Teratology Study of a Cross-Linked Polyacrylate Superabsorbent Polymer

Abstract

The developmental toxicity (embryo-fetal toxicity/teratogenicity) of FAVOR SAB-922 SK, cross-linked polyacrylate superabsorbent (PAS), administered as an inhaled dust in concentrations of 0.3, 1.0, and 10.0 mg/m³ for 6 h/day from day 6 through day 15 of gestation was investigated in time-mated Sprague-Dawley rats. On day 20 of presumed gestation, the rats were asphyxiated with carbon dioxide, necropsied, and examined for pregnancy. Gravid uteri were examined for the number and status of implants, early and late resorptions, live and dead fetuses, and the number of corpora lutea in each ovary. Fetuses were weighed, sexed, and examined for external, soft tissue, and skeletal alterations. There were 315, 297, 299, and 286 liveborn fetuses from 25, 25, 23, and 24 litters in the four respective groups. Fetal processing and evaluations were conducted in compliance with FDA “Good Laboratory Practice Regulations; Final Rule.” The results indicate that breathing PAS in concentrations as high as 10 mg/m³ did not cause statistically significant or biologically important differences in dam body weight, caesarean-sectioning or litter data or the incidences of gross external, soft tissue or skeletal alterations, as compared with the control group values. No alterations believed to be related to PAS occurred in the fetuses of dams exposed to PAS at incidences that exceeded the ranges reported historically. Based on these data, both the developmental and maternal no-observable-effect-levels (NOEL) were greater than the dosage inhaled by rats exposed to the 10 mg/m³ concentration of respirable particulate PAS.

References

Christian, M.S. , Hoberman, A.M. , Martin, T. , and Martinova, M.S. (1991). Spontaneous occurring “problems” in Charles River Sprague Dawley rats that can affect reproductive and developmental toxicity studies. Proceedings from the twelfth annual meeting of the American College of Toxicology, October 21–23, 1991. Abstract in J. Am. Coll. Toxicol. 10:623.

Dunn, O.J. (1964). Multiple comparisons using rank sums. Technometrics 6(3):241–252.

Dunnett, C.W. (1955). A multiple comparison procedure for comparing several treatments with a control. J Am. Stat. Assoc. 50:1096–1129.

Lang, P.L. (1988). Embryo and Fetal Developmental Toxicity (Teratology) Control Data in the Charles River Crl:CD/BR Rat. Charles River Laboratories, Inc: Wilmington, MA. (Data base provided by Argus Research Laboratories, Inc.)

Marple, V.A. , Liu, B.Y.H. , and Rubow, K.L. (1978). A Dust Generator for Laboratory Use. Am. Ind. Hyg. Assoc. J. 39:26–32.

Mcgrath, J.J. , and Oyervides, J. (1983). Response of NO2-exposed mice to Klebsiella challenge. Adv. Modem Environ. Toxicol. 5:475–485.

Siegel, S. (1956). Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill: New York, pp. 96–104.

Snedecor, G.W. , and Cochran, W.G. (1967a). Analysis of variance, in: Statistical Methods, 6th Ed. Iowa State University Press: Ames, pp. 258–275.

Snedecor, G.W. , and Cochran, W.G. (1967b). Variance test for homogeneity of the binomial distribution, in: Statistical Methods, 6th Ed. Iowa State University Press: Ames, pp. 240–241.

10.

Sokal, R.R. , and Rohlf, R.J. (1969a). Bartlett's test of homogeneity of variances, in: Biometry. W.H. Freeman: San Francisco, pp. 370–371.

11.

Sokal, R.R. , and Rohlf, F.J. (1969b). Kruskal-Wallis Test, in: Biometry. W.H. Freeman: San Francisco, pp. 388–389.

12.

Staples, R.E. , and Schnell, V.L. (1963). Refinements in rapid clearing technique in the KOH-alizarin red S method for fetal bone. Stain Technol. 39:61–63.

13.

U.S. FOOD AND DRUG ADMINISTRATION (1987). Good Laboratory Practice Regulations; Final Rule, in: Federal Register, Friday, September 4, 1987. Part VI, Vol. 52, No. 172.

14.

Wilson, J.G. (1965). Methods for administering agents and detecting malformations in experimental animals, in: Teratology Principles and Techniques. J.G. Wilson and J. Warkany (eds.). Chicago: Chicago Press, p. 262–277.