Consequences of Oral Gavage during Gestation and Lactation on Rat Dams and the Neurodevelopment and Behavior of Their Offspring.

Oral gavage is a popular route of drug administration during preclinical testing. Despite the growing body of information regarding the effects of oral gavage and the stress associated with this technique, the consequences of such exposure during pregnancy or lactation have rarely been investigated. Therefore, we sought to determine the consequences of oral gavage exposure during pregnancy and lactation on the neurodevelopment and behavior of rat offspring. Pregnant Sprague-Dawley dams underwent either no treatment or oral gavage of distilled water once daily from gestational day 7 until postnatal day 21. Oral gavage treatment had no significant effect on maternal parameters, including bodyweight gain, duration of gestation, litter size, and incidence of neonatal death. Compared with their counterparts from untreated dams, male and female progeny of gavaged dams had longer body lengths on PND 7 and 14 but reduced forelimb grip performance on PND 14 and 17. Therefore, the use of oral gavage during pregnancy and lactation in rats can have opposite effects on the somatic and behavioral development of the offspring. These factors should be considered when using oral gavage as a route of administration during pregnancy. In addition, the inclusion of no-treatment controls is important because they may reveal various restraint-associated effects.

Multiple myeloma and occupation: a pooled analysis by the International Multiple Myeloma Consortium.

OBJECTIVE: We investigated occupational risk of multiple myeloma (MM) in a pooled analysis of five international case-control studies. METHODS: We calculated the odds ratio and its 95% confidence interval for selected occupations with unconditional regression analysis in 1959 MM cases and 6192 controls, by pooling study-specific risks using random-effects meta-analysis. Exposure to organic solvents was assessed with a job-exposure matrix (JEM). RESULTS: Gardeners and nursery workers combined, most likely exposed to pesticides, showed a 50% increase in risk (OR = 1.50, 95% CI 0.9-2.3), while other farming jobs did not. Metal processors (OR = 1.55, 95% CI 0.9-2.3), female cleaners (OR = 1.32, 95% CI 1.0-1.8), and high level exposure to organic solvents (OR = 1.38, 95% CI 0.96-1.8) also showed moderately increased risks. CONCLUSIONS: Additional case-control studies of MM aetiology are warranted to further investigate the nature of the repeatedly reported increase in MM risk in several occupational groups.

Multiple Myeloma and lifetime occupation: results from the EPILYMPH study.

BACKGROUND: The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case-control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set. METHODS: 277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/- 5 years), centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI) were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures. RESULTS: A low level of education was associated with MM OR=1.68 (95% CI 1.02-2.76). An increased risk was observed for general farmers (OR=1.77; 95% CI 1.05-2.99) and cleaning workers (OR=1.69; 95% CI 1.04-2.72) adjusting for level of education. Risk was also elevated, although not significant, for printers (OR=2.06; 95% CI 0.97-4.34). Pesticide exposure over a period of ten years or more increased MM risk (OR=1.62; 95% CI 1.01-2.58). CONCLUSION: These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.

Occupational exposure to ethylene oxide and risk of lymphoma.

BACKGROUND: Ethylene oxide, a high-volume commodity, is an established human carcinogen, although the relevant epidemiologic evidence is limited. METHODS: We explored the association between occupational exposure to ethylene oxide and risk of lymphoma in a case-control study, including 2347 lymphoma cases first diagnosed in 1998-2004 and 2463 controls, from 6 European countries. The diagnosis of lymphoma was based on the 2001 World Health Organization Classification of lymphoma. Occupational exposure to ethylene oxide was retrospectively assessed by industrial hygienists and occupational physicians based on detailed self-reported information. We modeled risk of lymphoma with unconditional logistic regression analysis as a function of various exposure measures, adjusting for age, sex, and participating center. RESULTS: Thirty-one cases and 27 controls (1.2% of the total study population) were defined as ever having been exposed to ethylene oxide (odds ratio = 1.3 [95% confidence interval [CI] = 0.7-2.1]). Lymphoma risk showed a 4.3-fold increase associated with medium-high frequency of exposure to ethylene oxide (95% CI = 1.4-13). Among major subtypes, chronic lymphocytic leukemia was consistently associated with ethylene oxide exposure, related in a dose-response manner to probability, frequency, and duration of exposure, as well as to cumulative exposure and (less definitively) with exposure intensity. CONCLUSIONS: Our results add to the evidence that ethylene oxide is a human carcinogen.