AMBBICAN JOURNAL or EPIDEMIOLOGY
Copyright © 1979 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
Vol. 109, No. 3 Printed in
SPERM COUNT DEPRESSION IN PESTICIDE APPLICATORS EXPOSED TO DIBROMOCHLOROPROPANE R I. GLASS,1 R N. LYNESS,2 D. C. MENGLE,1 K. E. POWELL1 AND E. KAHN» Glass, R. I. (CDC, Atlanta, GA 30333), R. N. Lyness, D. C. Mengle, K. E. Powell and E. Kahn. Sperm count depression In pesticide applicators exposed to dibromochloropropane. Am J Epidemiol 109:346-351, 1979. Male pesticide applicators who worked with the nematocide dibromochloropropane (DBCP) were examined to determine the possible testlcular toxlcity from this exposure. Infertility and azoospermia which were first noted among factory workers exposed to DBCP were not observed among the applicators. Sperm count depression, however, was associated with the duration of exposure In the current year but not with exposure in past years. The extent of exposure to DBCP In the current year was also associated with an elevation of serum follicle stimulating hormone (FSH) but not of lutelnizing hormone (LH). Sperm count depression was limited to applicators Involved in irrigation setup work and In the calibration of equipment. These results suggest that the testlcular toxlcity of DBCP for men may occur In a shorter period than was previously reported, that the effect may be reversible in men with mild sperm count depression, and that public health measures might be directed at controlling specific application techniques. antinematodal agents; FSH; hydrocarbons, halogenated; LH; occupational diseases; oligospermia; propane; sterility
In September, 1977, dibromochloropropane (DBCP), a nematocide, was banned from production and field application in the US when male factory workers extensively exposed to DBCP were found to be infertile. DBCP had been known as a testicular toxin in animals, but its testicular toxicity for man had not been previously investigated. A series of epidemiologic studies are in progress to verify the original findings of male infertility and sperm count depression in factory workers involved in manufacturing
and formulating DBCP products. Environmental monitoring has not been optimal, but Whorton et al. (1) have noted azoospermia and elevated levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in men exposed for three years or more to airborne DBCP at levels of 0.4-0.6 ppm. The largest group of people exposed to DBCP are workers who apply the chemical in the field. In 1976, in California alone, several thousand independent farmers and professional pesticide
Received for publication July 5, 1978, and in final form October 16, 1978. Abbreviations: DBCP, dibromochloropropane; FSH, follicle stimulating hormone; LH, luteinizing hormone; Log SC, logarithmic transformation of the sperm count; SC, sperm count. 1 Chronic Diseases Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, GA 30333. (Reprint requests to Dr. Roger Glass at this address.) 1 Community Studies on Pesticides, California Department of Health, Berkeley, CA 94704. 3 Epidemiological Studies Laboratory, California
Department of Health, Berkeley, CA 94704. This study was funded by the Human Effects Monitoring Branch, Office of Pesticide Programs, Environmental Protection Agency. The authors thank the following: Ellen Bulf and Addison Truxton, California Department of Health (Fresno), and C. W. Miller and Frank Davida, Environmental Protection Agency, for their help with the field work; N. Okajio, Alta Bates Hospital, Berkeley, for laboratory assistance; and Dr. Philip Landrigan, Dr. Renate Kimbrough and Mary Ellen Gist for administrative support and encouragement.
