ACCORDING TO NIOSH, ORTHO-TOLUIDINE CAUSES BLADDER CANCER - KEEP YOURSELF AND YOUR FAMILY SAFE

NIOSH Study Contributes to Classification of o-Toluidine as Human Carcinogen

o-Toluidine has been listed as a Known Human Carcinogen in the 13th Report on Carcinogens, a science-based public health document that identifies substances in our environment that are considered cancer hazards. A NIOSH study conducted at a rubber chemical manufacturing plant in New York State “…provided substantial evidence that o-toluidine was the agent causally related to the observed increase in urinary Mont bladder cancer risk among o-toluidine-exposed workers.” To learn more about o-toluidine and how to keep workers safe, visit the NIOSH o-toluidine webpage at http://www.cdc.gov/niosh/topics/ot/default.html.

NIOSH considers o-toluidine most likely responsible for the bladder cancer incidence elevation at workers at a rubber manufacturing plant and recommended a re-examination of occupational exposure limits.

ORTHO-TOLUIDINE

About o-Toluidine

Below is some information about o-toluidine and the health problems it may cause. This information may be helpful to determine whether you are or have been exposed to o-toluidine in your job or whether symptoms you’ve experienced could be related to o-toluidine exposure.

What it looks like

· At room temperature, it is a thick, light yellow liquid

· When exposed to air and light, it will darken to reddish/orange brown

What it smells like

· It has a fishy odor

· It has a low odor threshold, which means most people will smell it even at very low levels.

How you can be exposed

· Breathing it in

· Getting it on your skin

Who is most likely exposed

· Industrial workers who use it

Beyond the industrial setting, there is little information available about o-toluidine exposure among other workers and the general public. We know that others may also be exposed, but probably at lower levels, including:

· Hair stylists because o-toluidine is used in some hair dyes.

· Laboratory workers who use o-toluidine to stain tissues or as part of a reagent to analyze glucose.

· The general public because o-toluidine is in

o cigarette smoke

o certain hair dyes

o Prilocaine, a cream that is applied to the skin to numb it for minor dental and surgical procedures and blood draws. Our bodies convert Prilocaine to o-toluidine after it is absorbed.

o air, soil, or water contaminated with o-toluidine

Health problems it may cause

Short-term effects

· skin, eye, and respiratory irritation

· cyanosis from a decrease in the supply of oxygen to the body due to methemoglobinemia. This condition occurs when o-toluidine changes hemoglobin, which carries oxygen in the blood, to methemoglobin, which hinders the release of oxygen.

· central nervous system depression including dizziness, headache, and confusion

Long-term effects

· bladder cancer

· anemia

· decreased appetite and weight loss

· cyanosis and methemoglobinemia

· skin lesions

· central nervous system depression including dizziness, headache, and confusion

After 24 years, OSHA decided to list ortho-toluidine as a human carcinogen.

Information for Industrial Workers

We know that o-toluidine can cause cancer. If you work with o-toluidine, there are ways you can keep yourself and your family safe.

Keep yourself and your family safe

· Be sure you use personal protective equipment (PPE) that will keep you from breathing in o-toluidine. If a respirator is needed, use one that is NIOSH-approved with an organic vapor cartridge (containing activated charcoal) or one that supplies breathing air. Do not use disposable filtering-facepiece respirators designed to protect against dusts since they don’t provide protection against o-toluidine.

· Good instruction and supervision are necessary to ensure skin protection against o-toluidine. Skin protection includes wearing gloves, protective arm sleeves, lab coats, and boot covers. When using gloves, remember that not all glove materials prevent o-toluidine from going through the glove and getting on your skin:

o Gloves made from butyl rubber, and some trademark materials, provide the best protection.

o Gloves made from neoprene would be expected to provide some protection (rated 1-4 hours of protection) against o-toluidine.

o Some laboratory tests have found gloves and other PPE made from polyethylene and polyvinyl chloride do not protect against o-toluidine.

o Natural rubber, nitrile rubber, and polyvinyl alcohol have not been tested for protection against o-toluidine.

o Glove manufacturers will have the most up to date information on whether a glove you are using will offer you the proper protection.

o For more information about glove selection and information concerning the protective qualities of different types of glove materials, see the Quick Selection Guide to Chemical Protective Clothing, 5th edition (2007) by Krister Forsberg and S.Z. Mansdorf (Wiley-Interscience, Hoboken, NJ; ISBN 978-0-470-14681-1).

· If your worksite offers showers and locker rooms, use them. If you do not shower or if you wear your work clothes home, you can expose your family to chemicals. If your worksite does not have showers or a changing room, shower and change immediately after you get home. Wash your work clothes separate from the other clothes. Chemicals that are on your work clothes can still get on other clothes if they are washed together.

· If your worksite offers a medical surveillance program, use it. There is a reason it is in place. If your worksite does not have a surveillance program, be sure your doctor knows you work with o-toluidine. Your doctor may want to monitor you for bladder cancer, since o-toluidine is a known cause. There are medical tests that can tell you whether you’ve been exposed to o-toluidine. Talk with your doctor to learn more and to decide whether this would be beneficial.

