Di-(2-ethylhexyl) phthalate is without adjuvant effect in mice on ovalbumin

Dearman, Rebecca J.; Beresford, Lorna; Bailey, Laura; Caddick, Helen Theresa; Betts, Catherine J.; Kimber, Ian

doi:10.1016/j.tox.2007.11.017

Cited by 27 publications

(17 citation statements)

References 42 publications

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“…Experiment 2: 1 μg OVA, 1.209 g ± 0.033; 1 μg OVA 100% BBP same site, 1.484 g ± 0.034; 1 μg OVA 100% BBP distant site, 1.477 g ± 0.045.) As reported previously (Dearman et al, 2008), in both experiments conducted, subcutaneous injection of 1 μg of OVA resulted in suboptimal anti-OVA IgG1 antibody expression, with significantly (p < 0.05 or p < 0.01) higher levels of IgG1 antibody detected following exposure to 10 μg OVA (Fig. 1).…”

Section: Resultssupporting

confidence: 82%

“…Some investigators have reported that exposure to phthalates such as DEHP by nonphysiological routes (subcutaneous or intraperitoneal injection) resulted in enhanced antibody and/or cytokine responses stimulated by a reference protein (Larsen et al, 2001a(Larsen et al, ,b, 2002Lee et al, 2004). In contrast, we and others have demonstrated previously that topical exposure to DEHP, even under conditions where marked systemic effects were detected on liver weight, failed to cause adjuvant effects (Butala et al, 2004;Dearman et al, 2008).…”

Section: Introductionmentioning

confidence: 55%

“…Similar topical exposure to DEHP was without significant influence on immune responses (Butala et al, 2004;Dearman et al, 2008;Imai et al, 2006). Other authors using less physiological routes of exposure (subcutaneous or intraperitoneal) have shown that certain phthalates have the potential to impact on the quality of immune response, causing changes consistent with activation of type 2 T cells.…”

Section: Discussionmentioning

confidence: 89%

“…Despite topical application of up to 100% BBP daily for five consecutive days, there was no discernable treatment-related redness or thickening of the skin. Subsequently, in two independent experiments, groups of BALB/c strain mice (n = 10) received a subcutaneous injection in the nape of the neck of 1 μg of OVA, a concentration that has been shown previously to be suboptimal for IgG1 antibody production, or of 10 μg of OVA, a dose that provokes maximal IgG1 antibody expression (Dearman et al, 2008). Further groups received the suboptimal dose of OVA (1 μg) and topical application of 100% BBP to the same site (neck) or to a distant site (flanks).…”

Section: Resultsmentioning

confidence: 99%

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Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice

Dearman

Betts

Beresford

et al. 2008

J of Applied Toxicology

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During recent decades the prevalence of IgE-mediated (atopic) allergic diseases in Western Europe and the USA has been increasing dramatically. It has been suggested that one possible cause is the presence in the environment of chemicals that may act as adjuvants, enhancing immune and allergic responses. Certain commonly used phthalate plasticizers such as butyl benzyl phthalate (BBP) have been implicated in this way. In the current experiments, the impact of BBP, applied by a physiologically relevant exposure route, on the vigour of immune responses induced in BALB/c strain mice has been examined. Mice were immunized via subcutaneous injection with the reference allergen ovalbumin (OVA) and received concurrent topical treatment with doses of BBP that induced significant changes in liver weight. The generation of specific anti-OVA IgE and IgG1 antibodies was measured by passive cutaneous anaphylaxis and by enzyme-linked immunosorbant assays, respectively. Topical administration of BBP was without impact on anti-OVA IgE antibody responses, regardless of whether BBP was applied locally or distant to the site of OVA immunization. However, same-site treatment with high-dose BBP (100 mg) did result in a modest elevation in anti-OVA IgG1 antibody production, a subclass of antibody used as a surrogate marker of IgE responses. Taken together with human exposure data, these results suggest that the doses of phthalate encountered in the home environment are unlikely to be a major factor contributing to the increased incidence of asthma and allergy in the developed world.

