This document provides information on acute eye irritation testing methods. It discusses using topical anesthetics and systemic analgesics to minimize animal pain and distress during testing. Procedures are outlined for applying the test substance to a rabbit's eye while maintaining anesthesia. Lesions are then scored at intervals to evaluate irritation effects. The test aims to assess reversibility of eye damage in a humane manner.

1. ADITYA INSTITUTE OF PHARMACY
DEPARTMENT OF PHARMACOLOGY
PHARMACOLOGICAL AND TOXICOLOGICAL SCREENING METHOD
PRESENTATION ON
Acute eye irritation , skin sensitization and dermal toxicity
SUBMITED TO: DR. N.VENKATESAN
Submitted by ,
RAJESH YADAV

2. UNIT 2
TOXICOLOGICAL SCREENING METHODS
OBJECTIVE
1 Acute eye irritation and skin sensitization.
Irritation,
in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-
lining damage. A stimulus or agent which induces the state of irritation is an
irritant.
Irritants are typically thought of as chemical agents (for example phenol and capsaicin) but
mechanical, thermal (heat), and radiative stimuli (for example ultraviolet light or ionising
radiations) can also be irritants. Irritation also has non-clinical usages referring to bothersome
physical or psychological pain or discomfort.
Irritation can also be induced by some allergic response due to exposure of some allergens for
example contact dermatitis, irritation of mucousal membranes and pruritus. Mucosal
membrane is most common site of irritation because it contains secretory glands that release
mucous which attracts the allergens due to its sticky nature.
Chronic irritation is a medical term signifying that afflictive health conditions have been
present for a while. There are many disorders that can cause chronic irritation, the majority
involves the skin, vagina, eyes and lungs.
Types of irritation
1 eye irritation
2 skin irriatation
3vaginal irritation
4 stomach irritation
Eye irritation
Infant with blepharitis on the right eye
Modern office work with use of office equipment has raised concerns about possible adverse
health effects.[1] Since the 1970s, reports have linked mucosal, skin, and general symptoms to
work with self-copying paper. Emission of various particulate and volatile substances has
been suggested as specific causes. These symptoms have been related to Sick Building

3. Syndrome, which involves symptoms such as irritation to the eyes, skin, and upper airways,
headache and fatigue.[2]
The eye is also a source of chronic irritation. Disorders like Sjögren's syndrome, where one
does not make tears, can cause a dry eye sensation which feels very unpleasant. The
condition is difficult to treat and is lifelong. Besides artificial tears, there is a drug called
Restasis which may help.[3]
Blepharitis is dryness and itching on the upper eyelids. This condition is often seeing in
young people and can lead to reddish dry eye and scaly eyebrows. To relieve the itching
sensation, one may need to apply warm compresses and use topical corticosteroid creams.
Acute eye irritation/corrosion- 405
OECD Guidelines for Testing of Chemicals are periodically reviewed to ensure that they
reflect the best available science. The latest update mainly focused on the use of analgesics
and anesthetics without impacting the basic concept and structure of the Test Guideline.
ICCVAM and an independent international scientific peer review panel reviewed the
usefulness and limitations of routinely using topical anesthetics, systemic analgesics, and
humane endpoints during in vivo ocular irritation safety testing.The review concluded that
the use of topical anesthetics and systemic analgesics could avoid most or all pain and
distress without affecting the outcome of the test, and recommended that these substances
should always be used. Topical anesthetics, systemic analgesics, and humane endpoints
should be routinely used during acute eye irritation and corrosion in vivo testing. Exceptions
to their use should be justified. The refinements described in this proposal will substantially
reduce or avoid animal pain and distress in most testing situations where in vivo ocular safety
testing is still necessary.
BALANCED PREEMPTIVE PAIN MANAGEMENT SHOULD INCLUDE:
 Routine pretreatment with a topical anesthetic (e.g., proparacaine or tetracaine) and a
systemic analgesic (e.g. buprenorphine).
 Routine post-treatment schedule of systemic analgesia (e.g., buprenorphine and
meloxicam). Scheduled observation, monitoring, and recording of animals for clinical
signs of pain and/or distress, and
 Scheduled observation, monitoring, and recording of the nature, severity, and
progression of all eye injuries.
 No additional topical anesthetics or analgesics should be applied in order to avoid
interference with the study.
 Analgesics with anti-inflammatory activity (e.g., meloxicam) should not be applied
topically, and doses used systemically should not interfere with ocular effects.
PRINCIPLE OF THE IN VIVO TEST
Following pretreatment with a systemic analgesic and induction of appropriate topical
anesthesia, the substance to be tested is applied in a single dose to one of the eyes of the
experimental animal; the untreated eye serves as the control. The degree of eye
irritation/corrosion is evaluated by scoring lesions of conjunctiva, cornea, and iris, at
specific intervals. Other effects in the eye and adverse systemic effects are also described

