Human data

Human data adequate to serve as the sole basis for a hazard assessment are rare however, when available, reliable and relevant human data are preferable over animal data. 

Closer to the target of clinical effects are data obtained in humans. Here of course the problem of interspecies differences is avoided, but other problems become foremost. One of these is genetic differences between humans, with the discovery of genetic polymorphism in enzymes (Meyer et al., 1990) and receptors (Strange, 1994). Ethnopharmacology was born with the discovery that variations in genotypes and phenotypes between human populations are observed that cause many interethnic differences in drug responses (Kalow and Bertilsson, 1994). 

---

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories ... 

B1 orB2 Probable human carcinogen B1 indicates that limited human data are available B2 indicates sufficient evidence in animals and inadequate or no evidence in human... 

COMPARISON OF ANIMAL AND HUMAN DATA FROM EUROPE... 

Although a number of studies have reported the effects of inhalation exposure to methyl parathion in humans, no inhalation MRLs were derived based on human data because of the lack of adequate quantitative exposure information. Animal data were also insufficient to support the derivation of an acute-, intermediate-, or chronic-duration inhalation MRL. 

Ware GW, Morgan DP, Estesen BJ, et al. 1973. Establishment of reentry intervals for organophosphate-treated cotton fields based on human data. I. Ethyl-and methyl parathion. Arch Environ Contam Toxicol 1 48-59. 

The chapter covers end points in the same order they appear within the Discussion of Health Effects by Route of Exposure section, by route (inhalation, oral, dermal) and within route by effect. Human data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also considered in this chapter. If data are located in the scientific literature, a table of genotoxicity information is included. 

Human data as well as studies in animals have provided negative evidence of carcinogenicity for endosulfan (Hack et al. 1995 Hoechst 1988b, 1989a). However, endosulfan promoted the development of altered hepatic foci in rats initiated with nitrosodiethylamine (Fransson-Steen et al. 1992). Although the mechanism of tumor promotion of endosulfan is not known, it has been suggested that it involves inhibition of cellular communication (Kenne et al. 1994). A brief discussion of this topic is provided in Section 2.5 under Cancer Effects. 

Dourson ML, Andersen ME, Erdreich LS, MacGregor JA. Using human data to protect the public s health. Regul Toxicol Pharmacol 2001 33 234-56. 

Although human data are not extensive, the data suggest that dermal effects may be a concern for some humans exposed to trichloroethylene, particularly through bathing with contaminated water however, it is unlikely that exposure to trichloroethylene in the air or soil at hazardous waste sites would be irritating to human skin. Some people may develop immunological sensitivity to trichloroethylene which may manifest as a dermal response following inhalation, oral, or dermal exposure to trichloroethylene. 

MESSINA M, GUGGER E T and ALEKEL D L (2001) Soy protein, soybean isoflavones, and bone health a review of the animal and human data. In Wildman REC, Handbook of Nutraceuticals and Functional Foods, Boca Raton, CRC Press EEC, 77-98. 

It is unfortunate, and this is a real deficit in this field, that we cannot do the very human studies that I know you would all like to do and, therefore, we rely upon whatever evidence we have to reach conclusions. But we have to be wary of the fact that the human data are weak in comparison. 

Since no human data exist to determine its safe use in pregnant women, sibutramine is not recommended therefore, women of childbearing potential should use effective methods of contraception while taking sibutramine. Further, sibutramine is not recommended for lactating mothers because its excretion in breast milk is likewise unknown.29... 

Presumed role in Animal data in Human data in... 

Molecule Cell expression Presumed role in atherosclerosis Animal data in atherosclerosis Human data in atherosclerosis... 

No animal or human data were available for inhalation exposure. There are no data regarding effects in humans after oral exposure. Information is available in animals regarding health effects following acute, intermediate, and chronic oral ingestion of diisopropyl methylphosphonate. The animal data obtained after oral exposure indicate that diisopropyl methylphosphonate is moderately toxic after acute bolus exposure but has a lower order of toxicity after intermediate and chronic exposures in food. No data were found on the toxicity of diisopropyl methylphosphonate after exposure in drinking water. Further, diisopropyl methylphosphonate is rapidly metabolized and excreted and does not accumulate. It does not appear to have reproductive or developmental effects. At the doses tested, it does not appear to be an acetylcholinesterase inhibitor, although this issue has not been resolved yet. Limited data are available for dermal exposure in humans and animals. Diisopropyl methylphosphonate does not appear to be a... 

Human data divided into specific problems that occur during the reproductive cycle in which caffeine might be implicated. 

In conclusion, the limited animal and human data suggest that acute to intermediate exposures to mineral oil hydraulic fluids do not represent a major hazard to the neurological health of workers or the general public. The possible presence of low levels of neurotoxic organophosphate esters in these fluids, however, may lead to some concern to limit exposure. 

---