· If you are concerned that you are being exposed to o-toluidine or another workplace hazard, contact our Health Hazard Evaluation Program and request to have your work environment assessed for free. For more details and to fill out a request, visit the NIOSH Health Hazard Evaluation website.

· Learn what your employer can do to help keep you safe.

· Find more information and resources related to o-toluidine.

New Substances Added To List Of Carcinogens

Four new substances have been added to a list of chemicals that may cause cancer compiled by the U.S. Department of Health and Human Services (HHS).

The list of known carcinogens now includes a chemical called ortho-toluidine, which is used to make rubber chemicals, pesticides and dyes. Recent research has linked the substance to bladder cancer in people.

Three other substances were added to a list of agents that are "reasonably anticipated to be human carcinogens." These include a cleaning solvent called 1-bromopropane, a wood preservative mixture known as pentachlorophenol and cumene, which can be found in fuel products and even tobacco smoke. [12 Worst Hormone-Disrupting Chemicals & Their Health Effects]

"Identifying substances in our environment that can make people vulnerable to cancer will help in prevention efforts," Linda Birnbaum, director of the National Institute of Environmental Health Sciences and the National Toxicology Program, said in a statement. "This report provides a valuable resource for health regulatory and research agencies, and it empowers the public with information people can use to reduce exposure to cancer-causing substances."

Ortho-toluidine was originally classed as "reasonably anticipated" to be a human carcinogen in 1983. But HHS scientists re-evaluated the substance, looking at three studies of dye workers and two studies of rubber-chemical workers who were regularly exposed to ortho-toluidine. They found enough evidence of a link between ortho-toluidine exposure and an increased risk of bladder cancer to call the chemical a known carcinogen, according to HHS. Rats also developed bladder tumors after they ingested ortho-toluidine.

Ortho-toluidine is no longer produced in the United States, but at least 1 million lbs. (450,000 kilograms) of the substance is imported into the country each year, according to HHS. The people who have the greatest risk of exposure are employees who work in chemical plants where ortho-toluidine is used to make rubber chemicals, dyes and pesticides.

HHS officials said they didn't have enough evidence to definitively prove that exposure to the other three chemicals can cause human cancers. But these substances do cause rats and mice to develop tumors, according to the agency.

In experiments, rodents that inhaled fumes of 1-bromopropane — a colorless to light yellow liquid solvent — developed tumors in several organs, including their skin, lungs and large intestine. The substance is used as a cleaner for optics, electronics and metals. It has also become popular in dry cleaning as a replacement for perchloroethylene, another chemical considered a health and environmental hazard.

Mice that inhaled cumene fumes developed lung tumors and liver tumors, according to HHS's review. The flammable liquid with a gasoline-like odor is found in coal tar and petroleum, as well as tobacco smoke. It is used primarily to make acetone and phenol.

Pentachlorophenol — a substance used to treat utility poles, wood pilings and fence posts — caused tumors in the liver and other organs of mice. In small studies of humans, exposure to this compound was associated with an increased risk of the blood cancer non-Hodgkin lymphoma, but the HHS said it considered the evidence too limited to call pentachlorophenol a known carcinogen.

The HHS's 13th Report on Carcinogens, which now includes 243 listings total, is available online: http://ntp.niehs.nih.gov/pubhealth/roc/roc13/index.html

High bladder cancer rate shrouds New York plant, exposing chemical hazards in the workplace

The Goodyear chemical plant in Niagara Falls, N.Y., has been plagued for decades by high rates of bladder cancer within its workforce. Federal health investigators blame a chemical called ortho-toluidine, used in a tire antioxidant.

NIAGARA FALLS, N.Y. — Ray Kline, it’s said, bled Goodyear blue.

Compact and laconic, Kline signed on as an operator at the Goodyear chemical plant here in 1960 and logged just short of 40 years. He routinely worked six days a week, 12 hours a day, retiring in 1999 as head of maintenance.

“I made a good living,” Kline said in the dining room of his comfortable home in Lewiston, N.Y., two blocks from the Niagara River — betraying little bitterness over the price his family paid for economic stability.

Kline, 75, has endured two bouts of bladder cancer. Strong evidence suggests the disease was work-related.

In a yet-to-be published study, federal health investigators have confirmed 50 cases of bladder cancer among plant employees through 2007, nearly three times the number that would have been expected in the general population of New York State. The unofficial tally to date, compiled by a lawyer for some of the cancer victims, is 58 cases.

The likely trigger in most instances, investigators concluded, was a chemical, still used by Goodyear and others, called ortho-toluidine.

The disease made its appearance in 1972 and continues to plague this decaying pocket of western New York. Workers at the 67-year-old plant, a collegial place that sustained generations, called it “the ginch.” Those who survived it fear its return. Those who avoided it wonder when their luck will run out. Many question why the chemical’s most prominent manufacturer, DuPont, took so long to issue warnings.

