Laboratory Mammals

There are very limited data on the kinetics and metabolism of organotins in laboratory mammals. A widespread distribution of organotins throughout body tissues has been observed. Transplacental transfer seems to occur, whereas transfer across the blood-brain barrier is limited, since brain levels are usually low. The only compound for which data are available on metabolites is dibutyltin, which has butyl(3-hydroxybutyl)tin as its major metabolite. Limited information suggests quite rapid metabolism and elimination, with half-lives of several days. Much of an oral dose of dioctyltin was eliminated in the faeces, with the remainder in urine. 

EFFECTS ON LABORATORY MAMMALS AND IN VITRO TEST SYSTEMS... 

The organotins covered in this assessment have low acute toxicity to laboratory mammals, with most studies indicating LD50S above 100 mg/kg body weight, and many above 1000 mg/kg body weight. 

Table 24 Summary of critical toxicological data in laboratory mammals. ...

Gordon CJ. 1994. Thermoregulation in laboratory mammals and humans exposed to anticholinesterase agents. Neurotoxicol Teratol 16 427-453. 

In mammals, the toxicity of nickel is a function of the chemical form of nickel, dose, and route of exposure. Exposure to nickel by inhalation, injection, or cutaneous contact is more significant than oral exposure. Toxic effects of nickel to humans and laboratory mammals are documented for respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal, ocular, immunological, developmental, neurological, and reproductive systems (NAS 1975 Nielsen 1977 USEPA 1980, 1986 WHO 1991 USPHS 1993). 

Threshold effects on lung function or morphology in several species of laboratory mammals occur at airbome nickel concentrations of 0.1 to 0.2 mg/m3, depending on nickel compound and duration of exposure. 

No data were found on the effects of silver compounds on avian or mammalian wildlife. All controlled studies with silver were with domestic poultry, livestock, or small laboratory mammals. Signs of chronic silver ion intoxication in tested birds and mammals included cardiac enlargement, vascular hypertension, hepatic necrosis, anemia, lowered immunological activity, altered membrane permeability, kidney pathology, enzyme inhibition, growth retardation, and a shortened life span (Smith and Carson 1977 Freeman 1979 Fowler and Nordberg 1986 USPHS 1990). 

No studies have been conducted with silver and avian or mammalian wildlife, and it is unreasonable to extrapolate the results of limited testing with domestic poultry and livestock to wildlife to establish criteria or administratively enforced standards. Research on silver and avian and terrestrial wildlife merits the highest priority in this subject area. No silver criteria are available for the protection of avian and mammalian health, and all criteria now proposed are predicated on human health (Table 7.8). As judged by the results of controlled studies with poultry and small laboratory mammals, safe concentrations of silver ion were less than 250 pg/L in drinking water of mammals, less than 100 mg/L in drinking water of poultry, less than 6 mg/kg in diets of mammals, less than 10 mg/kg in copper-deficient diets of poultry, less than 200 mg/kg in copper-adequate diets of poultry, and less than 1.8 mg/kg in chicken eggs. The proposed short-term (10-day) allowable limit of 1142 pg Ag/L in drinking water for human health protection (Table 7.8) should... 

Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during lifetime exposure to diets containing 0.022 pg 2,3,7,8-TCDD/kg (Newton and Snyder 1978), or when administered orally at 0.01 pg/kg body weight once a week for 45 weeks (Cantoni et al. 1981). Liver residues of rats fed 2,3,7,8-TCDD were 0.54 pg/kg, or about 25 times dietary levels livers of rats dosed orally contained 1.05 pg/kg, or about 2.3 times the total dose received on a unit weight basis. Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDD were within a relatively narrow range. The estimated retention times of 2,3,7,8-TCDD in small laboratory mammals (rats, mice, guinea pigs, and... 

Mirex has considerable potential for chronic toxicity because it is only partly metabolized, is eliminated very slowly, and is accumulated in the fat, liver, and brain. The most common effects observed in small laboratory mammals fed mirex included weight loss, enlarged livers, altered liver enzyme metabolism, and reproductive failure. Mirex reportedly crossed placental membranes and accumulated in fetal tissues. Among the progeny of mirex-treated mammals, developmental abnormalities included cataracts, heart defects, scoliosis, and cleft palates (NAS 1978 Blus 1995). 

Table 25.8 Some Effects of PAHs on Selected Laboratory Mammals...

The final Section 7 of the guidance (Terminology) defines five terms or phrases used in the documents. Readers should also be aware that relatively large efforts by groups of developmental toxicologists from around the world have established a set of common terminology for abnormalities in common laboratory mammals (9, 10). 

Wise LD, Beck SL, Beltrame D, Beyer BK, Chahoud I, Clark RL, Clark R, Druga AM, Feuston MH, Guittin P, Henwood SM, Kimmel CA, Lindstrom P, Palmer AK, Petrere JA, Solomon HM, Yasuda M, York RG (1997) Terminology of developmental abnormalities in common laboratory mammals (Version 1). Teratology 55 249-292... 

Makris SL, Solomon HM, Clark R, Shiota K, Barbellion S, Buschmann J, Ema M, Fujiwara M, Grote K, Hazelden KP, Hew KW, Horimoto M, Ooshima Y, Parkinson M, Wise LD (2009) Terminology of developmental abnormalities in common laboratory mammals (Version 2). Birth Defects Res B Dev Reprod Toxicol 86 227-327... 

Wise LD, Beck SL, Beltrame D et al (1997) Terminology of developmental abnormalities in common laboratory mammals (version 1). Teratology 55 249-292... 

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