4. to provide a complete evaluation of the effects. The duration of the study should be
sufficient to evaluate the reversibility or irreversibility of the effects. Animals showing
signs of severe distress and/or pain at any stage of the test or lesions consistent with the
humane endpoints described in this Test Guideline should be humanely killed, and the
substance assessed accordingly. Criteria for making the decision to humanely kill
moribund and severely suffering animals are the subject of a separate Guidance
Document.
PREPARATIONS FOR THE IN VIVO TEST
Selection of species
The albino rabbit is the preferable laboratory animal and healthy young adult animals are
used. A rationale for using other strains or species should be provided.
Preparation of animals
Both eyes of each experimental animal provisionally selected for testing should be examined
within 24 hours before testing starts. Animals showing eye irritation, ocular defects, or pre-
existing corneal injury should not be used.
Housing and feeding conditions
Animals should be individually housed. The temperature should be 20°C (± 3°C) for rabbits.
Relative humidity should be at least 30% and preferably not exceed 70%, other than during
room cleaning; the aim should be 50-60%. Lighting should be 12 hours light, 12 hours dark.
TEST PROCEDURE
Use of topical anesthetics and systemic analgesics
The following procedures are recommended to avoid or minimize pain and distress in ocular
safety testing procedures. Sixty minutes prior to test substance application (TSA),
buprenorphine 0.01 mg/kg is administered by subcutaneous injection (SC) to provide a
therapeutic level of systemic analgesia. Five minutes prior to TSA, one or two drops of a
topical ocular anesthetic (e.g. 0.5% proparacaine hydrochloride or 0.5% tetracaine
hydrochloride) are applied to each eye. The eye of each animal that is not treated with a test
article, but which is treated with topical anesthetics, serves as a control. Eight hours after
TSA, buprenorphine 0.01 mg/kg SC and meloxicam 0.5 mg/kg SC are administered to
provide a continued therapeutic level of systemic analgesia. After the initial 8-hour post-TSA
treatment, buprenorphine 0.01 mg/kg SC should be administered every 12 hours, in
conjunction with meloxicam 0.5 mg/kg SC every 24 hours, until the ocular lesions resolve
and no clinical signs of pain and distress are present.
“Rescue” analgesia should be given immediately after TSA if pre-emptive analgesia and
topical anesthesia are inadequate. If an animal shows signs of pain and distress during the
study, a “rescue” dose of buprenorphine 0.03 mg/kg SC would be given immediately and
repeated as often as every 8 hours, if necessary, instead of 0.01 mg/kg SC every 12 hours.
Meloxicam 0.5 mg/kg SC would be administered every 24 hours in conjunction with the
“rescue” dose of buprenorphine, but not until at least 8 hours post-TSA.
Application of the test substance

