National Toxicology Program

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

Regulatory Actions for Year 2014




Agency for Toxic Substances and Disease Registry (ATSDR)

Notice Type Title Summary of Notice NTP Information Cited CASRN
Notice Prohibition of Children’s Toys and Child Care Articles Containing Specific Phthalates Section 108 of the Consumer Product Safety Improvement Act of 2008 (CPSIA), requires the United States Consumer Product Safety Commission (Commission or CPSC) to convene a Chronic Hazard Advisory Panel (CHAP) to study the effects on children’s health of all phthalates and phthalate alternatives as used in children’s toys and child care articles and to provide recommendations to the Commission regarding whether any phthalates or phthalate alternatives other than those already permanently prohibited should be prohibited. The CPSIA requires the Commission to promulgate a final rule after receiving the final CHAP report. The Commission is proposing this rule pursuant to section 108(b) of the CPSIA. The Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA), § 104(i)(3),[42 U.S.C. 9604(i)(3)], directs the ATSDR administrator to prepare Toxicological Profiles of priority hazardous substances and, as necessary, to revise and publish each updated toxicological profile.

December 30, 2014 -- 79 FR 78324
‘‘Review all relevant data, including the most recent, best-available, peer reviewed, scientific studies of these phthalates and phthalate alternatives that employ objective data collection practices or employ other objective methods.’’ The CHAP reviewed all of the available data on phthalates, including publications in peer-reviewed scientific journals; reports submitted by manufacturers to the U.S. EPA; 10 and authoritative reviews from agencies such as the Agency for Toxic Substances and Disease Registry (ATSDR), the European Chemical Agency (ECHA), the International Agency for Research on Cancer (IARC), Center for the Evaluation of Research on Human Reproduction (CERHR), National Toxicology Program (NTP); and the National Research Council (NRC). (CHAP, 2014, p. 12). In addition, the CHAP invited scientific experts to present their latest research in areas such as biomonitoring, epidemiology, phthalate syndrome, toxicology of phthalates mixtures, phthalates mode of action, and species differences. The CHAP also invited a coauthor of an NRC report (NRC, 2009) to present the NRC panel’s perspective on risk assessment methodology, especially as applied to phthalates risk assessment. Furthermore, the CHAP heard testimony from federal agency scientists, as well as scientists representing manufacturers of phthalates alternatives.
Notice Availability of Draft Toxicological Profiles This notice announces the availability of Set 26 Toxicological Profiles for review and comment. Comments can include additional information or reports on studies about the health effects of Set 26 substances. Although ATSDR considered key studies for each of these substances during the profile development process, this Federal Register notice solicits any relevant, additional studies, particularly unpublished data. ATSDR will evaluate the quality and relevance of such data or studies for possible inclusion into the profile. ATSDR remains committed to providing a public comment period for this document as a means to best serve public health and our clients. The Set 26 Toxicological Profiles are available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp and http://www.regulations.gov/#!home, docket ATSDR–2014–0001. The Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA), as amended by the Superfund Amendments and Reauthorization Act of 1986 (SARA), § 104(i)(3),[42 U.S.C. 9604(i)(3)], directs the ATSDR administrator to prepare Toxicological Profiles of priority hazardous substances and, as necessary, to revise and publish each updated toxicological profile.

December 15, 2014 -- 79 FR 74093

Each profile will include an examination, a summary, and an interpretation of available toxicological information and epidemiological evaluations. This information and these data identify the levels of significant human exposure for the substance and for the associated health effects. The profiles must also include a determination of whether adequate information on the health effects of each substance is available (or in the process of development) in order to identify levels of significant human exposure. If adequate information is not available, ATSDR, in cooperation with the National Toxicology Program (NTP), is required to ensure the initiation of a program of research to provide such information. 

