The induction of respiratory allergy in guinea-pigs following intradermal injection of trimellitic anhydride: a comparison with the response to 2,4-dinitrochlorobenzene

Botham, Philip A.; Rattray, N.J.; Woodcock, D.R.; Walsh, Stephanie; Hext, Paul M.

doi:10.1016/0378-4274(89)90083-0

Cited by 104 publications

(51 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations indicate that systemic effects can be induced in orally sensitized animals on an oral challenge. In literature, a drop in breathing frequency below 70% of the normal breathing frequency is considered an indication of severe respiratory effects (Botham et al 1989). Although we observed severe respiratory effects in only a few animals (~10-15% of the animals), this low incidence agrees with observations from food allergic patients, of whom only about 10% react with respiratory problems (Monteleone and Sherman 1997).…”

Section: Resultsmentioning

confidence: 99%

Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

Knippels¹,

Penninks²

2003

Environ Health Perspect

View full text Add to dashboard Cite

The need for widely accepted and validated animal models to test the potential allergenicity and potency of novel (biotechnology-derived) proteins has become an important issue for their safety evaluation. In this article, we summarize the results of the development of an oral sensitization protocol for food proteins in the rat. Young Brown Norway rats were exposed to either various purified allergenic proteins (e.g., ovalbumin, partly purified), a whole food (cow's milk), or total protein extracts (hen's egg white, peanut) by daily gavage dosing during 42 days without the use of an adjuvant. The results showed that Brown Norway rats can be sensitized orally to the various allergenic food proteins tested, resulting in antigen-specific immunoglobulin (Ig) G and IgE responses, without the use of adjuvants. Animals orally exposed to cow's milk or total protein extracts of egg white also developed specific IgE and IgG antibodies that recognized the same proteins compared with antibodies from patients allergic to egg white or cow's milk. We also studied local and systemic immune-mediated effects. In ovalbumin-sensitized rats, some clinical symptoms of food allergy were studied upon an oral challenge with ovalbumin. The results demonstrated that gut permeability was increased and that in some animals breathing frequency and systolic blood pressure were temporarily decreased. The results obtained show that the Brown Norway rat provides a suitable animal model for food allergy research and for the study of relative allergenicity of existing and novel food proteins.

show abstract

Section: Resultsmentioning

confidence: 99%

Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

Knippels¹,

Penninks²

2003

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…The target dose of 1 mg TMA dust (~2.2 mg/kg) used to elicit the asthmatic response is comparable to exposures in previous studies of others examining the respiratory effects of TMA in sensitized guinea pigs. These previous studies challenged animals by inhalation to concentrations of TMA dust ranging from 8-150 mg/m 3 for 15-60 min (Botham et al, 1989;Hayes et al, 1992aHayes et al, , 1993Obata et al, 1992;Tao et al, 1991). Assuming an average range of respiration rate and tidal volume (Terril and Clemons, 1998), we estimated guinea pigs in these studies were exposed to 0.004-7.7 mg TMA.…”

