Survey of ocular irritation predictive capacity using Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test historical data for 319 personal care products over fourteen years.

The Chorioallantoic Membrane Vascular Assay (CAMVA) and Bovine Corneal Opacity and Permeability (BCOP) test are widely used to predict ocular irritation potential for consumer-use products. These in vitro assays do not require live animals, produce reliable predictive data for defined applicability domains compared to the Draize rabbit eye test, and are rapid and inexpensive. Data from 304 CAMVA and/or BCOP studies (319 formulations) were surveyed to determine the feasibility of predicting ocular irritation potential for various formulations. Hair shampoos, skin cleansers, and ethanol-based hair styling sprays were repeatedly predicted to be ocular irritants (accuracy rate=0.90-1.00), with skin cleanser and hair shampoo irritation largely dependent on surfactant species and concentration. Conversely, skin lotions/moisturizers and hair styling gels/lotions were repeatedly predicted to be non-irritants (accuracy rate=0.92 and 0.82, respectively). For hair shampoos, ethanol-based hair stylers, skin cleansers, and skin lotions/moisturizers, future ocular irritation testing (i.e., CAMVA/BCOP) can be nearly eliminated if new formulations are systematically compared to those previously tested using a defined decision tree. For other tested product categories, new formulations should continue to be evaluated in CAMVA/BCOP for ocular irritation potential because either the historical data exhibit significant variability (hair conditioners and mousses) or the historical sample size is too small to permit definitive conclusions (deodorants, make-up removers, massage oils, facial masks, body sprays, and other hair styling products). All decision tree conclusions should be made within a conservative weight-of-evidence context, considering the reported limitations of the BCOP test for alcohols, ketones, and solids.

28-day repeated dose oral toxicity of recombinant human holo-lactoferrin in rats.

Recombinant human holo-lactoferrin (holo-rhLF) was orally administered, via gavage, to Wistar rats at 1000, 500 and 100mg/kgbw/day for 28 days. The test article, holo-rhLF, was expressed in rice grain, extracted, purified and saturated with iron. During the 28-day period, animals were examined for evidence of toxicity. On day 29, the animals were exsanguinated, examined for gross pathology, and tissues preserved for histopathology. There were no deaths caused by holo-rhLF and in-life physical signs were generally normal. Although statistical differences were noted in some hematology, clinical chemistry and heart/body weight ratios, they were of questionable biological significance. A significantly greater total iron binding capacity (TIBC) was detected in the blood of male animals dosed with holo-rhLF. Serum was analyzed for the presence of IgG and IgE antibodies; demonstrating low levels of IgG antibodies to the human protein, but no increase in IgE antibodies. There was no increase in serum lactoferrin levels. The results of the 28-day oral administration demonstrate a lack of toxicity of holo-rhLF in rats. There were no treatment related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weights or pathology. The no observed adverse effect level (NOAEL) is greater than 1000 mg/kg/day.

28-Day repeated dose oral toxicity of recombinant human apo-lactoferrin or recombinant human lysozyme in rats.

Lactoferrin and lysozyme are important proteins of the human innate immune system. These proteins are found in breast milk and have been associated with improved infant health. Recombinant human apo-lactoferrin (apo-rhLF), 1800 and 180mg/kg bw/day, and recombinant human lysozyme (rhLZ), 360 and 36mg/kg bw/day, were orally administered to Wistar rats for 28 days. Apo-rhLF and rhLZ were expressed in rice grain, extracted, purified; the lactoferrin was iron desaturated. The animals were examined for evidence of toxicity; there were no deaths and in-life physical signs were normal. Transient differences in mean food consumption occurred in high dose apo-rhLF and low dose LZ females at week three. There were no biologically significant differences in hematological or clinical chemistry parameters. Necropsy results were normal and microscopic evaluation showed no treatment related changes in animals dosed with 1800mg/kg/day apo-rhLF or 360mg/kg/day rhLZ. The results of the 28-day oral administration demonstrate a lack of toxicity of apo-rhLF and rhLZ in rats. There were no treatment related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weight and pathology. The no observed adverse effect level (NOAEL) is greater than 1800mg/kg/day for apo-rhLF and 360mg/kg/day for rhLZ.

Assessment of the chorioallantoic membrane vascular assay (CAMVA) in the COLIPA in vitro eye irritation validation study.

The chorioallantoic membrane vascular assay (CAMVA) is an alternative to the Draize rabbit eye irritation method. The CAMVA employs the vascularized membrane of a fertile hen's egg to assess eye irritation potential. This irritation potential is a function of alterations in the vasculature following the administration of test material. Because of the history of use of the CAMVA it was selected as one of the methods for a validation study organized and sponsored by COLIPA. For this validation study mathematical prediction models (PMs) were developed to convert the CAMVA results into predicted Draize eye irritation scores known as a modified maximum average Draize score (MMAS). These predicted scores were statistically compared with the observed scores to assess the relevance of the CAMVA. The assay was conducted on the same set of test materials by two independent laboratories. These two sets of data were compared to assess the interlaboratory reproducibility of the assay. The results of this validation study of the CAMVA show that for test materials with MMASs in the 0 to 5 range or the 55 to 110 range, the CAMVA did not give a good prediction. The predictions were better for samples of mild to moderate irritation (MMAS 5-55). The difficulty in predicting at the low end of the irritation scale appears to be due to the biological variability of the test system and the subjective nature of the CAMVA evaluation. For those samples with an MMAS above 55, the CAMVA appeared to be limited in demonstrating the more severe response. This may be due to the fact that the PMs were developed using historical data sets of test materials with MMASs below this range. Two approaches for improving the CAMVA for eye irritation prediction are (1) to decrease the variability at the low end by reducing the subjectivity in the scoring and (2) to develop better prediction models using more data in the range of severe irritants.

[Toxoplasma gondii]. / Toxoplasma gondii.

The authors offered a general view on Toxoplasma gondii from the historical, taxonomic, biological and epidemiological point of view. They also studied the problems of pathogenesis, pathology, clinics, diagnosis, as well as therapy and prevention. (Tab. 1, Ref. 9)