Nominations Reviewed 2000

http://ntp.niehs.nih.gov/go/21197

Substances Recommended for Study:

Aluminum complexes
Bilberry fruit extract
Black cohosh
Blue-Green algae (dietary supplements)
Cefuroxime
Clarithromycin
D&C Red No. 27 and D&C Red No. 28
N,N-Dimethyl-p-toluidine
Lemon Oil and Lime Oil
Local anesthetics that metabolize to 2,6-xylidine or o-toluidine
Microcystin-LR
Organotins occurring in drinking water
All-trans-retinyl palmitate
S-Adenosylmethionine
Senna

Substances for Which No Study is Recommended at this Time:

Dichloropropane & Dichloropropene
- 1,3-Dichloropropane
- 2,2-Dichloropropane
- 1,1-Dichloropropane
Hydergine
Yohimbe bark extract/Yohimbine

Chemicals studied by the NTP are selected mainly on the basis of human exposure, production levels, chemical structure, and available toxicological data. Selection of an agent for a study does not imply that the agent is hazardous or a potential carcinogen in laboratory animals; likewise, an agent not selected for toxicologic study by the Program should not be taken to mean that the agent is not potentially hazardous or potentially carcinogenic in laboratory rodents. Substances are identified by a common or generic name and CAS Registry No. where appropriate.

For information, questions or comments, contact:
Dr. Scott A. Masten
Office of Chemical Nomination and Selection
Environmental Toxicology Program
National Institute of Environmental Health Sciences

P.O. Box 12233, MD A3-07
111 T.W. Alexander Drive
Research Triangle Park, NC
(919) 541-5710 (voice)
(919) 541-3647 (fax)

[Send Email]

Aluminum Complexes found in drinking water
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Aluminum Complexes found in drinking water Aluminum fluoride [7784-18-1] Aluminum citrate [31142-56-0]	Environmental Protection Agency National Institute of Environmental Health Sciences	Drinking water contaminants with a high health research priority; known neurotoxicity of aluminum; need for better understanding of pharmacokinetics and toxicity of aluminum species occurring in drinking water	Long-term drinking water studies to address pharmacokinetics, neurotoxicity, bone development, and reproductive and developmental toxicity Consider testing in transgenic animal models of neurodegenerative disease

Bilberry fruit extract
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Bilberry fruit extract [84082-34-8]	National Cancer Institute	widespread human exposure through use as a dietary supplement lack of toxicity information	In vitro and in vivo genotoxicity testing

Black Cohosh
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Black cohosh [84776-26-1]	National Cancer Institute National Institute of Environmental Health Sciences	widespread human exposure through use as a dietary supplement reported estrogenic activity inadequate toxicity information	subchronic toxicity testing in young and aged female animals Two-generation reproductive and developmental toxicity study

Blue-Green algae (dietary supplements and selected toxins)
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Blue-Green algae (dietary supplements and selected toxins) [No CAS No.]	National Cancer Institute	widespread human exposure through drinking water and via contamination of algal dietary supplements demonstrated acute toxicity but only limited chronic toxicity information available	subchronic toxicity and neurotoxicity studies of commercial blue-green algae dietary supplements consider testing specific cyanobacterial toxins pending results of Blue-Green algae dietary supplement and microcystin-LR studies

Cefuroxime
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Cefuroxime [55268-75-2]	Food and Drug Administration	prescription drug with widespread and potentially long-term use lack of chronic toxicity data for any member of this class of drugs	genotoxicity testing (Syrian hamster embryo in vitro cell transformation assay in vivo micronucleus assay)

Clarithromycin
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Clarithromycin [81103-11-9]	Food and Drug Administration	prescription drug with widespread and potentially long-term use numerous known toxicities in short-term studies lack of chronic toxicity data	Genotoxicity testing (Syrian hamster embryo in vitro cell transformation assay; in vivo micronucleus assay)

D&C Red No. 27 and D&C Red No. 28
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
D&C Red No. 27 and D&C Red No. 28 [13473-26-2],[18472-87-2]	Food and Drug Administration	approved colorings for drugs and cosmetics that can lead to DNA damage lack of sufficient data on long-term phototoxicity or photocarcinogenicity	in vitro percutaneous absorption testing Photocarcinogenicity testing dependent on results of absorption studies

N,N-Dimethyl-p-toluidine
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
N,N-Dimethyl-p-toluidine [99-97-8]	National Cancer Institute	high production volume chemical with potential for widespread human exposure and limited chronic toxicity or carcinogenicity data genotoxic suspicion of carcinogenicity	Subchronic toxicity testing pending review of industry test plans and/or data developed under EPA's High Production Volume Chemical Challenge Program

