National Toxicology Program

National Toxicology Program
http://ntp.niehs.nih.gov/go/regact

Regulatory Actions for Year 2014




California Office of Environmental Health Hazard Assessment (OEHHA)

Notice Type Title Summary of Notice NTP Information Cited CASRN
Notice Chemical Listed Effective May 2, 2014 as Known to the State Of California to Cause Cancer: N,N-dimethyl-p-toluidine Effective May 2, 2014, the Office of Environmental Health Hazard Assessment (OEHHA) is adding N,N-dimethyl-p-toluidine to the list of chemicals known to the State to cause cancer for purposes of Proposition 65.

May 02, 2014 -- Proposition 65
NTP (2012). National Toxicology Program. Toxicology and Carcinogenesis Studies of N,N-Dimethyl-p-Toluidine (CAS No. 99-97-8) in F344/N Rats and B6C3F1/N Mice (Gavage Studies). Technical Report Series No. 579. NIH Publication No. 12-5921. U.S. Department of Health and Human Services, NTP, Research Triangle Park, NC. 99-97-8
Notice Intent To List: Ethylene Glycol The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list the chemical ethylene glycol (EG) as known to the state to cause reproductive toxicity (developmental endpoint) under the Safe Drinking Water and Toxic Enforcement Act of 1986.1 This action is being proposed under the authoritative bodies listing mechanism.

April 11, 2014 -- Proposition 65
NTP-CERHR (2004). NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol. Research Triangle Park, NC, National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction: NIH Publication No. 04 – 4481. 107–21–1
Notice Comments Received on the Notice of Intent to List for Ethylene Glycol The California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) intends to list the chemical ethylene glycol (EG) as known to the state to cause reproductive toxicity (developmental endpoint) under the Safe Drinking Water and Toxic Enforcement Act of 1986. This action is being proposed under the authoritative bodies listing mechanism

July 01, 2014 -- Proposition 65
NTP-CERHR (2004). NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Ethylene Glycol. Research Triangle Park, NC, National Toxicology Program, Center for the Evaluation of Risks to Human Reproduction: NIH Publication No. 04 – 4481.
107-21-1
107-21-1
Notice Notice of Adoption of Reference Exposure Levels for Benzene The Office of Environmental Health Hazard Assessment (OEHHA) is adopting new and revised Reference Exposure Levels (RELs) for benzene.

June 27, 2014 -- Proposition 65
The National Toxicology Program (NTP, 1986) conducted a chronic (2 year) toxicity
“bioassay” in F344 rats and B6C3F1 mice of benzene by gavage in corn oil. Doses
were 0, 25, 50, and 100 mg/kg-day for females and 0, 50, 100, and 200 mg/kg-day for males. Dose-related lymphocytopenia and leukocytopenia were observed in both
species in all dosed groups. Mice exhibited lymphoid depletion of the thymus and
spleen and hyperplasia of the bone marrow.
71-43-2
Comment Notice of Public Comment Period and Workshops on Draft Reference Exposure Levels for Carbonyl Sulfide The Office of Environmental Health Hazard Assessment (OEHHA) is releasing for public review a draft document on the toxicity and derivation of Reference Exposure Levels (RELs) for Carbonyl Sulfide (COS).

October 17, 2014 -- Proposition 65

The National Toxicology Program (NTP) studied 4 strains of mutant Salmonella (TA97, TA98, TA100, and TA1535) in the Ames test and used from 0.58 to 2.89 µg COS per test plate with and without induced liver extract from rats or hamsters. They reported a weakly positive response based on positive results in one strain (TA97) (NTP, 1995).

NTP. (1995). Genetic Toxicology - Bacterial Mutagenicity. NTP Study ID: A35125.  CEBS Accession Number: 002-01834-0001-0000-9 from http://tools.niehs.nih.gov/cebs3/ntpViews/?studyNumber=A35125.

463-58-1
Notice Request for Relevant Information on the Carcinogenic Hazards of Diaminotoluenes In order to clarify the scope of the listing, OEHHA is referring diaminotoluene (mixed) to the CIC for a determination as to whether the chemical should continue to be included on the list of chemicals known to the state to cause cancer pursuant to Title 27, Cal. Code of Regs., section 25306 (j).

