DNA variants and organophosphate neurotoxicity among emerging farmers in the Western Cape of South Africa.

BACKGROUND: Previous epidemiological studies investigating modification of organophosphate (OP) neurotoxicity by xenobiotic metabolizing enzymes (XMEs) polymorphisms have produced inconsistent results. METHODS: A cross-sectional study of 301 emerging farmers was conducted. Neurotoxicity testing included forward and backward recall, digit span, and vibration sensitivity testing. Questionnaire data included demography, potential confounders, and work history of pesticide exposures. Genomic DNA was analyzed from study participants for DNA variants of two glutathione S-transferases (GSTM1 and GSTT1), N-acetyltransferase 2 (NAT2), and Paraoxonase 1 (PON1). RESULTS: There was evidence of OP pesticide neurotoxicity modification by rs1799931 (NAT2), rs662 (PON1), and the null allele of GSTM1 in multivariate analysis. The strongest evidence of modification was observed for rs1799931 (NAT2) on the relationship between pesticide poisoning and impaired vibration sense. CONCLUSIONS: DNA variants of NAT2, PON1, and GSTM1 may modify OP neurotoxicity, and this requires further exploration.

Community mercury levels in the vicinity of peri-urban waste disposal sites and fossil fuel burning operations.

INTRODUCTION: A study was conducted as a result of concern about mercury absorption amongst residents of a peri-urban area in Cape Town, South Africa, in close proximity to waste disposal sites and an industrial area. STUDY METHODS: The study compared urine mercury concentrations in a random sample of adult residents and children in both the formal and informal housing settlements of the "exposure" area (n = 90) and a control area (n = 90). A short questionnaire elicited demographic, lifestyle and medical details and possible occupational, household and environmental mercury exposures. RESULTS: The two samples were comparable with respect to background and potential confounding variables. The prevalence of urinary mercury levels>or=the WHO reference range in the exposure area was also higher than that in the control area (13% vs. 0%). The median urinary mercury concentrations in both study areas were below the World Health Organisation (WHO) reference level of 5.0 microg/g creatinine. The median level in the exposure area was slightly, but statistically significantly, higher than in the control area (1.1 vs. 0.25 microg/g creatinine), and the excess persisted after controlling for known possible mercury exposures. CONCLUSIONS: This is to our knowledge the first study of community inorganic mercury absorption in a developing country setting, and where airborne mercury was the exposure of concern. It was concluded that the health risk associated with the urinary mercury levels of residents in the exposure area was very low. However, low level environmental exposure in the area of concern could not be excluded.

Relationship between Urinary Pesticide Residue Levels and Neurotoxic Symptoms among Women on Farms in the Western Cape, South Africa.

BACKGROUND: This cross-sectional study aimed to investigate the relationship between urinary pesticide residue levels and neurotoxic symptoms amongst women working on Western Cape farms in South Africa. METHOD: A total of 211 women were recruited from farms (n=121) and neighbouring towns (n=90). Participant assessment was via a Q16 questionnaire, reporting on pesticide exposures and measurement of urinary OP metabolite concentrations of dialkyl phosphates (DAP) and chlorpyriphos, 3,5,6-trichloropyridinol (TCPY) and of pyrethroid (PYR) metabolite concentrations (3- phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), cis-2,2-dibromovinyl-2,2-dimethylcyclopropane-1-carboxylic acid (DBCA), and the cis- and trans isomers of 2,2-dichlorovinyl-2,2-dimethylcyclopropane-1-carboxylic acid. RESULTS: Median urinary pesticide metabolites were slightly (6%-49%) elevated in the farm group compared to the town group, with 2 metabolites significantly higher and some lower in the farm group. The prevalence of all Q16 symptoms was higher amongst farm women compared to town women. Three Q16 symptoms (problems with buttoning, reading and notes) were significantly positively associated with three pyrethroid metabolites (cis- and trans-DCCA and DBCA), although associations may due to chance as multiple comparisons were made. The strongest association for a pyrethroid metabolite was between problems with buttoning and DBCA (odds ratio (OR)=8.93, 95% confidence interval (CI):1.71-46.5. There was no association between Q16 symptoms and OP metabolites. CONCLUSIONS: Women farm residents and rural women from neighbouring towns in the Western Cape are exposed to OP and PYR pesticides. The study did not provide strong evidence that pesticides are associated with neurotoxic symptoms but associations found could be explored further.

Contamination of rural surface and ground water by endosulfan in farming areas of the Western Cape, South Africa.