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Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

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Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice

Dearman

Betts

Beresford

et al. 2008

J of Applied Toxicology

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“…In a study which tested whether PPARα may be involved in the adjuvant effect of DEHP, it was shown that DEHP induced highly increased levels of ovalbumin-specific IgG1 and IgG2a, both in wild-type and in PPARα-null mice, indicating that it is a mixed Th1/Th2 adjuvant and that the adjuvant mechanism is mediated through a PPARα-independent mechanism [204]. The findings that DEHP can act as an adjuvant have been challenged in a study [205] where topical administration of DEHP was without impact on antibody responses, regardless of whether it was applied locally or distant to the site of ovalbumin immunization. Inhalational exposure to MEHP (60 minutes; 0.3–43.6 mg/m 3 ) in mice led to a concentration-dependent decrease in tidal volume and an increased number of alveolar macrophages, but no change in numbers of neutrophils, lymphocytes, eosinophils, or epithelial cells in broncho-alveolar lavage fluid [206].…”

Section: Toxic Effects Of Dehp In the Immune Systemmentioning

confidence: 99%

Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate

Rusyn

Corton

2012

Mutation Research/Reviews in Mutation Research

111

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Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and environmental (medical devices, contamination of food, or intake from air, water and soil) routes of exposure to DEHP are of concern for human health. There is sufficient evidence for carcinogenicity of DEHP in the liver in both rats and mice; however, there is little epidemiological evidence on possible associations between exposure to DEHP and liver cancer in humans. Data are available to suggest that liver is not the only target tissue for DEHP-associated toxicity and carcinogenicity in both humans and rodents. The debate regarding human relevance of the findings in rats or mice has been informed by studies on the mechanisms of carcinogenesis of the peroxisome proliferator class of chemicals, including DEHP. Important additional mechanistic information became available in the past decade, including, but not limited to, sub-acute, sub-chronic and chronic studies with DEHP in peroxisome proliferator-activated receptor (PPAR) α-null mice, as well as experiments utilizing several transgenic mouse lines. Activation of PPARα and the subsequent downstream events mediated by this transcription factor represent an important mechanism of action for DEHP in rats and mice. However, additional data from animal models and studies in humans exposed to DEHP from the environment suggest that multiple molecular signals and pathways in several cell types in the liver, rather than a single molecular event, contribute to the cancer in rats and mice. In addition, the toxic and carcinogenic effects of DEHP are not limited to liver. The International Agency for Research on Cancer working group concluded that the human relevance of the molecular events leading to cancer elicited by DEHP in several target tissues (e.g., liver and testis) in rats and mice can not be ruled out and DEHP was classified as possibly carcinogenic to humans (Group 2B).

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Esters of Aromatic Diacids (Phthalates)

Greim

2023

Patty's Toxicology

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Phthalate esters are used as plasticizers for a variety of plastic materials; those of C8 and above are used to add flexibility to polyvinyl chloride (PVC). They also are used with vinyl and cellulose resins to lend toughness and flexibility. They are commonly used in wire and cable coverings, moldings, vinyl consumer products, and medical devices. Some low‐molecular‐weight phthalate esters (e.g., methyl, ethyl, and butyl) are preferentially used as industrial solvents and in consumer products, such as ink and lacquer. Phthalates occur mainly in liquid form with high boiling ranges and very low vapor pressures, both contributing to the high stability of these materials. The critical health effects of phthalate esters like DEHP, butylbenzyl phthalate (BBP), di‐ iso ‐butyl phthalate (DIBP), di‐ n ‐butyl phthalate (DNBP), and dipentyl phthalate (DPP) are their interaction with the endogenous production of fetal testicular testosterone in rats. This impairs the reproduction of rodents by decreasing sperm production so that ECHA has labeled this group as toxic for reproduction (1B), whereas high molecular phthalates (HMP) such as DINP do not warrant classification for effects on sexual function, fertility, and developmental toxicity. Currently, di‐isononylphthalate (DINP) is replacing di(2‐ethylhexyl) phthalate (DEHP) widely in industrial and consumer products. Photodegradation half‐lives of dimethyl‐ and diethylphthalate are about 14 and 3 days, respectively, those of the other esters below 1 day. Half‐lives of aerobic degradation differ largely. The acute aquatic EC or LD50 values determined in algae, daphnids, and minnows mostly did not show effects at the solubility limits. Legal limits of European Commission (EC) for phthalates in plastic layer in direct contact with food are as follows: DBP up to 0.3 mg/kg, BBP, up to 30 mg/kg, DEHP, up to 1.5 mg/kg, sum of DINP and DIDP up to 9 mg/kg.

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Di-(2-ethylhexyl) phthalate is without adjuvant effect in mice on ovalbumin

Cited by 27 publications

References 42 publications

Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice

Butyl benzyl phthalate: effects on immune responses to ovalbumin in mice

Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate

Esters of Aromatic Diacids (Phthalates)

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