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Aldicarb sulfone
CASRN 1646-88-4
Contents
0312
Aldicarb sulfone; CASRN 1646-88-4
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR Aldicarb sulfone
File On-Line 09/26/1988
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 11/01/1993
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
Last Revised -- 11/01/1993
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ---------
Brain ChE inhibition NOAEL: 5 ppm 100 1 1E-3
in females (0.11 mg/kg-day) mg/kg-day
1-Year Dog Feeding LOAEL: 25 ppm
Study (0.58 mg/kg/day)
Union Carbide
Agricultural Products
Co., 1987
*Conversion Factors and Assumptions -- Actual dose calculated by weekly food
intake
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Union Carbide Agricultural Products Company. 1987. MRID No. 40259901.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Groups of beagle dogs (6/sex/dose) were administered aldicarb sulfone in
the diet for 1 year at levels of 0, 5, 25, or 100 ppm (0, 0.11, 0.58 or 2.21
mg/kg-day). Since aldicarb sulfone was found to be unstable in the diet at
room temperature, fresh diets were prepared weekly and frozen immediately
following mixing. Plasma and red blood cell cholinesterase activities were
determined for each animal three times prior to treatment (weeks -3, -2, and -
1) and during weeks 5, 13, 26, and 52. Brain cholinesterase was determined at
termination only.
No treatment-related clinical signs were noted at any dose level in this
study. Brain cholinesterase activity at study termination showed
statistically significant inhibition in high-dose males (24% inhibition of
control value) and mid- and high-dose females (19-23% inhibition of control).
At the lowest dose tested, no significant effects were noted in either sex.
Statistically significant inhibition of plasma cholinesterase was observed in
males at all doses tested (20-80% inhibition of control value) and at the mid-
and high-doses in females (40-72% inhibition of control value) at all test
intervals. Red blood cell cholinesterase was also significantly inhibited in
high-dose males and females (25-36% inhibition of concurrent control value)
and in mid-dose females (up to 22%). However, at the low dose, the effect was
marginal on plasma ChE in males (mean value is 25%), and insignificant in
females; no significant effect on red blood cells ChE was noted at this dose
in either sex.
Based on brain cholinesterase, the LOAEL for systemic toxicity is 25 ppm
(0.58 mg/kg-day). The NOAEL for systemic toxicity is 5 ppm (0.11 mg/kg-day).
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 100 was used to account for the inter- and
intraspecies differences (10 each). An additional uncertainty factor to
account for the lack of a chronic rat study was not considered necessary,
since the available subchronic data in both the dog and rat indicated
that the dog is a more sensitive species. Although the lack of a chronic rat
study is still considered a data gap, it is not of considerable concern given
the available information on both aldicarb sulfone and its parent compound,
aldicarb.
MF -- None
___I.A.4. ADDITIONAL STUDIES / COMMENTS (ORAL RfD)
1) 1-Year Feeding - dog: Principal study -- see previous description; core
grade supplementary (Union Carbide Agricultural Prod. Co., 1987).
2) 3-Generation Reproduction - rat: Core grade minimum (Union Carbide Corp.,
1977).
Harlan-Wistar rats (10 males and 20 females/group) were administered
aldoxycarb in the diet at dose levels of 0, 0.6, 9.6, 2.4 and 9.6 mg/kg-day
for 3 generations (1 litter per generation). Male rats fed 9.6 mg/kg-day
exhibited reduced body weights. Cholinesterase depression was noted at 9.6
mg/kg-day. Reduced pup survival and marginal effects on lactation were noted
at 9.6 mg/kg-day. Based on reduced body weight in males, the NOEL and LEL for
systemic toxicity are 2.4 and 9.6 mg/kg-day, respectively. Based on reduced
pup survival, the NOEL and LEL for reproductive toxicity are 2.4 and 9.6
mg/kg-day, respectively.
3) Developmental toxicity - rat: Core grade minimum (Union Carbide Corp.,
1977).
