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Alachlor
CASRN 15972-60-8
Contents
0129
Alachlor; CASRN 15972-60-8
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 Alachlor
File On-Line 03/31/1987
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 09/01/1993
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 -- Alachlor
CASRN -- 15972-60-8
Last Revised -- 09/01/1993
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
-------------------- ----------------------- ----- --- ---------
Hemosiderosis, NOAEL: 1 mg/kg-day 100 1 1E-2
hemolytic anemia mg/kg-day
LOAEL: 3 mg/kg-day
1-Year Dog Feeding
Study
Monsanto Co., 1984a
*Conversion Factors and Assumptions: Actual dose tested
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
Monsanto Company. 1984a. MRID No. 00148923; HED Doc No. 004660. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
Beagle dogs (6/sex/dose) were administered alachlor at levels of 0, 1, 3,
and 10 mg/kg-day for 1 year. The test material was given neat (with no
dilution) in gelatin capsules and administered daily at least 1 hour after
feeding a ration of pellated dog chow. Control dogs were given empty gelatin
capsules. Animals were observed twice daily during the study for signs of
toxicity and mortality. Body weight and food consumption were measured, and
clinical chemistry, hematology, and urinalysis testing were performed. All
surviving animals were sacrificed after 12 months and examined for gross
pathological changes.
The LEL for systemic toxicity is 3 mg/kg-day based on hemosiderosis seen
in the kidney (1/6) and spleen (1/6). No hemosiderosis was associated with
the liver in the mid-dose group. In the high-dose group, the hemosiderosis
was seen in the liver (3/6) and correlated with hematologic findings showing
red cell destruction and consequent red cell replenishment. The hematologic
findings noted in the high-dose males were also seen as a trend (except for
the increased reticulocyte count) in the mid-dose dogs. In addition, liver
weights (absolute and relative-to-body-weight) were significantly (p < 0.05)
higher in high-dose males. High-dose females also showed dose-related
increases, but they were not statistically significant. Therefore, the NOEL
for systemic toxicity is 1 mg/kg-day.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- The uncertainty factor of 100 reflects 10 for interspecies extrapolation
and 10 for intraspecies-variability.
MF -- None
___I.A.4. ADDITIONAL STUDIES / COMMENTS (ORAL RfD)
1) 1-Year Feeding - dog: Principal study -- see previous description; core
grade guideline (Monsanto Co., 1984a)
2) 2-Year Feeding/Oncogenicity - rat: Dietary levels tested: 0, 0.5, 2.5, and
15 mg/kg-day; Groups of Long-Evans rat (50/sex/dose) were administered
alachlor in the diet for 2 years. The LEL for systemic toxicity is 15 mg/kg-
day based on molting of retinal pigmentation and increased mortality rate in
females and abnormal disseminated foci in the liver of males. The NOEL for
systemic toxicity is therefore 2.5 mg/kg-day. Core grade minimum (Monsanto
Co., 1984b)
3) 3-Generation Reproduction - rat: Dietary levels tested: 0, 3, 10, and 30
mg/kg-day; Groups of Charles River Sprague-Dawley CD rats were fed diets
containing alachlor over three generations. No significant adverse effects on
the reproduction of adult rats were observed at any dose tested. Therefore
the NOEL for reproductive toxicity is equal to or greater than 30 mg/kg-day.
