1 / 89

I U C L I D

Data Set

Existing Chemical : ID: 124-68-5

CAS No. : 124-68-5

EINECS Name : 2-amino-2-methylpropanol

EC No. : 204-709-8

TSCA Name : 1-Propanol, 2-amino-2-methylMolecular Formula : C4H11NO

Producer related part

Company : Dow Chemical, TERC

Creation date : 01.03.2004

Substance related part

Company : Dow Chemical, TERC

Creation date : 01.03.2004

Status :

Memo : AMP

Printing date : 30.11.2006

Revision date :

Date of last update : 30.11.2006

Number of pages : 89

Chapter (profile) : Chapter: 1, 2, 3, 4, 5, 6, 7, 8, 10

Reliability (profile) : Reliability: without reliability, 1, 2, 3, 4

Flags (profile) : Flags: without flag, confidential, non confidential, WGK (DE), TA-Luft (DE), 

Material Safety Dataset, Risk Assessment, Directive 67/548/EEC, SIDS
1. General Information Id 124-68-5

Date 30.11.2006

2 / 89

1.0.1 APPLICANT AND COMPANY INFORMATION

Type : manufacturer

Name : The Dow Chemical Company

Contact person : Dr. William T. Stott

Date : 27.04.2005

Street : 1803 Building

Town : 48674 Midland, MI

Country : United States

Phone : 989 636 1000

Telefax :

Telex :

Cedex :

Email :

Homepage : http://www.dow.com/Homepage/index.html

27.04.2005

1.0.2 LOCATION OF PRODUCTION SITE, IMPORTER OR FORMULATOR

Type : manufacturer

Name of plant : ANGUS Chemical Company

Street :

Town : Sterlington, Louisiana

Country : United States

Phone :

Telefax :

Telex :

Cedex :

Email :

Homepage : http://www.dow.com/Homepage/index.html

Source : Frauson, L. (2003). Internal E-mail of the Dow Chemical Company to C. 

Houtman.

Reliability : (2) valid with restrictions

2g

27.04.2005

Type : manufacturer

Name of plant : Angus Chemie GmbH

Street :

Town : Ibbenburen

Country : Germany

Phone :

Telefax :

Telex :

Cedex :

Email :

Homepage : http://www.dow.com/Homepage/index.html

Source : Frauson, L. (2003). Internal E-mail of the Dow Chemical Company to C. 

Houtman.

Reliability : (2) valid with restrictions

2g

27.04.2005
1. General Information Id 124-68-5

Date 30.11.2006

3 / 89

1.0.3 IDENTITY OF RECIPIENTS

1.0.4 DETAILS ON CATEGORY/TEMPLATE

1.1.0 SUBSTANCE IDENTIFICATION

IUPAC Name : 2-Amino-2-methyl-1-propanol

Smiles Code : OCC(N)(C)C

Molecular formula : C4H11NO

Molecular weight : 89.14

Petrol class :

Reliability : (2) valid with restrictions

2g

28.06.2004 (1)

1.1.1 GENERAL SUBSTANCE INFORMATION

Purity type : measured for specific batch

Substance type : organic

Physical status : liquid

Purity : ca. 100 % w/w

Colour : colourless

Odour : faint amine odor

Remark : The test material is sold in formulations of >99% ai, 95% ai, 90% ai, and 

75% ai.

AMP-Regular is 92% minimum ai, maximum 8% impurities.

Source : MSDS of The Dow Chemical Company. 2003.

Reliability : (2) valid with restrictions

2g

27.04.2005

1.1.2 SPECTRA

1.2 SYNONYMS AND TRADENAMES

2-Amino-2-methyl-1-propanol

Reliability : (2) valid with restrictions

18.03.2004 (1)

Aminomethylpropanol

Source : ANGUS Chemie GmbH Ibbenburen

European Commission- European Chemicals Bureau Ispra(VA)

Reliability : (2) valid with restrictions

01.03.2004

AMP

Source : ANGUS Chemie GmbH Ibbenburen
1. General Information Id 124-68-5

Date 30.11.2006

4 / 89

European Commission- European Chemicals Bureau Ispra(VA)

Environmental Evaluation Report, DR-0001-9476. The Dow Chemical 

Company.

Reliability : (2) valid with restrictions

01.03.2004

AMP 100R

27.04.2005

AMP-75

27.04.2005

AMP-90

27.04.2005

AMP-90 Textile

27.04.2005

AMP-95

Source : Environmental Evaluation Report, DR-0001-9476. The Dow Chemical 

Company.