October 23, 2014 -- Proposition 65

Under the Safe Drinking Yater and Toxic Enforcement Act of 1986 [Health and Safety Code Section 25249.8(b)], one of the ways a chemical is known to the State to cause cancer or reproductive toxicity is if a body considered to be authoritative by the Scientific Advisory Panel has formally identified it as causing cancer or reproductive toxicity. The Heald1 and Welfare Agency has adopted a regulation to guide this part of the implementation of the Act  (Title 22, California Code of Regulations, Section 12306).  The Panel has identified the U.S. Environmental Protection Agency (EPA), the International Agency for Research on Cancer (ARC), and the National Toxicology Program (NTP) as authoritative bodies, National Toxicology Program, NTP Technical Report on the Toxicology and Carcinogenesis Studies of Two Pentachlorophenol Technical-Grade Mixtures in B6C3Fl Mice, NTP TR 349, NIH Publication No. 89•2804,  March, 1989.

2687-25-4
95-70-5
823-40-5
496-72-0
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Environmental Protection Agency (EPA)

Notice Type Title Summary of Notice NTP Information Cited CASRN
Final Rule Control of Air Pollution From Motor Vehicles: Tier 3 Motor Vehicle Emission and Fuel Standards This action establishes more stringent vehicle emissions standards and will reduce the sulfur content of gasoline beginning in 2017, as part of a systems approach to addressing the impacts of motor vehicles and fuels on air quality and public health. The gasoline sulfur standard will make emission control systems more effective for both existing and new vehicles, and will enable more stringent vehicle emissions standards. The vehicle standards will reduce both tailpipe and evaporative emissions from passenger cars, light-duty trucks, medium-duty passenger vehicles, and some heavy-duty vehicles. This will result in significant reductions in pollutants such as ozone, particulate matter, and air toxics across the country and help state and local agencies in their efforts to attain and maintain health-based National Ambient Air Quality Standards. Motor vehicles are an important source of exposure to air pollution both regionally and near roads. These vehicle standards are intended to harmonize with California's Low Emission Vehicle program, thus creating a federal vehicle emissions program that will allow automakers to sell the same vehicles in all 50 states. The vehicle standards will be implemented over the same timeframe as the greenhouse gas/fuel efficiency standards for light-duty vehicles (promulgated by EPA and the National Highway Safety Administration in 2012), as part of a comprehensive approach toward regulating emissions from motor vehicles.

April 28, 2014 -- 79 FR 23414
In the National Toxicology Program’s Report on Carcinogens (ROC), the following compounds have been listed as: a) known carcinogens to humans: benzene, 1,3-butadiene, formaldehyde; b) possibly carcinogenic to humans: acetaldehyde; or c) reasonably anticipated to be a human carcinogen: naphthalene. 71-43-2
106-99-0
75-07-0
91-20-3
50-00-0
Final Rule Diflubenzuron; Pesticide Tolerances This regulation establishes tolerances for residues of diflubenzuron (N-[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzimide) in or on fruit, citrus, group 10-10 and citrus, oil. Chemtura Corporation, requested these tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

January 31, 2014 -- 79 FR 5294
para-chloroaniline hydrochloride (PCA), a plant metabolite of diflubenzuron, tested positive for splenic tumors in male rats and hepatocellular adenomas/carcinomas in male mice. TR-351, 1989). 20265-96-7
Proposed Rule Fragrance Components; Proposed Exemption From the Requirement of a Tolerance This document proposes to establishes an exemption from the requirement of a tolerance for residues of various fragrance component substances (when used as inert ingredients) in antimicrobial pesticide formulations for use on food contact surfaces in public eating places, dairy processing equipment, and food processing equipment and utensils

July 25, 2014 -- 79 FR 43350
The derivation of TTC human exposure threshold values for non-cancer endpoints is based on an extensive reference database compiled by Munro, (Ref. 1) which included data on chronic, subchronic, reproductive and developmental toxicity studies primarily derived from the reports of the US National Toxicology Program (NTP), the toxicological monographs of JECFA, the EPA Integrated Risk Information System (IRIS), and the Developmental and Reproductive Toxicology (DART) database compiled by the US National Library of Medicine. These sources were considered to contain well-validated toxicological data for well-defined chemical structures, covering pesticides, food additives, industrial and other types of chemicals. Only studies using the oral route of administration (gavage, diet, drinking water, or capsule) were included. In all, the reference database contained 2941 no-observed-adverse-effect levels (NOAELs) from studies conducted on 613 substances, and from these the most conservative (lowest) NOAEL for each substance was entered on the published database. The NOAELs in the reference database were those selected by the original authors of each study, apart from the studies in the IRIS database, for which the NOAELs were selected by the EPA. Munro commented that some authors were highly conservative in their selection of a NOAEL, but such NOAELs were still used for the database to maintain a conservative approach. Munro also stated that, in the calculation of the TTC values, NOAELs from subchronic studies were divided by a factor of 3 to approximate the NOAELs that are likely to be derived from a chronic study. 75-07-0
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112-54-9 112-53-8
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Food and Drug Administration (FDA)

Notice Type Title Summary of Notice NTP Information Cited CASRN
Proposed Rule Revocation of General Safety Test Regulations That Are Duplicative of Requirements in Biological License Applications The Food and Drug Administration (FDA) is proposing to amend the biologics regulations by removing the general safety test (GST) requirements for biological products. FDA is proposing this action because the existing codified GST regulations are duplicative of requirements that are also specified in biologics licenses, or are no longer necessary or appropriate to help ensure the safety, purity, and potency of licensed biological products. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation, in response to an Executive order.