Compound-related effects were not observed in litter size, survival and
lactation indices, or the pup body weights. However, gross pathology
examinations indicated compound-related effects on kidneys (in parents and
progeny) in the high-dose males and females especially in the F2 parent
generation and F3b pups. These effects were kidney discoloration and
significant increases (5-18%, p < 0.05) in kidney weights and kidney-to-body-
weight ratios. These adverse effects were further confirmed microscopically
by the presence of chronic nephritis in the F2 high-dose males (8/10 compared
with 1/10 animals in the control groups) and a healing infarct in 1/10 F3b
male pups in addition to hydronephrosis in another F3b male pup (total of 2/10
animals as compared with none in the control group). Lower ovary weights were
also noted in the high-dose females of each parental generation and in F3b
pups. This decrease was maximal in the F0 generation in which a 17% decrease
(p < 0.05) in ovary weights was noted. This decrease was also associated with
17% decrease (p < 0.05) in the ovaries-to-body-weight ratio in the F0 high-dose
females. This effect on kidneys is more remarkable in male. Based on kidney
effects in both F2 adults and F3b pups, the LEL for systemic toxicity is 30
mg/kg-day. The NOEL for systemic toxicity is 10 mg/kg-day. Core grade
minimum (Monsanto Co., 1981a)
4) Developmental Toxicity - rat: Dose levels tested: 0, 50, 150, and 400
mg/kg-day; Groups of pregnant Charles River COBS CD rats (25/dose) were
administered alachlor in a corn oil vehicle by gavage on days 6 though 19 of
gestation. High-dose dams exhibited soft stools, red matter around the nose
and mouth, hair loss, and anogenital staining. Four high-dose dams died
during the last 5 days of gestation. The cause of death was not apparent at
necropsy. Mean body weight gains were moderately reduced in the high-dose
group throughout the treatment period. Uterine examinations indicated that
for each group of 25 females, 0, 5, 2, and 2 in each of the control, low-,
mid-, and high-dose groups, respectively, were non-gravid. The four high-dose
dams which died were gravid. All were viable fetuses in the treated groups.
There were no statistically significant differences in mean numbers of viable
fetuses, resorptions, post-implantation losses, total implantations, corpora
lutea, sex distribution of pups, or mean fetal body weights in any of the
treated groups when compared to the control group. In the high-dose group, a
slight increase in the mean numbers of early and late resorptions resulted in
a slight increase in mean post-implantation loss and a slight decrease in the
mean number of viable fetuses. Based on soft stools, hair loss, anogenital
staining, and maternal death, the NOEL and LEL for maternal toxicity are 150
and 400 mg/kg-day, respectively. Based on a slight decrease in mean fetal
body weight and a slight increase in mean post-implantation loss, the NOEL and
LEL for developmental toxicity are 150 and 400 mg/kg-day, respectively. Core
grade guideline (Monsanto Co., 1980)
5) Developmental Toxicity - rabbit: Dose levels tested: 0, 50, 100, and 150
mg/kg-day; Groups of pregnant New Zealand White rabbits (18/dose) were
administered alachlor by gastric intubation from gestation days 7 through 19,
inclusive. Due to the death of two females in the control group during the
treatment period, two additional females were mated and added to this group.
Maternal toxicity was noted at the high dose in the form of reduced body
weight gain during the dosing period with a rebound increase in body weight
gain in the period following dosing. No other maternal toxicity was noted.
No biologically relevant fetal external, visceral, or skeletal anomalies were
noted. The NOEL and LEL for maternal toxicity are 100 and 150 mg/kg-day,
respectively. The NOEL for developmental toxicity is equal to or greater than
150 mg/kg-day. Core grade minimum (Monsanto Co., 1988)
Other Data Reviewed:
1) 2-Year Feeding/Oncogenicity - rat: Dietary levels tested: 0, 100, 300, and
1000 ppm (0, 14, 42, and 126 mg/kg-day); Groups of Long-Evans rats
(50/sex/dose with a additional 10/sex/dose for clinical studies) were fed
diets containing alachlor for 2 years. Degenerative ocular and hepatic
changes as well as other pathological gross and microscopic findings in the
thyroid, kidneys, brain, spleen, heart, prostate, and ovaries were noted at
all dose levels tested. The LEL for systemic toxicity is therefore 100 ppm
(14 mg/kg-day), the lowest dose tested. A NOEL for systemic toxicity could
not be established. Core grade minimum (Monsanto Co., 1981b)
2) 6-Month Feeding - dog: Dietary levels tested: 0, 5, 25, 50, and 75/100
mg/kg-day; Groups of beagle dogs (6/sex/dose) were administered alachlor daily
in capsules for 6 months. The high-dose level was 100 mg/kg-day for weeks 1
through 3 but due to the severe toxicity the dose was reduced to 75 mg/kg-day
for the remainder of the study. Liver weight values (absolute, relative-to-
body-weight, and relative-to-brain) increased in males at 5 mg/kg-day and in
both sexes at 25 mg/kg-day and above. The increases were often statistically
significant (p < 0.05). Discoloration of the liver, fatty degenerations and
billiary hyperplasia were also noted in both sexes at 25 mg/kg-day and above.
