UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF 

PREVENTION, PESTICIDES AND

TOXIC SUBSTANCES 

Tuesday, March 30, 2010

MEMORANDUM

SUBJECT: Acute Toxicity Review for EPA Reg. No.: 85808-R-STABICIDE 71

 DP Barcode: 373957

FROM: Leon Johnson, Biologist

Chemistry and Toxicology Team

Product Science Branch

Antimicrobials Division (7510P)

THRU: Karen Hicks, Team Leader

Chemistry and Toxicology Team

Product Science Branch

Antimicrobials Division (7510P)

TO: Marshall Swindell, PM 33/ Demson

 Regulatory Management Branch

 Antimicrobials Division (7510P)

Applicant: Schulke & Mayr GmBH

 Robert-Koch-Str. 41

 22851 Norderstedt

 Germany

FORMULATION FROM LABEL:

Active Ingredient(s): % by wt.

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

Other Ingredient(s): 0.91

Total: 100.00
1) BACKGROUND: 

Schulke & Mayr GmbH has applied for registration of their new Industrial Bactericide 

product STABICIDE 71 “ EPA Reg. No. 85808-R “. Schulke & Mayr has resubmitted 

the acute oral toxicity study (MRID 479596-01 ) and the acute dermal toxicity study 

(MRID 479596-02) in response to acute toxicity data deficiences noted in a 

previously submitted acute oral and dermal toxicity study.

2) RECOMMENDATIONS: PSB findings are: 

a) The acute oral toxicity study MRID# 479596-01 is acceptable.

b) The acute dermal toxicity study MRID# 479596-02 is acceptable.

c) MBO is a new active ingredient and EPA does not have any data to support the 

acute inhalation claim. MBO has the potential to be aerosolized and inhaled and 

therefore there is the potential for deep lung deposition by the handler. This 

scenario could lead to a more toxic effect being caused by MBO lower in the 

respiratory tract. Depending on MBO particle size, it may be possible for the 

particles to reach the deep lung before they hydrolyze. A waiver for the acute 

inhalation toxicity study is denied. 

d) The primary eye irritation study does not meet the requirements of GLP and 

differs in the following ways:

i. No Study Director

ii. No Quality Assurance inspections performed

 There are a number of issues with the primary eye irritation study. However, the 

lab has assessed the product as being severely irritating to the eye and this would 

place the product in category one for toxicity. This classification is acceptable for 

registering this product.

e) The primary skin irritation study does not meet the requirements of GLP and 

 differs in the following ways:

i. No study Director

ii. No Quality Assurance inspections were performed

 There are a number of concerns about the primary skin irritation study. 

 However, the lab has assessed the product as being severely irritating to the 

 Skin and this would place the product in category one for toxicity. This 

 Classification is acceptable for registering this product.

 

 f) The dermal sensitization is acceptable.

 
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 47597204 II Acceptable

Acute Inhalation Toxicity Waiver Request - Denied

Primary Eye Irritation 475972-05 I Acceptable

Primary Skin Irritation 475972-05 I Self-validated

Dermal Sensitization 475972-06 Non-sensitizer Acceptable

3) PRECAUTIONARY LABELING:

 Precautionary labeling for MBO cannot be determined until the acute inhalation 

toxicity study has been satisfied. 

 
DATA REVIEW FOR ACUTE ORAL TOXICITY TESTING (§ 81-1, 870.1100)

 (ACUTE TOXIC CLASS METHOD)

Testing Laboratory: Laboratory for Pharmacology and Toxicology, Hamburg, Germany 

Study Director: Dr. Phil Leuschner

Quality Assurance (40 CFR §160.12): A Quality Assurance (QA) statement was 

included. A Good Laboratory Compliance Statement was included, stating that this study 

meets the requirements of 40 CFR PART 160. This study was performed according to: 

Good Laboratory Practice’ Regulations of the EC enacted in Germany in the’ 

Chemikaliengesetz [ Chemicals Act ] current edition; United States Food and Drug 

Administration Good Laboratory Practice Regulations- 21 Code of Federal Regulations, 

Part 58, current edition. The following regulations were also considered ‘ OECD 

Principles of Good Laboratory Practice’ ( as revised in1997 ) ENV/MC/CHEM (98) 17, 

January 21st, 1998. 

Test Material: N,N-Methylene-bis(5-methyloxazolidine)

(batch no. 24773) ( clear, colourless liquid )

Dosage: 200 and 2000 mg/kg b.w.

