LEAD-ASSOCIATED HEALTH HAZARDS AND IMMUNOTOXIC EFFECT AMONG PLUMBERS

*El-Safty A.M.K., **Metwally F.M.

*Dept. of Industrial Medicine and Occupational Diseases, Faculty of Med.Cairo Univ.

**Dept. of Industrial Medicine and Occupational Diseases. National Research Center

Abstract:

Although the toxicity of lead was recognized centuries ago, cencern was restricted to overt symptoms as colic, enchephalopathy, anemia or renal disease. Recently extensive investigations indicated that lead has a potential immunotoxicity. We studied chronic lead effect on both humoral immunoglobulins and urinary NAG as indicators of early lead toxicity. We observed a reduction of IgA, IgM, IgG levels among the exposed workers. This is negatively correlated with blood lead levels. A positive correlation between renal function parameters (NAG, serum urea, creatinine) and blood lead levels was also demonstrated. We suggested monitoring the level of immunoglobulin and urinary NAG as indicators of lead toxicity.

Introduction:

Lead is one of the oldest toxins. Reports of lead poisoning date to ancient Greece and high levels of lead have been found in ancient Egyptian mummies. Industrial lead-induced toxicity commonly occurs after prolonged exposure to lead or its compounds. Chronic lead intoxication most commonly presents with: gastrointestinal complaints (abdominal discomfort, constipation, colic), CNS effects (lack of concentration, mood changes, irritability), peripheral neuropathy (tremors, muscle aches, wrist and foot drop) other organ damage (anaemia , kidney impairment, hypertension) ⁽¹⁾.

Recently, it was reported that the immunotoxic effects of chemicals tend to precede the occurrence of traditional toxicological manifestations and have therefore the potential to serve as early warning mechanisms of impending disease among lead exposed persons⁽²⁾.

Aim of the work:

The aim of our work is to study lead-induced toxicity among a group of plumbers. Special emphasis was directed towards renal and immunotoxic lead effects.

Subjects and Methodology:

The effect of lead exposure among 32 plumbers working in a sanitary appliances workshop, was investigated. Workers were engaged mainly in melting lead alloy for soldering of pig iron pipes used for sewage disposal. The workers were not acquainted with using protective equipment. The duration of exposure ranged from 5 to 30 yrs., with a mean of 18.16 +8.17 yrs. A control group of 20 males with matching age , socioeconomic status and smoking habits, was included in our work. All participants were subjected to full history taking, clinical examination and investigations involving:

(1) Blood lead level, (2) Serum immunoglobulins IgA, IgM, IgG levels were measured using deep frozen serum samples and radial immuno-diffusion (RID) technique was applied. (3)Renal function tests serum urea, creatinine and N acetyl β-D glucosaminidase (NAG).

Results & Discussion:

It is certain that, immunotoxic effects tend to appear before traditional toxicological manifestations, they have the potential to serve as early warning mechanisms of impending clinical disease⁽³⁾. Early studies reported that, data on immunological effects in humans occupationally exposed to lead are inconsistent, but indicated that while lead may have an effect on the cellular component of the immune system, the humoral component is relatively unaffected. Experimental studies suggest that lead alters the humoral immune system and lead-induced immun-suppression occurs at low dosages in experimental animals in which there is no apparent evidence of toxicity⁽⁴⁾.

The immunosuppressive effect of lead on humoral responsiveness was found in workers chronically exposed to lead. This was ascribed to the peripheral B-lymphocytes pool reduction. Immunoglobulin A (IgA) is the major immunoglobulin class of sero-mucous secretions, part of the defense system for external body surface (respiratory and gastrointestinal). Workers occupationally exposed to lead with blood lead levels of 21-85Ug/dL (median: 55Ug/dL) have a significant suppression of secretory IgA levels and have more colds and influenza infections per year⁽⁵⁾. Also children with asymptomatic increase in blood lead levels appear to have more frequent febrile illness⁽⁶⁾. Similarly our study showed a significant decrease in IgA level in exposed group compared to the control group. Also we found a negative correlation between blood lead and IgA levels (table3). Further support for our results was demonstrated by Castillo and his coworkers in 1991⁽⁷⁾, who assessed the level of immunoglobulin in lead exposed workers and found a decreasing immunoglobulin level while increasing lead concentration in blood.