Reliability : (2) valid with restrictions

01.03.2004

AMP-95 Diagnostic

27.04.2005

AMP-95 SG

27.04.2005

AMP-Regular Diagnostic

27.04.2005

AMP-ULTRA PC 1000 Neutralizing Amine

27.04.2005

AMP-ULTRA PC 2000 Neutralizing Amine

27.04.2005

AVT-75 Amino Alcohol

27.04.2005

Corrguard-100 Animo Alcohol

27.04.2005

Corrguard-75 Animo Alcohol

27.04.2005

Corrguard-95 Animo Alcohol
1. General Information Id 124-68-5

Date 30.11.2006

5 / 89

27.04.2005

Corrguard-A Animo Alcohol

27.04.2005

P-1826

27.04.2005

1.3 IMPURITIES

Purity : typical for marketed substance

CAS-No : 124-68-5

EC-No : 204-709-8

EINECS-Name : 2-amino-2-methylpropanol

Molecular formula : C4H11NO

Value : 75 - 100 % w/w

Source : MSDS of The Dow Chemical Company. 2003.

Reliability : (2) valid with restrictions

2g

18.11.2004

Purity : typical for marketed substance

CAS-No : 27646-80-6

EC-No :

EINECS-Name : MMAMP

Molecular formula :

Value : < 6.9 % w/w

27.04.2005

1.4 ADDITIVES

Purity type : other

CAS-No : 7732-18-5

EC-No : 231-791-2

EINECS-Name : water

Molecular formula : H2O

Value : 0 - 25 % w/w

Function of additive : Solvent

Source : MSDS of The Dow Chemical Company. 2003.

Reliability : (2) valid with restrictions

2g

01.03.2004

1.5 TOTAL QUANTITY

1.6.1 LABELLING

Labelling : as in Directive 67/548/EEC

Specific limits : yes
1. General Information Id 124-68-5

Date 30.11.2006

6 / 89

Symbols : Xi, , , 

Nota : C, , 

R-Phrases : (36/38) Irritating to eyes and skin

(52) Harmful to aquatic organisms

(53) May cause long-term adverse effects in the aquatic environment

S-Phrases : (2) Keep out of reach of children

(61) Avoid release to the environment. Refer to special instructions/Safety 

data sets

Source : European Commission - European Chemicals Bureau Ispra (VA)

01.03.2004

1.6.2 CLASSIFICATION

Classified : as in Directive 67/548/EEC

Class of danger : irritating

R-Phrases : (36/38) Irritating to eyes and skin

(52) Harmful to aquatic organisms

(53) May cause long-term adverse effects in the aquatic environment

Specific limits :

Remark : Phrases apply for concentrations of AMP > 25%.

Source : European Commission - European Chemicals Bureau Ispra (VA)

27.04.2005

1.6.3 PACKAGING

1.7 USE PATTERN

Type of use : industrial

Category : Paints, lacquers and varnishes industry

27.04.2005

Type of use : industrial

Category : other: paper coating, personal care, metalworking fluid

Reliability : (2) valid with restrictions

2g

01.03.2004 (1)

1.7.1 DETAILED USE PATTERN

1.7.2 METHODS OF MANUFACTURE

1.8 REGULATORY MEASURES

1.8.1 OCCUPATIONAL EXPOSURE LIMIT VALUES

Type of limit : other
1. General Information Id 124-68-5

Date 30.11.2006

7 / 89

Limit value :

Remark : none established

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

01.03.2004

1.8.2 ACCEPTABLE RESIDUES LEVELS

1.8.3 WATER POLLUTION

1.8.4 MAJOR ACCIDENT HAZARDS

1.8.5 AIR POLLUTION

1.8.6 LISTINGS E.G. CHEMICAL INVENTORIES

1.9.1 DEGRADATION/TRANSFORMATION PRODUCTS

1.9.2 COMPONENTS

1.10 SOURCE OF EXPOSURE

Source of exposure : Human: exposure by production

Exposure to the : Substance

Source : Frauson, L. (2003). Internal E-mail of the Dow Chemical Company to C. 

Houtman.

Reliability : (2) valid with restrictions

2g

01.03.2004

Source of exposure : Human: exposure of the consumer/bystander

Exposure to the : Substance

Source : Frauson, L. (2003). Internal E-mail of the Dow Chemical Company to C. 

