Strychnine (CASRN 57-24-9)
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0103
Strychnine;
CASRN 57-24-9
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 Strychnine
File First On-Line 01/31/1987
Category (section) |
Status |
Last Revised |
---|---|---|
Oral RfD Assessment (I.A.) | on-line | 03/01/1988 |
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 — Strychnine
CASRN — 57-24-9
Last Revised — 03/01/1988
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 |
---|---|---|---|---|
Toxicity/histopathology Rat Oral Short-term Seidl and Zbinden, 1982 |
NOAEL: none LOAEL/FEL: |
10,000 |
1 |
3E-4 mg/kg/day |
*Conversion Factors: none
__I.A.2. Principal and Supporting Studies (Oral RfD)
Seidl, I. and G. Zbinden. 1982. Subchronic oral toxicity of strychnine in
rats. Arch. Toxicol. 51(3): 267-271.
This is the only oral short-term or subchronic study reported, in which rats
received daily doses of 0 - 10 mg/kg of strychnine by gavage for 28 days.
Data recorded for the surviving animals included blood cell counts,
electrocardiograms, eye examinations, urine chemistry, weight gain, tissue
histology, organ weights, behavioral tests,and food and water consumption.
Mortality was observed in 5/12 male rats receiving 10 mg/kg, 1/12 in each of
the 5 mg and 2.5 mg/kg groups. All deaths occurred 0.5-6 hours after oral
doses. While one rat that died in the 2.5-mg/kg/day group showed signs of
poisoning, no symptoms were exhibited by survivors, nor did any of the
survivors differ from controls histologically or in any of the parameters
monitored. The systemic level of this rapidly degradable toxicant [based on
pharmacokinetics data, Sgaragli and Mannaioni (1973)] was probably much higher
than in normal oral intake with food and water because it was administered all
at once by gavage. Thus, 2.5 mg/kg/day could be considered a short-term to
subchronic LOAEL for rats.
Additional studies (Gritzelmann et al., 1978) reported that a 6-month-old
human patient received strychnine doses of 0.3-1.1 mg/kg/day over an 18-month
period without any adverse effects. However, the patient may have had a
higher strychnine tolerance as a result of nonketotic hyperglycinemia. The
Oil and Hazardous Materials-Technical Assistance Data Systems (1984) reported
that "adults may safely drink daily 0.078-0.25 gallons of water containing 10
mg/L of strychnine" (equivalent to 2.9-9.5 mg/day). This corresponds to
0.041-0.136 mg/kg.
__I.A.3. Uncertainty and Modifying Factors (Oral RfD)
UF — An RfD of 0.0003 mg/kg/day or 0.02 mg/day for a 70-kg person is derived
from the Seidl and Zbinden (1982) short-term to subchronic study by applying
an uncertainty factor of 10,000. This factor accounts for extrapolation from a
less-than-chronic to a chronic exposure study, extrapolation from animals to
humans, and differences in sensitivity among the human population. An
additional 10 is used because a LOAEL/FEL (2.5 mg/kg/day) was utilized in the
estimation of the RfD instead of a NOAEL. In view of this concern and the
limitations in the database, the derived RfD should be viewed as an interim
estimate. Despite the limitations of the database, the additional factor of
10 should result in a sufficiently protective level.
MF — None
__I.A.4. Additional Studies/Comments (Oral RfD)
None.
__I.A.5. Confidence in the Oral RfD
Study — Low
Database — Low
RfD — Low
Confidence in the chosen study is low because a small number of animals were tested, a NOEL was not established, and the study was extremely short. Confidence in the database is low because of the limited supporting studies. Low 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 — 08/05/1985
Verification Date — 08/05/1985
Screening-Level Literature Review Findings — A screening-level review conducted by an EPA contractor of the more recent toxicology literature pertinent to the RfD for Strychnine conducted in September 2002 did not identify any critical new studies. IRIS users who know of important new studies may provide that information to the IRIS Hotline at hotline.iris@epa.gov or (202)566-1676.
__I.A.7. EPA Contacts (Oral RfD)
Please contact the IRIS Hotline for all questions concerning this assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 (FAX) or hotline.iris@epa.gov (internet address).
_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)
Substance Name — Strychnine
CASRN — 57-24-9
Not available at this time.
_II. Carcinogenicity Assessment for Lifetime Exposure
Substance Name — Strychnine
CASRN — 57-24-9
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 — Strychnine
CASRN — 57-24-9
Last Revised — 01/01/1990
_VI.A. Oral RfD References
Gitzelmann, R., B. Steinmann and M. Cuenod. 1978. Strychnine for the
treatment of nonketotic hyperglycinemia. New England J. Med. 298: 1424.
Seidl, I. and G. Zbinden. 1982. Subchronic oral toxicity of strychnine in
rats. Arch. Toxicol. 51(3): 267-271.
Sgaragli, G.P. and P.F. Mannaioni. 1973. Pharmacokinetic observations on a
case of massive strychnine poisoning. Clin. Toxicol. 6(4): 533-540.
_VI.B. Inhalation RfC References
None
_VI.C. Carcinogenicity Assessment References
None
_VII. Revision History
Substance Name — Strychnine
CASRN — 57-24-9
Date |
Section |
Description |
---|---|---|
03/31/1987 | I.A.6. | Documentation corrected |
03/01/1988 | I.A.4. | Text deleted |
01/01/1990 | VI. | Bibliography on-line |
01/01/1992 | I.A.7. | Primary contact changed |
01/01/1992 | IV. | Regulatory actions updated |
04/01/1997 | III., IV., V. | Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from IRIS on or before April 1997. IRIS users were directed to the appropriate EPA Program Offices for this information. |
12/03/2002 | I.A.6. | Screening-Level Literature Review Findings message has been added. |
_VIII. Synonyms
Substance Name — Strychnine
CASRN — 57-24-9
Last Revised — 01/31/1987
- 57-24-9
- Certox
- Dolco Mouse Cereal
- Kwik-Kil
- Mole Death
- Mouse-Nots
- Mouse-Rid
- Mouse-Tox
- Pied Piper Mouse Seed
- Ro-Dex
- Sanaseed
- Strychnidin-10-one
- Strychnin
- Strychnine
- Strychnos