Sex difference of free erythrocyte protoporphyrin (FEP) level. III. Effect of estradiol on porphyrin metabolism, especially in FEP, in lead poisoned rats]

An experimental study of sex hormone on FEP level in rats was conducted to clarify sex difference of FEP level. A total of 42 male Donryu rats were divided into 7 groups; group I (control 1; olive oil injection without castration), group II (control 2; olive oil alone), group III (EL; estradiol in olive oil, 50 micrograms/kg.BW), group IV (EH; estradiol in olive oil, 250 micrograms/kg.BW), group II' (Pb; Pb 5 mg/kg.BW), group III' (PbEL; Pb 5 mg/kg.BW + estradiol in olive oil, 50 micrograms/kg.BW) and group IV' (PbEH; Pb 5 mg/kg.BW+estradiol in olive oil, 250 micrograms/kg.BW). Excluding group I, all rats of the 6 groups were castrated. After one week from castration, estradiol was subcutaneously injected 4 times a week, and lead was intraperitoneally injected once a week for 6 wk. Estradiol suppressed growth, Ht, Hb value and liver function, but did not show any evident effect on FEP, ALA-U and CP-U. Erythrocyte ALA-D activity in group IV' (Pb+estradiol at high dose) showed a level higher than that in group II' (Pb-treatment alone).     

Sex difference in free erythrocyte protoporphyrin (FEP) level. I. Sex difference in FEP level in healthy rural residents]

FEP and other hematological parameters were measured in 157 healthy rural residents (98 females and 59 males). The mean FEP in females was higher than in males (p less than 0.05); mean +/- SD = 62.98 +/- 19.36 and 54.57 +/- 21.20 micrograms/dl.pcv, respectively, although both of the means were within normal limits. There was no significant sex difference in erythrocyte ALA-D activity. Whole blood lead (Pb-B) level in females showed a tendency to be lower than in males, but there was no significant sex difference in erythrocyte lead level. The mean value of hematocrit (Ht), hemoglobin (Hb) and iron in serum (Fe-S) were lower in females than in males (p less than 0.01). Serum GOT and GPT level tended to be lower in females than in males (0.05 less than p less than 0.1). There was hardly any significant relationship between Pb-B and each parameter of lead exposure, because the subjects in this study were only rural residents with no occupational lead exposure and with their Pb-B levels being extremely low. As for the parameters of anemia, Fe-S was positively correlated with Ht and Hb level and negatively correlated with FEP level. By sex, Fe-S was correlated with Ht and FEP level only in females. As for the possible reasons why FEP level in females in higher than in male, women tended to have iron-deficiency induced by blood loss due to menstruation, pregnancy, and difference in dietary pattern from males.     

Effects of ethyl alcohol ingestion on the disturbance of porphyrin metabolism by lead

A study was made on the possibility of synergistic effects of ethyl alcohol and lead on porphyrin metabolism in rabbits. Experimental rabbits were divided into 4 groups. Group A was the control group not given any treatment, and the other 3 groups (Groups B, C and D) were treated with ethyl alcohol, lead, and ethyl alcohol and lead respectively, for 2 months. Ethyl alcohol solution (5%) was administered to rabbits in Groups B and D as drinking water on every weekday. The average dose of alcohol was 6 ml/kg/day (18 ml/cap/day). Lead was injected intravenously to rabbits in Groups C and D at a dose of 0.5 mg Pb/kg on alternate days (3 times per week). Furthermore, a large dose of Pb was administered to other rabbits (Group C'). In rabbits treated with alcohol alone (Group B), no effect was observed in the biochemical indicators related to porphyrin metabolism. In the groups treated with lead (Groups C and C') and with lead and alcohol combined (Group D), some biochemical changes in porphyrin metabolism developed with increase of Pb-B, i.e. increase of ALA-S activity and total porphyrin content in the bone marrow, elevation of FEP level, increase of ALA-U and CP-U, and decrease of ALA-D activity in erythrocytes. Comparison of Groups C and D showed that CP-U and ALA-U increased significantly in Group D, but no significant difference was observed between both groups in FEP and in ALA-S activity in the bone marrow and liver. The other laboratory measurements, such as total porphyrin contents in the liver and plasma, and GOT or GPT level in serum, showed no significant change in all the groups. In the present study, the biochemical changes suggesting synergism of lead and ethyl alcohol were observed slightly in ALA-U and CP-U but not in ALA-S and FEP. These results suggest that these changes are essentially due to lead rather than mutual enhancement of the direct effects of these two toxins on porphyrin metabolism. However, it still remains to be determined whether or not ethyl alcohol affects the liver and kidney functions which may be related to ALA and CP excretion.     

