Low-level Exposure to Multiple Chemicals: Reason for Human Health Concerns?

Overview

Journal Environ Health Perspect

Date 2008 Jan 5

PMID 18174958

Citations 59

Authors

Andreas Kortenkamp

Michael Faust

Martin Scholze

Thomas Backhaus

Affiliations

Soon will be listed here.

Abstract

Background: A key question in the risk assessment of exposures to multiple chemicals is whether mixture effects may occur when chemicals are combined at low doses which individually do not induce observable effects. However, a systematic evaluation of experimental studies addressing this issue is missing.

Objectives: With this contribution, we wish to bridge this gap by providing a systematic assessment of published studies against well-defined quality criteria.

Results: On reviewing the low-dose mixture literature, we found good evidence demonstrating significant mixture effects with combinations of chemicals well below their individual no observable adverse effect levels (NOAELs), both with mixtures composed of similarly and dissimilarly acting agents.

Conclusions: The widely held view that mixtures of dissimilarly acting chemicals are "safe" at levels below NOAELs is not supported by empirical evidence. We show that this view is also based on the erroneous assumption that NOAELs can be equated with zero-effect levels. Thus, on the basis of published evidence, it is difficult to rule out the possibility of mixture effects from low-dose multiple exposures.

Citing Articles

Air pollution mixture exposure during pregnancy and postpartum psychological functioning: racial/ethnic- and fetal sex-specific associations.

Chiu Y, Coull B, Wilson A, Hsu H, Xhani N, Nentin F J Expo Sci Environ Epidemiol. 2024; .

PMID: 39567710 DOI: 10.1038/s41370-024-00726-2.

Reproductive toxicology: keeping up with our changing world.

Miller L, Feuz M, Meyer R, Meyer-Ficca M Front Toxicol. 2024; 6:1456687.

PMID: 39463893 PMC: 11502475. DOI: 10.3389/ftox.2024.1456687.

Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function.

Rosa M, Gennings C, Curtin P, Alcala C, Lamadrid-Figueroa H, Tamayo-Ortiz M Sci Total Environ. 2024; 938:173352.

PMID: 38796021 PMC: 11238599. DOI: 10.1016/j.scitotenv.2024.173352.

Metal mixtures and oral health among children and adolescents in the National Health and Nutrition Examination Survey (NHANES), 2017-2020.

Akinkugbe A, Midya V, Duffy J, Landero J, Wright R, Wright R Int J Hyg Environ Health. 2024; 257:114335.

PMID: 38330728 PMC: 10939733. DOI: 10.1016/j.ijheh.2024.114335.

Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers.

Wang Z, Zhang C, Williams P, Bellavia A, Wylie B, Kannan K Front Reprod Health. 2024; 5:1285444.

PMID: 38260052 PMC: 10800537. DOI: 10.3389/frph.2023.1285444.

References

Carpy S, Kobel W, Doe J . Health risk of low-dose pesticides mixtures: a review of the 1985-1998 literature on combination toxicology and health risk assessment. J Toxicol Environ Health B Crit Rev. 2000; 3(1):1-25. DOI: 10.1080/109374000281122. View

Groten J, Schoen E, van Bladeren P, Kuper C, van Zorge J, Feron V . Subacute toxicity of a mixture of nine chemicals in rats: detecting interactive effects with a fractionated two-level factorial design. Fundam Appl Toxicol. 1997; 36(1):15-29. DOI: 10.1006/faat.1996.2281. View

Crofton K, Craft E, Hedge J, Gennings C, Simmons J, Carchman R . Thyroid-hormone-disrupting chemicals: evidence for dose-dependent additivity or synergism. Environ Health Perspect. 2005; 113(11):1549-54. PMC: 1310917. DOI: 10.1289/ehp.8195. View

Walter H, Consolaro F, Gramatica P, Scholze M, Altenburger R . Mixture toxicity of priority pollutants at no observed effect concentrations (NOECs). Ecotoxicology. 2002; 11(5):299-310. DOI: 10.1023/a:1020592802989. View

KONEMANN H . Structure-activity relationships and additivity in fish toxicities of environmental pollutants. Ecotoxicol Environ Saf. 1980; 4(4):415-21. DOI: 10.1016/0147-6513(80)90043-3. View