Houtman.

Reliability : (2) valid with restrictions

2g

01.03.2004

1.11 ADDITIONAL REMARKS

1.12 LAST LITERATURE SEARCH
1. General Information Id 124-68-5

Date 30.11.2006

8 / 89

1.13 REVIEWS
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

9 / 89

2.1 MELTING POINT

Value : 30.5 °C

Decomposition : no, at 31 °C

Sublimation : no

Method : other: unknown 

Year : 1989

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Reliability : (2) valid with restrictions

2 (data from a collection)

Flag : Critical study for SIDS endpoint

10.05.2006 (2)

2.2 BOILING POINT

Value : 165.5 °C at 1013 hPa

Decomposition : no

Method : other 

Year : 1989

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Reliability : (2) valid with restrictions

2 (data from a collection)

Flag : Critical study for SIDS endpoint

10.05.2006 (2)

2.3 DENSITY

Type : relative density

Value : = .934 at 40 °C

Method : other:unknown 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : Budavari, S. (1989) The Merck Index (Eleventh Edition).

Merck & Co., INC. Rahway, NJ, USA.

Not GLP, Published

Reliability : (2) valid with restrictions

2 (data from a collection)

Flag : Critical study for SIDS endpoint

17.05.2005

Type : density

Value : = .928 g/cm3 at 40 °C

Method : other:unknown 

Year :

GLP : no

Test substance :

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

10 / 89

4 (documentation insufficient for assessment)

17.05.2005

2.3.1 GRANULOMETRY

2.4 VAPOUR PRESSURE

Value : = .45 hPa at 20 °C

Decomposition :

Method : other (measured): gas saturation method 

Year : 2005

GLP :

Test substance : as prescribed by 1.1 - 1.4

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

17.05.2005 (3)

Value : = 1.33 hPa at 20 °C

Decomposition :

Method : other (measured): EPA Chemical Fate Test Guidelines, CG-1600, "Vapor 

Pressure", August 1982 and Federal Register, Vol. 45, 77345, No. 

772.122-3 (Nov. 21, 1980) 

Year : 1997

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Reliability : (2) valid with restrictions

2 (data from a collection)

28.06.2004 (4)

2.5 PARTITION COEFFICIENT

Partition coefficient : octanol-water

Log pow : ca. -.63 at 20 °C

pH value : 

Method : OECD Guide-line 107 "Partition Coefficient (n-octanol/water), Flaskshaking Method"

Year : 1996

GLP :

Test substance : as prescribed by 1.1 - 1.4

Reliability : (1) valid without restriction

1 (well-documented and acceptable for assessment)

Flag : Critical study for SIDS endpoint

17.05.2005 (5)

Partition coefficient : octanol-water

Log pow : ca. -.74 at 20 °C

pH value : 

Method :

Year : 1999

GLP :

Test substance : as prescribed by 1.1 - 1.4
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

11 / 89

Source : Meylan, W. (1999) SRC-KOW for Microsoft Windows, v1.65, 

Octanol/Water partition coefficient estimating software.

Not GLP / Published

Reliability : (2) valid with restrictions

2 (accepted calculation method)

17.05.2005

2.6.1 SOLUBILITY IN DIFFERENT MEDIA

Solubility in : Water

Value : at °C

pH value : 

concentration : at °C

Temperature effects :

Examine different pol. :

pKa : at 25 °C

Description : miscible

Stable : yes

Deg. product :

Method :

Year : 1989

GLP :

Test substance : as prescribed by 1.1 - 1.4

Reliability : (2) valid with restrictions

2 (data from a collection)

Flag : Critical study for SIDS endpoint

10.05.2006 (6)

Solubility in : Water

Value : = 0 - 99.9 vol% at 20 °C

pH value : = 11.3 

concentration : .1 other:molar at 20 °C

Temperature effects :

Examine different pol. :

pKa : 9.72 at 25 °C

Description : miscible

Stable :

Deg. product :

Method : other:unknown

Year : 1989

GLP : no data

Test substance :

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (original reference not available)

01.03.2004

2.6.2 SURFACE TENSION

2.7 FLASH POINT

Value : ca. 78 °C

Type : closed cup

Method : other: Tag Closed Cup 
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

12 / 89

Year : 1993

GLP :

Test substance : no data

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.03.2004

2.8 AUTO FLAMMABILITY

Value : = 437.7 °C at 1013 hPa

Method : other: ASTM D 2155 

Year : 1980

GLP : no

Test substance :

Source : ANGUS Chemie GmbH Ibbenburen

European Commission- European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.03.2004

2.9 FLAMMABILITY

Method :

Year : 1993

GLP :

Test substance : as prescribed by 1.1 - 1.4

Remark : The material is considered combustible.

