I:\set 12 tps\arsenic-set12.wpd - ATSDR

74 Pages·2001·1.09 MB·English

ETHION 13
2. HEALTH EFFECTS
2.1 INTRODUCTION
The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and
other interested individuals and groups with an overall perspective on the toxicology of ethion. It contains
descriptions and evaluations of toxicological studies and epidemiological investigations and provides
conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.
A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile.
2.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE
To help public health professionals and others address the needs of persons living or working near
hazardous waste sites, the information in this section is organized first by route of exposure (inhalation,
oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive,
developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure
periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more).
Levels of significant exposure for each route and duration are presented in tables and illustrated in
figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or
lowest-observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the
studies. LOAELS have been classified into "less serious" or "serious" effects. "Serious" effects are
those that evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute
respiratory distress or death). "Less serious" effects are those that are not expected to cause significant
dysfunction or death, or those whose significance to the organism is not entirely clear. ATSDR
acknowledges that a considerable amount of judgment may be required in establishing whether an end
point should be classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some
cases, there will be insufficient data to decide whether the effect is indicative of significant dysfunction.
However, the Agency has established guidelines and policies that are used to classify these end points.
ATSDR believes that there is sufficient merit in this approach to warrant an attempt at distinguishing
between "less serious" and "serious" effects. The distinction between "less serious" effects and "serious"
effects is considered to be important because it helps the users of the profiles to identify levels of
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exposure at which major health effects start to appear. LOAELs or NOAELs should also help in
determining whether or not the effects vary with dose and/or duration, and place into perspective the
possible significance of these effects to human health.
The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and
figures may differ depending on the user's perspective. Public health officials and others concerned with
appropriate actions to take at hazardous waste sites may want information on levels of exposure
associated with more subtle effects in humans or animals (LOAEL) or exposure levels below which no
adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans
(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike.
Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been
made for ethion. An MRL is defined as an estimate of daily human exposure to a substance that is likely
to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of
exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of
effect or the most sensitive health effect(s) for a specific duration within a given route of exposure.
MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs
can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes.
Appropriate methodology does not exist to develop MRLs for dermal exposure.
Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990),
uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional
uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an
example, acute inhalation MRLs may not be protective for health effects that are delayed in development
or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic
bronchitis. As these kinds of health effects data become available and methods to assess levels of
significant human exposure improve, these MRLs will be revised.
A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in
the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs.
Ethion is a pesticide, and its use is regulated under the Federal Insecticide, Fungicide, and Rodenticide
Act (FIFRA). Virtually all of the toxicity information on ethion is from unpublished studies performed
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by the manufacturer and submitted for review to the EPA. A few of these studies were unable to be
retrieved by ATSDR. In these cases, NOAEL and LOAEL values were taken from study summaries in
“Guidance for the Reregistration of Pesticide Products Containing Ethion as the Active Ingredient” (EPA
1989d) and are so cited in the text.
2.2.1 Inhalation Exposure
2.2.1.1 Death
Male and female rats (number and strain not specified) were exposed to technical ethion via inhalation
and the LC (lethal concentration, 50% kill), was calculated. The acute inhalation LC was 2.31 mg/m3
50 50
for male rats and 0.45 mg/m3 for females (Feiser 1983 as cited in EPA 1989d).
No studies were located regarding the following effects in humans or animals after inhalation exposure
to ethion:
2.2.1.2 Systemic Effects
2.2.1.3 Immunological and Lymphoreticular Effects
2.2.1.4 Neurological Effects
2.2.1.5 Reproductive Effects
2.2.1.6 Developmental Effects
2.2.1.7 Genotoxic Effects
Genotoxicity studies are discussed in Section 2.5.
2.2.1.8 Cancer
No studies were located regarding cancer in humans or animals afer inhalation exposure to ethion.
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2.2.2 Oral Exposure
2.2.2.1 Death
No studies were located regarding death in humans after oral exposure to ethion.
Several acute lethality studies have demonstrated the high toxicity of ethion by the oral route. In a study
reporting results for 98 (single dose) pesticides, (Gaines 1969) LD (lethal dose, 50% kill) values for
50
ethion via gavage were 65 mg/kg for male and 27 mg/kg for female Sherman rats. The minimum
survival time was 3 hours for males and 4 hours for females. The maximum time to death was 9 days for
males and 6 days for females. The lowest dose to kill a rat was 50 mg/kg for males and 20 mg/kg for
females. LD (lethal dose, 1% kill) values were calculated at 27 mg/kg/males and 15 mg/kg for females.