Lemon Oil and Lime Oil
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Lemon Oil and Lime Oil [8008-56-8],[8008-26-2]	Food and Drug Administration	widespread consumer exposure as a fragrance component known phototoxicity long-term toxicity unknown	photogenotoxicity testing photocarcinogenicity testing dependent on results of phototogenotoxicity studies

Local anesthetics that metabolize to 2,6-xylidine or o-toluidine
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Local anesthetics that metabolize to 2,6-xylidine or o-toluidine Bupivacaine [38396-39-3] Prilocaine [721-50-6]	Private Individual National Institute of Environmental Health Sciences	widespread clinical use and human exposure potentially metabolized to carcinogenic and neurotoxic intermediates little available quantitative metabolism or genotoxicity data	Short-term in vitro/in vivo mechanistic studies to evaluate carcinogenic metabolite formation and genotoxicity of representative local anesthetic compounds

Microcystin-LR
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Microcystin-LR [101043-37-2]	National Institute of Environmental Health Sciences	cyanobacteria and their toxins are drinking water contaminants with a high health research priority many have high acute toxicity and known hepatotoxicity and hepatocarcinogenicity	Toxicokinetic, subchronic, reproductive toxicity, chronic toxicity and carcinogenicity studies including doses relevant to environmental concentrations in drinking water Consider carcinogenicity testing in Japanese Medaka fish model

Organotins occurring in drinking water
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Organotins occurring in drinking water Monomethyltin trichloride [993-16-8] Dimethyltin dichloride [753-73-1] Monobutyltin trichloride [1118-46-3] Dibutyltin dichloride [683-18-1]	Environmental Protection Agency; National Institute of Environmental Health Sciences	drinking water contaminants with a high health research priority numerous organotins have demonstrated a broad spectrum of toxicity chronic toxicity information on organotin species primarily found in drinking water is limited	Long-term single chemical and binary mixture drinking water studies to address pharmacokinetics, neurotoxicity, immunotoxicity, and reproductive and developmental toxicity Consider testing in transgenic animal models of neurodegenerative disease

All-*trans*-retinyl palmitate
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
All-trans-retinyl palmitate [79-81-2]	Food and Drug Administration	widespread use in cosmetic products known biochemical and histological cutaneous alterations other retinoids known to enhance photocarcinogenesis	Phototoxicity and photocarcinogenicity testing

S-Adenosylmethionine
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
S-Adenosylmethionine [29908-03-0]	National Cancer Institute	widespread exogenous human exposure through use as a dietary supplement limited toxicity data available	In vitro genotoxicity testing (Syrian hamster embryo cell transformation and DNA alkylation assays) Subchronic toxicity testing dependent on results of genotoxicity studies

Senna
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Preliminary Study Recommendations
Senna [8013-11-4]	Food and Drug Administration	data needed to complete safety evaluation of stimulant laxatives transgenic studies will complement manufacturer sponsored carcinogenicity studies	Carcinogenicity testing in p53 transgenic mouse model

Dichloropropane & Dichloropropene
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Additional Information Needed
Dichloropropane & Dichloropropene 1,3-Dichloropropane [142-28-9] 2,2-Dichloropropane [594-20-7] 1,1-Dichloropropene [563-58-6]	Environmental Protection Agency; National Institute of Environmental Health Sciences	drinking water contaminants with high health research priority very limited toxicity data known toxicity and carcinogenicity of structurally similar compounds	Additional drinking water occurrence data production volumes potential sources of drinking water contamination anticipated regulatory value of additional toxicity data

Hydergine
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Additional Information Needed
Hydergine [8067-24-1]	National Cancer Institute	ergot alkaloid prescription drug with recent increase in "off label" and dietary supplement use in healthy individuals lack of availableinformation on toxicity and carcinogenicity	dietary supplement sales and use information regulatory agency information needs

Yohimbe bark extract/Yohimbine
Substance [CAS No.]	Nominated by	Nomination Rationale (Principles)	Additional Information Needed
Yohimbe bark extract/Yohimbine [85117-22-2],[146-48-5]	National Cancer Institute	significant human exposure through use as a dietary supplement suspicion of carcinogenicity of yohimbine based on structural similarity to reserpine	dietary supplement use levels and patterns regulatory agency information needs

Web page last updated on September 23, 2008