In normal adults, immunoglobulin G (IgG) constitutes approximately 75% of the total serum immunoglobulins. It has been found that chronic lead exposure results in reduced IgG levels⁽³⁾. Our results demonstrated statistically lower IgG level in lead exposed group than in control group, and this decrease was negatively correlated with the increased blood lead level among exposed group (table2). Further support was documented by Ewers and his colleagues in 1982⁽⁵⁾, who found a significant negative correlation between blood lead levels and serum levels of IgG in a group of lead workers and this goes with what Kowolenko et al. (1992) ⁽⁸⁾ had found. Also, a statistically significant decrease of IgG titers was found especially in those chronically exposed lead workers, leading to immunosuppressive effects⁽⁹⁾.

Immunoglobulin M is the first class of immunoglobulin synthesised in response to particulate antigens. It is a multivalent globulin and deals most efficiently with polyvalent antigens such as bacteria and viruses. It also works by activating complement. A decline of IgM serum concentrations has been suggested by Jaremin (1990) in exposure to lead⁽⁹⁾. Similarly, statistically significant reduction of serum IgM among plumbers was demonstrated in our study (table2). Table(3) showed a negative correlation between serum IgM and blood lead levels among exposed workers to lead.

In our study, N-acetyl β-D glucosaminidase (NAG) has been used as a marker of proximal tubular dysfunction among workers occupationally exposed to lead. The selection of this parameter is based on many studies concluding that monitoring NAG showed superiority over β2 microglobulin or retinol binding protein (RBP) as an early and sensitive marker of probable renal impairment⁽¹⁰⁾. Also in our study we measured serum urea and creatinine levels to monitor renal affection. Significantly elevated serum urea, creatinine and NAG levels were demonstrated in the exposed group compared to the control group (table 2). This elevation was positively correlated with the blood lead levels in the exposed group (table 3).

Our data derived from this relatively small number of workers exposed to lead (N=32) may limit its generalizability. We cannot determine from our data whether immuno-toxicity or nephrotoxicity of lead occur first.Based on the results derived from our study, together with data from previous studies, we recommend measuring the level of humoral immunoglobulins and urinary NAG for proper monitoring of early lead toxicity.

Table (1) Prevalence of lead exposure associated manifestations among the studied groups:

	Control group No %	Exposed group No %	X2 test	P value
Gastrointestinal complaints: - Abdominal discomfort - Constipation - Colic CNS effects: - Lack of concentration - Mood changes - Irritability - Headache Peripheral nervous system effects: - Tremors - Numbness - Muscle aches - Wrist or foot drop Other organ affection: - Anemia (pallor) - Loin pain - Hypertension	1 5 1 5 0 0 3 15 2 10 0 0 3 15 0 0 0 0 1 5 0 0 2 10 0 0 3 15	4 12.5 3 9.4 4 12.5 14 43.8 12 37.5 13 40.6 23 71.9 14 43.8 21 65.6 4 12.4 0 0 7 21.9 5 15.6 22 68.8	0.17 0.33 *1.23 3.41 3.44 9.85 13.73 9.85 19.37 0.17 ----- 0.53 *1.89 12.17	>0.05 >0.05 >0.05 >0.05 >0.05 <0.01 <0.01 <0.01 <0.01 >0.05 ----- >0.05 >0.05 <0.01

* an expected value is less than 5, so the test of significance used is the Fisher exact test.

Table (2) Results of blood investigations among the studied groups:

	Control group Mean S.D	Exposed group Mean S.D	t-test	P value
Blood Lead level (μg/dL) Immunoglobulin level - IgG (gm/L) - IgM (gm/L) - IgA (gm/L) Renal function tests: - Urea - Creatinine - NAG (U/ m mol. Urinary creatinine)	18.99 2.12 9.7 2.69 1.37 0.21 4.79 0.29 26.65 2.46 0.79 0.09 2.72 0.51	38.49 9.35 5.77 5.16 0.45 0.27 2.89 0.57 36.66 6.52 1.08 0.2 10.31 5.69	83.69 9.85 34.92 36.24 43.03 34.77 35.08	<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01

Table (3) Correlation coefficient between blood lead and immunoglobulins and kidney function test results:

Correlation coefficient	R =	F test	P value
Immunoglobulin level - IgG (gm/L) - IgM (gm/L) - IgA (gm/L) Renal function tests: - Urea - Creatinine - NAG (U/ m mol. Urinary creatinine)	- 0.52 - 0.72 - 0.91 + 0.69 + 0.76 + 0.59	18.11 57.36 97.3 70.25 45.71 26.92	<0.01 <0.01 <0.01 <0.01 <0.01 <0.01

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