Cumulative skin irritation

Many industries regularly conduct repeat insult patch tests on human volunteers to evaluate topical irritancy. Groups of human volunteers are patched with test substance. One to five concentrations can be tested simultaneously, a wide enough range to yield results relevant to the usage. Cumulative skin irritancy is measured by applying patch applications each day for 3 weeks. Skin irritation is usually assessed visually, but blood flow and skin temperature can be measured objectively by laser Doppler flowmetry, ultrasound Doppler, heat flow disk measurement, sensitive thermocouple devices, or noncontact infrared radiative techniques. In these tests, dose-response curves can be obtained. Skin thickness can be measured with calipers as a measure of edema formation. 

It is unlikely that there will be significant percutaneous toxicity under the usual conditions of exposure to screening smokes. However, if primary and cumulative skin irritation tests suggest that there may be systemic effects, then it will be appropriate to conduct more detailed monitored studies for percutaneous toxicity. 

Alternatively, the cumulative skin irritation study and the skin sensitization study can be combined into a single study. The study design would be identical to that described for the skin sensitization study (see Section I.B), except that patch application during the induction phase should be daily for 23 hours (+1 hour) each day over 21 days. 

Kappes UP, Goritz N, Wigger-Alberti W, et al. Tandem application of sodium lauryl sulfate and n-propanol does not lead to enhemcement of cumulative skin irritation. Acta Derm Venereol. 2001 81 403-5. 

These are conducted to gain information on the cumulative irritancy of a product. This type of test is designed to mirror the intended use of the product, but exposure may also be exaggerated, to provide a greater margin of safety in the risk assessment on the product and also to provide information on problems that may be encountered should the product be misused. Some methods are designed to simulate the normal use of products, with controlled exposure. The skin irritation is monitored and comparisons made between the test and control product in the same panellist. The controls are... 

PURPOSE AND RATIONALE Inflammation produced late in the induction phase of sensitization tests without positive responses at challenge is cumulative irritation. The HRIPT for skin allergy was modified to evaluate skin irritation. As with single-application patch tests, many investigators developed their own version of the repeat application patch test. 

Skin irritation (inflammation) from cutaneous exposures that are acute (primary irritation) and repeated (cumulative irritation). 

Glycidol is an eye, lung, and skin irritant. The pure compound caused severe but reversible corneal injury in rabbit eyes (ACGIH 1986). Exposure to its vapor caused irritation of lung in mice, resulting in pneumonitis. There is no evidence of any cumulative toxicity. From the limited toxicity data, it appears that the health hazard to humans from its exposure is, primarily, respiratory irritation, stimulation of the central nervous system, and depression. 

Surgical scrub formulations are designed to remove both transient and normal (resident) microorganisms from the hand surfaces [16]. Surgical scrubs, to be effective when used with or without a scrub brush, must demonstrate immediate, persistent, and residual antimicrobial properties and must be low in skin irritation effects when used repeatedly over a prolonged period of time. The product s immediate antimicrobial efficacy is a quantitative measurement of both the mechanical removal and immediate inactivation of microorganisms residing on the skin surface [17]. The persistent antimicrobial effectiveness is a quantitative measurement of its ability to prevent microbial recolonization of the skin surfaces, either by microbial inhibition or by lethality. The residual efficacy is a measurement of the product s cumulative antimicrobial properties after it has been used repeatedly over time. That is, as the antimicrobial product is used over time, it is absorbed into the stratum corneum of the skin and, as a result, prevents microbial recolonization of the skin surfaces. 

Toxicology Nuisance dust, TLV/TWA 10 mg/m (8 h, total dust) long-term cumulative inh. may cause restriction of airways may cause minor skin irritation... 

Properties Wh. acicuiar powd., faint odor 3 pm median particie size 100% -20 p, 96% -10 p fineness Hegman 6-7 soi. 0.01 g/100 cc in water sp.gr. 2.9 dens. 24.2 ib/soiid gai buik dens. 0.48 g/cc (ioose) buik vaiue 0.0413 gai/ib surf, area 4.1 mVg oii absorp. 24 GE brightness 95 m.p. 1540 C ref. index 1.63 pH 9.9 (10% siurry) hardness (Mohs) 4.5 > 99% woiiastonite, < 1 % proprietary treatments Toxicology Nuisance dust, TLV/TWA10 mg/m (8 h, totai dust) long-term cumulative inh. can cause restriction of airways may cause minor skin irritation... 