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

27.04.2005

2.10 EXPLOSIVE PROPERTIES

Result : not explosive

Method :

Year : 1993

GLP :

Test substance :

Remark : Based on the structure of the chemical and our experience this substance 

is not explosive.

Source : ANGUS Chemie GmbH Ibbenburen

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.03.2004

2.11 OXIDIZING PROPERTIES
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

13 / 89

Result : no oxidizing properties

Method :

Year : 1993

GLP :

Test substance : as prescribed by 1.1 - 1.4

Remark : Material is considered corrosive to copper, brass, and aluminum.

Source : ANGUS Chemie GmbH Ibbenburen

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

27.04.2005

2.12 DISSOCIATION CONSTANT

Acid-base constant : 9.81

Method : other

Year : 1993

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Method : Potassium nitrate (5.05g, 0.05 mole) was added to a 500mL volumetric 

flask, which was subsequently purged with N2 to exclude CO2. 

Approximately 490mL of purified water that had been previously boiled was 

added to the flask. A N2 purge ensured a good mixing of the solution. The 

test material and addition water were added, bringing the total volume of 

the solution to 500mL. Half of the solution was transferred to a 400mL 

jacket beaker containing a magnetic stir bar, the pH electrode, the ATC 

probe, and a N2 purge. A Neslab headed / refrigerated circulator was used 

to jeep the temperature of the solution from 25.0-25.3C. The solution was 

titrated with 0.2000N hydrochloric acid and the pH and temperature was 

recorded with the addition of each mL of acid.

pKa was calculated from the experimental data.

Reliability : (2) valid with restrictions

2 (calculations based on experimental titration data)

01.03.2004 (7)

Acid-base constant : 9.88 @ 293K

Method : other

Year : 1990

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Method : The pKa value of the conjugate acid was determined by potentiometric 

titration of the basic compounds at constant ionic strength. Titration curves 

were recorded by computerized equipment. The pH meter was read by a 

digital voltmeter connected to a computer interface. The motorburet was 

also driven by this computer interface. The sample and buffer solutions 

were thermostated at the required temperature before use. CO2 was 

excluded from the titrations using a N2 purge. The pKa values were 

calculated from titration data. The experiments were run in triplicate at 

each temperature, and the mean of the 3 at each temperature are reported.

Result : The triplicates were reproducible within +/-0.02pKa.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.03.2004 (8)
2. Physico-Chemical Data Id 124-68-5

Date 30.11.2006

14 / 89

2.13 VISCOSITY

Test type : other

Test procedure :

Method :

Year : 1993

GLP :

Test substance :

Remark : Viscosity at 30C = 102 centipoise

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.03.2004

2.14 ADDITIONAL REMARKS

Memo : Henry's Law Constant

Result : 6.95 x 10^-3 Pa*m3 / mole

29.08.2006 (9)
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

15 / 89

3.1.1 PHOTODEGRADATION

Type : air

Light source : Sun light

Light spectrum : ca. 200 - 225 nm

Relative intensity : based on intensity of sunlight

Method : The experimental technique involved formation of OH radicals in a flow 

system by pulsed vacuum ultraviolet photolysis of H2O at >105nm and 

monitoring their resulting decay rates by detection of the OH resonance 

fluorescence band at 306.4nm with a cooled multiplier tube. The reaction 

was studied at 50+-1 torr total pressure of Argon. The concentration of the 

amines in the argon flow was determined by UV absorption at 200-225nm.

Result : k1(AMP) = (2.8+-0.5)x10^-11 cm3molecule-1s-1

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (10)

3.1.2 STABILITY IN WATER

Type : abiotic

t1/2 pH4 : at °C

t1/2 pH7 : at °C

t1/2 pH9 : at °C

Deg. product :

Method :

Year : 2006

GLP :

Test substance : as prescribed by 1.1 - 1.4

Remark : AMP lacks functional groups that would be subject to hydrolysis under 

typical environmental conditions.