Female Wistar rats were administered aldoxycarb at dose levels of 0, 0.6,
2.4 and 9.6 mg/kg-day at one of the following time intervals of gestation: 1-
20 days, 6-15 days, or 7-9 days following evidence of mating. The percentage
of pregnant control dams was 77% as compared with 82, 83, and 88% for the
groups treated at 0-20, 6-15 and 7-9 days post-mating, respectively.
Resorption sites per female were slightly increased in the 9.6 mg/kg-day
treated females in the 6-15 day treatment period. No increase in resorption
was seen at the same dosage level in females treated from days 1-20.
Anomalies in treated pups were virtually non-existent as in controls. At 9.6
mg/kg-day diarrhea due to possible ChE inhibition was observed. Based on the
occurrence of diarrhea, the NOEL and LEL for maternal toxicity are 2.4 and 9.6
mg/kg-day, respectively. The NOEL for developmental effects is greater than
or equal to 9.6 mg/kg-day, the highest dose tested.
Other Data Reviewed:
1) 3-Month Feeding - dog: Core grade minimum (supplementary for
cholinesterase) (Union Carbide Corp., 1968a).
Beagle dogs were fed diets containing 0, 0.2, 0.6, 1.8 and 5.4 mg/kg-day
aldicarb sulfone for 3 months. Mean body weights were only slightly reduced
in the animals but some showed a loss of weight from the start of dosing at
5.4 mg/kg-day. Cholinesterase activity was significantly reduced at 5.4
mg/kg-day in both sexes at 1.5 weeks. RBC ChE activity on the average was not
significantly different from the control group after 3 months of treatment.
Brain tissue ChE mean values were reduced in both sexes at doses above 0.2
mg/kg-day. However, due to removal of the animals up to 24 hours prior to
analysis, the ChE data is only applicable to reversal ChE inhibition and does
not give an accurate indication of ChE depression immediately following
dosing. Therefore, based on weight loss the NOEL and LEL for systemic
toxicity are 1.8 and 5.4 mg/kg-day, respectively. The NOEL and LEL for Brain
ChE inhibition are 0.2 and 0.6 mg/kg-day, respectively. The NOEL for RBC ChE
inhibition is equal to or greater than 5.4 mg/kg-day, the highest dose tested.
2) 3 and 6-Month Feeding - rat: Core grade minimum (Union Carbide Corp.,
1968b).
Harlan-Wistar rats (15/sex/dose) were fed diets containing 0, 0.2, 0.6,
1.8, 5.4 or 16.2 mg/kg-day aldicarb sulfone for a maximum period of 6 months.
Five animals/sex were sacrificed at 3 months and the remaining animals were
sacrificed at 6 months. Gross and histopathological examination were
performed. Cholinesterase activity was determined for plasma, RBC, and brain
by acetic acid liberation and titration. 3-Month Results: Body weight gains
were only slightly (not statistically) reduced at the 16.2 mg/kg-day dose
level in both sexes. Liver and kidney weights were not significantly
different from controls for either sex. Plasma ChE was reduced in males at
1.8 mg/kg-day by 36% and at 5.4 mg/kg-day in females by 62%. RBC ChE levels
were depressed 31% in both males and females at 1.8 mg/kg-day and 52%, in both
males and females at 5.4 mg/kg-day. Brain ChE was reduced 15% in males and
27% in females at 5.4 mg/kg-day. 6-Month Results: Body weights were
significantly reduced at 16.2 mg/kg-day in males. At 1.8 mg/kg-day plasma ChE
was reduced by 24% in females but not in males. RBC ChE in males and females
was reduced by 28 and 26%, respectively. Brain ChE was lower by 26% in males
at 5.4 mg/kg-day and 15% at 1.8 mg/kg-day, while females exhibited a reduction
of 16% (p<0.05) at 1.8 mg/kg-day. A 16% reduction in brain ChE was also noted
in females at 0.2 mg/kg-day.
