**1.5.9 Recreational and illicit substances and male reproductive toxicity**

Heavy marijuana use has been associated with gynecomastia, decreased serum testosterone levels, decreased sperm concentration, and pyospermia (white cells in the semen indicating possible infection) (Close et al., 1990). Patients experience variable sensitivity to marijuana, and it may take 2 to 3 months for symptoms to improve.

Oligospermia (abnormally low sperm concentration in the ejaculate) and defects in sperm morphology and motility have been reported in users of cocaine. Opiates have also been shown to decrease libido and erectile function through induction of hypogonadotropic hypogonadism. This also is important to note when prescribing opioids for pain. Chronic opioid use whether, oral or intrathecal, may lead to sexual dysfunction (Bracken et al., 1990). Cumulative evidence suggests that cigarette smoking may have a deleterious effect on male fertility by reducing sperm production, motility, and morphology. Cigarette smoking may also lead to development of pyospermia, decreased sperm penetration, and hormonal alterations (Nudell et al., 2002; Close et al., 1990). Long-term abuse of alcohol has detrimental effects in the HPG axis. Alcoholics exhibit significant decreases in semen volume, sperm count, motility, and number of morphologically normal sperm. They also show signs of pyospermia. Alcohol in excess can thus exert profound deleterious effects on all aspects of the male reproductive system. However, there is no evidence that moderate alcohol intake impairs male fertility (Nudell et al., 2002; Close et al., 1990).


#### **The examples of few chemicals which are reported to disrupt the sex hormones and/or damage the male in animal studies are summarized below (Woodruff et al., 2008).**

Environmental Toxicants Induced

PCBs PCBs are used in a variety of

Dioxins Dioxins are a group of chemicals

Diesel fuel Exhaust As diesel is used as a fuel in many cars

widespread.

Common environmental

Toxicants

Tobacco smoke (Polycyclic aromatic hydrocarbons (PAH)

Alkylphenols Nonylphenol Octylphenol

Male Reproductive Disorders: Identification and Mechanism of Action 491

applications, including electrical applications, dielectric fluids for transformers and capacitors, hydraulic and heat transfer systems, lubricants, gasket sealers, paints, fluorescent lights, plasticizers, adhesives, carbonless copying paper, flame retardants, and brake linings. Human

exposure also arises due to contamination of the food chain.

relatively low temperature combustion. They can come from industrial or domestic sources, wherever a chlorine source is present. Such sources include, for example, domestic bonfires with PVC plastic, incinerators, certain chemical and metal factories (particularly

which are not intentionally produced, but are emitted during incomplete or

aluminium recovery sites), paper pulp production using chlorine, and coal burning in power stations and in fireplaces in the home. Exposure can arise from inhalation, but mainly comes from contamination of food.

It includes active or passive smoking a. Blocks androgen

and lorries, diesel exhaust is

Nonylphenol is the breakdown product of the surface active agent, nonylphenol ethoxylate. Many uses including in domestic cleaning and industrial and institutional cleaning, and in textiles and leather processing. Octyl phenol is used in the production

Common uses and routes of exposure The effects on male

reproductive system

b. Anti androgenic

activities

properties.

a. Hormone mimicking

a. Sex hormone disruptor b. Testicular dysfunctions c. Low sperm count d. Sperm abnormalities

a. Disrupts androgen action b. Prenatal exposure in animals leads to endocrine disruption after birth and suppresses testicular function in male rats.

b. Testicular dysfunctions c. Low sperm count d. Sperm abnormalities

a. Hormone mimicking

b. Reduce synthesis of

c. Reduce testicular size d. reduce male fertility and sperm number and quality.

synthesis

activities

testosterone


well as in other applications, including pharmaceuticals, and pesticides. There is widespread human exposure with reported uses in building materials, household furnishings, clothing, cosmetics, dentures, medical tubing and

bags, toys, modelling clay, cars, lubricants, waxes and cleaning materials. Exposure may arise via the air, through absorption when used on the skin, and through the diet.

of chemicals used as preservatives in cosmetics and body care products, including deodorants, creams and lotions. They are able to penetrate the

fungal chemical widely used in personal care products such as some soaps, toothpaste etc. Triclosan has also been added to plastic products such as kitchen chopping boards.

trichlorocarbanilide) is also used as an

There are actually 3 commercial PBDE products, which predominantly contain deca, octa and penta-BDEs, and are therefore called by these names. PBDEs are used as flame retardants to prevent fire taking hold quickly. Penta-BDE is used in polyurethane foam, for example, in mattresses and car and aeroplane seats. Apart from exposure via dust it is possible to transfer from hand to

anti- bacterial in personal care products such as soaps.