Reliability : (2) valid with restrictions

2 (data from a handbook or collection)

Flag : Critical study for SIDS endpoint

01.06.2006 (11)

3.1.3 STABILITY IN SOIL

3.2.1 MONITORING DATA

3.2.2 FIELD STUDIES

3.3.1 TRANSPORT BETWEEN ENVIRONMENTAL COMPARTMENTS

Type : fugacity model level III

Media : other: air, water, soil sediments

Air : % (Fugacity Model Level I)

Water : % (Fugacity Model Level I)
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

16 / 89

Soil : % (Fugacity Model Level I)

Biota : % (Fugacity Model Level II/III)

Soil : % (Fugacity Model Level II/III)

Method : other: Mackay fugacity model

Year : 2006

Method : Input Parameters for Level III Model:

Property Value

Data Temperature (°C) 25

Chemical Type 1 (can partition into all environmental 

compartments)

Molecular Mass (g/mol) 89.1

Water Solubility (g/m3) 1 x 10^6

Vapor Pressure @ 25°C (Pa) 78

Melting Point ( C) 30.5

Henry's Law Constant (Pa*m3/mole) 6.95 x 10^-3

Log Kow -0.63

Simulated Emission Rate (kg/hr) 1,000 (Default)

Simulated Environment Level III Default environment

Reaction Half-lives (hr) Input to Level III Model:

Air (vapor phase) 5

Water (no susp. solids) 3,600*

Soil 7,200*

Sediment 7,200*

Suspended Sediment 1.0 x 10^11

Fish 1.0 x 10^11

Aerosol 1.0 x 10^11

Result : Predicted Distribution to air, water, soil, and sediments

1000 kg/hr to water (most likely emission scenario)

Air <0.1% (2 kg)

Water 99.9% (8.38 x 10^5 kg)

Soil <0.1% (144 kg)

Sediment <0.1% (333 kg)

1000 kg/hr to air

Air 0.5% (2770 kg)

Water 59.1% (3.58 x 10^5 kg)

Soil 40.5% (2.45 x 10^5 kg)

Sediment <0.1% (142 kg)

1000 kg/hr to soil

Air <0.1% (278 kg)

Water 58.1% (7.49 x 10^5 kg)

Soil 41.8% (5.39 x 10^5 kg)

Sediment <0.1% (298 kg)

1000 kg/hr simultaneously to water, air, and soil

Air 0.1% (3050 kg)

Water 71.2% (1.94 x 10^6 kg)

Soil 28.7% (7.84 x 10^5 kg)

Sediment <0.1% (773 kg)

Conclusion : This substance has high water solubility, a low vapor pressure, and low log 

Kow. The substance has a low potential for adsorption to soil or 

sediments, and a low potential to volatilize from water or soil to the 

atmosphere. If released to air, the substance will react with hydroxyl 

radicals. If released directly to water, the most probable emission route 

based on physical properties and use patterns, most of the substance will 

remain in the water compartment and is expected to be biodegraded. If 
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

17 / 89

released to soil, the substance is expected to be biodegraded.

Reliability : (2) valid with restrictions

2 (accepted calculation method)

Flag : Critical study for SIDS endpoint

29.08.2006 (9)

Type : fugacity model level I

Media : other: air, water, soil sediments

Air : .1 % (Fugacity Model Level I)

Water : 99.8 % (Fugacity Model Level I)

Soil : .1 % (Fugacity Model Level I)

Biota : % (Fugacity Model Level II/III)

Soil : % (Fugacity Model Level II/III)

Method : other: Mackay fugacity model

Year : 2006

Method : Input Parameters for Level I Model:

Property Value

Data Temperature (°C) 25

Chemical Type 1 (can partition into all environmental 

compartments)

Molecular Mass (g/mol) 89.1

Water Solubility (g/m3) 1 x 10^6

Vapor Pressure @ 25°C (Pa) 78

Melting Point ( C) 30.5

Henry's Law Constant (Pa*m3/mole) 6.95 x 10^-3

Log Kow -0.63

Simulated Emission Rate (kg/hr) 1,000 (Default)

Simulated Environment Level I Default environment

Result : Predicted Equilibrium Distribution Among Air, Water, Soil, and Sediments

100 000 kg total emissions

Air 0.1% (140 kg)

Water 99.8% (99800 kg)

Soil <0.1% (21 kg)

Sediment <0.1% (<1 kg)

Conclusion : This substance has high water solubility, a low vapor pressure, and low log 

Kow. In the absence of advective and reactive processes, these physical 

properties dictate that the substance will be distributed primarily in the 

water compartment at equilibrium. The substance has a low potential for 

adsorption to soil or sediments, and a low potential to volatilize from water.

