Eye-irritation response

Roggeband R, York M, Pericoi M, and Braun W (2000) Eye irritation responses in rabbit and man after single applications of equal volumes of undiluted model liquid detergent products. Food and Chemical Toxicology 38 727-734. 

In order to gain a better understanding of how many test substances would be acceptable, a computer simulation based on the Draize eye irritation test was used to investigate the effects of changing sample size on the precision of future predictions of an in vivo test result from an alternative method test score. For this simulation, it was assumed that the relationship between a hypothetical alternative method response, X, and a corresponding eye irritation response, Y, has the linear form ... 

During the early validation studies, the evaluated alternative test methods showed good reproducibility, but no single method was found able to replace the animal test. The main reasons for such an outcome were as follows (a) the variability of the in vivo eye irritation responses, which are linked to the subjectivity of scoring and variability of animal responses (b) the in vitro tests, which... 

Roggeband R, York M, Pericoi M, Braun W (2000) Eye irritation responses in rabbit and... 

Bender JR, Mullin LS, Graepel GJ, et al. 1983. Eye irritation response of humans to formaldehyde. 

Schuck EA, Stephens ER, Middleton JT. 1966. Eye irritation response at low concentrations of irritants. Arch Environ Health 13 570-575. 

At the top of Figure 1, various points in the reaction are noted where samples were removed for specific analysis—i.e., for formaldehyde and total aldehyde. At the end of the reaction, one observes the eye-irritation response. Two panels of seven people each were used, and the average of each panel is shown at the top near the 6-hour reaction period. 

A comparison of Figure 5 with Figure 4 suggests that the scatter in eye irritation response indicates a weakening relationship between eye irritation and formaldehyde concentration. Tetrahydrofuran, toluene, and ethylbenzene exhibit high eye irritation and low formaldehyde concentra-... 

Table V compares the two laboratory investigations in terms of eye irritation. Here significant differences are observed. Toluene yields the highest eye-irritation reactivity in the Battelle chamber and the lowest in the SRI chamber. For MIBK and diacetone alcohol, both laboratories agree. The other rankings are not significant since the eye-irritation responses are so close to those obtained for air.

NCI3 > NHCI2 > NH2 Cl. Chloramines (primarily NHCI2 and NCl ) are usually responsible for complaints of eye irritation. Swimmers may blame this condition on too much chlorine, but the problem is caused by insufficient chlorine. Because inorganic chloramines are decomposed by sunlight, they pose less of a problem for bathers in outdoor swimming pools than in indoor pools. 

In summary, therefore, AOS (as far as has been determined) does not represent any significant health hazard. The most notable biological response is that of skin/eye irritation, which may be expected as a result of the physicochemical properties of a surfactant. 

Eye Irritation. Rabbit eyes were examined prior to experiments and found to be free of defects or irritation. Approximately 2 mg of 2,7-DCDD, 2,3,7,8-TCDD, HCDD, or OCDD were instilled in the conjunctival sac of one eye the contralateral eye served as a control. The eyes were examined at various times after treatment for conjunctival redness and chemosis, iritis, and corneal injury. Responses were cata-gorized according to intensity. 

Trichloramine is the most irritant of the chloramines together with dichloramine it is largely responsible for the chlrorine odours and eye irritation. 

In addition to stability effects, pH adjustment can influence comfort, safety, and activity of the product. Comfort can be described as the subjective response of the patient after instillation of the product in the cul-de-sac (i.e., whether it may cause a pain response such as stinging or burning). Eye irritation is normally accompanied by an increase in tear fluid secretion (a defense mechanism) to aid in the restoration of normal physiological conditions. Accordingly in addition to the discomfort encountered, products that produce irritation will tend to be flushed from the eye, and hence a more rapid loss of medication may occur with a probable reduction in the therapeutic response [15]. 

If the response to the chemical or agent is minor and reversible (such as minor eye irritation), the response-log dose curve is called the effective dose (ED) curve. Values for ED50, ED10, and so forth are also used. 

Testing of the subjects consisted of both subjective evaluations and physiological and central nervous system responses observed under medical supervision. The lowest concentration at which odor was detected was 0.2 ppm (four of nine subjects), but the ability to detect the odor disappeared within 5 min. Subjective symptoms consisted of headache and eye irritation. At 0.1 ppm, two of the subjects experienced mild headache (Table 2-3). One of these subjects had developed headache during each of the control exposures and during the exposure at 0.03 ppm. The other subject developed headache after 6 h, and the headache continued for several hours postexposure. 

At 0.35 ppm, all three subjects exposed for 2 h developed mild headaches, and one of three subjects exposed for 8 h developed a mild headache. Two of three subjects exposed for 8 h developed severe headaches. One subject also developed slight eye irritation, which persisted throughout the 2 h exposure. Four of the nine subjects detected the odor of the compound, which they described as mild at this concentration however, the odor was not detectable after 5 min of exposure. The morphology of the visual evoked response, while variable, was altered, particularly in three subjects exposed for 8 h. The exposure produced an increase in the peak-to-peak amplitude of the 3-4—5 wave complex. The authors interpreted the VER changes as consistent with the VER changes produced by central nervous system depression. 