Species: 12 rats, Sprague- Dawley

Sex: 6 Males and 6 Females

Age: Males: 36 days old; Females: 48 days old

Weight: Males: 183-197grams, Females:173-187grams 

Source: Charles River Deutschland GmbH,Sandhofer Weg 7,D-97633 Sulzfeld 

Housing: Temperature Range: 22° C ± 3°

Relative Humidity: 55± 15%

Photoperiod: 150 lux at approx.1.5 m room height/darkened for 12 hours

Acclimation: at least 5 days

Conclusion:

1. Acute Oral LD50 (mg/kg): Male and Female Rats 632 mg/kg

2. Toxicity Category: III Classification: acceptable

 

Procedure (Deviations from §81-1):

 No procedure deviations noted.

 

Product Manager: Marshall Swindell Reviewer: Leon Johnson

MRID No.: 479596-01 Study Completion Date: Mar. 07, 2002

 Lab Study No.: 14816/01
Results:

Dosage (mg/kg)

(Number Deaths/Number Tested)

Males Females Combined

2000 3/3 3/3 6/6

200 0/3 0/3 0/6

Observations:

200 mg/kg Dose level (6 animals ): All animals survived. No signs of intolerance 

reactions were noted.

2000 mg/kg Dose level ( 6 animals ) :All animals died. Reduced motility, ataxia, 

reduced muscle tone and dysponea were exhibited between 15 minutes and 24 hours.

Gross Necropsy: 

Gross necropsy revealed no specific pathological findings.
DATA REVIEW FOR ACUTE DERMAL TOXICITY TESTING (§81-2, 870.1200)

Testing Laboratory: Laboratory for Pharmacology and Toxicology, Hamburg, Germany 

Author: Dr. Phil Leuschner

Quality Assurance (40 CFR §160.12): A Quality Assurance (QA) statement was 

included. A Good Laboratory Compliance Statement was included, stating that this study 

meets the requirements of 40 CFR PART 160. This study was performed according to: 

Good Laboratory Practice’ Regulations of the EC enacted in Germany in the’ 

Chemikaliengesetz [ Chemicals Act ] current edition; United States Food and Drug 

Administration Good Laboratory Practice Regulations- 21 Code of Federal Regulations, 

Part 58, current edition. The following regulations were also considered ‘ OECD 

Principles of Good Laboratory Practice’ ( as revised in1997 ) ENV/MC/CHEM (98) 17, 

January 21st, 1998. 

Test Material: N,N-Methylene-bis(5-methyloxazolidine)

(batch no. 24773) ( clear, colourless liquid )

Dosage: 200 mg/kg, 750mg/kg and 2000 mg/kg b.w.

Species: 30 rats, Sprague- Dawley

Sex: 15 Males and 15 Females

Age: Males: 33 days to 43 days old; Females:44 days to 56 days old

Weight: Males: 215-267grams, Females:198-230grams 

Source: Charles River Deutschland GmbH,Sandhofer Weg 7,D-97633 Sulzfeld 

Housing: Temperature Range: 22° C ± 3°

Relative Humidity: 55± 15%

Photoperiod: 150 lux at approx.1.5 m room height/darkened for 12 hours

Acclimation: at least 5 days

Summary:

1. LD50 (mg/kg): 

2. The estimated LD50 is 1700 mg/kg at 24 hours and 790 mg/kg at 14 days

3. Tox. Category: II Classification: Acceptable

Product Manager: Marshall Swindell Reviewer: Leon Johnson

MRID No.: 479596-02 Study Completion 

Date: Mar 07, 2002

Lab Study No.: 14817/01

Males= 1700@24 hours, 1200@ 14 days

Females= >2000@ 24 hours, 760@14 days

Combined= 1700@24 hours, 790@ 14 days
Procedure (Deviation From §81-2):

No procedure deviations noted.

Results:

Reported Mortality

DOSAGE

(mg/kg)

(NUMBER DEATHS/NUMBER TESTED)

Males Females Combined

250 0/5 0/5 0/10

750 0/5 1/5 1/10

2000 5/5 5/5 10/10

Observations: 

250 mg/kg Dose Level ( 10 animals ):

 All animals survived. No signs of intolerance reactions were noted.

750 mg/kg Dose Level ( 10 animals ):

 Males and females exhibited signs of reduced motility, ataxia, dyspnoea and muscle 

tonus. One female died by day one. 

2000 mg/kg Dose Level ( 10 animals ):

All animals died. Males and females exhibited reduced motility, ataxia, tremors and 

dyspnoea by day one.

Gross Necropsy Findings: 

250 mg/kg Dose Level ( 10 animals ):

Gross necropsy revealed no abnormalities.

750 mg/kg Dose Level ( 10 animals ):

Gross necropsy revealed no abnormalities.

2000 mg/kg Dose Level ( 10 animals ):

Gross necropsy revealed no abnormalities in males and severe necrosis in two females.