Reliability : (2) valid with restrictions

2 (accepted calculation method)

29.08.2006 (9)

3.3.2 DISTRIBUTION

3.4 MODE OF DEGRADATION IN ACTUAL USE

3.5 BIODEGRADATION

Type : aerobic

Inoculum : activated sludge, domestic, non-adapted

Concentration : 2 mg/l related to Test substance

related to 
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

18 / 89

Contact time :

Degradation : ca. 40 (±) % after 28 day(s)

Result : other: not readily biodegradable

Deg. product :

Method : OECD Guide-line 301 D "Ready Biodegradability: Closed Bottle Test"

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : The study followed OECD Guide-line 301 D "Ready Biodegradability: 

Closed Bottle Test".

AMP was dissolved in mineral nutrient medium at a concentration of 2 

mg/L. The mineral medium had been prepared from aerated de-ionized 

water amended with nutrient salts and trace element stock solutions. The 

reaction mixtures were inoculated with a few drops of inoculum from the 

discharge of a community wastewater treatment plant. Corresponding 

control mixtures were prepared with the nutrient medium; nutrient medium 

with inoculum; and nutrient medium with inoculum and the reference 

substance sodium acetate to correct for background oxygen consumption 

and confirm the viability of the microbial inoculum. Equal volumes of the 

various reaction mixtures were dispensed into replicate bottles, sealed and 

incubated in the dark for 28 days at 20-21 oC. 

The dissolved oxygen concentration in duplicate samples was measured 

with an oxygen electrode on days 0, 5, 15, and 28. The percent 

biodegradation of the test substance was determined using the following 

formula: 

 Dt = (mg of BODx/L) o 100

 (mg of substance/L) o TOD

 Dt = percent biodegradation of the test substance

 BODx = biological oxygen demand after x days.

 TOD = Theoretical oxygen consumption

Result : The results for replicate samples, expressed as percent biodegradation, 

are as follows:

AMP: 5 days (0.1%, 0.1%); 15 days (1.9%, 1.9%); 28 days (40.7%, 38.9%)

Average biodegradation after 28 days was 40%.

Sodium acetate: 5 days (51.5%, 51.5%); 15 days (70.9%, 58.0%); 28 days 

(77.3%, 83.6%)

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (12)

Type : aerobic

Inoculum : activated sludge, domestic, non-adapted

Concentration : 560 mg/l related to COD (Chemical Oxygen Demand)

related to 

Contact time :

Degradation : ca. 50 (±) % after 28 day(s)

Result : other: moderate degradation

Deg. product :

Method : other: DIN 38 412 part 25 (static test) 

Year : 1986

GLP : no

Test substance : as prescribed by 1.1 - 1.4
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

19 / 89

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

Type : aerobic

Inoculum : other: soil

Contact time :

Degradation : ca. 50 (±) % after 35 day(s)

Result :

Deg. product :

Method : other: GSF-Test 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

Type : anaerobic

Inoculum : other: soil

Contact time :

Degradation : ca. 15 (±) % after 35 day(s)

Result :

Deg. product :

Method : other: GSF-Test 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

Type : anaerobic

Inoculum : activated sludge, domestic, non-adapted

Concentration : 1 g/l related to Test substance

related to 

Contact time :

Degradation : ca. 4 (±) % after 5 day(s)

Result : other: low under test conditions

Deg. product :

Method : other: degradation in activated sludge 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

3.6 BOD5, COD OR BOD5/COD RATIO
3. Environmental Fate and Pathways Id 124-68-5

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BOD5

Method : other:unknown 

Year : 1979

Concentration : 1 g/l related to Test substance

BOD5 : < 10 mg/l

GLP : no

COD

Method : other: dichromate method 

Year : 1979

COD : = 2050 mg/g substance

GLP : no

RATIO BOD5 / COD

BOD5/COD : ca. .005

Source : ANGUS Chemie GmbH Ibbenburen

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

3.7 BIOACCUMULATION

Species : Leuciscus idus (Fish, fresh water)

Exposure period : 3 day(s) at °C

Concentration : 50 μg/l

BCF : < 1 

Elimination : no data

Method : other: GSF-test; BCF-3-days 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : Five Gold orfes were raised in a test vessel with 8L of water, in which the 