Effect of estradiol on heme biosynthetic pathway in lead-poisoned rabbits

Objectives To clarify the effect of the female hormone estradiol (Est) on heme biosynthesis in lead-poisoned rabbits, parameters indicating lead exposure, such as free erythrocyte protoporphyrin (FEP) level and δ-aminolevulinic acid dehydratase (ALA-D) activity, were determined. Methods Twenty-six male Japanese white rabbits (body weight (BW), 3kg) were divided into four groups: I (control), II (Est), III (Pb), IV (Est+Pb). About 3 weeks after castration, Est (3 mg/kg of BW) was injected intramuscularly, and 2 weeks thereafter, lead (1.2 mg/kg of BW) was injected intravenously. After the initial injection of each of these substances, the same dose of each of these substances was injected once a week until the 9th week. Results In groups III and IV, FEP level increased and ALA-D activity in the erythrocytes, bone marrow and liver decreased with an increase in lead concentration in blood. FEP level decreased significantly (p<0.01) in the 8th and 10th weeks after Est injection in group IV compared to with that in group III and was not elevated in group II compared with that in group I. ALA-D activity in the erythrocytes, bone marrow and liver increased significantly in group II compared with that in group I, whereas Ht and Hb levels decreased in group II compared with those in group I, and decreased in group IV compared with those in group III. The level of iron in plasma (Fe−P) was within the normal range during experiment. Conclusions In this study, Est did not increase FEP level. From the above results regarding FEP level and ALA-D activity, Est may prevent an increase in FEP level caused by lead. Ht and Hb levels, which are the parameters of anemia, decreased mainly as a result of Est exposure rather than lead exposure.     

Response of free erythrocyte porphyrin and urinary δ -aminolevulinic acid in men and women moderately exposed to lead

Summary The responses of various biological parameters of the haem biosynthesis pathway in a group of adult male and female workers moderately exposed to inorganic lead have been compared. The identical range of blood lead levels in both groups indicates a similar degree of exposure. Women, however, exhibit a larger increase in free erythrocyte porphyrin (FEP) and in urinary -aminolevulinic acid (ALA-U) than men.The earlier response in women is probably not due to a relative degree of anaemia (menstrual blood loss) as compared to men, since there is no significant correlation between haemoglobin (Hb) and FEP or ALA-U, and consequently standardization for the same Hb-content does not modify the independent effect of lead on the FEP and ALA-U responses. A greater susceptibility to Pb of the haem biosynthesis pathway in women has therefore been confirmed by the results of the present epidemiological survey among workers of both sexes.A preliminary and limited survey on children (11 to 12 years old) of schools situated at less than 1 km from a Pb-processing plant revealed increased FEP and blood lead concentrations and demonstrated that like women children exhibit an earlier biological response to Pb-B than adult men.     

Parameters indicative of absorption and biological effect in new lead exposure: a prospective study

Tola, S., Hernberg, S., Asp, S., and Nikkanen, J. (1973).British Journal of Industrial Medicine,30, 134-141. Parameters indicative of absorption and biological effect in new lead exposure: a prospective study. Determinations have been made of the blood and urinary lead concentrations (Pb-B, Pb-U), haemoglobin concentrations (Hb), packed blood cell volumes (Hcr), urinary δ-aminolevulinic acid (ALA-U) and coproporphyrin concentrations (CP-U), as well as erythrocyte δ-aminolevulinic acid dehydratase activities (ALA-D), in respect of 33 workers entering occupational lead exposure for the first time in their lives. In a follow-up study lasting from one to four months samples were taken before exposure began, initially at intervals of two days and subsequently at intervals of one to two weeks. Nine control subjects were studied for Pb-B once, and for Hb, Hcr, and ALA-D weekly.

