Feeding, studies

Health and Safety Factors. Butyrolactone is neither a skin irritant nor a sensiti2er however, it is judged to be a severe eye irritant in white rabbits. The acute oral LD q is 1.5 ml,/kg for white rats or guinea pigs. Subacute oral feeding studies were carried out with rats and with dogs. At levels up... 

When PET is extracted with water no detectable quantities of ethylene glycol or terephthaUc acid can be found, even at elevated extraction temperatures (110). Extractable materials are generally short-chained polyesters and aldehydes (110). Aldehydes occur naturally iu foods such as fmits and are produced metabohcaHy iu the body. Animal feeding studies with extractable materials show no adverse health effects. 

Most of the bacteria, yeasts, molds, and higher fungi of interest for SCP production are deficient in methionine and must be supplemented with this amino acid to be suitable for animal feeding or human food appHcations. Also, lysine—arginine ratios should be adjusted in poultry rations in which yeast SCP is used (62). Human feeding studies have shown that only limited quantities of yeast such as Candida utilis can be added to food products without adverse effects on flavor (63). 

Table 11 presents data on the protein quaUty of a variety of LPC products obtained from rat-feeding studies. Typical protein efficiency ratio (PER) values for LPCs derived from alfalfa range from 1.41 without supplementation to 2.57 with 0.4% methionine added casein can be adjusted to a PER of 2.50 (98,100). Biological values (BV) of mixtures of LPCs, such as barley and rye grass or soybean and alfalfa, maybe higher than either LPC alone. The effect has been attributed to the enhanced biological availabihty of lysine in these mixtures (99). 

Amino acid profiles of FPC ate excellent and compare favorably with whole egg except for tryptophan and lysiae (140). Hake and Atlantic FPCs prepared by isoptopanol extraction have PERs of 3.29 and 3.05, respectively, as compared with 3.0 for caseia (140). Numerous human feeding studies have been conducted with FPC. The results iadicate that high quaUty, bland FPC products can be used as proteia supplemeats but they ate aot suitable for use as a sole source of proteia. 

NTP Technical Teport on the Toxicology and Carcinogenesis Studies of Ethylene Glycol (CAS No. 107-21-1) in B6C3F1 Mice (Feed Studies), NIH Pubhcation... 

Liver Effects. In 1980 a 2-year feeding study carried out as part of the NTP/NCI Bioassay Program in the United States (38,39) indicated that DEHP causes increased incidence of Hver tumors in rats and mice and that DEHA had a similar effect in mice but not rats. In these studies the levels of plasticizers fed were very high, this being possible only because of thek low acute toxicity. 

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. 

Undiluted DMAMP, AMP-95, and AB cause eye bums and permanent damage, if not washed out immediately. They are also severely irritating to the skin, causing bums by prolonged or repeated contact. Of these three aLkanolarnines, only AMP has been studied in subchronic and chronic oral studies. The principal effect noted was the action of AMP on the stomach as a result of its alkalinity. The no-observed-effect level (NOEL) in a one-year feeding study in dogs was 110 ppm in the diet. In general, the low volatility and appHcations for which these products are used preclude the likelihood of exposure by inhalation. 

Based on tests with laboratory animals, aniline may cause cancer. The National Cancer Institute (NCI) and the Chemical Industry Institute of Toxicology (CUT) conducted lifetime rodent feeding studies, and both studies found tumors of the spleen at high dosage (100 —300 mg/kg pet day of aniline chloride). CUT found no tumors at the 10—30 mg/kg per day feeding rates. The latter value is equivalent to a human 8-h inhalation level of 17—50 ppm aniline vapor. In a short term (10-d) inhalation toxicity test by Du Pont, a no-effect level of 17 ppm aniline vapor was found for rats. At high levels (47—87 ppm), there were blood-related effects which were largely reversible within a 13-d recovery period (70). 

The health effects of sorbic acid and sorbates have been reviewed (165—167). The extremely low toxicity of sorbic acid enhances its desirabiHty as a food preservative. The oral LD q for sorbic acid in rats is 7—10 g/kg body weight compared to 5 g/kg for sodium chloride (165—169). In subacute and chronic toxicity tests in rats, 5% sorbic acid in the diet results in no abnormal effects after 90 days or lifetime feeding studies. A level of 10% in rat diets results in a slight enlargement of the Hver, kidneys, and thyroid gland (170). This same dietary level fed to mice also resulted in an increase in Hver and kidney weight... 

Gas-phase ammoxidation of trichlorotoluenes in the presence of catalyst affords the corresponding ben2onitri1e derivatives (90). In a 28-day feeding study,... 

In the early 1950s, a number of cases of sickness occurred in children who had reportedly eaten candy and popcorn colored with excessive amounts of dye. As a result of these illnesses, new animal feeding studies were undertaken by the FDA. These studies were conducted at higher levels and for longer test periods than any experiments previously conducted and resulted in unfavorable findings for FD C Orange No. 1, FD C Orange No. 2, and FD C Red No. 32. 

Further support for this pathway was provided by competition feeding studies. If 104 were not a true biosynthetic intermediate and were incorporated due to some flexibility in the biosynthetic enzymes, then its incorporation would be expected to be reduced by an equivalent concentration of the true substrate 102 or 103. If it were a real intermediate, then it would be expected that incorporation of earlier intermediates would be reduced by an equivalent concentration of 104. Precursor 104, labeled with deuterium at the O-methyl group, was co-fed with an approximately equal concentration of either 102 or 103 labeled with deuterium at the C-5 methyl group, and relative incorporation levels were compared by measurement of the CD3 peak intensities in the 2H NMR spectrum of the labeled azinomycin B. In each case, there was approximately twice as much deuterium labeling at the O-methyl group as at the other methyl group, consistently with 104 being a true biosynthetic intermediate. 

Penninks Seinen (1982) reported reduced weights of thymus and spleen at both dose levels from a 14-day feeding study in rats fed dioctyltin dichloride at concentrations of 50 and 150 mg/kg diet (equivalent to 2.5 and 7.5 mg/kg body weight). 

In a 3-month feeding study on rats using a 65 35 mixture of mono- and dioctyltin chlorides at 0, 3, 10, 30, or 100 mg/kg diet, no treatment-related effects on food... 

Suba, LA. 1981. Information in support of the registration of methyl parathion One-year chronic feeding study in dogs. Monsanto Agricultural Products Company, St. Louis, MO. 

EPA. 1989a. Data evaluation report 30-Day feeding study in rats. Office of Pesticides and Toxic Substances. Washington, DC U.S. Environmental Protection Agency. Document no. 007163. 

FMC. 1959b. Thiodan technical Two-year chronic feeding study - rats. Final report. Conducted for Food Machinery and Chemical Corporation, Niagara Chemical Division. Hazleton Laboratories, Inc., Falls Church, VA. 

Hoechst. 1985b. Endosulfan - substance technical (code HOE 002671 OI ZD97 0003) 42-Day feeding study in mice. Hoechst Aktiengesellschaft, Frankfurt, Germany. Report no. A38104. [unpublished study]... 

Hoechst. 1988e. Endosulfan - Substance Technical (Code HOE 002671 01ZD97 0003)/ Carcinogenicity study in mice 24 month feeding study. Hoechst Celanese Corporation, Somerville, New Jersey (author HH Donaubauer). TOXN NO. 83.0113 (Volume 1 of 13). April 6,1988. [unpublished study]... 

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