79-01-6
127-18-4
7783-06-4
463-58-1
56-38-2

Back to Top




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

Back to Top




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
64-19-7
107-92-6
71-36-3
5392-40-5
106-22-9
150-84-5
23726-92-3
112-31-2
65405-70-1
334-48-5
112-30-1
106-72-9
20407-84-5
452-79-1
106-24-1
105-87-3
111-71-7
111-14-8
111-70-6
66-25-1
142-62-1
111-27-3
828-96-1
3681-71-8
142.92-7
111-27-3
143-07-7
112-54-9 112-53-8
5989-27-5
127-42-4
1191-16-8
110-41-8
124-25-4
544-63-8
141-12-8
124-19-6
112-05-0
143-08-8
124-13-0
124-07-2
111-87-5
57-10-3
79-09-4
57-11-4
7774-82-5
5435-64-3
112-44-7
112-42-5
110-62-3
109-52-4
Supplemental Proposed Rulemaking National Emissions Standards for Hazardous Air Pollutants: Primary Aluminum Reduction Plants This action supplements our proposed amendments to the national emission standards for hazardous air pollutants (NESHAP) for the Primary Aluminum Production source category published in the Federal Register on December 6, 2011. In that action, the Environmental Protection Agency (EPA) proposed amendments based on the initial residual risk and technology reviews (RTR) for this source category, and also proposed certain emission limits reflecting performance of Maximum Achievable Control Technology (MACT). Today’s action reflects a revised technology review and a revised residual risk analysis for the Primary Aluminum Production source category and proposes new and revised emission standards based on those analyses, newly obtained emissions test data, and comments we received in response to the 2011 proposal, including certain revisions to the technology-based standards reflecting performance of MACT. This action also proposes new compliance requirements to meet the revised standards. This action, if adopted, will provide improved environmental protection regarding potential emissions of hazardous air pollutant (HAP) emissions from primary aluminum production facilities.

December 08, 2014 -- 79 FR 72922

National Toxicology Program (NTP), 2011. Report on Carcinogens. 12th ed. Research Triangle Park, NC: US Department of Health and Human Services (DHHS), Public Health Service. Available online at http://ntp.niehs.nih.gov/ntp/roc/twelfth/roc12.pdf

Based on consistent views of major scientific bodies (i.e., National Toxicology Program (NTP) in their 12th Report of the Carcinogens (ROC), 7 International Agency for Research on Cancer (IARC) 8 and other international agencies) 9 that consider all Ni compounds to be carcinogenic, we currently consider all Ni compounds to have the potential of being carcinogenic to humans. The 12th Report of the Carcinogens states that the ‘‘combined results of epidemiological studies, mechanistic studies, and carcinogenic studies in rodents support the concept that Ni compounds generate Ni ions in target cells at sites critical for carcinogenesis, thus allowing consideration and evaluation of these compounds as a single group.’’  Although the precise Ni compound (or compounds) responsible for the= carcinogenic effects in humans is not always clear, studies indicate that Ni sulfate and the combinations of Ni sulfides and oxides encountered in the Ni refining industries cause cancer in humans (these studies are summarized in a review by Grimsrud et al., 2010 10). The major scientific bodies mentioned above have also recognized that there are differences in toxicity and/or carcinogenic potential across the different Ni compounds.

Back to Top




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.
Notice Information Collection; Qualified Products Lists for Fire Chemicals for Wild Land Fire Management In accordance with the Paperwork Reduction Act of 1995, the Forest Service is seeking comments from all interested individuals and organizations on the extension with no revision of a currently approved information collection, Qualified Products Lists for Fire Chemicals for Wild Land Fire Management.

November 14, 2014 -- 79 FR 68210

SUPPLEMENTARY INFORMATION:

Title: Qualified Products Lists for Fire Chemicals for Wild Land Fire Management. OMB Number: 0596–0182. Expiration Date of Approval: January 31, 2015. Type of Request: Extension with no revision.

• National Toxicology Program (NTP) ‘‘Annual Report on Carcinogens’’.

Back to Top




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.

Back to Top

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