Exposure-triggered reproductive toxicity testing under the REACH legislation: A proposal to define significant/relevant exposure

Bernauer, Ulrike; Heinemeyer, Gerhard; Heinrich-Hirsch, Barbara; Ulbrich, Beate; Gundert‐Remy, Ursula

doi:10.1016/j.toxlet.2007.10.008

Cited by 42 publications

(34 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moving away from the cancer bioassays, analyzing a reference database of more than 600 substances tested in more than 2,900 sub-chronic and chronic toxicity studies, Munro et al (1990Munro et al ( , 1996Munro et al ( , 1999 Cheeseman et al, 1999;Felter et al, 2009;Müller et al, 2006 General toxicity 0.025 -1 (depending on Cramer classes) Munro et al, 1996Munro et al, , 1999 Munro et al, 1996Munro et al, , 1999Escher et al, 2010;Bernauer et al, 2008Genotoxicity 0.025 -2 Rulis 1986, 1989Kroes et al, 2005;Müller et al, 2006 Carcinogenicity (genotoxic) 0.0025 Kroes et al, 2005;Cheeseman et al, 1999 Carcinogenicity (non-genotoxic) 0.025 -0.75 Kroes et al, 2005; (depending on Ames test and acute toxicity) Cheeseman et al, 1999 Acute toxicity (inhalation) 4 -1,000 μg/m 3 Grant et al, 2007;Escher et al, 2010 Neurotoxicity 0.3 Munro andKroes, 1998;Kroes et al, 2000 Developmental toxicity 1 a -8 -131 Munro and Kroes, 1998; (depending on Cramer class) Bernauer et al, 2008;0.5 -1 μg/m 3 (inhalation) van Ravenzwaay et al, 2011;Laufersweiler et al 2012 Reproductive toxicity 1 -100 Bernauer et al, 2008;van Ravenzwaay et al, 2011van Ravenzwaay et al, , 2012van Ravenzwaay et al, , 2017 Estrogenic endocrine disruption 0.025 Kroes et al, 2000 Immunotoxicity 0.15 -1,000 Kroes et al, 2000;Hartung and Corsini, 2013 Skin sensitization (dermal) 0.91 -900 μg/cm 2 Sa...…”

Section: IImentioning

confidence: 99%

“…Munro et al (1996) used the 5 th percentiles of the lowest NOEL for each substance tested in chronic studies; NOELs of sub-chronic studies were divided by 3; and they then applied an additional assessment factor of 100. Bernauer et al, (2008), in contrast, used the lowest value and applied a safety factor of 100-1,000. The resulting TTC values are given in Table 3.…”

Section: Threshold Setting In Toxicologymentioning

confidence: 99%

“…Analyzing data on 91 chemical substances from the EU existing chemicals program on fertility or developmental toxicity, Bernauer et al (2008) derived TTC values for reproductive toxicity. For oral exposure, 58 NOAEL for fertility and 62 NOAEL for developmental toxicity were found.…”

Section: Threshold Setting In Toxicologymentioning

confidence: 99%

“…A number of studies expanded the concept also to inhalation toxicology as an alternative route of administration (Munro et al, 1996(Munro et al, , 1999Bitsch et al, 2006;Grant et al, 2007;Bernauer et al, 2008;Carthew et al, 2009;Escher et al, 2010;Tluczkiewicz et al, 2011). Recently, Schüürmann et al (2016) derived structural alerts that discriminate between high-and low-toxic compounds for inhalation repeated-dose TTC.…”

Section: Non-cancer Ttcmentioning

confidence: 99%

“…Concern of member states dampened the application of TTC. The Nordic Council of Ministers in 2005 came to the conclusion that application of the TTC principle at the higher tonnage levels within REACH would be premature and raised some concerns, for example that the TTC concept has not been evaluated for the diverse group of industrial chemicals and for different routes of exposure (Bernauer et al, 2008).…”