The long-running episode underscores the limits of regulation and points up the insidious nature of occupational illnesses, which by one estimate take more than 50,000 lives in America each year.

It’s a cautionary tale at a time when more than 80,000 chemicals, many carrying unknown or little-understood health effects, are on the market in the United States. Workers can become unwitting test subjects, made vulnerable by employers that fail to act on scientific knowledge or, in extreme cases, suppress the truth.

Three years before Kline landed at Goodyear, the plant began making Nailax, an antioxidant that keeps tires from cracking. Three U.S. companies supplied a key ingredient, ortho-toluidine, at various times from the 1950s into the 1990s; DuPont supplied Goodyear for the longest period, almost four decades.

By 1955, records show, DuPont knew the chemical caused bladder cancer in laboratory animals and protected its own workers from it. But it didn’t issue warnings to Goodyear and other customers until 1977, the year Kline’s son-in-law, Harry Weist, started at the Niagara Falls plant.

It would be another 13 years before Goodyear would take significant steps to reduce exposures to ortho-toluidine in the plant. By then, the outbreak of bladder cancer was under way.

Kline was case No. 21, diagnosed in 1997. Weist was No. 37, diagnosed in 2004.

“None of us are simple-minded,” said Weist, 57, who worked at the plant for 34 years. “If we knew this stuff was bad and we were getting exposed to it back in the day, we would have protected ourselves.”

In a statement to the Center for Public Integrity, Goodyear said it “takes the issue of ortho-toluidine exposure at the Niagara Falls plant very seriously. We are deeply concerned and continue to be committed to actions to address the issue.”

DuPont said it “conducts its business in accordance with the highest ethical standards and in compliance with all applicable laws to ensure the safety and health of our employees, our customers, and the people of the communities in which we operate. Our experience with ortho-toluidine was no exception.”

Its communications about the chemical were, DuPont said, “commensurate with the state of scientific knowledge” at the time.

Steve Wodka, a lawyer in Little Silver, N.J., maintains DuPont could have told Goodyear how to use ortho-toluidine safely by 1957, when Goodyear’s rubber chemicals division opened in Niagara Falls.

“There were so many warning signals,” said Wodka, who has sued DuPont and other ortho-toluidine suppliers on behalf of 24 bladder cancer victims from Goodyear and three from the now-shuttered Morton International chemical plant in Paterson, N.J. “If people had simply heeded them, there would have been a lot of lives saved.”

The disease cluster “wouldn’t have been detected by the medical community” had the Oil, Chemical and Atomic Workers union not pushed for a federal investigation at Goodyear, Wodka said. “It would have just blended into the background.”

Bladder cancer incidence among workers exposed to o-toluidine, aniline and nitrobenzene at a rubber chemical manufacturing plant

1. Tania Carreón1,

2. Misty J Hein1,

3. Kevin W Hanley1,

4. Susan M Viet2,

5. Avima M Ruder1

+ Author Affiliations

1. ¹Division of Surveillance, Hazard Evaluations and Field Studies, National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA

2. ²Westat, Rockville, Maryland, USA

1. Correspondence to Dr Tania Carreón, National Institute for Occupational Safety and Health, 4676 Columbia Pkwy, Mailstop R-15, Cincinnati, OH 45226, USA; tjc5@cdc.gov

· Received 19 September 2013

· Revised 3 December 2013

· Accepted 5 December 2013

· Published Online First 24 December 2013

Abstract

Background An earlier investigation found increased bladder cancer incidence among workers at a rubber chemical manufacturing plant that used o-toluidine, aniline and nitrobenzene. The cohort was expanded to include additional workers (n=1875) and updated through 2007 to assess bladder cancer with improved exposure characterisation.

Methods Work histories were updated and exposure categories and ranks were developed for o-toluidine, aniline and nitrobenzene combined. Incident cancers were identified by linkage to six state cancer registries. Residency in time-dependent cancer registry catchment areas was determined. SIR and standardised rate ratios for bladder cancer were calculated by exposure category and cumulative rank quartiles for different lag periods. Cox regression was used to model bladder cancer incidence with estimated cumulative rank, adjusting for confounders. Indirect methods were used to control for smoking.

Results Excess bladder cancer was observed compared to the New York State population (SIR=2.87, 95% CI 2.02 to 3.96), with higher elevations among workers definitely exposed (moderate/high) (SIR=3.90, 95% CI 2.57 to 5.68), and in the highest cumulative rank quartile (SIR=6.13, 95% CI 2.80 to 11.6, 10-year lag). Bladder cancer rates increased significantly with estimated cumulative rank (10-year lag). Smoking only accounted for an estimated 8% elevation in bladder cancer incidence.

Conclusions Bladder cancer incidence remains elevated in this cohort and significantly associated with estimated cumulative exposure. Results are consistent with earlier findings in this and other cohorts. Despite other concurrent chemical exposures, we consider o-toluidine most likely responsible for the bladder cancer incidence elevation and recommend a re-examination of occupational exposure limits.