BPA is the building block of polycarbonate plastic used in baby bottles, CDs, motor cycle windshields etc. It is also used for the production of epoxy resins used in the coating of the

food packaging.

mouth.

Paraben Paraben is the name given to a group

skin

Triclocarban Triclocarban (TCC or 3,4,4'-

Triclosan Triclosan is an anti-bacterial and anti-

Common uses and routes of exposure The effects on male

reproductive system

immature male. c. Reduce male fertility d. Foetal toxicity and malformation of male

organs.

activities

activities

testosterone

testosterone

undescended of testes in

a. Hormone mimicking

b. Reduce synthesis of

a. Hormone mimicking

b. Reduce synthesis of

a. It has sex hormone disrupting properties.

a. Oestrogenic activities

reproductive organs and induce early puberty c. Anti androgenic activity.

b. Altered male

a. Altered male reproductive organs c. Anti androgenic properties.

Common environmental

BBP = benzyl butyl

DCHP = dicyclohexyl

Toxicants

phthalate DEHP = di(2 ethylhexyl)phthalate DPP = dipentyl phthalate DINP = diisononyl

phthalate

phthalate

BPA

(Bisphenol A)

Penta-BDE (Penta-brominated diphenyl ether)


Environmental Toxicants Induced

Common environmental

Heat, Ionizing radiation, Non-ionizing radiation,

electromagnetic fields

cyclophosphamide, procarbazine, and doxirubicine, and vincristine etc.)

Chemotherapeutic drugs

**2. Identifying hazards** 

**2.1 High-throughput assays** 

microwaves,

(Cisplatin,

Certain sun-screens

Toxicants

4-MBC 3-BC

Male Reproductive Disorders: Identification and Mechanism of Action 493

A few ultraviolet (UV) filters have been found as contaminants in waste water treatment plants and rivers.

Mostly occupational exposures in home or industry as well as the mobile

A discrepancy exists between the number of chemicals in commerce (approximately 84,000) and the number that have been evaluated in model species for reproductive toxicity potential (4,000) (U.S. EPA 1998a and 1998b). It is not feasible to allocate additional resources to test the 80,000 or so untested chemicals through traditional testing protocols, particularly given that about 2,000 new chemicals are introduced into commerce each year (U.S. EPA 1998). Instead, new, more rapid methods are needed to screen large numbers of chemicals and to identify those that are potential reproductive hazards. In the near term, top priorities will be to develop the most promising alternative models and to test their ability to

High-throughput assays evaluate the effect of a test substance on a single biologic process using an automated manner that allows thousands or tens of thousands of compounds to be tested in a short time at a reasonable cost. Robotics and genetic engineering make it possible to produce large quantities of receptors or genetically engineered cells for use in these assays. Knowledge about mechanisms of toxicity is often central to the strategy of highthroughput assays. For example, cells are being developed that are bioengineered to express human hormone receptors for estrogens and androgens. These cells can be used for highthroughput chemical screening for steroid hormone receptor affinity or the potential to act as endocrine disruptors. Both isoforms of recombinant human estrogen receptor and human androgen receptor are commercially available for this purpose. Based on the same principles, other batteries of high-throughput assays are available to screen for activity against various receptors and cytochrome P-450 enzyme isoforms (Lawson et al., 2003). The

appropriately classify the toxicity of sets of known toxicants and non-toxicants.

phone users.

Common uses and routes of exposure The effects on male

Anticancer treatment. a. Testicular dysfunctions

reproductive system

a. Estrogenic activity b. Anti-androgenic activity c. Interfere male sexual

d. delay male puberty e. reduce reproductive organ weights in male

a. Testicular toxicity b. Low sperm count and motility and density. c. Reduce male fertility d. Azospermia

b. Low sperm count and motility and density.

activity

offspring.

c. Infertility d. Azospermia and oligospermia.