Section: Discussionmentioning

confidence: 99%

Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs

Larsen

Regal

2002

Toxicology

View full text Add to dashboard Cite

Trimellitic anhydride (TMA) causes asthma after a latency period of sensitization. In non-sensitized humans and animals, limited studies indicate that TMA exposure may also cause symptoms of asthma without a latency period. Our previous studies (J. Pharmacol. Exp. Ther. 296 (2001) 284) in a guinea pig model of TMA-induced asthma demonstrated that sensitization and the complement system were required for eosinophilia. TMA conjugated to guinea pig serum albumin (TMA-GPSA) was used to elicit the response. Since occupational exposure to TMA occurs by inhalation of dust, the present studies determined if exposure to TMA dust in a non-sensitized guinea pig elicited airway obstruction and inflammation, and whether a significantly greater response occurred after a latency period of sensitization. Guinea pigs were intradermally injected with either corn oil (non-sensitized animals) or 30% TMA (sensitized animals). Three weeks later they were challenged by intratracheal insufflation with 1 mg TMA dust or lactose dust (control) using a dry powder delivery device. Pulmonary resistance, dynamic lung compliance, mean arterial blood pressure and heart rate were monitored for 10 min. In non-sensitized guinea pigs, significant increases in pulmonary resistance and decreases in dynamic lung compliance and blood pressure occurred after TMA challenge. In sensitized animals, the same dose of TMA caused significantly greater effects compared to nonsensitized animals. In a separate experiment, cellular infiltration into the lung was determined 24 h after challenge with TMA dust or lactose dust. In both non-sensitized and sensitized animals, eosinophils in the lung tissue were increased after TMA dust challenge compared to controls. Thus, these studies suggest that the response in non-sensitized animals differs depending on whether TMA dust or TMA-GPSA is used to elicit the response. TMA dust elicits significant airway obstruction and eosinophilia in a non-sensitized animal, with even greater airway obstruction occurring in a sensitized animal.

show abstract

“…A guinea-pig model has been developed for assessment of allergenicity of occupational agents [15,19,[29][30][31], and has received rigorous review [32]. The model assesses a chemical's ability to cause airway hypersensitivity via a "relevant" route of exposure.…”

Section: Guinea-pig Modelsmentioning

confidence: 99%

“…Several variations of the model have been described [30,32] in attempts to either simplify the induction process (i.e. avoid the need to generate and monitor chemical atmospheres) or the elicitation phase (by monitoring EAR exclusively).…”

Section: Guinea-pig Modelsmentioning

confidence: 99%

See 1 more Smart Citation

Animal models of occupational asthma

Mh¹

1994

Eur Respir J

121

View full text Add to dashboard Cite

A An ni im ma al l m mo od de el ls s o of f o oc cc cu up pa at ti io on na al l a as st th hm ma a M.H. KarolAnimal models of occupational asthma. M.H. Karol. ERS Journals Ltd 1994. ABSTRACT: Occupational asthma is characterized by variable airflow obstruction occurring in the workplace. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Since its pathogenic mechanism(s) are unknown, animal models have been developed to investigate the various disease processes, as well as to enable study of environmental and genetic factors which may contribute to disease development.Numerous parameters can be measured in animal systems, including specific and total immunoglobulin E (IgE), pulmonary eosinophilia, diaphragm contractions and airflow muscle hypertrophy. It is recognized that no single factor is sufficient to lead to a conclusion of occupational asthma, but rather that a selected combination of parameters is most fitting. Animal species selected for study have included: mice, rats, guinea-pigs, rabbits, sheep, horses and nonhuman primates. A guinea-pig system has been utilized for more than 90 yrs and has contributed to the basic understanding of physiological and immunological processes involved in allergic respiratory sensitization. The benefits as well as the disadvantages to be derived from each of the animal systems have been enumerated in this review.Certain caveats must be recognized in using animal systems. Attention must always be given to identifying differences which exist between animal and human systems, including morphological, physiological and immunological factors. The extent of bronchus-associated lymphoid tissue (BALT) differs greatly among animal species and probably plays a major role in development of allergic responsiveness in animals. In using animal systems, it must be appreciated that animals are only surrogates. Results from such studies must be compared with information obtained from clinical evaluation in order to avoid faulty extrapolations. Prudent employment of animal models is expected to advance the recognition, treatment and prevention of occupationally-based asthma.

show abstract

The induction of respiratory allergy in guinea-pigs following intradermal injection of trimellitic anhydride: a comparison with the response to 2,4-dinitrochlorobenzene

Cited by 104 publications

References 14 publications

Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model.

Trimellitic anhydride (TMA) dust induces airway obstruction and eosinophilia in non-sensitized guinea pigs

Animal models of occupational asthma

Contact Info

Product

Resources

About