Dermal and systemic toxicity after application of semisynthetic metal-working fluids in B6C3F1 mice.

About 10 million industrial workers of both sexes are exposed to metal-working fluids (MWFs) via inhalation, skin or both. Our preliminary results, following dermal application of 200 microl of 50% unused (neat) semisynthetic MWF (pH 7 or pH 9.7) to the unshaved backs of 6-wk-old B6C3F1 mice, twice a week for 6 wk, produced significant increase in weights of the liver of both sexes. The purpose of the present study was to determine if this weight change was related to oxidative stress subsequent to MWF exposure and also to determine whether ethanol intake influences this effect. Therefore, 6-mo-old mice of both sexes were exposed to MWFs following the protocol just described, except that the topical application was with 5% MWFs (pH 7 and 9.7, 5 d/wk) with or without adding 5% ethanol to their drinking water (7 d/wk) for 13 wk. The skin histamine levels and mast-cell numbers were significantly increased in the female group treated with 55% MWF (pH 7). The ascorbic acid levels in the liver (both sexes) (all groups except 5%, MWF pH 9.7 males) and testes were reduced significantly. Malondialdehyde levels in the male liver were significantly increased with topical MWF exposure. Glutathione levels were reduced significantly in both male and female liver after 5% MWF (pH 7). Alcohol dehydrogenase activity of the male liver increased significantly after MWF (pH 7). These results suggest that MWFs are absorbed through the skin and produce toxicity in the liver of both sexes and in the male gonads. This may represent an important health risk to MWF-exposed industrial workers, and ethanol may exacerbate this risk.

Relationship between mechanical properties and pentosidine in tendon: effects of age, diet restriction, and aminoguanidine in broiler breeder hens.

Nonenzymatic glycosylation contributes to the formation of crosslinks, which leads to the structural and functional deterioration of tissue protein. The accumulation of these crosslinks in tissue proteins has been implicated in the alteration of biomechanical properties of connective tissues. The objective of this study was to determine whether tendon breaking time (TBT) and tendon breaking strength (TBS) of the flexor perforans et perforatus digiti iii tendon were related to concentrations of pentosidine in tendons (Pt) of broiler breeder hens from 8 to 125 wk of age. In addition, effects of diet restriction (DR) and a crosslinking inhibitor, aminoguanidine (AG) on Pt, TBS, and TBT were determined. Female chicks (n = 450) were randomly assigned to four treatment groups immediately after hatch: ad libitum-fed (AL); diet-restricted (DR; 60% of AL); and AL and DR groups supplemented with 1.35 mg/kg BW per day AG in the feed (AL+AG and DR+AG, respectively). In AL hens, Pt increased with increasing age (P < or = 0.0001). Concurrently, an age-related parallel increase was found for TBS (P < or = 0.0001) and TBT (P < or = 0.0001). Rate of Pt accumulation was lower in DR (P < or = 0.001), TBS (P < or = 0.01), and TBT (P < or = 0.02) hens compared with AL hens. Concentration of Pt in the AL + AG group was lower (P < or = 0.0002) than in the AL group; TBS and TBT (P < or = 0.01) followed a similar pattern. Supplementation of DR with AG did not affect Pt, TBS, or TBT. The age-related increase in Pt and loss of elasticity in the tendon was retarded by diet restriction and AG.

Ovalbumin aeroallergen exposure-response in Brown Norway rats.

A major route of exposure to allergens is through the respiratory tract. Comparatively few animal studies have used aerosolized high-molecular-weight allergens for sensitization, and in these studies, proper characterization of the aeroallergen exposure was usually missing. The purpose of this study was to profile the exposure-response relationship in Brown Norway rats (BNR) to well-characterized ovalbumin (OVA) aerosols. Rats were exposed 30 min/wk x 6 wk to respirable OVA aerosols from <1 mg/m(3) to 64 mg/m(3) air. Ovalbumin-specific circulating immunoglobulin (Ig)E, IgG, and IgA were measured throughout the study period. Rats were sacrificed 1 day after the last exposure. Pulmonary tissue was processed for histopathological and histochemical analysis. Tracheas were isolated, perfused, and assessed for in vitro responsiveness to methacholine. Serum concentrations of OVA-specific antibodies increased with both exposure concentration and number of exposures. The number of BNR with measurable titers also increased with both dose and time. Pulmonary inflammatory changes were noted only in BNR exposed to higher OVA concentrations (15 and 64 mg/m(3) air). Increased tracheal reactivity to methacholine was not found in any of the sensitized BNR. In summary, sustained aeroallergen concentration-dependent changes in specific antibody responses and pulmonary inflammation have been demonstrated.

Adjuvant effect of respiratory irritation on pulmonary allergic sensitization: time and site dependency.

It has been suggested that airway irritation, by acting as an adjuvant, as well as producing damage, may be an important factor related to asthma. The present study examined the window of time following acute upper and lower airway irritant exposure to determine the period of increased risk of immunological sensitization. Brown Norway rats were exposed to 87 ppm NO2 or 1000 ppm NH3 for 1 hr. A 30-min ovalbumin (OVA) exposure of 18.14 microg/liter air was given at various times based upon the time course of irritant associated inflammatory response (either immediately prior to or 1 or 7 days after the irritant exposure). OVA-only, NO2-only or NH3-only controls, and saline controls were also studied. Weekly booster exposures of OVA (or saline) were given. Circulating OVA-specific IgE, IgA, and IgG levels were quantified periodically during the 6 weeks of the study. Bronchoalveolar lavage (BAL) was also performed to examine the inflammatory response to allergic and irritant challenge. Significant increases in OVA-specific IgE, IgG, and IgA antibody titers were seen in rats given the sensitizing OVA exposure within 1 day of the NO2, but not NH3 exposures. Enhancement of cellular infiltrate in BAL was noted in groups given the sensitizing OVA exposure within 1 day of the NO2 or NH3. It is concluded that the inflammatory and immunological response to antigen exposure can be modified by the site of respiratory tract irritation and the relative times of irritant and antigen exposure.