1
In a toxicokinetic study in Sprague-Dawley rats (Selim 1985a), two of seven males died after a gavage
dose of 100 mg/kg; clinical signs of toxicity preceding death included salivation, tremors, diarrhea, and
convulsions. Five of seven females died after receiving 25 mg/kg. Female rats appear to be more
susceptible to ethion than males, but no explanations have been proposed.
Multiple oral exposures to ethion at lower doses in animals have generally not resulted in fatalities. For
example, no deaths occurred in pregnant Charles River rats receiving up to 2.5 mg/kg/day ethion by
gavage over gestation days (Gd) 6–15 (Hoberman et al. 1983a) or pregnant New Zealand rabbits
receiving up to 9.6 mg/kg/day over Gd 6–18 (Hoberman et al. 1983b).
In an intermediate-duration exposure to ethion in feed to groups of albino rats (25/dose/sex), survival
was similar after 96 days at doses of #9 mg/kg/day in males and 10 mg/kg/day in females (Keller and
Paynter 1958). No deaths occurred in the parental generation (F ) in a three-generation reproductive
0
study in CD rats (Enloe and Salamon 1985). Exposure to ethion in feed was #1.25 mg/kg/day for
236–238 days. One of a group of four female Beagle dogs was sacrificed in a moribund condition after
90 days of exposure to ethion in feed at a dose of 8.25 mg/kg/day (Bailey 1988). Clinical signs included
emesis, dehydration, and thin body mass. The other females in the group and the males exposed at
#6.9 mg/kg/day survived.
In a 2-year feeding study in Sprague-Dawley rats and CF mice (Morrow 1985a, 1985b), survival was
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similar between control and treated groups. Exposures in rats were #2 mg/kg/day (80/dose/sex) and
#1.2 mg/kg/day in mice (10–50/dose/sex).
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All reliable LD values and LOAELs for death in each species and duration category are recorded in
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Table 2-1 and plotted in Figure 2-1.
2.2.2.2 Systemic Effects
Most, if not all, of the systemic effects observed after oral exposure to ethion are the result of the
neurological effects of this chemical (see Section 2.2.2.4).
The highest NOAEL values and all LOAEL values from each reliable study for each systemic effect in
each species and duration category are recorded in Table 2-1 and plotted in Figure 2-1.
Respiratory Effects. A 6-month-old boy who accidentally ingested 15.7 mg/kg ethion from a
contaminated milk bottle presented with diaphragmatic respiration with shallow excursions and
intercostal retraction (Comstock et al. 1967). Respiratory rate was 60/minute. Auscultation revealed
generalized rales and rhonchi and inspiratory and expiratory wheezes. Symptoms appeared one hour
following ingestion and were treated with atropine and Protopam® (pralidoxime). Approximately
5 hours after ingestion, respiratory arrest occurred and mechanical ventilation was necessary for the next
3 hours. Treatment with atropine and pralidoxime continued for 5 days until symptoms ceased. Follow-
up examinations after 1 week, 1 month, and 1 year indicated that a complete recovery was made by this
patient. The respiratory effects seen in this case are consistent with cholinergic overstimulation caused
by ethion (see Section 2.2.2.4).
Histopathological examinations of respiratory tract tissues after oral exposure to ethion in animals have
shown no effect of treatment. Doses and durations include 96 days in male and female albino rats at
#10 mg/kg/day in feed (Keller and Paynter 1958), 6–24 months in male and female Sprague-Dawley rats
at #2 mg/kg/day (Morrow 1985a), 6–24 months in male and female CF mice at #1.2 mg/kg/day
1
(Morrow 1985b), and 13 weeks in male and female Beagle dogs at #8.25 mg/kg/day (Bailey 1988).
Cardiovascular Effects. Tachycardia was reported in a 6-month-old boy who accidentally ingested
15.7 mg/kg ethion (Comstock et al. 1967).
Blood pressure and pulse rate were measured in a group of 6 male volunteers (age range, 23–43 years)
who were given ethion in corn oil solutions in 3 divided doses (9:00 a.m., noon, and 5:00 p.m.) via