Document ID: EPA-HQ-OPPT-2009-0112-0178
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2013-11-29T05:00Z

SRC TR-12-043

HPV3 REPRODUCTION/DEVELOPMENTAL TOXICITY STUDY PLAN REVIEW 

(FINAL – DOES NOT CONTAIN CBI)

Benzenesulfonic acid, 3-nitro-, sodium salt (1:1), CASRN 127-68-4

Prepared by:

Teresa Manyin, William L. Richards, and Laura Morlacci

Chemical, Biological and Environmental Center

SRC, Inc.

7502 Round Pond Road

North Syracuse, NY 13212

Contract No. EP-W-09-027

Task FG007.2.009.006

Submitted to:

OCSPP/OPPT/RAD (7403M)

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue

Washington, D.C. 20460

Debra Milligan, Project Officer

Meena Sonawane, Work Assignment Manager

David Brooks, Alternate Work Assignment Manager

June 5, 2012

HPV3 Reproduction/Developmental Toxicity Study Plan Review: 

Benzenesulfonic acid, 3-nitro-, sodium salt (1:1), CASRN 127-68-4

The test rule, “Testing of Certain High Production Volume Chemicals;
Third Group of Chemicals” (76 FR 65385, October 21, 2011), requires F2
toxicity testing for benzenesulfonic acid, 3-nitro-, sodium salt (1:1)
(CASRN 127-68-4).  The F2 requirement consists of a
Reproduction/Developmental Toxicity Screening Test following 40 CFR
799.9355.  A study plan for this test, to be conducted by Jai Research
Foundation, was submitted to EPA by Tiarco Chemical on February 24,
2012.  Given that the study plan stated that the purity of the test
substance would be 96.9%, which does not meet the test rule requirement
for a purity of at least 99%, EPA requested that Tiarco Chemical submit
a detailed description of the test substance’s composition to
determine if the proposed test substance would yield toxicity test data
that were representative of the test rule chemical.  The composition of
the proposed test substance was submitted to EPA by Tiarco Chemical in a
CBI submission (DCN 40120000059) received by EPA on April 11, 2012.

The study plan is reviewed herein for compliance with the test rule
guideline, 40 CFR 799.9355.  The composition of the proposed test
substance is also evaluated.

Review of Study Plan:

The submitted study plan, “Reproduction/Developmental Toxicity
Screening Test of Sodium 3-Nitrobenzene Sulfonate (CAS # 127-68-4; US
EPA HPV3) in Wistar Rats” is considered adequate to satisfy the
mammalian reproduction/developmental toxicity testing requirement with
the following stipulations and modifications:

In section 5.11: Mating Procedure (p. 10), the study plan states: “If
mating has not occurred during two weeks mating period, re-mating of
females with proven males of the same group may be performed.”  This
appears to indicate that the mating period could be longer than two
weeks, whereas the 40 CFR 799.9355 indicates that the mating period
should be no longer than two weeks.  This statement should be revised to
more clearly explain the mating procedure, while adhering to the test
rule guideline.

The study plan does not indicate when unmated females will be
sacrificed.  According to 40 CFR 799.9355, females showing no evidence
of copulation are sacrificed 24-26 days after the last day of the mating
period.  These details should be added to the study plan.

The test guideline cited in section 2.2: Regulatory Guidelines (p. 5 of
the study plan) is OPPTS 870.3550.  This section should also cite the
test rule guideline, 40 CFR 799.9355 (“TSCA Reproduction/Developmental
Toxicity Screening Test”, December 15, 2000); the laboratory
conducting this test should ensure compliance with 40 CFR 799.9355.

In section 5.7: Housing (p. 9), the study plan states: “Throughout
experiment period, the rats will be housed individually.  Except during
the mating period, the rats will be housed in groups of 2 rats/cage (one
male plus one female).”  This is unclear.  This section should be
revised to state: “Throughout the experiment period, the rats will be
housed individually, with the exception that during the mating period,
the rats will be housed in groups of 2 rats/cage (one male plus one
female).”  

In section 7.2: Pups (p. 12), the study plan should be modified to
include the identification of runts (pups that are significantly smaller
than corresponding control pups) during the examination of pups at
birth.

In section 7.2.1: Pup Body Weight (p. 12), the study plan states that
individual pup body weights will be recorded.  Additionally, the total
weight of pups in each litter should be calculated (by summing the
individual pup body weights for each litter); litter weights should be
statistically analyzed to determine treatment effects.

In section 7.3: Necropsy (p. 13), the word “scarified” should be
replaced with “sacrificed”.

In section 8.2: Data Evaluation (p. 14), a statement should be added to
indicate that statistical analyses on pup data (e.g., number of pups
born, pup body weights, pup survival) will be conducted on a per-litter
or per-dam basis.

Review of Test Substance Composition:

The composition of the proposed test substance, which was submitted to
EPA by Tiarco Chemical in a CBI submission (DCN 40120000059), is
considered to be acceptable, with the stipulation that the dose levels
must be expressed as the concentration of active ingredient (i.e., CASRN
127-68-4).  A more detailed review of the test substance composition,
which includes CBI, is contained in DCN 40120000064.

Conclusion:

The submitted study plan and proposed test substance are acceptable with
the stipulations described above.

HPV3 Reproduction/Developmental Toxicity Study Plan Review (Final)	CASRN
127-68-4

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