Significant increases in SAP and LDH activity were also indicative of liver
pathology. Other organ weight changes were noted at 5 mg/kg-day. Dose-
related emaciation and mortality were noted in both sexes at 25 mg/kg-day and
above. Mortality in the mid- and high-dose groups was high; all but 1 high-
dose female died during the first 2-3 months of the study, and 4/6 males and
3/6 females of the mid-dose group were sacrificed in extremis during the
study. A slight reduction in body weight gain was also noted at 5 mg/kg-day
as compared with the control group. Based on the effects noted at the all
dose levels, the LEL for systemic toxicity is equal to 5 mg/kg-day. A NOEL
for systemic toxicity was not established. Core grade minimum (Monsanto Co.,
1981c)
Data Gap(s): None
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- High
Data Base -- High
RfD -- High
The principal study is of good quality and is given a high confidence
rating. In addition, there are generally good toxicologic studies available
on alachlor which, overall provide high confidence in the data base. High
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 -- None
Agency Work Group Review -- 03/11/1986, 03/27/1991
Verification Date -- 03/27/1991
___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 -- Alachlor
CASRN -- 15972-60-8
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- Alachlor
CASRN -- 15972-60-8
Not available at this time.
_VI. BIBLIOGRAPHY
Substance Name -- Alachlor
CASRN -- 15972-60-8
Last Revised -- 11/01/1993
__VI.A. ORAL RfD REFERENCES
Monsanto Company. 1980. MRID No. 00043645; HED Doc. No. 000399, 001021.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Monsanto Company. 1981a. MRID No. 0075062; HED Doc. No. 001338. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
Monsanto Company. 1981b. MRID No. 00091050, 00109319; HED Doc. 001991.
Available from EPA. Write to FOI, EPA, Washington, DC 20460.
Monsanto Company. 1981c. MRID No. 00100659; HED Doc. No. 002483. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
Monsanto Company. 1984a. MRID No. 00148923; HED Doc No. 004660. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
Monsanto Company. 1984b. MRID No. 00091050, 00109319, 40284001; HED Doc. No.
003753, 004091, 004855. Available from EPA. Write to FOI, EPA, Washington,
DC 20460.
Monsanto Company. 1988. MRID No. 40579402; HED Doc. No. 006886. Available
from EPA. Write to FOI, EPA, Washington, DC 20460.
__VI.B. INHALATION RfD REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- Alachlor
CASRN -- 15972-60-8
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
03/01/1988 III.A. Health Advisory added
12/01/1988 I.A.4. Core graded added to studies 1, 3 and 4
11/01/1989 VI. Bibliography on-line
01/01/1992 IV. Regulatory actions updated
09/01/1993 I.A. Oral RfD revised; same study and number
09/01/1993 VI.A. Oral RfD references revised
11/01/1993 III.A.2. Ten-day Health Advisory corrected
11/01/1993 III.A.9 Documentation revised
11/01/1993 IV.B.2. Discussion corrected
11/01/1993 VI.D. Health Advisory references revised
VIII. SYNONYMS
Substance Name -- Alachlor
CASRN -- 15972-60-8
Last Revised -- 03/31/1987
15972-60-8
ACETAMIDE, 2-CHLORO-N-(2,6-DIETHYLPHENYL)-N-(METHOXYMETHYL)-
ACETANILIDE, 2-CHLORO-2',6'-DIETHYL-N-(METHOXYMETHYL)-
Alachlor
ALANEX
ALOCHLOR
CHLORESSIGSAEURE-N-(METHOXYMETHYL)-2,6-DIAETHYLANILID
2-CHLORO-2',6'-DIETHYL-N-(METHOXYMETHYL)ACETANILIDE
2-CHLORO-N-(2,6-DIETHYL)PHENYL-N-METHOXYMETHYLACETAMIDE
CP 50144
LASSO
LAZO
METACHLOR
METHACHLOR
PILLARZO
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0129.HTM
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