BACKGROUND: In South Africa there is little data on environmental pollution of rural water sources by agrochemicals. METHODS: This study investigated pesticide contamination of ground and surface water in three intensive agricultural areas in the Western Cape: the Hex River Valley, Grabouw and Piketberg. Monitoring for endosulfan and chlorpyrifos at low levels was conducted as well as screening for other pesticides. RESULTS: The quantification limit for endosulfan was 0.1 microg/L. Endosulfan was found to be widespread in ground water, surface water and drinking water. The contamination was mostly at low levels, but regularly exceeded the European Drinking Water Standard of 0.1 microg/L. The two most contaminated sites were a sub-surface drain in the Hex River Valley and a dam in Grabouw, with 0.83 +/- 1.0 microg/L (n = 21) and 3.16 +/- 3.5 microg/L (n = 13) average endosulfan levels respectively. Other pesticides including chlorpyrifos, azinphos-methyl, fenarimol, iprodione, deltamethrin, penconazole and prothiofos were detected. Endosulfan was most frequently detected in Grabouw (69%) followed by Hex River (46%) and Piketberg (39%). Detections were more frequent in surface water (47%) than in groundwater (32%) and coincided with irrigation, and to a lesser extent, to spraying and trigger rains. Total dietary endosulfan intake calculated from levels found in drinking water did not exceed the Joint WHO/FAO Meeting on Pesticide Residues (JMPR) criteria. CONCLUSION: The study has shown the need for monitoring of pesticide contamination in surface and groundwater, and the development of drinking water quality standards for specific pesticides in South Africa.

Disposal of obsolete pesticides, the case of Ethiopia.

Ethiopia has accumulated obsolete pesticide stocks since pesticides were first imported in the 1960s due to prolonged storage of pesticides, inappropriate storage conditions because of poor storage facilities, the lack of trained staff and lack of national legislation for pesticide registration and monitoring system of pesticide use in the country. The first pesticide inventory conducted in 1995 led by FAO in collaboration with the government of Ethiopia had identified about 426 tonnes of obsolete pesticides mainly on state-owned agricultural farms and held by the Ministry of Health. However, these stocks have increased to over 1500 tonnes (including 200 active ingredients) as found in a detailed inventory conducted in 1999. The stocks included organochlorines (258.3 tonnes), organophosphates (155.4 tonnes), carbamates (58.5 tonnes), coumarines (14.9 tonnes), inorganics (30.2 tonnes), others (257.2 tonnes), mixed pesticides (70.4 tonnes) and unknown pesticides (307.1 tonnes) including both liquid and solid state formulations. The obsolete organochlorine pesticides stocks were mostly pesticides such as chlordane, DDT, dieldrin and lindane that are banned or restricted in most countries. The highest amount of a single active ingredient found was the organophosphate insecticide pirimiphos methyl (172.1 tonnes). All these stocks were disposed of in the first phase of disposal in Finland (during 2000-2003) by the hazardous waste management company Ekokem at a cost of about US$ 4.44 million. Another 1000 tonnes of obsolete pesticides have been identified and are currently being eliminated in a second disposal phase at a total cost of US$ 8,135,500. Along with the disposal process, a number of activities are being implemented to prevent future pesticides accumulation. These activities include the development and enforcement of pesticide policy, the implementation of Integrated Pest Management (IPM) and Integrated Vector Management (IVM), capacity building in terms of providing professional trainings, creating awareness among stakeholders on the environmental and human health hazard posed by obsolete pesticides as well as other actions to prevent their accumulation and enforcement of national legislations and policies related to pesticides use. However, pesticide use in the country is increasing. For instance, 12 years of pesticides import data (1996-2007) by the Ministry of Agriculture shows that 2973 tonnes of pesticides were imported between 1996-1998, 3670 tonnes between 1999-2001, 5079 tonnes between 2002-2004 and 8302 tonnes between 2005-2007. Moreover, 6 years of insecticide import data (1996/97-2001/02) by the Ministry of Health shows that around 919 tonnes of insecticides were imported between 1996/97-1997/98, 812 tonnes between 1998/99-1999/00 and 970 tonnes between 2000/01-2001/02 for malaria and other vector borne diseases control.

Change in the quantity and acute toxicity of pesticides sold in South African crop sectors, 1994-1999.

BACKGROUND: South African pesticide market sales data, for two years, 1994 and 1999, were audited to identify change in total and per hectare mass sold and acute toxicity indicator (ATI) (kg sold/rat oral LD50) in the grape, pome, stone fruit, potato and wheat sectors. RESULTS: Total pesticide sales (62%), amount per hectare (42%) and number of active ingredients (23%) increased in 1999 compared to 1994 with the grape fruit sector, the most significant contributor over the two years. Total (14%) and per hectare ATI (19%) decreased in 1999, but not substantially with the potato sector the most significant contributor. CONCLUSIONS: Toxic pesticides were still used in 1999 which highlights a need to develop alternative agricultural and non-chemical pest control methods that reduce usage of pesticides.

The impact of aerial application of organophosphates on the cholinesterase levels of rural residents in the Vaalharts district, Northern Cape Province, South Africa.