5. The test substance should be placed in the conjunctival sac of one eye of each animal after
gently pulling the lower lid away from the eyeball. The lids are then gently held together for
about one second in order to prevent loss of the material. The other eye, which remains
untreated, serves as a control.
Irrigation
The eyes of the test animals should not be washed for at least 24 hours following instillation
of the test substance, except for solids and in case of immediate corrosive or irritating effects.
At 24 hours a washout may be used if considered appropriate.
DOSE LEVEL
(1)Testing of liquids
For testing liquids, a dose of 0.1 mL is used. Pump sprays should not be used for instilling the
substance directly into the eye. The liquid spray should be expelled and collected in a
container prior to instilling 0.1 mL into the eye.
(2) Testing of solids
When testing solids, pastes, and particulate substances, the amount used should have a
volume of 0.1 mL or a weight of not more than 100 mg. The test material should be ground to
a fine dust. The volume of solid material should be measured after gently compacting it, e.g.
by tapping the measuring container. If the solid test substance has not been removed from the
eye of the test animal by physiological mechanisms at the first observation time point of 1
hour after treatment, the eye may be rinsed with saline or distilled water.
(3) Testing of aerosols
It is recommended that all pump sprays and aerosols be collected prior to instillation into the
eye. The one exception is for substances in pressurised aerosol containers, which cannot be
collected due to vaporisation. In such cases, the eye should be held open, and the test
substance administered to the eye in a simple burst of about one second, from a distance of 10
cm directly in front of the eye. This distance may vary depending on the pressure of the spray
and its contents. Care should be taken not to damage the eye from the pressure of the spray.
In appropriate cases, there may be a need to evaluate the potential for “mechanical” damage
to the eye from the force of the spray.
Initial test (in vivo eye irritation/corrosion):
Initially using one animal.Observations should allow for determination of severity and
reversibility before proceeding to a confirmatory test in a second animal.If the results of this
test indicate the substance to be corrosive or a severe irritant to the eye using the procedure
described, further testing for ocular irritancy should not be performed.
Confirmatory test (in vivo eye irritation test):
If a corrosive or severe irritant effect is not observed in the initial test, the irritant or negative
response should be confirmed using up to two additional animals. If an irritant effect is
observed in the initial test, it is recommended that the confirmatory test be conducted in a
sequential manner in one animal at a time, rather than exposing the two additional animals

6. simultaneously. If the second animal reveals corrosive or severe irritant effects, the test is not
continued. If results from the second animal are sufficient to allow for a hazard classification
determination, then no further testing should be conducted.
Observation period
The duration of the observation period should be sufficient to evaluate fully the magnitude
and reversibility of the effects observed. The experiment should be terminated at any time
that the animal shows signs of severe pain or distress. To determine reversibility of effects,
the animals should be observed normally for 21 days post administration of the test
substance. If reversibility is seen before 21 days, the experiment should be terminated at that
time.
Clinical observations and grading of eye reactions
The eyes should be comprehensively evaluated for the presence or absence of ocular lesions
one hour post-TSA, followed by at least daily evaluations. Animals should be evaluated
several times daily for the first 3 days to ensure that termination decisions are made in a
timely manner. Test animals should be routinely evaluated for the entire duration of the study
for clinical signs of pain and/or distress (e.g. repeated pawing or rubbing of the eye, excessive
blinking, excessive tearing) at least twice daily, with a minimum of 6 hours between
observations, or more often if necessary.Fluorescein staining should be routinely used and a
slit lamp biomicroscope used when considered appropriate (e.g., assessing depth of injury
when corneal ulceration is present) as an aid in the detection and measurement of ocular
damage, and to evaluate if established endpoint criteria for humane euthanasia have been
met.Digital photographs of observed lesions may be collected for reference and to provide a
permanent record of the extent of ocular damage. Animals showing severe pain or distress
should be humanely killed without delay, and the substance assessed accordingly.
Animals with the following eye lesions post-instillation should be humanely killed:
i. corneal perforation or significant corneal ulceration including staphyloma;
ii. blood in the anterior chamber of the eye.
iii. grade 4 corneal opacity.
iv. absence of a light reflex (iridial response grade 2) which persists for 72 hours;
v. ulceration of the conjunctival membrane;
vi. necrosis of the conjunctivae or nictitating membrane; or sloughing.
vii. This is because such lesions generally are not reversible. Furthermore, it is
recommended that the following ocular lesions be used as humane endpoints to
terminate studies before the end of the scheduled 21-day observation period
The grades of ocular reaction (conjunctivae, cornea and iris) should be obtained and recorded
at 1, 24, 48, and 72 hours following test substance application (Table 1). Animals that do not
develop ocular lesions may be terminated not earlier than 3 days post instillation. Animals
with ocular lesions that are not severe should be observed until the lesions clear, or for 21
days, at which time the study is terminated. Observations should be performed and recorded
at a minimum of 1 hour, 24 hours, 48 hours, 72 hours, 7 days, 14 days, and 21 days in order
to determine the status of the lesions, and their reversibility or irreversibility. Examination of
reactions can be facilitated by use of a binocular loupe, hand slit-lamp, biomicroscope, or