14-C-labeled chemical was dissolved at a concentration of 50ppb. The fish 

were not fed during the 3-day test. The vessel was closed and the water 

surface was stirred with a blade stirrer gently to provide air exchange and 

movement of water. At the end of the experiment, the concentration of 

AMP was determined by measuring the radioactivity of the fish and in the 

water and, from that, the accumulation factor was determined.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (12)

Species : other: algae (Chlorella fusca)

Exposure period : 1 day(s) at °C

Concentration : 50 μg/l

BCF : ca. 320 

Elimination : no data

Method : other: GSF-Test, BCF-1-day 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

EUROPEAN COMMISSION - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006
3. Environmental Fate and Pathways Id 124-68-5

Date 30.11.2006

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3.8 ADDITIONAL REMARKS
4. Ecotoxicity Id 124-68-5

Date 30.11.2006

22 / 89

4.1 ACUTE/PROLONGED TOXICITY TO FISH

Type : static

Species : Lepomis macrochirus (Fish, fresh water)

Exposure period : 96 hour(s)

Unit : mg/l

NOEC : = 100 measured/nominal

LC50 : = 190 calculated

Limit test :

Analytical monitoring : no

Method :

Year : 1980

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : Bluegill sunfish were obtained from a commercial supplier, and held in 

culture tanks with a 16-hour light cycle, and acclimated for 14 days prior to 

exposure to the test material. Fish received a standard commercial fish 

food until 48 hours prior to testing, at which time feeding was discontinued. 

The fish had a mean weight of 0.21 grams and a mean standard length of 

22 mm. 

The static bioassay was conducted in 5-gallon glass vessels containing 15 

liters of reconstituted water (48mg NaHCO3, 30mg CaSO4, 30mg MgSO4, 

and 2mg KCl). Vessels were kept in a water bath at 21-23C, and the fish 

were acclimated to the dilution water and test temperature, and fasted for 

48 hours prior to testing. Dissolved oxygen was 8.8 mg/L, pH was 7.0, 

total hardness was 45 mg/L as CaCO3, and total alkalinity was 25 mg/L 

CaCO3. 

Dose levels for the definitive 96-hour study were set in a 72-hour rangefinding test at 1, 10, 100, 560, 1000 mg/L. Dose levels for the definitive 

assay were 32-560 mg/L in logarithmic series. Concentrations are reported 

based on nominal dose.

Result : The LC50 data was reported as follows:

AMP 24-hour LC50 = 220 (170-280) mg/L

AMP 48-hour LC50 = 220 (170-280) mg/L

AMP 96-hour LC50 = 190 (150-250) mg/L

Antimycin A 24-hour LC50 = 0.000056 mg/L

Antimycin A 48-hour LC50 = 0.000037 mg/L

Antimycin A 96-hour LC50 = 0.000028 mg/L

There were no sublethal effects reported.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

18.09.2006 (13)

Type : semistatic

Species : Pleuronectes platessa (Fish, marine)

Exposure period : 96 hour(s)

Unit : mg/l

LC50 : = 184 calculated

Limit test : no

Analytical monitoring : no

Method :
4. Ecotoxicity Id 124-68-5

Date 30.11.2006

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Year : 1983

GLP : no

Test substance : other TS:AMP-95

Result : LC50 values were calculated based on nominal concentrations and 

observed mortality, at a 95% CI:

24 hour LC50 = 231 mg/L

48 hour LC50 = 184 mg/L

72 hour LC50 = 184 mg/L

96 hour LC50 = 184 mg/L

Nominal temperature of the test solution was 15C (14.4-15C during the 

test). Dissolved O2 range during the test was 7.0-8.2 mg/L. The pH range 

during the test was 8.1-10.3. Hardness was not reported.