A cluster of Guillaine-Barre syndrome cases in the Vaalharts region, South Africa prompted an investigation of the impact of aerial organophosphate spraying on cholinesterase levels of residents in the region. A prospective study of cholinesterase levels among residents and workers in the area and a control area was performed. Standardized red blood cell cholinesterase levels amongst participants were monitored before (round 1), during (round 2), and after (round 3) the 1996/1997 aerial spraying season. Participants were assigned environmental exposure categories based on the time since (within 10 or 30 days) and distance from (on farm, on neighboring farm, <10 km from farm) aerial pesticide application. There were 342 participants in round 1, of whom 78% participated in round 2, 62% in round 3, and 56% in all three rounds. There was an increase in cholinesterase levels in round 2 (mean increase = 5.96+/-6.25 IU/g hemoglobin) and then a decrease in round 3 (6.17+/-6.51), significantly associated with environmental exposure (participants living on farm or neighboring farm and <10 km from spraying area) controlling for age, gender, alcohol dependence, and usual and recent domestic and occupational pesticide use (e.g., for round 2-round 1 cholinesterase differences, beta; (exposed group relative to unexposed)=5.72+/-1.21 IU/g hemoglobin, P = 0.000, R2 = 0.27, n = 171). The results show a shift in cholinesterase levels associated with residence in the spraying area, but in the direction opposite to that expected from the spraying of pesticides. Seasonal fluctuations in ambient temperature during the study may have influenced the results.

The relationship between reproductive outcome measures in DDT exposed malaria vector control workers: a cross-sectional study.

BACKGROUND: The utility of blood reproductive endocrine biomarkers for assessing or estimating semen quality was explored. METHODS: A cross-sectional study of 47 DDT exposed malaria vector control workers was performed. Tests included blood basal and post gonadotrophin releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), estradiol (E2) and inhibin; a questionnaire (demographics and general medical history); a physical examination and semen analysis. Semen parameters were determined using either/or or both WHO or the strict Tygerberg criteria. Relationships between semen parameters and endocrine measures were adjusted for age, duration of abstinence before sampling, presence of physical abnormalities and fever in the last two months. All relationships between specific endocrine hormones were adjusted for age and basal SHBG. RESULTS: Multiple logistic regression showed a consistent positive relationship (prevalence odds ratio (POR) = 8.2, CI:1.4-49.2) between low basal inhibin (< 100 pg/ml) and low semen count (< 40 million) and density (< 20 million/ml); consistent positive, but weaker relationships (1 > POR < 2) between abnormally low semen count as well as density and baseline and post GnRH FSH; and positive relationships (POR = 37, CI:2-655) between the prevalence of high basal estradiol (> 50 pg/ml) and abnormal morphology (proportion < 5%) and low motility (proportion < 50%). Most of the expected physiological relationships between specific endocrines were significant. CONCLUSION: The study has demonstrated that low basal inhibin, elevated basal FSH and high basal E2 can serve as markers of impaired semen quality.

Cost analysis of ELISA, solid-phase extraction, and solid-phase microextraction for the monitoring of pesticides in water.

The implementation of a pesticide water monitoring program in South Africa is limited by a lack of financial and analytical resources. A cost analysis of three analytical methods, enzyme-linked immunosorbent assays (ELISA), solid-phase microextraction (SPME), and traditional solid-phase extraction methods (SPE), was conducted. The cost analysis assumed a hypothetical scenario in terms of the sampling area (a grape farming rural region in the Western Cape province of South Africa), sample collection (weekly grab samples collected from eight sites by an environmental health officer in a nearby town), transport of samples (via courier), and analysis (endosulfan and chlorpyrifos analysis conducted by a local higher educational institution laboratory in Cape Town). The cost per sample for the three analytical methods was determined by estimating the annual capital costs, including building and equipment, and recurrent costs, including transport, personnel, supplies, and building operating costs. At the optimal utility of resources, SPME had the lowest cost per sample (US $37), followed by SPE (US $48.50) and ELISA (US $60). Recurrent costs formed the bulk of the costs of all three methods (91-97%). The cost of supplies was particularly high for ELISA (US $34 per sample). The cost per sample estimated for all three methods is substantially lower than those quoted by other laboratories in South Africa. The low cost of SPME is particularly important because of the sensitivity and reliability of this method and the faster output compared to SPE, and SPME is recommended for the long-term monitoring of pesticide pollution.

Exploration of different methods for measuring DDT exposure among malaria vector-control workers in Limpopo Province, South Africa.