7. other suitable device. After recording the observations at 24 hours, the eyes may be further
examined with the aid of fluorescein.
Skin sensitization
skin sensitisers are substances able to elicit an allergic response following contact with the
skin, termed allergic contact dermatitis (ACD) in humans.
INTRODUCTION
1. OECD Guidelines for Testing of Chemicals are periodically reviewed in light of scientific
progress. In such reviews, special attention is given to possible improvements in relation to
animal welfare. This updated version of the original guideline 406, adopted in 1981, is the
outcome of a meeting of OECD experts held in Paris in May 1991.
2. Currently, quantitative structure-activity relationships and in vitro models are not yet
sufficiently developed to play a significant role in the assessment of the skin-sensitisation
potential of substances which therefore must continue to be based on in vivo models.
3. The guinea pig has been the animal of choice for predictive sensitisation tests for several
decades. Two types of tests have been developed: adjuvant tests in which sensitisation is
potentiated by the injection of Freunds Complete Adjuvant (FCA), and non-adjuvant tests. In
the original guideline 406, four adjuvant tests and three non-adjuvant tests were considered to
be acceptable. In this updated version, the Guinea Pig Maximisation Test (GPMT) of
Magnusson and Kligman which uses adjuvant (1)(2)(3)(4) and the non-adjuvant Buehler Test
(5)(6) are given preference over other methods and the procedures are presented in detail. It is
recognised, however, that there may be circumstances where other methods may be used to
provide the necessary information on sensitisation potential.
GENERAL PRINCIPLE OF SENSITISATION TESTS IN GUINEA PIGS
6. The test animals are initially exposed to the test substance by intradermal injection and/or
epidermal application (induction exposure). Following a rest period of 10 to 14 days
(induction period), during which an immune response may develop, the animals are exposed
to a challenge dose. The extent and degree of skin reaction to the challenge exposure in the
test animals is compared with that demonstrated by control animals which undergo sham
treatment during induction and receive the challenge exposure
ELEMENTS COMMON TO SENSITISATION TESTS IN GUINEA PIGS
Sex of animals
7. Male and/or female healthy young adult animals can be used. If females are used they
should be nulliparous and non-pregnant.
Housing and feeding conditions