346
347
SPERM COUNT DEPRESSION FROM DBCP
applicators applied more than one million pounds (>450,000 kg) of DBCP to more than 50,000 acres (>20,000 hectares) of fields. Because their exposure to DBCP differed from that of the factory workers, we studied these male pesticide applicators to determine whether or not current application practices place them at risk of depressed spermatogenic function. MATERIALS AND METHODS
We elected to study the pesticide applicators employed by professional firms in five counties of California. The counties were chosen because each had reported heavy DBCP use for 1976-1977 to the annual pesticide registry maintained by the California Department of Food and Agriculture. Records of the county agricultural agents were consulted to determine the firms which had applied DBCP in the past year. Twentytwo firms were identified and all but two agreed to participate in this study. The work records of each firm were reviewed to quantify the extent of DBCP exposure of each employee. The quality of record keeping varied widely between firms, making accurate quantification of exposure impossible, but it did allow men with heavy exposure to be identified as well as those with lesser or no exposure. The original study involved a matched pairs design in which 50 applicators with extensive DBCP exposure in the previous 8-12 months were to be compared with 50 other applicators, with no DBCP use, who were of the same age group (±5 years) and who were selected from a firm in the same area. We found that the firms' records generally underestimated the individuals' use, so that many controls had in fact extensive DBCP exposure in the current year. Exposure was therefore quantified for analysis using the number of days of DBCP use in the current year obtained from detailed work histories. At the end of the study, analysis of results of
31 perfectly matched pairs were the same as those found when the entire group was studied as a cohort with a wide range of exposures. We have presented the data in cohort form, since use of the larger numbers of men permitted further assessment of the risk involved in different application practices. All of the men were interviewed for occupational, medical and reproductive histories, and examined briefly by a physician. Blood was drawn for a hemogram (hematocrit, hemoglobin, WBC), clinical chemistries (SMA12) serum luteinizing hormone (LH), and follicle stimulating hormone (FSH). The men were instructed how to obtain a proper semen specimen and were asked to submit a sample for analysis the following morning. We did not require three days of abstinence before semen collection. All men with sperm counts below 20 million were asked to submit a second specimen following three days of abstinence. Analysis included a sperm count and morphologic reading. The laboratory work was performed at the Alta Bates Hospital, Berkeley, CA, and the sperm morphologies were read by Dr. John MacLeod of Cornell University Medical College, Ithaca, NY. RESULTS
Of 112 pesticide applicators selected for study, 101 (90 per cent) came for their initial screening exam, and 96 returned with a semen specimen the following day. Nine men (10 per cent) complained of clinical infertility defined as one year of unprotected coitus without conception (table 1). Of these, two had sperm counts of 2 weeks—2 months >2 months Past yearst 0 1 2-4 5-7 8+
Sperm count/cc «U x 10' «10*
Copyright © 1979 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
Vol. 109, No. 3 Printed in
SPERM COUNT DEPRESSION IN PESTICIDE APPLICATORS EXPOSED TO DIBROMOCHLOROPROPANE R I. GLASS,1 R N. LYNESS,2 D. C. MENGLE,1 K. E. POWELL1 AND E. KAHN» Glass, R. I. (CDC, Atlanta, GA 30333), R. N. Lyness, D. C. Mengle, K. E. Powell and E. Kahn. Sperm count depression In pesticide applicators exposed to dibromochloropropane. Am J Epidemiol 109:346-351, 1979. Male pesticide applicators who worked with the nematocide dibromochloropropane (DBCP) were examined to determine the possible testlcular toxlcity from this exposure. Infertility and azoospermia which were first noted among factory workers exposed to DBCP were not observed among the applicators. Sperm count depression, however, was associated with the duration of exposure In the current year but not with exposure in past years. The extent of exposure to DBCP In the current year was also associated with an elevation of serum follicle stimulating hormone (FSH) but not of lutelnizing hormone (LH). Sperm count depression was limited to applicators Involved in irrigation setup work and In the calibration of equipment. These results suggest that the testlcular toxlcity of DBCP for men may occur In a shorter period than was previously reported, that the effect may be reversible in men with mild sperm count depression, and that public health measures might be directed at controlling specific application techniques. antinematodal agents; FSH; hydrocarbons, halogenated; LH; occupational diseases; oligospermia; propane; sterility