DDT compounds are used in many developing countries, including South Africa, for the control of malaria vectors. This study investigated biological exposures among workers in relation to job history. A cross-sectional study of 59 workers at the Malaria Control Centre (MCC) in Tzaneen, South Africa, was performed. Tests included a job history questionnaire and the measurement of serum o'p' and p'p' isomers of DDE, DDT, and DDD, corrected for serum total lipids. Forty-seven (80%) workers donated a blood sample for the determination of serum DDT. The mean number of years worked at the MCC (malaria years) was 15.8+/-7.8 years and the mean serum DDT was 94.3+/-57.1 microg/g of lipid. There were no significant associations between short-to-medium-term serum DDT exposure measures (o'p'-DDE and o'p' and p'p' isomers of DDD and DDT) and malaria years. The long-term exposure measure, p'p'-DDE, was significantly associated with malaria years (beta=3.0+/-1.2 microg/g lipid/year; P=0.001; n=47; adjusted for age), but only 27% variance of p'p'-DDE was explained. Blood total DDT uncorrected for lipid content was strongly related to corrected levels (B=0.74+/-0.48, P=0.00, R2=0.77), but uncorrected p'p'-DDE had a weaker association (B=0.0024+/-0.0013, P=0.074; R2=0.53) with malaria years than did corrected levels (beta=0.042+/-0.017; P=0.016; R2=0.56). The results show that serum DDT levels for malaria vector-control workers in South Africa with a long-term spraying history are high. Job history information on DDT exposures must be very detailed in order to provide valid estimates of exposure.

The long-term effects of DDT exposure on semen, fertility, and sexual function of malaria vector-control workers in Limpopo Province, South Africa.

Hormonally active chemicals in the environment such as DDT have been associated with declining male reproductive health, especially semen quality. A cross-sectional study of 60 workers was performed near the Malaria Control Center (MCC) in Tzaneen, Limpopo Province, South Africa. Tests included a questionnaire (sexual function, fertility, and job history), a physical examination of the reproductive system, and semen analysis (produced via coitus interruptus or masturbation). Sperm count, density, and motility using the World Health Organization criteria and morphology using the strict Tygerberg criteria were determined. Serum o'p' and p'p' isomers of DDE, DDT, and DDD were measured. Forty-eight (81.0%) participants produced a semen sample, while all completed the questionnaires and physical examination. The mean sperm count was 93.8+/-130.3 million, and sperm density was 74.6+/-85.1 million/mL. The mean normal morphology score was 2.5+/-1.8% of subjects. Eighty-four percent of morphology scores were below either the WHO or the Tygerberg criteria, with the highest individual score being 6%. Self-perceived current problems with sexual function ranged between 10% and 20%. The most prevalent genital abnormality was abnormal testis disposition at 71%. There were few significant associations between DDT exposure measures (measured as years worked at MCC and serum DDT) and reproductive outcomes. p'p'-DDT was negatively associated with semen count (beta=-3.7+/-1.7; P=0.04; R2=0.05 adjusted for age, abstinence, physical abnormality, and fever in last 2 months). While the semen quality in the study was less than normal, no strong evidence for a DDT effect was found.

The hormonal effects of long-term DDT exposure on malaria vector-control workers in Limpopo Province, South Africa.

DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] compounds, used in many developing countries, including South Africa, for the control of malaria vectors, have been shown to be endocrine disruptors in vitro and in vivo. The study hypothesis was that male malaria vector-control workers highly exposed to DDT in the past should demonstrate clinically significant exposure-related anti-androgenic and/or estrogenic effects that should be reflected in abnormalities in reproductive hormone levels. A cross-sectional study of 50 workers from three camps situated near the Malaria Control Center (MCC) in Tzaneen was performed. Tests included blood sampling before and after a gonadotropin-releasing hormone (GnRH) challenge (100 microg). Serum o'p' and p'p' isomers of DDE, DDT, and DDD and basal and post-GnRH challenge hormone levels, including luteinizing hormone, follicle-stimulating hormone, testosterone, sex hormone-binding globulin, estradiol (E2), and inhibin, were measured. The mean number of years worked at the MCC was 15.8+/-7.8 years and the mean serum DDT was 94.3+/-57.1 microg/g of lipid. Mean baseline E2 levels (62.4+/-29.9 pg/mL) exceeded the laboratory reference range. Associations between DDT exposure measures (years worked at the MCC and DDT compounds) and hormonal outcomes were weak and inconsistent. The most important finding was a positive relationship of baseline E2 and baseline testosterone with DDT compounds, especially with p'p'-DDT and -DDD. The strongest association found, adjusted for age and SHBG, was between baseline estradiol and p'p'-DDT (beta=1.14+/-0.33 pg/mL/microg/ g lipid, P=0.001, R2=0.31, n=46). An overall anti-androgenic mechanism best explains the results, but with a number of inconsistencies. Associations might be due to chance, as multiple comparisons were made. The results therefore do not suggest an overt anti-androgenic or estrogenic effect of long-term DDT exposure on hormone levels, but correlations do exist in a manner that is not understood.