The Pb-B rose and the ALA-D activity fell with no demonstrable time lag, while the latency periods of ALA-U, Pb-U, and CP-U were about two weeks. All of these laboratory tests reached a steady state during the follow-up.

ALA-D showed the highest correlation to Pb-B and proved to be the most sensitive indicator of lead effect. Both CP-U and ALA-U were useful indicators of the effect of lead upon the organism, although a stepwise regression analysis, and their correlation coefficients with Pb-B, led to the conclusion that CP-U had better explaining power than ALA-U.

The mean Hb and Hcr values were significantly lower at the end of the observation period than at the beginning, providing an indication that anaemia begins to develop early in the course of lead absorption.

     

Free erythrocyte protoporphyrin (FEP) in a general population,workers exposed to low-level lead,and organic-solvent workers

The present study deals with a response of free erythrocyte protoporphyrin (FEP) to decreasing hemoglobin (Hb) concentration, low-level lead exposure, and organic-solvent exposure. FEP and Hb levels were determined for 1079 nonexposed persons (191 males and 888 females), 455 workers exposed to low-level lead (193 males and 262 females), and 312 employees working with various organic solvents (228 males and 84 females). The mean FEP in relation to Hb and sex was calculated for the three study groups. The major findings concern a sex-related difference in the response of FEP: women showed a more intense and earlier response to decreasing Hb and lead exposure than men. A significantly higher mean FEP at various normal Hb levels in the female lead workers than the male lead workers seemed to eliminate the possibility that a relative iron deficiency in women may play a role in the sex-related difference in the FEP response to lead. Exposure to organic solvents showed no effect on the heme biosynthesis as reflected by FEP.     

Comparison of colorimetric and HPLC methods for determination of delta-aminolevulinic acid in urine with reference to dose-response relationship in occupational exposure to lead

Both traditional colorimetry and recently developed HPLC-fluorometry have been in use for determination of delta-aminolevulinic acid in urine (ALA-U), an effect marker of occupational exposure to lead (Pb). The present study was initiated to compare the values by the two methods on an epidemiology basis among workers occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry-associated increment over the values by the HPLC method, to evaluate ALA-U determination in occupational health service for Pb-exposed workers, and to identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood and urine samples were collected from three groups of Pb-exposed workers (both men and women in combination, including smokers) and analyzed for Pb in blood (Pb-B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1 (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by colorimetry was higher than the values by HPLC, and that the mean difference on a group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B levels. It was also found that the increase in ALA-U was small when Pb-B was relatively low (e.g., < or = 40 microg/100 ml), and that the increase on a group basis in response to an increase in Pb-B from 5 to 40 microg/100 ml was as small as < or = 0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb effects at low Pb-B levels. ALA-U however increased substantially with a point of inflection at the Pb-B level of about 17-34 microg/100 ml. Thus it was concluded that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l on average irrespective of intensity of Pb-exposure, which may induce bias in evaluation of health effect, and that ALA-U levels will increase when Pb-B is in excess of 17-34 microg/100 ml.     

Relationships between three indicators of lead exposure in workers: Blood lead, δ-aminolevulinic acid and free Erythrocyte Protoporphyrin

Summary Whole blood lead (Pb-B), urinary -aminolevulinic acid (ALA-U) and free erythrocyte protoporphyrin (FEP) were measured in three groups of workers (n = 196) with different degrees of exposure to lead, and one group of men with no previous exposure to the metal (n = 48). Inter-group comparison showed a correlation of r = 0.73 between Pb-B and log of ALA-U, and r = 0.91 between Pb-B and log of FEP. ALA-U and FEP values rose sharply after Pb-B values reached 450–500 g/1.     

