Immunotoxicity Evaluation of Jet A Jet Fuel in Female Rats After 28-Day Dermal Exposure

Abstract

The potential for jet fuel to modulate immune functions has been reported in mice following dermal, inhalation, and oral routes of exposure; however, a functional evaluation of the immune system in rats following jet fuel exposure has not been conducted. In this study potential effects of commercial jet fuel (Jet A) on the rat immune system were assessed using a battery of functional assays developed to screen potential immunotoxic compounds. Jet A was applied to the unoccluded skin of 6- to 7-wk-old female Crl:CD (SD)IGS BR rats at doses of 165, 330, or 495 mg/kg/d for 28 d. Mineral oil was used as a vehicle to mitigate irritation resulting from repeated exposure to jet fuel. Cyclophosphamide and anti-asialo GM1 were used as positive controls for immunotoxic effects. In contrast to reported immunotoxic effects of jet fuel in mice, dermal exposure of rats to Jet A did not result in alterations in spleen or thymus weights, splenic lymphocyte subpopulations, immunoglobulin (Ig) M antibody-forming cell response to the T-dependent antigen, sheep red blood cells (sRBC), spleen cell proliferative response to anti-CD3 antibody, or natural killer (NK) cell activity. In each of the immunotoxicological assays conducted, the positive control produced the expected results, demonstrating the assay was capable of detecting an effect if one had occurred. Based on the immunological parameters evaluated under the experimental conditions of the study, Jet A did not adversely affect immune responses of female rats. It remains to be determined whether the observed difference between this study and some other studies reflects a difference in the immunological response of rats and mice or is the result of other factors.

Subacute effects of inhaled Jet Fuel-A (Jet A) on airway and immune function in female rats

“…Likewise, the number and percentage of CD45þ, CD5þ (total T cells), CD4 þ CD5þ (T helper) and CD8 þ CD5þ (cytotoxic T cells) cells were not altered at any tested dose (Mann et al, 2008). Based on the alveolar ventilation rate for rats provided by Brown et al (1997), the $150 g rats in the current study would breathe $4.8 l/h.…”

“…Rossi et al, 2001 andPfaff et al, 1995 used male rats only). Also, female rats have historically been preferred for immunotoxicity evaluation due to their greater immune response, compared to males, improving the likelihood of detecting a response, if one is present (Mann et al, 2008). In particular, females typically have stronger antibody responses than males (World Health Organization, 2012).…”

“…A dermal study in female Sprague-Dawley rats, however, found jet fuel to lack immunotoxicity. Mann et al (2008) suggest that the differences between studies may be due to species susceptibility differences or factors such as the minimization of irritancy in their study, thus potentially eliminating changes in immune system parameters that are secondary to inflammation. In laboratory animals, cutaneous JP-8 exposures cause irritation.…”

Assessment of the immunotoxic potential of trichloroethylene and perchloroethylene in rats following inhalation exposure

“…AFC responses were slightly variable across the dose groups, but within known and established variability for this endpoint in the literature (White et al, 2005;Mann et al, 2008) and consistent with the lack of an immunosuppressive response to PERC. In contrast, animals administered room air but receiving IP injections of the positive control CYP (20 mg/kg for 4 days) demonstrated a marked reduction in splenocyte numbers and a suppression of the AFC responses.…”

A 13-Week Dermal Repeat-Dose Neurotoxicity Study of Hydrodesulfurized Kerosene in Rats

“…15 Repeated application will cause severe skin injury in many common animal models. Some methods of mitigating jet A dermal irritation in rats were explored previously, 21 including rotating the site of application, diluting 50% with 4:1 acetone-olive oil, and diluting 50% with mineral oil. Only the use of mineral oil resulted in an acceptable degree of skin irritation over 28 days of repeated application.…”