studies into effects of pesticide combinations on laboratory rats. 1st communication Determination of the acute oral toxicity (ED50) of pesticide combinations]. Arch Exp Vet Med Leipzig 32 557-561. (German)... 

Hoechst. 1975. Beta-endosulfan pure (analysis GOE 1495) Acute oral toxicity in female SPF-Wistar rats. Hoechst Aktiengesellschaft, Frankfurt, Germany. Doc A05270.[unpublished study]... 

Enslein, K. An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol Industrial Health 1988 4 479-98. 

Much toxicological data are available on this red pigment acute oral toxicity in mice, 90-day subchronic toxicological study, acute dermal irritation and corrosion, acute eye irritation and corrosion, anti-tumor effectiveness, micronucleus test in mice, AMES test Salmonella typhimurium reverse mutation assay), estimation of antibiotic activity, and results of estimation of five mycotoxins. A new patent on Arpink Red was filed in 2001 with claims of anti-cancer effects of the anthraquinone derivatives and apphcations in the food and pharmaceutical fields. 

The Danish EPA has developed an advisory list for self-classification of dangerous substances including 20 624 substances. The substances have been identified by means of QSAR models (Quantitative Structure-Activity Relationship) as having acute oral toxicity, sensitization, mutagenicity, carcinogenicity, and/or danger to the aquatic environment. 

Acute-Duration Exposure. Acute oral LD50 data are available for mice and rats (Hart 1976) and for ducks (Aulerich et al. 1979). Acute oral toxicity studies, including histopathological observations, are available for ducks, mice, rats, dogs, and mink (Aulerich et al. 1979 Hardisty et al. 1977 Hart 1976, 1980). Limited acute dermal toxicity are available for rats (Hart 1976). These data suggest a relatively low toxicity. However, a clear relationship between dose and effect has not been elucidated. Inhalation data of any kind were not identified, and dermal data were very limited. 

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