8. 8. The temperature of the experimental animal room should be 20oC (+ 3oC) and the relative
humidity 30-70 per cent. Where the lighting is artificial, the sequence should be 12 hours
light, 12 hours dark. For feeding, conventional laboratory diets may be used with an
unlimited supply of drinking water. It is essential that guinea pigs receive an adequate
amount of ascorbic acid.
Preparation of the animals
9. Animals are acclimatised to the laboratory conditions for at least 5 days prior to the test.
Before the test, animals are randomised and assigned to the treatment groups. Removal of
hair is by clipping, shaving or possibly by chemical depilation, depending on the test method
used. Care should be taken to avoid abrading the skin. The animals are weighed before the
test commences and at the end of the test.
Reliability check
10. The sensitivity and reliability of the experimental technique used should be assessed
every six months by use of substances which are known to have mild-to-moderate skin
sensitisation properties.
11. In a properly conducted test, a response of at least 30% in an adjuvant test and at least
15% in a non-adjuvant test should be expected for mild/moderate sensitisers. Preferred
substances are hexyl cinnamic aldehyde (CAS No. 101-86-0), mercaptobenzothiazole (CAS
No. 149-30-4) and benzocaine (CAS No. 94-09-7). There may be circumstances where, given
adequate justification, other control substances meeting the above criteria may be used
Removal of the test substance
12. If removal of the test substance is considered necessary, this should be achieved using
water or an appropriate solvent without altering the existing response or the integrity of the
epidermis
DESCRIPTION OF THE GUINEA-PIG MAXIMISATION TEST METHOD
Number of animals
13. A minimum of 10 animals is used in the treatment group and at least 5 animals in the
control group. When fewer than 20 test and 10 control guinea pigs have been used, and it is
not possible to conclude that the test substance is a sensitiser, testing in additional animals to
give a total of at least 20 test and 10 control animals is strongly recommended.
Dose levels
14. The concentration of test substance used for each induction exposure should be well-
tolerated systemically and should be the highest to cause mild-to-moderate skin irritation.
The concentration used for the challenge exposure should be the highest non-irritant dose.
The appropriate concentrations can be determined from a pilot study using two or three
animals. Consideration should be given to the use of FCA-treated animals for this purpose.
Induction: Intradermal Injections

9. Day 0 - treated group
15. Three pairs of intradermal injections of 0.1 ml volume are given in the shoulder region
which is cleared of hair so that one of each pair lies on each side of the midline.
Injection 1: a 1:1 mixture (v/v) FCA/water or physiological saline
Injection 2: the test substance in an appropriate vehicle at the selected concentration
Injection 3: the test substance at the selected concentration formulated in a 1:1 mixture
(v/v) FCA/water or physiological saline.
16. In injection 3, water soluble substances are dissolved in the aqueous phase prior to mixing
with FCA. Liposoluble or insoluble substances are suspended in FCA prior to combining
with the aqueous phase. The concentration of test substance shall be equal to that used in
injection 2.
17. Injections 1 and 2 are given close to each other and nearest the head, while 3 is given
towards the caudal part of the test area.
Day 0 - control group
18. Three pairs of intradermal injections of 0.1 ml volume are given in the same sites as in the
treated animals.
Injection 1: a 1:1 mixture (v/v) FCA/water or physiological saline
Injection 2: the undiluted vehicle
Injection 3: a 50% w/v formulation of the vehicle in a 1:1 mixture (v/v) FCA/water or
physiological saline.
Induction: Topical Application
Day 5-7 - treated and control groups
19. Approximately twenty-four hours before the topical induction application, if the
substance is not a skin irritant, the test area, after close-clipping and/or shaving is painted
with 0.5 ml of 10% sodium lauryl sulphate in vaseline, in order to create a local irritation.
Day 6-8 - treated group
20. The test area is again cleared of hair. A filter paper (2 x 4 cm) is fully-loaded with test
substance in a suitable vehicle and applied to the test area and held in contact by an occlusive
dressing for 48 hours. The choice of the vehicle should be justified. Solids are finely
incorporated in a suitable vehicle. Liquids can be applied undiluted, if appropriate.
Day 6-8 - control group