Broderius S, Kahl M, Elonen G, Hammermeister D, Hoglund M . A comparison of the lethal and sublethal toxicity of organic chemical mixtures to the fathead minnow (Pimephales promelas). Environ Toxicol Chem. 2006; 24(12):3117-27. DOI: 10.1897/05-094r.1. View

Feron V, Groten J, van Zorge J, Cassee F, Jonker D, van Bladeren P . Toxicity studies in rats of simple mixtures of chemicals with the same or different target organs. Toxicol Lett. 1995; 82-83:505-12. DOI: 10.1016/0378-4274(95)03580-x. View

Faust M, Altenburger R, Backhaus T, Blanck H, Boedeker W, Gramatica P . Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants. Aquat Toxicol. 2001; 56(1):13-32. DOI: 10.1016/s0166-445x(01)00187-4. View

Backhaus , Scholze , Grimme . The single substance and mixture toxicity of quinolones to the bioluminescent bacterium Vibrio fischeri. Aquat Toxicol. 2000; 49(1-2):49-61. DOI: 10.1016/s0166-445x(99)00069-7. View

10.

Mileson B, Chambers J, Chen W, DETTBARN W, Ehrich M, Eldefrawi A . Common mechanism of toxicity: a case study of organophosphorus pesticides. Toxicol Sci. 1998; 41(1):8-20. DOI: 10.1006/toxs.1997.2431. View

11.

Allen B, Kavlock R, Kimmel C, Faustman E . Dose-response assessment for developmental toxicity. II. Comparison of generic benchmark dose estimates with no observed adverse effect levels. Fundam Appl Toxicol. 1994; 23(4):487-95. DOI: 10.1006/faat.1994.1133. View

12.

Jonker D, Woutersen R, van Bladeren P, Til H, Feron V . 4-week oral toxicity study of a combination of eight chemicals in rats: comparison with the toxicity of the individual compounds. Food Chem Toxicol. 1990; 28(9):623-31. DOI: 10.1016/0278-6915(90)90170-r. View

13.

Faust M, Altenburger R, Backhaus T, Blanck H, Boedeker W, Gramatica P . Joint algal toxicity of 16 dissimilarly acting chemicals is predictable by the concept of independent action. Aquat Toxicol. 2003; 63(1):43-63. DOI: 10.1016/s0166-445x(02)00133-9. View

14.

Ito N, Hasegawa R, Imaida K, Kurata Y, Hagiwara A, Shirai T . Effect of ingestion of 20 pesticides in combination at acceptable daily intake levels on rat liver carcinogenesis. Food Chem Toxicol. 1995; 33(2):159-63. DOI: 10.1016/0278-6915(94)00118-8. View

15.

Brian J, Harris C, Scholze M, Backhaus T, Booy P, Lamoree M . Accurate prediction of the response of freshwater fish to a mixture of estrogenic chemicals. Environ Health Perspect. 2005; 113(6):721-8. PMC: 1257597. DOI: 10.1289/ehp.7598. View

16.

Tinwell H, Ashby J . Sensitivity of the immature rat uterotrophic assay to mixtures of estrogens. Environ Health Perspect. 2004; 112(5):575-82. PMC: 1241924. DOI: 10.1289/ehp.6831. View

17.

Jonker D, Woutersen R, van Bladeren P, Til H, Feron V . Subacute (4-wk) oral toxicity of a combination of four nephrotoxins in rats: comparison with the toxicity of the individual compounds. Food Chem Toxicol. 1993; 31(2):125-36. DOI: 10.1016/0278-6915(93)90126-j. View

18.

Crump K . A new method for determining allowable daily intakes. Fundam Appl Toxicol. 1984; 4(5):854-71. DOI: 10.1016/0272-0590(84)90107-6. View

19.

van den Berg M, Birnbaum L, Bosveld A, Brunstrom B, Cook P, Feeley M . Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Environ Health Perspect. 1998; 106(12):775-92. PMC: 1533232. DOI: 10.1289/ehp.98106775. View

20.

Zbinden G . The no-effect level, an old bone of contention in toxicology. Arch Toxicol. 1979; 43(1):3-7. DOI: 10.1007/BF00695868. View