3) 2-Month Feeding - rat: Core grade minimum (Union Carbide Corp., 1975).
Wistar rats were fed diets containing 2.4 and 16.2 mg/kg-day aldoxycarb
for 56 days. At 16.2 mg/kg-day ChE in plasma, RBC, and brain was depressed in
both sexes by 70%. No physical signs or symptoms were noted. At 2.4 mg/kg-
day, only plasma ChE was depressed and then only sporadically. Based on ChE
inhibition, the NOEL and LEL for systemic effects are 2.4 and 16.2 mg/kg-day,
respectively.
Data Gap(s): 2-Year Rat Feeding/Carcinogenicity Study; Rabbit Developmental
Toxicity Study
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Medium
RfD -- Medium
The critical study is given a medium confidence rating. Although the
study did identify a NOAEL and LOAEL, detailed procedures for assay and
sampling of brain cholinesterase activity were not provided in the study.
Since a chronic feeding study in rats and a rabbit developmental study are
lacking, the data base is given a medium confidence rating. Medium confidence
in the RfD follows.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- Registration Standard, November, 1983; U.S. EPA,
1987
Agency Work Group Review -- 04/20/1988, 06/20/1990, 07/26/1990, 04/24/1991, 04/25/1991,
09/22/1992
Verification Date -- 09/22/1992
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
Last Revised -- 11/01/1993
__VI.A. ORAL RfD REFERENCES
Union Carbide Agricultural Products Company. 1987. MRID No. 40259901.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Union Carbide Corporation. 1968a. MRID No. 00054404, 00057337, 00069645,
0090574. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Union Carbide Corporation. 1968b. MRID No. 00057337, 00069645, 0090574,
00100381. Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Union Carbide Corporation. 1975. MRID No. 00044738. Available from EPA.
Write to FOI, EPA, Washington, DC 20460.
Union Carbide Corporation. 1977. MRID No. 0054409, 0065890. Available from
EPA. Write to FOI, EPA, Washington, DC 20460.
U.S. EPA. 1987. Health Advisory for Aldicarb, Aldicarb Sulfoxide, and
Aldicarb Sulfone. Office of Water, Washington, DC.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
09/26/1988 I.A. Oral RfD summary on-line
02/01/1989 I.A.7. Secondary contact's phone number corrected
08/01/1989 I.A. Citations clarified
08/01/1989 VI. Bibliography on-line
07/01/1990 I.A. Withdrawn; new RfD verified (in preparation)
07/01/1990 VI. Bibliography withdrawn
09/01/1990 I.A. Oral RfD summary replaced; RfD changed
09/01/1990 VI. Bibliography replaced
05/01/1991 I.A. Oral RfD withdrawn pending additional review
05/01/1991 VI. Bibliography withdrawn
01/01/1992 IV. Regulatory Action section on-line
10/01/1992 I.A. Work group review date added
04/01/1993 I.A. Date corrected in withdrawn message
11/01/1993 I.A. Oral RfD summary replaced; new RfD
11/01/1993 VI.A. Oral RfD references replaced
VIII. SYNONYMS
Substance Name -- Aldicarb sulfone
CASRN -- 1646-88-4
Primary Synonym -- Aldoxycarb
Last Revised -- 09/26/1988
1646-88-4
Aldicarb Sulfone
Aldoxycarb
aldoxycarbe
ENT 4.9
ENT AI3-29261
2-mesyl-2-methylpropionaldehyde O-methylcarbamoyloxime
2-methyl-2-(methylsulfonyl)propanal O-((methylamino)carbonyl)oxime
2-methyl-2-(methylsulfonyl)propionaldehyde O-(methylcarbamoyl)oxime
propionaldehyde, 2-methyl-2-(methylsulfonyl)-, O-(methylcarbamoyl)oxime
standak
UC-21865
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0312.HTM
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