REACH’s Looming Deadline
Safety Assessment
Regina Kelder

REACH’s Looming Deadline

It’s been 11 years since the EU passed legislation requiring companies to register their use of chemicals by 2018. How’s that working? Day Two of our SOT coverage.

It’s been 11 years since the European Community passed REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), a massive piece of legislation that is requiring companies to register their use of 30,000 chemicals by 2018 in the European Chemicals Agency (ECHA) in Finland.

How’s that working? REACH was designed to get industries to assess and manage the risks posed by chemicals, but companies have known for a while now that compliance is not that simple, and that other countries—from the US which  recently updated its Toxic Substances Control Act (TSCA) to China and Japan—need to be considered in the context of REACH.

How REACH fits into the wider world of chemical regulation and the push toward green chemistry was the focus of an exhibitor’s session at the Society of Toxicology chaired by Jeannette Paulussen, who heads up the Regulatory Affairs Department at Charles River’s Den Bosch facility in the Netherlands. Paulussen was joined by Dan Newton, Senior Manager of Government Relations for the Society of Chemical Manufacturers and Affiliates, where he primarily analyzes and advocates on legislative regulatory affairs related to chemical management policies, primarily the TSCA. 

While consumers may be able to learn the dangers of the chemicals they use, Paulussen said companies have struggled to adjust to the demands and costs of analyzing and characterizing chemical compositions, and to embrace alternatives to animals for tests that guide the labeling of thousands of consumer products ranging from anti-freeze to flame-retardant materials.                                          

Paulussen said taking a more global approach in designing REACH can help companies. Identifying areas of efficiency, such as grouping substances that can be tested together, using Q(SAR) models to help identify where the toxicity might occur, using existing data for analogue substances and developing a testing strategy that accounts for registration in other markets not covered by REACH are all approaches that can help make the process more cost-effective. Contract research organizations have the in-house skills to help companies meet REACH compliance.

Companies in the US are also adjusting to significant changes in regulations. Last year, in a rare moment of harmony, the US Congress to undertake the biggest overhaul of the TSCA in 40 years. The amended legislation requires new testing and regulation of thousands of chemicals used in everyday products.

How things will progress under the Trump administration is unclear, says Newton. The number of manufacturing requests to make new chemicals has doubled, mostly caused by an amendment in TSCA. While Scott Pruitt, the new administrator of the Environmental Protection Agency, adheres to positions that run counter to the EPA’s—he does not agree, for instance, that human activity is contributing to global warming’s and opposes the EPA’s 2015 reduction of the national ozone standard—he has been supportive of the TSCA and how to meet the statutory deadlines for issuing the rules.

Dengue Fever Vaccine & Pregnancy

Fifteen months ago, Mexico, the Philippines and Brazil approved Dengvaxia®, the world’s first vaccine against dengue fever, a virus spread by Aedes aegypti mosquitoes. It was a truly landmark moment in vaccine history. Dengue infects 390 million people worldwide, it kills, and scientists had struggled for years to find a vaccine that would help control vulnerable populations caught in the crosshairs of dengue’s four and possibly five strains.

Today 14 countries in tropical regions of Asia and South America have green-lighted Dengvaxia—also referred to as CYD-DVD—for the prevention of dengue. But the vaccine is not recommended for everyone. In various clinical trials in children ages 2-16, the vaccine seemed to be least effective in children younger than 9, particularly those under 6, which is why the vaccine is only indicated for ages 9-45. The vaccine also works better for some subtypes of dengue than others.

The vaccine is also contraindicated in pregnant and lactating women, due to the fact that insufficient data has been gathered during pregnancy. However, limited data generated from inadvertent pregnancies that occurred during clinical trials suggests the vaccine is safe and a recent developmental and reproductive toxicology (DART) study in rabbits and mice seems to support this observation. A poster presented Monday at SOT by Guillaume Ravel, a scientist with Sanofi Pasteur, the developer of Dengaxia, found that maternal toxicity “would not be the expected outcome in women of childbearing potential given a human dose of dengue vaccine.”

The study, which included Elise Lewis, Charles River’s Director of Reproductive and Neurobehavioral Toxicology in Horsham, Pa., examined the impact of the dengue vaccine on both rabbits and mice. In one study, scientists measured the effects of exposure to the vaccine and the antibody response throughout pre-implantation, embryonic, fetal and early post-natal periods in 20 vaccinated rabbits  and compared them to matched controls. In the mouse study, scientists looked at the effects of exposure to the virus throughout embryonic, fetal periods and during lactation.

Rabbits were used in the study to investigate the effects of exposure to repeated injections of the dengue vaccine. Mice were used to investigate the effects of exposure to the virus.

The study found no adverse effects in mating performance and fertility in vaccinated rabbits, and no teratogenic (birth defect) potential or effect on pre- and post-natal development in either mice or rabbits.

Ravel, who has been working on dengue vaccines for about a decade, said there are many more countries grappling with dengue outbreaks that haven’t approved the vaccine yet, including the US where Hawaii saw its first outbreak in several decades. Future improvements to Dengvaxia, a live-attenuated tetravalent vaccine, might mean more countries and more people could be protected.