Properties Colorless to amber oily liq. turns red to brn. on exposure to light and air sol. in DMSO, 95% ethanol, acetone sol. 5-10 mg/ml in water m.w. 137.18 sp.gr. 1.0652 (16/4 C) vapor pressure 3.48 mm Hg (25 C) m.p. 2-4 C b.p. 250 C flash pt. 115 C ref. index 1.5528 (20 C) Toxicology LD50 (oral, rat) 580 mg/kg, (IP, mouse) 692 mg/kg LCLo (inh., rat) 250 mg/m harmful liq. and fumes highly toxic by inh. mod. toxic by ing. and unknown routes toxic by skin absorp. may cause irritation on contact readily absorbed thru skin danger of cumulative effects irritating to eyes, skin, respiratory system may cause cyanosis, hypothermia, headache, drowsiness, vomiting, nephritis and irritation of the alimentary tract TSCA listed... 

Toxicology LD50 (oral, rat) 1297 mg/kg poison mod. toxic by ing. toxic by inh., skin contact readily absorbed thru skin irritating to eyes, skin, respiratory system danger of cumulative effects may cause headache, cyanosis, mental confusion, convulsions, nervous system/blood effects, drowsiness, anorexia, fatigue, loss of... 

Skin irritation can be produced by nonimmune-mediated idiosyncratic cutaneous reactions resulting from cumulative toxicity, overdose, drug interactions, and metabolic alterations (Lee and Thompson, 2006). RhE skin irritation tests (SIT) have been validated and adopted by OECD as TG 439 for determining the irritation hazard from topical exposure to chemicals and mixtures (Kandarova et al., 2009 OECD, 2009). TG 439 is based on the ability of irritant chemicals to penetrate the stratum comeum and produce cytotoxicity in the underlying cell layers. The TG classifies test substances as either irritating or nonirritating based on results of the MTT viability assay. 

Widmer J, Eisner P, Burg G (1994) Skin irritant reactivity following experimental cumulative irritant contact dermatitis. Contact Dermatitis 30 35-39... 

Schwarz T (1988) Die Bedeutung epidermaler Zytokine in der UV-induzierten Immunsuppression. Hautarzt 39 642-646 Tupker RA, Pinnagoda J, Coenraads PJ, Nater P (1990) Susceptibility to irritants role of barrier function, skin dryness and history of atopic dermatitis. Br J Dermatol 123 199-205 Widmer J, Eisner P, Burg G (1994) Skin irritant reactivity following experimental cumulative irritant contact dermatitis. Contact Dermatitis 30 35-39... 

Whilst the test described above is a common way in which an attempt is made at predictive identification of those substances or products with significant skin-irritation potential, other information can also be used. Consideration is given to structure-activity relationships, although it must be said that this subject is in its infancy for skin irritants (Whittle et al. 1996 Barratt 1996). Data may also come from non-standard animal tests, predictive human tests and from human experience. These may cover either acute and/or cumulative irritant responses in skin. It is also possible for manufacturers to use data from in vitro studies. Lastly, where the product is a mixture of two or more substances [a preparation in European Union (EU) terminology], the manufacturer may elect to calculate the likely irritancy on the basis of the knowledge of the skin irritancy of the component substances and the concentration at which they occur in the product. For certain types of product, this process has been formalised in the EU as the conventional method (European Community 1988). 

Most commonly, skin irritation to chemicals occurs clinically as cumulative irritant dermatitis. MSDS data is most often based on evidence of the acute skin-irritation potential of the product. Such data may not always be fully predictive of cumulative irritation potential (Hannuksela and Hannuksela 1995). Furthermore, if the product is a preparation rather than a single substance, MSDS information may be based on the conventional calculation method, in which labeling is only applied if the sum of classified irritants is at least 20% (European Community 1988). To put this in simple terms, it means that 20% aqueous sodium lauryl sulphate would be described as irritant, whilst 19.9% would not be so labeled. 

Other animal tests have been used to study skin irritation by surfactants or other chemicals and have been reviewed by Gabriel [50]. They are the mouse ear swelling test, the guinea pig immersion technique, the cumulative irritation test on rabbits, and the rabbit ear test. As their usage is continually declining, the reader is referred to Ref. 50 for further details. 

This cumulative application test has the advantage over the previous ones because it is able to detect even weak irritants so that false negatives are extremely rare and a product causing minimal irritation in this test is very unlikely to cause skin irritation when placed on the market. 

Highly toxic by inhalation and skin absorption, if swallowed danger of cumulative effects. Irritant. BX3400000. 

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