10. 21. The test area is again cleared of hair. The vehicle only is applied in a similar manner to
the test area and held in contact by an occlusive dressing for 48 hours.
Challenge: Topical Application
Day 20-22 - treated and control groups
22. The flanks of treated and control animals are cleared of hair. A patch or chamber loaded
with the test substance is applied to one flank of the animals and, when relevant, a patch or
chamber loaded with the vehicle only may also be applied to the other flank. The patches are
held in contact by an occlusive dressing for 24 hours.
Observations -treated and control groups
23. - approximately 21 hours after removing the patch the challenge area is cleaned and
closely-clipped and/or shaved or depilated if necessary;
- approximately 3 hours later (approximately 48 hours from the start of the challenge
application) the skin reaction is observed and recorded according to the grades shown below;
- approximately 24 hours after this observation a second observation (72 hours) is made and
once again recorded.
Blind reading of test and control animals is encouraged.
TABLE: MAGNUSSON AND KLIGMAN GRADING SCALE FOR THE
EVALUATION
OF CHALLENGE PATCH TEST REACTIONS
0 = no visible change
1 = discrete or patchy erythema
2 = moderate and confluent erythema
3 = intense erythema and swelling
Rechallenge
24. If it is necessary to clarify the results obtained in the first challenge, a second challenge
(i.e. a rechallenge), where appropriate with a new control group, should be considered
approximately one week after the first one. A rechallenge may also be performed on the
original control group.
Clinical observations
25. All skin reactions and any unusual findings, including systemic reactions, resulting from
induction and challenge procedures should be observed and recorded. Other procedures, e.g.

11. DESCRIPTION OF THE BUEHLER TEST METHOD
Number of animals
26. A minimum of 20 animals is used in the treatment group and at least 10 animals in the
control group.
Dose levels 27. The concentration of test substance used for each induction exposure should
be the highest to cause mild irritation. The concentration used for the challenge exposure
should be the highest non-irritating dose. The appropriate concentration can be determined
from a pilot study using two or three animals.
28. For water soluble test materials, it is appropriate to use water or a dilute non-irritating
solution of surfactant as the vehicle. For other test materials 80% ethanol/water is preferred
for induction and acetone for challenge
Topical application
Day 0 - treated group
29. One flank is cleared of hair (closely-clipped). The test patch system should be fully
loaded with test substance in a suitable vehicle (the choice of the vehicle should be justified;
liquid test substances can be applied undiluted, if appropriate). The test patch system is
applied to the test area and held in contact with the skin by an occlusive patch or chamber and
a suitable dressing for 6 hours.
30. The test patch system must be occlusive. A cotton pad is appropriate and can be circular
or square, but should approximate 4-6 cm2. Restraint using an appropriate restrainer is
preferred to assure occlusion. If wrapping is used, additional exposures may be required.
Day 0 - control group
31. One flank is cleared of hair (closely-clipped). The vehicle only is applied in a similar
manner to that used for the treated group. The test patch system is held in contact with the
skin by an occlusive patch or chamber and a suitable dressing for 6 hours. If it can be
demonstrated that a sham control group is not necessary, a naive control group may be used.
Observations -treated and control groups
34. - approximately 21 hours after removing the patch the challenge area is cleared of hair;
- approximately three hours later (approximately 30 hours after application of the challenge
patch) the skin reactions are observed and recorded according to the grades shown in the
Guinea-Pig Maximisation Test (see paragraph 23);
- approximately 24 hours after the 30 hour observation (approximately 54 hours after
application of the challenge patch) skin reactions are again observed and recorded.
Blind reading of test and control animals is encouraged

12. Rechallenge
35. If it is necessary to clarify the results obtained in the first challenge, a second challenge
(i.e. a rechallenge), where appropriate with a new control group, should be considered
approximately one week after the first one. The rechallenge may also be performed on the
original control group.
Clinical observations
36. All skin reactions and any unusual findings, including systemic reactions, resulting from
induction and challenge procedures should be observed and recorded. Other procedures, e.g.
histopathological examination, measurement of skin fold thickness, may be carried out to
clarify doubtful reactions.
DATA AND REPORTING