August 22, 2014 -- 79 FR 49729
Furthermore, we anticipate that the proposal to eliminate the codified GST regulations would encourage the implementation of the principles of the ‘‘3Rs,’’ to reduce, refine, and replace animal use in testing, thus addressing the need to minimize the use of animals in such testing and promoting more humane, appropriate, and specific test methods for assuring the safety of biological products.

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Authorization Act of 2000 (42 U.S.C. 2851–3). Additional information on the Federal Government’s implementation of the principles of the 3Rs may be found at the ICCVAM Web site at http://ntp.niehs.nih.gov/go/iccvam.

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Occupational Safety and Health Administration (OSHA)

Notice Type Title Summary of Notice NTP Information Cited CASRN
Proposed Rule Chemical Management and Permissible Exposure Limits (PELs); Proposed Rule OSHA is reviewing its overall approach to managing chemical exposures in the workplace and seeks stakeholder input about more effective and efficient approaches that addresses challenges found with the current regulatory approach. This review involves considering issues related to updating permissible exposure limits (PELs), as well as examining other strategies that could be implemented to address workplace conditions where workers are exposed to chemicals. The notice details the role of past court decisions on the Agency’s current approach to chemical management for the purpose of informing stakeholders of the legal framework in which the Agency must operate. It then describes possible modifications of existing processes, along with potential new sources of data and alternative approaches the Agency may consider. The Agency is particularly interested in information about how it may take advantage of newer approaches, given its legal requirements. This RFI is concerned primarily with chemicals that cause adverse health effects from long-term occupational exposure, and is not related to activities being conducted under Executive Order 13650, Improving Chemical Facility Safety and Security.

October 10, 2014 -- 79 FR 61384

Question IV.A.3: OSHA is considering greater reliance on peer-reviewed toxicological evaluations by other Federal agencies, such as NIOSH, EPA, ATSDR, NIEHS and NTP for hazard identification and dose-response analysis in the observed range. What advantages and disadvantages would result from this approach and could it be used in support of the PEL update process?

 

4. Use of Systems Biology and Other Emerging Test Data in Risk Assessment Toxicity testing is undergoing transformation from an approach primarily based on pathological outcomes in experimental animal studies to a more predictive paradigm that characterizes critical molecular/cellular perturbations in toxicity pathways using in vitro test systems.  The paradigm shift is being largely driven by the technological advances in molecular systems biology such as the use of high throughput screening (HTS) assays, new computational methods to predict chemical properties, and computer models able to associate molecular events with a biological response. The vision, strategies, and frameworks for applying the new toxicity data to risk-based decision making are laid out in landmark reports by the National Research Council (NRC, 2009; Ex. #24, NRC, 2007; Ex. #25). A collaborative Federal initiative known as ‘‘Tox21’’ has been established between the National Toxicology Program (NTP), the EPA Office of Research and Development, the NIH

Chemical Genomics Center (NCGC), and the Food and Drug Administration (FDA) to collaborate on development, validation, and translation of innovative HTS methods to characterize key steps in toxicity pathways (NTP, 2013; Ex. #40). Tox21 has already screened over a 1000 compounds in more than 50 quantitative HTS assays that have been made available to the scientific community through publically accessible databases (e.g., EPA ACToR, NTP CEBS). EPA has launched a program, known as ‘‘NexGen’’, to implement the NRC vision and advance the next generation of risk assessment (EPA, 2013b; Ex. #41). NexGen is a partnership among EPA, NTP, NCGC, AND FDA, along with ATSDR and California’s EPA Office of Environmental Health Hazard Assessment. The objectives of NexGen are to pilot the new NRC risk assessment framework, refine existing bioinformatics systems, and develop specific prototype health risk assessments. These objectives are expected to be achieved through an iterative development process that includes discussion with scientists, risk managers, and stakeholders

 

#40: National Toxicology Program (NTP). (2013). High Throughput Screening

Initiative. Retrieved from: http://ntp.niehs.nih.gov/go/28213.

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NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.