Registration Dossier

Toxicological information

Epidemiological data

Currently viewing:

Administrative data

epidemiological data
Type of information:
experimental study
Adequacy of study:
supporting study
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Sample size was limited. Participation among additives workers was low, and may have skewed results. It is unknown if the additives workers in the study were representative of the whole group. There was no follow-up study.

Data source

Reference Type:
Evaluation of reproductive function among men occupationally exposed to a stilbene derivative. I. Hormone and physical status.
Grajewski B. et al.
Bibliographic source:
Am. J. Ind. Med. 29, 49- 57.

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
repeated dose toxicity: inhalation
toxicity to reproduction / fertility
Test guideline
no guideline followed
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-diaminostilbene-2,2'-disulphonic acid
EC Number:
EC Name:
4,4'-diaminostilbene-2,2'-disulphonic acid
Cas Number:
Molecular formula:
2,2'-ethene-1,2-diylbis(5-aminobenzenesulfonic acid)
Details on test material:
no data


Details on study design:
Ninety-three (72%) of the 129 workers initially identified as potential subjects participated in the study. The study group consisted of 29 males (88%) currently exposed to substance, 23 males who had been exposed to the material in the past, but were no longer exposed (88%), and 41 males working in an area where plastic additives, but no substance was produced (59%). Fifteen were excluded (13 based on exposure criteria and 2 based on previous testicular abnormalities prior to employment). Seven workers were added after confirming eligibility. The final study group included 30 current workers (minimum of 30 days immediately previous to study), 20 former workers (currently working in other areas who had worked 30 days or more in the production area) and 35 additives workers.
Demographic characteristics, smoking and drinking habits, work habits, occupational exposures, medical history related to decreased libido such as diabetes, thyroid disease, obesity, use of certain medications, reproductive history and whether the subjects believe that workplace exposures could affect sex drive or fertility were listed on questionnaires. Blood serum was analyzed for total and free testosterone, follicle stimulating hormone (FSH), luteinizing hormone, prolactin and estradiol. The collection of blood samples was shift-standardized. A NIOSH physician blinded to exposure status conducted physical examinations, which consisted of an evaluation of secondary sexual characteristics and external genitalia (including testicular volume).
Exposure assessment:
not specified

Results and discussion

The mean ages of the current and former workers and controls were 45.9, 45.2, and 39.0 years, respectively. The ages of the current and former
workers were significantly higher than the additives workers (p < 0.01). The current workers had worked in the production area significantly longer than the former workers and controls. The numbers of subjects reported ever fathering a pregnancy were similar among groups. The proportion of current and former workers who believed that workplace exposures could cause sexual problems (68.0 and 60.0, respectively) was significantly (p < 0.01) greater than in the controls (23.3%). Current and former workers had significantly (p < 0.05) lower mean total testosterone concentrations (458 and 442 ng/dl, respectively) than controls (556 ng/dl). Current and former workers were 3.6 and 2.2 times more likely than additives workers to have lowest quartile total testosterone levels (<386 ng/dl) after adjustment for age and body mass index. Duration of employment was inversely correlated with total testosterone concentrations (p = 0.048). Average FSH concentrations were lower (but not significantly) in the former in the former workers than in the controls (6.7 vs. 10.3 mIU/ml, p < 0.06). The concentrations of the other hormones were similar among groups. The group mean concentrations of all hormones were within clinically normal ranges. There was no difference in testicular volumes between groups. Seven cases of bilateral gynecomastia were found (current workers, N = 2 [8%], former workers, N=3 [23%] and additives workers, n = 2 [8%]). A greater percentage of subjects in the additives control group (14.3%) had consulted a doctor because of a fertility problem than subjects in the worker (6.7%) or former worker groups (5.0%).
Confounding factors:
no data
Strengths and weaknesses:
no data

Applicant's summary and conclusion