16. DERMAL TOXICOLOGY
Introduction
Dermal toxicity, also known as cutaneous toxicity is the ability of a substance to poison
people or animals by contact with the skin. Toxic materials absorb through the skin to various
degrees depending on their chemical composition and whether they are dissolved in a solvent.
Occupational skin diseases are the second most common types of occupational disease.
Greatest number of occupational skin disease cases occur in the agricultural and
manufacturing industries
Functions of Skin
Environmental barrier
Diffusion barrier
Metabolic Barrier
Mechanical Support
Neurosensory Reception
Physiologically, Skin Participates Directly In
Thermal Regulation
Regulation Of Blood Flow, Hair And Fur, Sweating
Metabolism
Keratin, Collage, Melanin, Lipids, And Vitamin D Synthesis, Respiration And
Biotransformation
Electrolyte And Hormonal Regulation
Apocrine/Eccrine/Sebaceous Glandular Secretion

17. Manifestation
Contact Dermatitis
Allergic Contact Dermatitis
Ulcers
Utricaria
Toxic Epidermal Necrolysis
Acneiform Dermatoses
Pigment Disturbances
Photosensitivity
Skin Cancer
Contact Dermatitis
Irritant contact dermatitis is one of the most common occupational diseases. is confined to
the area of irritant exposure. Symptoms are hives (wheals), reddening of the skin (erythema),
blistering, eczemas or rashes that weep and ooze, hyperkeratosis (thickening of the skin),
pustules, and dryness and roughness of the skin. Treatment is by reducing or avoiding the
amount of exposure to the irritant. Wearing gloves to provide protection against wetness or
chemicals and minimizing wet working conditions and hand washing can be very helpful.
Extremely corrosive and reactive chemicals can cause immediate coagulative necrosis at the
site of contact resulting in substantial tissue damage. These are called primary irritants that
cause nonselective damage at the site of contact & also causes damage resulting from their
reactivity, such as acids precipitating proteins and solvents dissolving cell membranes, both
resulting in cell damage, death, or disruption of the keratin ultrastructure.

18. Allergic Contact Dermatitis
Allergic contact dermatitis is a delayed type IV hypersensitivity reaction that is mediated by
a triggered immune response. On first exposure to the allergenic chemical, little or no
response occurs. After this first exposure, the individual becomes sensitized to the chemical,
and subsequent exposures elicit the typical delayed type IV hypersensitivity reaction. The
allergenic agents (haptens) are typically low-molecular-weight chemicals that are
electrophilic or hydrophilic. These agents are seldom allergenic alone and must be linked
with a carrier protein to form a complete allergen. Some chemicals must be metabolically
activated in order to form an allergen. Patch testing is used to try to determine to which agent
a person with suspected allergic contact dermatitis may be sensitive. The best treatment,
however, is avoidance of the allergen or irritant. Baths and wet compresses, antibiotics,
antihistamines, and corticosteroids are used in various combinations to treat contact
dermatitis.
Ulcers
Some chemicals can cause ulceration of the skin. This involves sloughing of the epidermis
and damage to the exposed dermis. Ulcers are commonly triggered by acids, burns, and
trauma and can occur on mucous membranes and the skin. Two commonly encountered
compounds that induce ulcers are cement and chrome.
Utricaria
Triggered by immunity-related mechanisms, and minute quantities of allergen. Urticaria
results in the typical hives, which are pruritic red wheals that erupt on the skin. Asthma is
also a common occurrence after exposure to an inducer of urticaria. The symptoms often last
less than 24 h. In severe cases, however, anaphylaxis and/or death may occur. Most
compounds that induce urticaria must enter the systemic circulation. Some potential
nonimmune inducers of urticaria are curare, aspirin, azo dyes, and toxins from plants and
animals. A smaller number of agents may cause contact urticaria on exposure only to the
epidermis. Cobalt chloride, benzoic acid, butylhydroxyanisol (BHA), and methanol have
been reported to cause this form of urticaria. One of the most common inducers of contact
urticaria seen in the medical community is caused by latex rubber products such as gloves.
Toxic Epidermal Necrolysis
Toxic epidermal necrolysis (TEN) is one of the most immediate lifethreatening skin diseases
caused by chemicals or drugs. The disease is characterized by a sudden onset of large, red,
tender areas involving a large percentage of the total body surface area. As the disease
progresses, necrosis of the epidermis with widespread detachment occurs at the affected
areas. Once the epidermis is lost, only the dermis remains, severely compromising the ability
of the skin to regulate temperature, fluid, and electrolyte homeostasis. Since the epidermis is
lost, the remaining dermis posses little resistance to chemicals entering the systemic
circulation and to infection from microorganisms.
Acneiform Dermatoses
Acne is a very disfiguring ailment & the most common causes of acne are petroleum, coal
tar, and cutting oil products. They are termed comedogenic since they induce the
characteristic comedo, which is either open (blackhead) or closed (whitehead). The

