50
S.T. Larsen et al. / Toxicology 169 (2001) 37–51
Fujimaki, H., Hirano, S., Takenaka, S., Murakami, M.,
Watanabe, N., 1986. Enhanced IgE antibody production in
mice injected with fly ash. Int. Arch. Allergy Appl. Im-
munol. 80, 127–131.
Gall, D., 1967. Observations on the properties of adjuvants.
Symp. Series Immunobiol. Standards 6, 39–48.
Goggans, J.F., Copenhaver, E., 1939. Monoalkyl phthalates
from normal aliphatic alcohols. J. Am. Chem. Soc. 61,
2909–2910.
Gue´ry, J.-C., Galbiati, F., Smiroldo, S., Adorini, L., 1996.
Selective development of T helper (Th)2 cells induced by
continuous administration of low dose soluble proteins to
normal and b2-microglobulin-deficient BALB/c mice. J.
Exp. Med. 183, 485–497.
Gupta, R.K., Relyveld, E.H., Lindblad, E.B., Bizzini, B.,
Ben-Efraim, S., Gupta, C.K., 1993. Adjuvants-a balance
between toxicity and adjuvanticity. Vaccine 11, 293–306.
Haseman, J.K., Hailey, J.R., Morris, R.W., 1998. Sponta-
neous neoplasm incidences in Fischer 344 rats and B6C3F1
mice in two-year carcinogenicity studies: a national toxicol-
ogy program update. Toxicol. Pathol. 26, 428–441.
Heindel, J.J., Powell, C.J., 1992. Phthalate ester effects on rat
Sertoli cell function in vitro: effects of phthalate side chain
and age of animal. Toxicol. Appl. Pharmacol. 115, 116–
123.
with effects of the corresponding diphthalates,
which we are currently studying in the same ani-
mal model. This should allow an overall evalua-
tion of the possible adjuvant effects of these
substances.
Acknowledgements
The authors thank laboratory technicians Ulla
Tegner, Maria Hammer and Jette Larsen and
animal technicians Gitte B. Jepsen and Lotte S.
Drifte for excellent technical support. This study
has been produced as part of the research activi-
ties in the Centre for the Environment and Res-
piratory System, which is supported by the
Danish Environmental Research Program.
References
Hoffmann, L., 1996. Mass balance for phthalates, Environ-
mental project nr. 320., Danish Environmental Protection
Agency, in Danish.
Holmgren, E.B., 1999. Establishing equivalence by showing
that a specified percentage of the effect of the active
control over placebo is maintained. J. Biopharm. Stat. 9,
651–659.
Adler, I.-D., Bootman, J., Favor, J., Hook, G., Schriever-
Schwemmer, G., Welzl, G., Whorton, E., Yoshimura, I.,
Hayashi, M., 1998. Recommendations for statistical de-
signs of in vivo mutagenicity tests with regard to subse-
quent statistical analysis. Mutat. Res. 417, 19–30.
Albro, P.W., Chapin, R.E., Corbett, J.T., Schroeder, J.,
Phelps, J.L., 1989. Mono-2-ethylhexyl phthalate, a metabo-
lite of di-(2-ethylhexyl) phthalate, causally linked to testic-
ular atrophy in rats. Toxicol. Appl. Pharmacol. 100,
193–200.
Carpenter, C.P., Shaffer, B., 1952. A study of the polyethylene
glycols as vehicle for intramuscular and subcutaneous in-
jection. J. Am. Pharm. Assoc. 41, 27–29.
Clausen, S.K., Sobhani, S., Poulsen, O.M., Nielsen, G.D.,
2000. Study of adjuvant effect of model surfactants from
the group of alkyl sulfates, alkylbenzene sulfonates, alco-
hol ethoxylates and soaps. Food Chem. Toxicol. 38, 1065–
1074.
Holt, P.G., 1996. Infections and the development of allergy.
Toxicol. Lett. 86, 205–210.
Jaakkola, J.J., Øie, L., Nafstad, P., Botten, G., Samuelsen,
S.O., Magnus, P., 1999. Interior surface materials in the
home and the development of bronchial obstruction in
young children in Oslo, Norway. Am. J. Public Health 89,
188–192.
Kawabata, T.T., Babcock, L.S., Horn, P.A., 1996. Specific IgE
and IgG1 responses to subtilisin Carlsberg (Alcalase) in
mice: development of an intratracheal exposure model.
Fundam. Appl. Toxicol. 29, 238–243.
Klaunig, J.E., Ruch, R.J., DeAngelo, A.B., Kaylor, W.H.,
1988. Inhibition of mouse hepatocyte intercellular commu-
nication by phthalate monoesters. Cancer Lett. 43, 65–71.
Larsen, S.T., Nielsen, G.D., Thygesen, P., 2001. Investigation
of the adjuvant effect of polyethylene glycol (PEG) 400 in
BALB/c mice. Int. J. Pharm., in press.
Li, L.H., Jester, W.F.J., Laslett, A.L., Orth, J.M., 2000. A
single dose of Di-(2-ethylhexyl) phthalate in neonatal rats
alters gonocytes, reduces sertoli cell proliferation, and de-
creases cyclin D2 expression. Toxicol. Appl. Pharmacol.
166, 222–229.
Constant, S.L., Bottomly, K., 1997. Induction of Th1 and Th2
CD4+ T cell responses: the alternative approaches. Annu.
Rev. Immunol. 15, 297–322.
Cox, J.C., Coulter, A.R., 1997. Adjuvants-a classification and
review of their modes of action. Vaccine 15, 248–256.
Di Tommaso, A., Saletti, G., Pizza, M., Rappuoli, R., Dou-
gan, G., Abrignani, S., Douce, G., De Magistris, M.T.,
1996. Induction of antigen-specific antibodies in vaginal
secretions by using a nontoxic mutant of heat-labile entero-
toxin as a mucosal adjuvant. Infect. Immun. 64, 974–979.
Foster, P.M., Lake, B.G., Thomas, L.V., Cook, M.W., Gan-
golli, S.D., 1981. Studies on the testicular effects and zinc
excretion produced by various isomers of monobutyl-o-ph-
thalate in the rat. Chem. Biol. Interact. 34, 233–238.
Løvik, M., Hogseth, A.K., Gaarder, P.I., Hagemann, R., Eide,
I., 1997. Diesel exhaust particles and carbon black have
adjuvant activity on the local lymph node response and