Impact of Air Pollution by Lead on the Heme Biosynthetic Pathway in School-Age Children

Blood-lead level (Pb-B), erythrocyte δ-aminolevulinic acid dehydratase (ALAD) activity, free erythrocyte porphyrin (FEP) concentration, δ-aminolevulinie acid concentration in urine (ALAU), hematocrit value, and hemoglobin concentration were compared for groups of children 10–13 years old from areas differently polluted by lead (rural area and lead smelter area). The biological responses of the children were also compared with those observed in adults similarly exposed to lead (Pb-B: 10–40 μ/100 ml). Compared with the rural children, children living less than 1 km from the smelter exhibited a significant increase of Pb-B and FEP, a significant inhibition of ALAD, and a slight positive correlation of ALAU with Pb-B; however, they showed no biological signs of anemia. In children living approximately 1.5 km from the smelter, there was still a signfiicant increase of Pb-B and a concomitant inhibition of ALAD, but no change in FEP concentration. Comparison of the dose-response curves between Pb-B and FEP in adult males, adult females, and children indicates that the sensitivity to lead is in the order of children ≥ women > men. Based on the FEP response, it is proposed that 25 μ Pb/100 ml blood be regarded as the maximum biologically allowable concentration of lead in blood of school-age children.     

Investigations on neurotoxicity of chemical substances at the workplace. V. Determination of the motor and sensory nerve conduction velocity in persons occupationally exposed to lead

A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The "Biological Monitoring" included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) delta-Aminolevulinic acid dehydratase (ALA-D) and (4) delta-Aminolevulinic acid in urine (ALA-U). Further "time-weighted-average (TWA)"-values of Pb-B were calculated on the basis of several determinations over the period 1975-1981. The following "actual" ("TWA") median values resulted: Pb-B 53 micrograms/dl (54 micrograms/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The "Biologischer Arbeitsstoff Toleranz Wert (BAT)" of 70 micrograms/dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using "TWA" than "actual" data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a "dose-effect-relationship" was found only in the case of Pb-B exceeding 70 micrograms/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 micrograms/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.     

Blood lead level to induce significant increase in urinary delta-aminolevulinic acid level among lead-exposed workers: a statistical approach

The present study was initiated to examine the quantitative relationship between blood lead (Pb-B) and urinary delta-aminolevulinic acid (ALA-U) among Pb-exposed workers, and to find a threshold Pb-B level to induce an increase in ALA-U. For this purpose, pairs of venous blood and spot urine samples were collected from 8,274 men and 5,856 women (14,130 workers in total) who were occupationally exposed to inorganic lead. The blood and urine samples were analyzed for Pb-B and ALA-U by atomic absorption spectrometry and colorimetry, respectively, and the correlation between pairs of measures were subjected to statistical analysis. The assumption of the 3rd degree regression for correlation gave a substantially greater correlation coefficient (0.645 for men and 0.619 for women) than 1st or 2nd degree regression, whereas only very small improvement in the coefficient was achieved with 4th to 6th degree ones. Logarithmic conversion of the parameters was not effective in improving the correlation. The assumption of the 3rd degree regression followed by calculation of the local minimum gave 22, 29 and 23 micrograms/100 ml Pb-B for men, women, and men + women, respectively, as the threshold Pb-B to induce ALA-U increase. Pb-B to elevate ALA-U to the 95% upper normal limit (8 mg/l, common to men and women) was 62, 50 and 58 micrograms/100 ml for men, women and men + women, respectively. The validity of the 3rd degree regression assumption as a tool to calculate a threshold from experimental or epidemiological data is discussed.     