19. comedogenic agents produce biochemical and physiological alterations in the hair follicle and
cell structure that cause accumulation of compacted keratinocytes in the hair follicles and
sebaceous glands. The keratinocytes clog the hair follicles and sebaceous glands.
Halogenated chemicals as polyhalogenated naphthalenes, biphenyls, dibenzofurans,
polychlorophenol and dichloroaniline—cause a very disfiguring and recalcitrant form of acne
called chloracne. It is typically characterized by the presence of many comedones and straw-
colored cysts behind the ears, around the eyes, and on the shoulders, back, and genitalia. To
prevent exposure to the halogenated chemicals could involve putting up splash guards and
other devices to prevent the chemicals from coming into contact with the skin along with
changing chemical soaked clothing frequently
Pigment Disturbances
Some chemicals can cause either an increase or decrease in pigmentation. These compounds
often cause hyperpigmentation (darkening of the skin) by enhancing the production of
melanin or by causing deposition of endogenous or exogenous pigment in the upper
epidermis. Hypopigmentation (loss of pigment from the skin) can be caused by decreased
melanin production and/or loss, melanocyte damage, or vascular abnormalities. Some
common hyperpigment inducers are coal tar compounds, metals (e.g., mercury, lead, arsenic),
petroleum oils, and a variety of drugs. Phenols and catechols are potent depigmentors that act
by killing melanocytes.
Photosensitivity
Photosensitivity is an abnormal sensitivity to ultraviolet (UV) and visible light and can be
caused by endogenous and exogenous factors. Chromophores, epidermal thickness, and water
content all affect the ability of light to penetrate the skin, and those parameters vary from
region to region on the body. Melanin is the most significant chromophore, since it can
absorb a wide range of radiation from UVB (290–320 nm) through the visible spectrum.
Exposure to intense sunlight causes erythema. Inflammatory mediators may be released at
these areas and have been implicated in the systemic symptoms of sunburn such as fever,
chills, and malaise. UVB is the most important radiation band in causing erythema. Ionizing
radiation can cause acute changes such as redness, blistering, swelling, ulceration, and pain.
Following a latent period or chronic exposure, epidermal thickening, freckling, nonhealing
ulcerations, and malignancies may occur. and chemicals. Photoallergy is very similar to
contact allergic dermatitis and is a delayed type IV hypersensitivity reaction. The difference
between an allergenic chemical and a photoallergenic chemical is that the photoallergenic
chemical must be activated by exposure to light—most often UVA.
Skin Cancer
Skin cancer is the most common neoplasm in humans with half a million new cases
occurring per year in the United States. Even though exposure to UV light is the primary
cause of skin cancer, chemicals can also induce malignancies. UV light and carcinogenic
agents induce alterations in epidermal cell DNA. These alterations can lead to permanent
mutations in critical genes that cause uncontrolled proliferation of the affected cells,
ultimately leading to a cancerous lesion. Since UVB light is the most potent inducer of DNA
damage, utilization of a sunscreen that blocks UVB radiation is critical in preventing skin
cancer along with the other skin effects associated with UV light exposure. The best

20. characterized chemical inducers of skin cancer are the polycyclic aromatic hydrocarbons
(PAH).