In September, 1977, dibromochloropropane (DBCP), a nematocide, was banned from production and field application in the US when male factory workers extensively exposed to DBCP were found to be infertile. DBCP had been known as a testicular toxin in animals, but its testicular toxicity for man had not been previously investigated. A series of epidemiologic studies are in progress to verify the original findings of male infertility and sperm count depression in factory workers involved in manufacturing
and formulating DBCP products. Environmental monitoring has not been optimal, but Whorton et al. (1) have noted azoospermia and elevated levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in men exposed for three years or more to airborne DBCP at levels of 0.4-0.6 ppm. The largest group of people exposed to DBCP are workers who apply the chemical in the field. In 1976, in California alone, several thousand independent farmers and professional pesticide
Received for publication July 5, 1978, and in final form October 16, 1978. Abbreviations: DBCP, dibromochloropropane; FSH, follicle stimulating hormone; LH, luteinizing hormone; Log SC, logarithmic transformation of the sperm count; SC, sperm count. 1 Chronic Diseases Division, Bureau of Epidemiology, Center for Disease Control, Atlanta, GA 30333. (Reprint requests to Dr. Roger Glass at this address.) 1 Community Studies on Pesticides, California Department of Health, Berkeley, CA 94704. 3 Epidemiological Studies Laboratory, California
Department of Health, Berkeley, CA 94704. This study was funded by the Human Effects Monitoring Branch, Office of Pesticide Programs, Environmental Protection Agency. The authors thank the following: Ellen Bulf and Addison Truxton, California Department of Health (Fresno), and C. W. Miller and Frank Davida, Environmental Protection Agency, for their help with the field work; N. Okajio, Alta Bates Hospital, Berkeley, for laboratory assistance; and Dr. Philip Landrigan, Dr. Renate Kimbrough and Mary Ellen Gist for administrative support and encouragement.
346
347
SPERM COUNT DEPRESSION FROM DBCP
applicators applied more than one million pounds (>450,000 kg) of DBCP to more than 50,000 acres (>20,000 hectares) of fields. Because their exposure to DBCP differed from that of the factory workers, we studied these male pesticide applicators to determine whether or not current application practices place them at risk of depressed spermatogenic function. MATERIALS AND METHODS
We elected to study the pesticide applicators employed by professional firms in five counties of California. The counties were chosen because each had reported heavy DBCP use for 1976-1977 to the annual pesticide registry maintained by the California Department of Food and Agriculture. Records of the county agricultural agents were consulted to determine the firms which had applied DBCP in the past year. Twentytwo firms were identified and all but two agreed to participate in this study. The work records of each firm were reviewed to quantify the extent of DBCP exposure of each employee. The quality of record keeping varied widely between firms, making accurate quantification of exposure impossible, but it did allow men with heavy exposure to be identified as well as those with lesser or no exposure. The original study involved a matched pairs design in which 50 applicators with extensive DBCP exposure in the previous 8-12 months were to be compared with 50 other applicators, with no DBCP use, who were of the same age group (±5 years) and who were selected from a firm in the same area. We found that the firms' records generally underestimated the individuals' use, so that many controls had in fact extensive DBCP exposure in the current year. Exposure was therefore quantified for analysis using the number of days of DBCP use in the current year obtained from detailed work histories. At the end of the study, analysis of results of
31 perfectly matched pairs were the same as those found when the entire group was studied as a cohort with a wide range of exposures. We have presented the data in cohort form, since use of the larger numbers of men permitted further assessment of the risk involved in different application practices. All of the men were interviewed for occupational, medical and reproductive histories, and examined briefly by a physician. Blood was drawn for a hemogram (hematocrit, hemoglobin, WBC), clinical chemistries (SMA12) serum luteinizing hormone (LH), and follicle stimulating hormone (FSH). The men were instructed how to obtain a proper semen specimen and were asked to submit a sample for analysis the following morning. We did not require three days of abstinence before semen collection. All men with sperm counts below 20 million were asked to submit a second specimen following three days of abstinence. Analysis included a sperm count and morphologic reading. The laboratory work was performed at the Alta Bates Hospital, Berkeley, CA, and the sperm morphologies were read by Dr. John MacLeod of Cornell University Medical College, Ithaca, NY. RESULTS
Of 112 pesticide applicators selected for study, 101 (90 per cent) came for their initial screening exam, and 96 returned with a semen specimen the following day. Nine men (10 per cent) complained of clinical infertility defined as one year of unprotected coitus without conception (table 1). Of these, two had sperm counts of 2 weeks—2 months >2 months Past yearst 0 1 2-4 5-7 8+
Sperm count/cc «U x 10' «10*