A multiple regression analysis of hemoglobin values and iron status in Japanese farmers

The authors performed multiple regression analysis of hemoglobin values and the parameters related to iron dynamics. The subjects consisted of 37 farmers whose Hb, Ht, GB, SI, %-St, SFR and FEP was examined once a month for one year. 19.2% of the female farmers had anemia of which 73.8% was iron-deficiency anemia, 13.7% being latent iron deficiency. Hb, GB and FEP in males and SI, %-St, SFR, FEP in females revealed clear seasonal variations. Multiple correlation coefficient between Hb and SI, %-St, SFR, FEP as independent variables was significant in females but not in males, and the ratio of contribution (38.7%) was not very high, however, the multiple correlation coefficient was significantly high (0.622). Standard regression coefficients between Hb and SFR, FEP were significantly high (p less than 0.01). When Ht and GB were added to these 4 variables, multiple correlation coefficients (male, 0.906; female, 0.957) were remarkably high, which means serum-related variables such as Ht and GB have an undeniably important role as explanatory variables of hemoglobin levels. These standard regression coefficients showed seasonal changes.     

Blood lead and serum iron levels in non-occupationally exposed males and females

Summary A study has been performed in 148 non occupationally exposed subjects (19–21 yrs) divided into three groups: males, females without and females using oral contraceptives. PbB-levels ranged from 46 to 238 ppb. Freeerythrocyte-porphyrins (FEP), serum iron (Fe-S), Hb, Ht, total iron-bindingcapacity and unsaturated-iron-binding-capacity were measured. A negative correlation was found between PbB and Fe-S in males only. In females FEP was higher than in males at same PbB-levels. Females using oral contraceptives had higher Fe-S-levels and total-iron-binding-capacity than females not taking these; no difference was found between individual preparations. Two hypotheses are suggested to explain the negative relationship between lead in blood and serum iron in males. In a study of 51 other male subjects, 19-21 yrs, again a negative trend for Fe-S with increasing PbB was observed; the pooled data showed a negative relation; there was no difference in morning and afternoon Fe-S levels.     

低浓度铅接触女工血铅与红细胞游离原卟啉的关系

为研究低浓度铅作业对女工是否有影响,调查了铅接触浓度（时间加权平均浓度）为０．０３１５ｍｇ／ｍ＾３的女工８２名,分别测定血游离原卟啉（ＦＥＰ）、血铅、尿铅。结果表明ＦＥＰ、血铅、尿铅与对照组比较差异有显著性（Ｐ＜０．０１）。指标间相关性较好呈剂量－反应关系。血铅和ＦＥＰ阳性检出率分别为２０．７３％和２１．９５％,２项均超过正常上限的检出率（１３．４％）。智商ＩＱ值为６０￣７９、８０￣８９、９０￣１     

Decreases in postural change of finger blood flow in ceramic painters chronically exposed to low level lead

To elucidate the effect of low level lead (Pb) exposure on somatic and automatic peripheral nerve functions in ceramic painters, 58 males and 70 females, aged 29–75 years (mean 53.3 years), with lead concentrations in blood (Pb-B) ranging from 2.1 to 69.5 μg/dl (geometric mean 13.3 μg/dl), were examined for median nerve maximal conduction velocity as a measure of motor nerve function, the coefficient of variation of R-R interval on electrocardiography as a measure of parasympathetic function, and postural changes in finger blood flow volume (ΔFBF), and changes in finger blood flow drop velocity (FDV) from the supine to standing position as a measure of sympathetic function. No significant association was found between Pb-B levels and the results of the neurophysiological tests, however, except for that between Pb-B and ΔFBF. ΔFBF was decreased linearly with increasing Pb-B levels. However, this association could not be concluded to be a reflection of sympathetic nerve dysfunction due to Pb exposure in the subjects, since ΔFBF was not a specific parameter of sympathetic nerve function. The possibility that the decrease in ΔFBF is a reflection of the atherosclerotic effect of chronic low level Pb exposure should be further investigated. © 1996 Wiley-Liss, Inc.     