Studies of the reactions of population groups to photochemical smog are reviewed in Chapter 10. Such studies played a major role in the establishment of the current federal standards. Included were eye irritation studies, effects on asthmatics, and the responses of groups of high-school athletes. Uncertainties in the design of these experiments and interpretation of the data make further epidemiologic studies essential. 

Many deleterious effects have been associated with photochemically polluted air ozone is deflnitely associated with respiratory problems, plant damage, and material damage PAN has deflnitely been associated with plant damage, and some other members of this class of chemical compounds have been associated with eye irritation the hydroxyl radical is considered to be an important factor in the conversion of gas-phase intermediates to end products, such as sulfur dioxide to particulate sulfate the particulate complex is responsible for haze formation and has also been associated with eye irritation and respiratory effects. The aldehydes have been associated with eye irritation. Ozone and PAN themselves do not cause eye irritation. For purposes of control, much more research is needed, in order to relate the laboratory data about the concentrations of these various materials that have significant effects to their formation in the atmosphere from emission and their atmospheric distribution. The lack of convenient measurement methods has hindered progress in gaining this understanding. 

Eye irritation has been a common complaint of people exposed to phohx hemical air poUution. Attempts to investigate this experimentally have encountered problems, because of the subjective nature of the human response and the multiphasic photochemical reactions involved. Human studies conducted until 1970 on eye irritation were cataloged and discussed in Air Quality Criteria for Hydrocarbons. 

For the two most prevalent symptoms related to photochemical-oxidant exposure—eye irritation and lacrimation—no method of quantification has been developed. Eye irritation, although undoubtedly real, is a purely subjective response of the subject, and no measurement, other than the complaint itself, has yet been developed. Similarly, a routine objective measure of lacrimation remains to be developed. However, studies on tears have demonstrated that, when a person is experiencing eye irritation, the lysozyme content of the tears is lower than normal. Measuring lysozyme content of the tears or the related pH variation appears promising, but more feasibility studies are necessary before the usefulness of the method is known. 

A survey of the state of knowledge of eye irritation and lacrimation in response to photochemical-oxidant pollution was carried out by Wilson of the Copley International Corporation for the Coordinating Research Council. After reviewing the studies cited above and related toxicolc c work, the report concluded (p. 43) ... 

Data from smdies other than skin or eye irritation smdies, e.g., other toxicological smdies on the substance in which local responses of skin, eye, and/or respiratory system were reported, may provide useful information. However, they may not be well reported in relation to, e.g., the basic requirements for information on skin and eye irritation. 

As mentioned above, a NOAEL can usually not be derived from the classic test guideline methods for skin and eye irritation. Based on information from acute and/or repeated dose toxicity smdies using inhalation, it may be possible to derive a NOAEL and/or LOAEL for respiratory tract irritation. In such smdies, the slope of the dose-response curve is a particularly useful parameter as it indicates the extent to which reduction of exposure will reduce the irritative response the steeper the slope, the greater the reduction in response for a particular finite reduction in exposure. 

Sensory response evaluations in humans indicated that exposure to 50 ppm for 15 minutes produced slight odor and eye irritation. At lOOppm for 5 minutes, the odor was plainly detectable and slight nasal and respiratory discomfort was noted by unacclimated subjects. At lOOOppm for 5 minutes, various degrees of eye irritation and throat and respiratory discomfort were noted. 

Rats exposed to 2 000 ppm 6 hours/day, 5 days/week, for 2 weeks exhibited lethargy and decreased response to noise. When exposed over a period of 90 days to 1000 ppm, there was nose and eye irritation, gel-like casts in seminal fluid of males, and increases in liver and kidney weight. Microscopic examination revealed hepatocyte hypertrophy and renal hyalin droplet formation in males. The toxicity of MIAK after inhalation exposure was not as extensive or severe as that resulting from a prior study in which male rats were dosed orally with 2000mg/kg/day for 13 weeks. 

Comparison of Threshold Irritant Response of Eyes of Guinea Pig and Rabbit and Eyes and Tongue of Man to CR Solutions ... 

Substance or subclass Ozone or oxidant Peroxyacyl nitrate Formaldehyde Aerosol particles Eye irritation Plant damage Averaged response... 

Many common VOCs have well-documented health effects at elevated levels. In most indoor environments however, the exposure is described as low since concentrations are negligible in comparison to occupational limit values. Sensory responses to VOCs also include odor response, nasal irritation (pungency) and eye irritation ( Devos et al., 1990 and Cometto-Mu iz and Cain, 1990). The maximum concentrations determined in Singapore buildings were compared with some of the common health and comfort guidelines. The values are presented in Table 10.5. It is observed that the maximum concentrations for the majority of the target compounds are within recommended guidelines. Levels are very low as compared to threshold limit values related to health and irritation. 

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