Section: Ttc For Industrial Chemicalsmentioning

confidence: 99%

See 4 more Smart Citations

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

Hartung

2017

ALTEX

View full text Add to dashboard Cite

Section: IImentioning

confidence: 99%

Section: Threshold Setting In Toxicologymentioning

confidence: 99%

Section: Threshold Setting In Toxicologymentioning

confidence: 99%

Section: Non-cancer Ttcmentioning

confidence: 99%

Section: Ttc For Industrial Chemicalsmentioning

confidence: 99%

See 3 more Smart Citations

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

Hartung

2017

ALTEX

View full text Add to dashboard Cite

Noncancer Risk Assessment: Principles and Practice in Environmental and Occupational Settings

Pecquet,

Haber

2023

Patty's Toxicology

View full text Add to dashboard Cite

The scientific process of risk assessment aims to define hazards associated with human exposure to chemicals. This chapter focuses primarily on the first two steps of the risk assessment process for noncancer endpoints, or more broadly, for modes of action not involving interaction with DNA. Hazard characterization consists of a systematic evaluation of available data to identify toxicologically relevant adverse outcomes, the associated mode of action, and evaluation of human relevance of the effects. Data quality and the overall weight of evidence are also evaluated. We summarize available technologies for dose–response assessment to define the critical effect and to extrapolate effect levels to human exposure scenarios and exposure durations, and we discuss methods for addressing uncertainties. Methods for evaluating data–poor chemicals or conducting screening assessments are also reviewed. Finally, we discuss how to interpret the dose–response information in the context of specific exposure data. Although this chapter focuses on the methods for deriving risk values from in vivo studies, we also address the use of data from the rapidly evolving field of new approach methodologies (including in vitro methods such as high‐throughput transcriptomics and in silico approaches such as modeling of structure–activity relationships). Ultimately, these new methodologies will foster a better understanding of how chemical exposures may cause toxicity, allow for more rapid assessment of chemicals, and support a reduction in the need for future toxicity testing in animals.

show abstract

Toxicology of Flavoring Ingredients in the Food Industry

Pecquet,

Bates,

Maier

2023

Patty's Toxicology

View full text Add to dashboard Cite

The present chapter represents toxicological information on selected flavoring ingredients commonly found in the food and beverage product manufacturing workplace. Many flavoring ingredients are considered Generally Recognized as Safe (GRAS) based on consumer oral ingestion but can present hazards in the occupational context depending on route of exposure and exposure concentration. Therefore, when occupational exposure limits do not exist, it is important that workers review safety data sheets (SDS) and other hazard information and participate in training to understand the verbiage on these resources as part of a comprehensive hazard communication program. New occupational hazard assessment approaches include hazard banding when data are scarce and use of the threshold of toxicological concern (TTC) to inform risk management planning in the food and beverage sectors. The Flavor Extract Manufacturers Association (FEMA) and the Joint FAO/WHO Expert Committee on Food Additives (JECFA) have adopted modified Cramer approaches and the TTC concept to classify flavor ingredients by structure for dietary exposure and safety assessment considerations when chemical‐specific data are limited. Today, new chemical entities are being designed and created to maximize and/or customize the interaction of the flavor ingredients with taste receptors, including new applications of flavoring compounds to use in Electronic Nicotine Devices (ENDs) that involve inhalation route exposures. Several important flavor chemicals have been covered in this chapter with respect to their properties, exposure assessment, toxicity, and regulations pertaining to risk and safety assessments for different use scenarios.

show abstract

Exposure-triggered reproductive toxicity testing under the REACH legislation: A proposal to define significant/relevant exposure

Cited by 42 publications

References 15 publications

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

Thresholds of Toxicological Concern – Setting a threshold for testing below which there is little concern

Noncancer Risk Assessment: Principles and Practice in Environmental and Occupational Settings

Toxicology of Flavoring Ingredients in the Food Industry

Contact Info

Product

Resources

About