UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

Antimicrobials Division (AD)

Friday, October 14, 2011

MEMORANDUM

Subject: Acute Toxicity Review for EPA Reg. No.: 85808-R

DP Barcode: D393665

Product Name: Stabicide 71

From: Ian Blackwell, Biologist

Chemistry and Toxicology Team

Product Science Branch

Antimicrobials Division (7510P)

Through: Karen Hicks, Team Leader

Chemistry and Toxicology Team

Product Science Branch

Antimicrobials Division (7510P)

To: Marshall Swindell, PM 33/ Demson Fuller 

Regulatory Management Branch 

Antimicrobials Division (7510P)

Applicant: Schulke & Mayr GmbH 

FORMULATION FROM LABEL:

Active Ingredient(s): % by wt.

N , N’- methylenebis (5-methyloxazolidin) (MBO) 99.09

Other Ingredient(s): 0.91

Total: 100.00
I BACKGROUND: Schulke and Mayr GmbH have submitted a supplement to an 

acute inhalation toxicity study that the Chemistry and Toxicology Team (CTT) 

reviewed on 4/20/2011. The results of that 4/20/2011 review were:

Study MRID Number Toxicity 

Category

Status

Acute Oral Toxicity 475972-03 III Acceptable

Acute Dermal Toxicity 475972-04 II Acceptable

Acute Inhalation Toxicity 482860-02 ? Supplementary

Primary Eye Irritation 475972-05 I Acceptable

Primary Skin Irritation 475972-05 I Acceptable

Dermal Sensitization 475972-06 Non-sensitizer Acceptable

The acute inhalation toxicity study was graded supplementary (needing the 

submission of additional information before it could be accepted) due to the 

following: 

A. The report does not state whether the test material was tested neat or diluted. 

The registrant needs to clarify this. 

B. The size of the exposure chamber was not reported. 

C. The lab did not conduct the assay by analyzing the chamber concentration of the 

active ingredient, N, N’-methylenebis (5-methyloxazolidin). Instead the report 

states, “Formaldehyde was used as the lead compound for analysis.” We do 

realize that MBO is a reaction product from paraformaldehyde and 2-

hydroxypropylamine. CTT knows from the Product Chemistry review of 85808-

R, that one method of measuring MBO concentration is by reacting it with 

hydroxylamine hydrochloride. The report does not state how the assay went 

from measuring the atmospheric aerosol concentration 85808-R to having gaseous 

formaldehyde in the impingers. These things need to be clarified. 

D. The test facility did not determine the Mass Median Aerodynamic Diameter 

(MMAD) of the aerosol. The report appears to state that due to evaporation of 

the aerosolized product, they could not measure the MMAD. CTT does not 

understand why they could determine a test material concentration (mg/L), but, 

could not determine an MMAD. The lab needs to explain this. 

E. As there was an issue with vaporization of the aerosol, CTT must ask if the lab 

intentionally vaporized the test material for testing. 

To correct the study deficiencies listed above, Schulke and Mayr GmbH consultant 

Technology Sciences Group has submitted a revised version (dated 9/1/2011) of the 

acute inhalation toxicity study. The original MRID Number was 482860-02. The 

MRID Number of the revised report is 485945-01. 
II RECOMMENDATIONS: 

1. The acute inhalation toxicity study is unacceptable. The specific study deficiency 

causing the rejection is that the laboratory did not conduct a particle size analysis 

for this study. Agency guideline OPPTS 870.1300 states, “During the 

development of the generating system, particle size analysis should be performed 

to establish the stability of aerosol concentrations. The MMAD particle size range 

should be between 1-4 μm.” This study did not assess the MMAD or any other 

form of particle size analysis of the aerosol generated in this study. 

A. The report states, “After spraying parts of the solution immediately

evaporate. When collecting the particle fractions of filters or impactor foils 

the semi-volatile nature of the inhalation atmosphere results in significant 

loss of the particle mass and therefore leads to false results.” The product 

chemistry data for this product (MRID Number 475972-02) reports the 

boiling point of this product as 204°C. With a boiling point this high, it is a 

non sequitur that the product would vaporize at the tested temperature of 

22°C. 

B. CTT received a telephone call from a representative of Schulke and Mayr 

GmbH, Zuhal Thompkins. Ms. Thompkins stated that due to guideline 

Agency guideline 830.7520, the laboratory felt that an MMAD was not 

required for this acute inhalation toxicity study. This explanation is not 

acceptable as 830 guidelines clearly apply to Product Chemistry studies, not 

acute toxicity studies. 

The registrant must properly address the data gap for the acute inhalation toxicity 

to support 85808-R. 

 

The acute toxicity profile for File Symbol 85808-R is currently:

Study MRID 

Number

Toxicity 

Category

Status

Acute Oral Toxicity 475972-03 III Acceptable

Acute Dermal Toxicity 475972-04 II Acceptable

Acute Inhalation Toxicity 482860-02 ? Data Gap

Primary Eye Irritation 475972-05 I Acceptable

Primary Skin Irritation 475972-05 I Acceptable

Dermal Sensitization 475972-06 Nonsensitizer Acceptable

III LABELING: 

1. The Signal Word is “DANGER”, based upon the results of the primary eye and 

skin irritation studies. 
2. Other than the Signal Word, CTT cannot prescribe Precautionary labeling for File 

Symbol 85808-R. The registrant must correct the lack of an acute inhalation 

toxicity. 
DATA REVIEW FOR ACUTE INHALATION TOXICITY (§81-3, 870.1300)

Testing Laboratory: Fraunhofer Institute for Toxicology and Experimental Medicine

 Author: Prof. Dr. Dr. U Heinrich

Quality Assurance (40 CFR §160.12): Included

Test Material: Stabicide 71, (Grotan OX)

Concentration: 0.543 and 1.189 mg/L 

Species: Wistar rats, Crl:WI(WU)

Weight: Males= 241.9-302.7 g Females= 188.1-197.8 g

Age: 8-10 weeks

 Source: Charles River Deutschland

Summary:

1. LC50 (mg/L) Males=

Females=

Combined=

2. The estimated LC50 is

3. MMAD: μm

4. Toxicity Category: Classification: Unacceptable

Procedure (Deviation From §81-3):

• No particle size determination was conducted. 

Results:

Reported Mortality

Exposure Concentration

(NUMBER DEATHS/NUMBER TESTED)

Males Females Combined

0.543 (nominal=1.022) 0/3 0/3 0/6

1.189 (nominal=2.038) 3/3 0/3 3/6

Product Manager: 33 Reviewer: I. Blackwell

MRID No.: 485945-01 Revised Final Report Date: 9/1/2011

 Lab Study No.: 02 G 10026
Chamber Atmosphere

Dose Level MMAD GSD particles < μm

0.543 mg/L ? μm ? μm Not determined

1.189 mg/L ? μm ? μm Not determined

Chamber Environment

Chamber Volume Not reported Not reported

Airflow 17.6 L/min. 17.6 L/min.

Temperature 21.3 ± 0.1 o C 21.3 ± 0.1 o C

Relative Humidity 61.2 ± 0.7% 63.1 ± 0.6%

Clinical Observations: Salivation, stains around mouth, coat soiled, gasping, 

respiratory sounds, general condition bad, abdominal breathing. 

Gross Necropsy Findings: Lungs showing areas that were read, partly red, spongy 

and/or glassy.