Humans sensitivity

Human sensitization studies were negative at 10% solution (47). Undiluted benzyl alcohol produces moderate dermal irritation in guinea pigs and mild dermal irritation in rabbits (48,49). Severe eye irritation was noted in a rabbit study (50). Acute oral rat LD q values were reported between 1.23 and 3.10 g/kg (50—52). A dermal rabbit LD q value of 2.0 g/kg has been reported (49). Rats died after 2 h when exposed to a 200-ppm vapor concentration (53). Benzyl alcohol is readily oxidized in animals and humans to benzoic acid [65-85-0] which is then conjugated with glycine [56-40-6], and rapidly eliminated in the urine as hippuric acid [495-69-2] (54). 

Numerous behavioral measures have been evaluated for their usefulness in providing a sensitive index of exposure to ionizing radiation. Radiation-related mental retardation is the most likely type of behavioral abnormality in humans sensitivity peaked between 8 and 15 weeks of conception... 

In addition to odor, several human health-related problems are potentially associated with the occurrence of hydrogen sulfide at concentration levels relevant for sewer networks. In this respect, it is interesting to compare values from Table 4.5 with Figure 4.2. The levels indicated in Table 4.5 depend on human sensitivity and time of exposure. 

The AEGL-1 values were based on concentrations at 0.5 ppm and 0.1 ppm, which were the thresholds for mild headaches in healthy individuals at exposure durations of 1 and 6 h, respectively (Stewart et al. 1974). This effect can be considered the threshold for mild discomfort (only one subject was affected at each exposure), which falls within the definition of an AEGL-1. The 0.5-ppm concentration was used to derive the 30-min and 1-h AEGL-1 values, and the 0.1-ppm concentration was used for the 4- and 8-h values. Because the time and concentration values were based on the most susceptible subject, these concentrations were adjusted by an uncertainty factor (UF) of 3 to account for potential differences in human sensitivity and scaled to the appropriate time periods using the C xt=k relationship. A UF of 3 was considered sufficient as no susceptible populations were identified (the headache effect is the same as that experienced by patients medicated with nitro... 

Intraspecies 3—no unusually susceptible populations were identified. Because the time and concentration values were based on a threshold, these concentrations were adjusted by an uncertainty factor of 3 to account for differences in human sensitivity. More severe headaches are often experienced by heart patients medicated with nitroglycerin for angina and these concentrations are far below those inducing methemoglobinemia in infants. ... 

Furthermore, the olfactometer should be able to deliver the above mentioned ranges of stimuli over a wide range of dilution ratios (from 1 to 10 6) in order to cover the variability of human sensitivity to different substances. Such a range may still be too small in some cases. If so, provisions for predilution may be required. Finally, it will be clear that both the dilution air and the ambient air in which the measurement takes place should be odour free. Although this may seem quite obvious, in many cases this requirement is not fulfilled. Either the dilution air has an intrinsic smell which is insufficiently filtered out or parts of the olfactometer give off an odour. Thus, contact of the dilution air to be delivered to the nose with pumps, ventilators, valves etc. should be avoided as much as possible. 

With respect to oral sensitization, attempts have been made to develop animal models of food allergy, which so far has proven to be complicated. One crucial point is the route of exposure experience indicates that it may not be possible to develop an animal model, which rnirnics the human sensitization via the oral route. Exposure via the diet or in drinking water appears in rodents to be more likely to cause immunological hyporesponsiveness (i.e., tolerance) than sensitization, and therefore it may be necessary to use parenteral induction in animal testing (Dearman and Kimber 2007). 

Polybrominated Diphenyl Ethers. A human sensitization study was conducted in which 77.4% decaBDE (containing 21.8% nonaBDE and 0.8% octaBDE) as a 5% suspension in petrolatum was applied via patch, 3 times a week for 3 weeks, to 50 subjects (Norris et al. 1975a). No skin sensitization responses... 

W.W. Weber, Influence of Heredity on Human Sensitivity to Environmental Chemicals , Environ. Mol. Mutagen., 25(Suppl.), 102-114 (1995). 

What possibilities are there to achieve sustainable development and reduce human sensitivity to forcings ... 

X] 3 for extrapolation from animals to humans- A comparison of species sensitivity suggests that even though there are wide ranges of sensitivity for some 2,3,7,8-TCDD-induced health effects, for most health effects, the LOAELs for the majority of animal species cluster within an order of magnitude. Based on the weight of evidence of animal species comparisons and human and animal mechanistic data, it is reasonable to assume that human sensitivity would fall within the range of animal sensitivity. 

Human Sensitization Assays allow chemicals to be tested for their ability to induce contact hypersensitivities on the skin of human volunteers with obtained informed consent. Human studies should only be undertaken for a new compound after the results of predictive tests in animals for such compound are available. If a compound contains significantly increased levels of common ingredients, it should also undergo predictive tests in animals prior to humans. 

Table 2 Principal features of human sensitization assays ...

There are 4 basic predictive human sensitization tests in current use (1) single induction/ single challenge patch tests (2) repeated insult patch tests (RIPT) (3) RIPT with continuous exposure (modified Draize) and (4) the maximization test. Principal features of human sensitization assays are summarized in Table 2. 

RIPT has four major variations that are commonly used (1) the Draize human sensitization test (1955, 1959) (2) the Shelanski/Shelanski test (1953) (3) the Voss/Griffith test (1969, 1976) and (4) Marzill/Maibach modification. 

In the Draize human sensitization test, an occlusive patch containing the test material is applied to the upper armor upper back of 200 volunteers. The patch remains in place for 24 h and is then removed. The test site is evaluated for erythema and edema at patch removal. Twenty-four hours after the removal of the 1st patch, a 2nd patch test is applied. This... 

The subcommittee chose the NOAEL of 1,000 mg/kg/d to calculate an unlikely effect level (UEL) for developmental toxicity. The aggregate uncertainty factor for human sensitivity is 1,000 (10 for inter-individual variation, 10 for extrapolation from rats to humans, 10 for an incomplete data set). The UEL is calculated by dividing the NOAEL by the aggregate uncertainty factor for human sensitivity ... 

SAFETY PROFILE Poison by ingestion and intraperitoneal routes. Moderately toxic by subcutaneous route. Questionable carcinogen with experimental carcinogenic, neoplastigenic, tumorigenic, and teratogenic data. Experimental reproductive effects. A human sensitizer. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOx. 

Standardized animal and human tests of allergic sensitization to the ethanolamines have been negative, but sporadic case reports of human sensitization and a low incidence of sensitization in specific work groups of dermatitis patients have been reported. 

Animal versus human animal and/or human sensitive subsets of population... 

D-Limonene causes skin sensitization however, see sections on Mechanism of Toxicity and Chronic Toxicity - Human for discussion and data useful for assessing human sensitization risks. 

Vanillin is a weak human sensitizer. It has induced skin sensitization in humans, and it was also reported to have highly irritating action on the eyes and mucous membranes of the respiratory tract. Ingestion of vanilla has provoked intolerance reaction it is pharmacologically active and may cause depressed blood pressure, increased respiratory rate, and even death due to cardiovascular collapse. Probable oral lethal dose to human is 500 mg kg for a 70 kg person. 

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