Interaction of tin and zinc in some processes of heme biosynthesis in rabbits

Female rabbits (2.5–3.0 kg) were divided into the five groups. Group I (control) received ip 0.9% NaCl, every day for 5 days; group II received ip SnCl₂ (dose of 2 mg Sn/kg) every day for 5 days; group III was given single sc injection of ZnSO₄ (dose of 50 mg Zn/kg); group IV, a single sc injection of ZnSO₄ followed by a single ip injection of SnCl₂ on the next day; and group V received a single ip injection of SnCl₂ followed next day by a single sc injection of ZnSO₄.Eighteen hours after the first dose of SnCl₂ and inhibition of δ-aminolevulinic acid dehydratase (ALA-D) by 60% was found in the blood of group II, while increases of urinary excretion of coproporphyrin (CP-U) and δ-aminolevulinic acid (ALA-U) with respect to the control group took place not earlier than after the fourth dose of SnCl₂ (correlation coefficients, respectively: ALA-D/ALA-U r = −0.91; CP-U/ALA-D r = −0.70; CP-U/ALA-U r = 0.81). The single dose of ZnSO₄ resulted in an increase of ALA-D by about 60% while administration of SnCl₂ to the animals in group IV decreased this value down to physiologic levels. Then an increased tendency was noted again for the activity of this enzyme. Administration of SnCl₂ and ZnSO₄ (group V) resulted in a decrease of ALA-D activity and in an increase in CP-U.     

Sex differences in response to immunonutrition in sepsis

BACKGROUND: Cell-mediated immune response is superior in females compared to males. Whether sex differences influenced mortality in sepsis while on immune-enhancing nutrients was investigated. MATERIALS AND METHODS: Seventy-two non-orchitectomized male and non-oophorectomized female rats (n = 36/group) were randomized into four groups. Rats were fed either an immune-enhancing diet or control diet for five days. Sepsis was induced with caecal ligation and puncture (CLP). An additional group of orchitectomized and oophorectomized rats (n = 36/group) were divided into four groups; fed either an immune-enhancing or control diet of one month, then following castration. Sepsis was induced with CLP. The influence of immune-enhancing nutrients on the effect of the rat's sex on mortality rates and serum cytokines were compared. RESULTS: Non-orchitectomized male rats had a decreased mortality (88.9% vs. 16.7%) on immune-enhancing diet. Low mortality among non-oophorectomized female rats persisted, on immune-enhancing diet (27.8% vs. 11.1%). Orchitectomized rats demonstrated reduced mortality (88.8% vs. 50%) on immune-enhancing diet. Oophorectomized rats showed a similar trend (55.6% vs. 44.4%). Orchitectomy increased mortality in spite of immune-enhancing diet (50% vs. 16.7%). Oophorectomy increased mortality on immune-enhancing diet (44.4% vs. 11.1%). Circulating IL-1beta was higher in non-oophorectomized female rats on control diet compared to immune-enhancing diet. Non-orchitectomized male and non-oophorectomized female rats had similar increases in IL-10 on immune-enhancing diet. CONCLUSIONS: Mortality rates on immunonutrition were less in male than female rats following sepsis. Orchitectomy did not confer an advantage for septic rats. Sex hormone was more important than immunonutrition in septic female rats.     

A 13-week subchronic toxicity study of D-xylose in F344 rats

A 13-week subchronic toxicity study of D-xylose was performed in male and female F344 rats at dose levels of 0%, 0.2%, 0.6%, 1.7%, and 5% D-xylose in the CRF-1 powder diet to determine the maximum tolerable dose (MTD) for subsequent investigation of carcinogenicity. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. Rats were randomly allocated to 5 groups each consisting of 10 males and 10 females. No treated groups showed changes in body weight gain or food intake, and all animals survived until the end of the experiment. Hematological examination revealed significant increases in RBC, Hb, and Ht in the male groups treated with 0.6% and 5% concentrations, whereas these values decreased significantly in all of the female groups treated with D-xylose. However, no clear dose-response effect was observed in the hematological data in either males or females given D-xylose. Serum biochemistry studies revealed decreases in AsT in the 0.2% and 5% D-xylose group male and 0.2%, 1.7%, and 5% group female, compared to the control value. However, the changes were not considered specific because of the lack of any clear dose-response effect. In addition, no histopathological changes indicating obvious toxicity of D-xylose were observed in the livers of either sex treated with D-xylose. Based on these data, the MTD of D-xylose in F344 rats of both sexes is judged to be 5% or more in the diet.     

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.