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Zineb (CASRN 12122-67-7)

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0204

Zineb; CASRN 12122-67-7

Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data, as outlined in the IRIS assessment development process. Sections I (Health Hazard Assessments for Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime Exposure) present the conclusions that were reached during the assessment development process. Supporting information and explanations of the methods used to derive the values given in IRIS are provided in the guidance documents located on the IRIS website.

STATUS OF DATA FOR Zineb

File First On-Line 03/31/1987

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 — Zineb
CASRN — 12122-67-7
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

Thyroid hyperplasia

Rat, Chronic Oral
Bioassay

Blackwell-Smith
et al., 1953

NOEL: none

LOAEL: 500 ppm (diet)
(converted to 25 mg/kg/day)

500 1 5E-2
mg/kg/day

* Dose Conversion Factors and Assumptions — Assumed rat food consumption = 5% bw/day

__I.A.2. Principal and Supporting Studies (Oral RfD)

Blackwell-Smith, Jr., R.J., J.K. Finnegan, P.S. Larson, P.F. Sahyoun, M.L. Dreyfuss and H.B. Haag. 1953. Toxicologic studies on zinc and disodium ethylene bisdithiocarbamates. J. Pharmacol. Exp. Therap. 109: 159-166.

Groups of 10 male and 10 female rats received 0, 500, 1000, 2500, 5000 or 10,000 ppm zineb in the diet for 2 years. Blackwell-Smith et al. (1953) used the criteria for grading thyroid hyperplasia established by Seifter and Ehrich (1948), who had published an earlier report on goitrogenic effects of zineb feeding in weanling rats. This system grades hyperplastic responses on a scale of 1-5, with a response of 2+ being regarded as within normal limits. In order to ensure consistency in grading of slides, Blackwell-Smith et al. (1953) submitted sections from 10 rats used in a short-term study to Dr. Seifter for evaluation. These readings were used as a guide for subsequent classification of responses. Thyroid hyperplasia was observed in rats of all treated groups, establishing the LOEL of 25 mg/kg/day (500 ppm). At this dose 6/16 rats exhibited hyperplasia graded 3+ or above as compared with the control group, for which no response greater than 2+ was observed. At higher dosages, rats developed more severe thyroid hyperplasia in addition to renal congestion, nephritis and nephrosis; increased mortality was noted for rats consuming the two highest dietary levels.

Other data summarized in U.S. EPA (1984) attest to the development of thyroid hyperplasia as a consequence of zineb consumption, and collectively support the choice of 25 mg/kg/day as the proper effect level from which to derive an RfD.

__I.A.3. Uncertainty and Modifying Factors (Oral RfD)

UF — A composite uncertainty factor of 500 was used consisting of 2 factors of 10 to account for inter- and intraspecies variability and a 5-fold factor for use of a LOAEL. The intermediate uncertainty factor of 5 was used as the observed effects were graded on a subjective, albeit controlled scale, with the resulting impression that these effects were only minimally adverse. Thus, a full 10-fold factor for the extrapolation of a LOAEL to a NOAEL was not deemed necessary.

MF — None

__I.A.4. Additional Studies/Comments (Oral RfD)

Several studies in rats and dogs support the choice of a LOAEL. Terata have been observed in rats administered amounts of zineb in excess of 2000 mg/kg/day (Short et al., 1980).

__I.A.5. Confidence in the Oral RfD

Study — Medium
Database — Medium
RfD — Medium

The critical study was of chronic duration, measured multiple endpoints, and included five dose levels. The numbers of animals, however, were relatively small, leading to a medium confidence rating. Supportive studies exist in several species, however, adequate reproductive data are not available. Thus, confidence in the database is also medium. Medium confidence in the RfD follows.

__I.A.6. EPA Documentation and Review of the Oral RfD

Source Document — U.S. EPA, 1984

The ADI in the 1984 Health and Environmental Effects Profile has received an Agency Review with the help of two external scientists.

Other EPA Documentation — None

Agency Work Group Review — 11/06/1985, 02/05/1986, 05/15/1986

Verification Date — 02/05/1986

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 Zineb conducted in November 2001 identified one or more significant new studies. IRIS users may request the references for those studies from 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).

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_I.B. Reference Concentration for Chronic Inhalation Exposure (RfC)

Substance Name — Zineb
CASRN — 12122-67-7

Not available at this time.

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_II.  Carcinogenicity Assessment for Lifetime Exposure

Substance Name — Zineb
CASRN — 12122-67-7

Not available at this time.

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_III.  [reserved]
_IV.  [reserved]
_V.  [reserved]


_VI.  Bibliography

Substance Name — Zineb
CASRN — 12122-67-7
Last Revised — 03/01/1990

_VI.A. Oral RfD References

Blackwell-Smith, R., J.K. Finnegan, P.S. Larson, P.F. Sahyoun, M.L. Dreyfuss and H.B. Haag. 1953. Toxicologic studies on zineb and disodium ethylene bis(dithiocarbamates). J. Pharmacol. Accol. Exp. Therap. 109: 159-166.

Seifter, J. and W.E. Ehrich. 1948. Goitrogenic compounds: Pharmacological and pathological effects. J. Pharmacol. Exp. Therp. 92: 303-314. (Cited in: Blackwell-Smith, R., et al. 1953)

Short, R.D., J.L. Minor and T.M. Unger. 1980. Teratology of a zineb formulation. U.S. EPA Report No. 600/1-80-017. NTIS PB80-181175.

U.S. EPA. 1984. Health and Environmental Effects Profile for Zineb. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH for the Office of Solid Waste, Washington, DC.

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_VI.B. Inhalation RfC References

None

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_VI.C. Carcinogenicity Assessment References

None

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_VII.  Revision History

Substance Name — Zineb
CASRN — 12122-67-7

Date
Section
Description
03/01/1988 I.A.2. Text revised
03/01/1988 I.A.4. Text added
03/01/1990 VI. Bibliography on-line
01/01/1992 I.A.7. Secondary contact changed
01/01/1992 IV. Regulatory Action section on-line
04/01/1997 III., IV., V. Drinking Water Health Advisories, EPA Regulatory Actions, and Supplementary Data were removed from the 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.

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_VIII.  Synonyms

Substance Name — Zineb
CASRN — 12122-67-7
Last Revised — 03/31/1987

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