Abstract
Prenatal exposure to elevated levels of boric acid (BA) causes reduced incidences of supernumerary ribs and shortening/absence of the 13th rib in multiple laboratory species. To explore this further, Sprague-Dawley rats received 500 mg/kg b.i.d. on gestation days (gd) 5–9, 6–9, 6–10, or on single days between gd 6 and 11 (plug day = gd 0); gd-21 fetuses were stained for skeletal examination. Following multiday exposures, malformations of the axial skeleton involved the head, sternum, ribs, and vertebrae. Shortening/absence of the 13th rib was seen particularly in the gd 5–9 and 6–10 exposure groups. Although most groups exposed on single days were generally unaffected, about 90% of the gd-9 exposed fetuses had only six cervical vertebrae; the deficient region was usually C3-C5. In contrast, gd-10 treatment caused agenesis of a thoracic/lumbar vertebra in over 60% of the fetuses; the deficient region was usually T11. For 13-ribbed fetuses, the length of rib 13 was shortened compared to controls. Postnatal assessment suggested increased mortality for gd-10 exposed pups. Embryos in culture showed reduced development when exposed to BA for 48 h. These findings demonstrate the critical periods for axial development in the rat and provide an experimental model for the study of homeotic shifts.
Similar content being viewed by others
References
J.J. Heindel, C. J. Price, E. A. Field, M. C. Marr, C. B. Myers, R. E. Morrissey, et al., Developmental toxicity of boric acid in mice and rats,Fundam. Appl. Toxicol.18, 266–277 (1992).
J. J. Heindel, C. J. Price, and B. A. Schwetz, The developmental toxicity of boric acid in mice, rats, and rabbits,Environ. Health Perspectives 102(Suppl. 7), 107–112 (1994).
B. C. Allen, P. L. Strong, C. J. Price, S. A. Hubbard, and G. P. Daston, Benchmark dose analysis of developmental toxicity in rats exposed to boric acid,Fundam. Appl. Toxicol.32, 194–204 (1996).
M. G. Narotsky, E. Z. Francis, and R. J. Kavlock, Developmental toxicity and structureactivity relationships of aliphatic acids, including dose-response assessment of valproic acid in mice and rats,Fundam. Appl. Toxicol.22, 251–265 (1994).
M. Kessel, Respecification of vertebral identities by retinoic acid,Development 115, 487–501 (1992).
G. A. De S. Wickramaratne, The postnatal fate of supernumerary ribs in rat teratogenicity studies,J. Appl. Toxicol.8, 91–94 (1988).
S. L. Beck, Assessment of adult skeletons to detect prenatal exposure to acetazolamide in mice,Teratology 28, 45–66 (1983).
A. R. Beaudoin, Teratogenicity of sodium arsenate in rats,Teratology 10, 153–158 (1974).
L. E. Connelly and J. M. Rogers, Methanol causes posteriorization of cervical vertebrae in mice,Teratology 55, 138–144 (1997).
C. A. Kimmel, J. M Cuff, G. L. Kimmel, D. J. Heredia, N. Tudor, P. M. Silverman, et al., Skeletal development following heat exposure in the rat,Teratology 47, 229–242 (1993).
M. Kessel, R. Balling, and P. Gruss, Variations of cervical vertebrae after expression of aHox-1.1 transgene in mice,Cell 61, 301–308 (1990).
K. M. Small and S. S. Potter, Homeotic transformations and limb defects inHox All mutant mice,Genes Dev. 7, 2318–2328 (1993).
J. W. Charité, W. de Graaff, S. Shen, and J. Deschamps, Ectopic expression ofHoxb-8 causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures,Cell 78, 589–601 (1994).
M. T. van der Lugt, J. Domen, K. Linders, M. van Roon, E. Robanus-Maandag, H. te Riele, et al, Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of thebmi-1 proto-oncogene,Genes Dev. 8, 757–769 (1994).
M. G. Narotsky, C. F. Brownie, and R. J. Kavlock, Critical period of carbon tetrachlorideinduced pregnancy loss in Fischer-344 rats, with insights into the detection of résorption sites by ammonium sulfide staining,Teratology 56, 252–261 (1997).
R. E. Linder, L. F. Strader, and G. L. Rehnberg, Effect of acute exposure to boric acid on the male reproductive system of the rat,J. Toxicol. Environ. Health 31, 133–146 (1990).
J. E. Andrews, M. Ebron-McCoy, T. R. Logsdon, L. M Mole, R. J. Kavlock, and J. M. Rogers, Developmental toxicity of methanol in whole embryo culture: a comparative study with mouse and rat embryos,Toxicology 81, 205–215 (1993).
D. A. T. New, Whole embryo culture and the study of mammalian embryos during organogenesis,Biol. Rev. 53, 81–125 (1978).
C. J. Price, P. L. Strong, F. J. Murray, and M. M. Goldberg, Developmental effects of boric acid in rats related to blood boron concentrations,Biol. Trace Element Res. 66, 359–372 (1999).
N. A. Brown and S. Fabro, Quantitation of rat embryonic development in vitro: A morphological scoring system,Teratology 24, 65–78 (1981).
R. M. Zucker, K. H. Elstein, D. L. Shuey, M. Ebron-McCoy, and J. M. Rogers, Utility of flourescence microscopy in embryonic/fetal topographical analysis,Teratology 51, 430–434 (1995).
G. P. Daston and G. J. Overmann, Lumbar ribs associated with posteriorization of Hox al0 expression in salicylate-treated mouse embryos,Teratology 53, 85 (1996).
Author information
Authors and Affiliations
Additional information
The information in this document has been funded wholly by the US Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
Rights and permissions
About this article
Cite this article
Narotsky, M.G., Schmid, J.E., Andrews, J.E. et al. Effects of boric acid on axial skeletal development in rats. Biol Trace Elem Res 66, 373–394 (1998). https://doi.org/10.1007/BF02783149
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF02783149