Test condition : In a 96-hour, semi-static seawater test system, the toxicity of AMP-95 to 

Plaice was studied. Fish (20 per dose level, mean weight of 4.1g and 

mean length of 63.2mm) were placed in 18L glass vessels containing 10L 

of the test solution. The pH of the system was 8.08-8.14, and salinity was 

34.76-34.82 o/oo. Concentrations tested were 100, 320, 560, 1000 mg/L.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (14)

Type : static

Species : Leuciscus idus (Fish, fresh water)

Exposure period : 48 hour(s)

Unit : mg/l

LC0 : = 320 

LC50 : = 331 

LC100 : = 340 

Method : other: DIN 38 412 L 15 

Year : 1986

GLP :

Test substance : no data

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

4.2 ACUTE TOXICITY TO AQUATIC INVERTEBRATES

Type : static

Species : Daphnia magna (Crustacea)

Exposure period : 48 hour(s)

Unit : mg/l

NOEC : = 100 measured/nominal

EC50 : = 193 calculated

Analytical monitoring : yes

Method : other 

Year : 1983

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : Test procedures per "Methods of Acute Toxicity Tests with Fish, 

Macroinvertebrates, and Amphibians" (USEPA, 1975) were followed. The 

daphnia used in the test were cultured at the testing facilities, and the adult 

daphnia were fed a suspension of trout chow and alfalfa daily until 24 hours 
4. Ecotoxicity Id 124-68-5

Date 30.11.2006

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prior to testing.

The static Daphnia bioassay was conducted in 250mL beakers containing 

200mL of test solution. The vessels were kept at 19-21C, with a 16-hour 

light / 8 hour dark photocycle.

An initial range-finding study was conducted using 10 Daphnia per 

concentration level. The range was found by beginning at 0.1 mg/L and 

increasing the amount of test material by a factor of 10 until a toxic level 

was found. Once this level had been determined, five concentrations, in 

duplicate, of the test compound with 10 Daphnia per beaker were selected 

for their respective bioassay. These concentrations were a logarithmic 

series ranging from 100 to 1000 mg/L.

Remark : There was no additional data provided on the results of the range-finding 

study referenced in the methods section.

Result : A computerized program calculated the LC50 for Daphnia based on the 

method of Stephan et.al. with a 95% CI using nominal concentrations. The 

24-hour LC50 was calculated to be 240 mg/L, and 48-hour LC50 was 

calculated to be 193 mg/L. 

Examination of water quality parameters revealed dissolved oxygen levels 

ranging from 8.3 mg/L in the control at study start, and levels of 8.5 

(control), 8.5 (100mg/L AMP), 8.6 (320 mg/L AMP), and 8.6 mg/L O2 (1000 

mg/L AMP) at 48 hours. The pH of the control at study start was 7.8. At 48 

hours, the pH data collected was: 8.1 in the control, 8.3 (100mg/L AMP), 

8.9 (320 mg/L AMP), and 9.4 (1000 mg/L AMP). Hardness was 225 ppm 

as CaCO3, and held at a temperature of 19-20C.

Test condition : Daphnias (Daphnia magna) first instar < 24 hours old. Test conditions 

were a temperature range of 19-20C, and a photoperiod of 16 hours light. 

Test solution (200mL) was placed in 250mL beakers, and ten daphnias 

were added per test solution. Concentrations tested were in duplicate at 0, 

100, 180, 320, 560, and 1000 mg/L AMP-95.

Test substance : AMP-95 (94.31% Active, 5.69% water, NVM 0.0004%.

Lot 216, the same as referenced in the report, "Acute Toxicity Effects of 

AMP-95 on Bluegill Sunfish, Ninety-Six Hour LC50" (C. Parekh, 1980).

Received as a clear liquid and stored at room temperature.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (15)

Type : semistatic

Species : Crangon crangon (Crustacea)

Exposure period : 96 hour(s)

Unit : mg/l

EC50 : ca. 179 calculated

Limit Test : no

Analytical monitoring : no data

Method :

Year : 1983

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : Concentrations of AMP-95 tested were 0, 56, 100, 320, and 560 mg/L 

under semi-static conditions for 96 hours. The 18L glass vessel was folled 

with 10L of the test solution, and 20 brown shrimp were added to each 

vessel after an on-site acclimation period of 5 days on a specially-prepared 

diet. Food was withheld during the test. The test solution was comprised 

of local filtered seawater (pH=8.10-8.16, salinity 34.86-34.90 o/oo), and 
4. Ecotoxicity Id 124-68-5

Date 30.11.2006

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was maintained within a temperature range of 14.7-15.8C. The solutions 

were aerated with compressed air and dissolved O2 ranged from 7.2-8.4 

mg/L. The pH range during the test was 8.0-10.1. Hardness was not 

reported.

Remark : Detailed information regarding pH and dissolved oxygen were not provided. 

Only target ranges were given.

Result : Results were as follows, with a 95% CI, based on nominal concentrations 

of test material:

24-hour LC50 = 241 mg/L

48-hour LC50 = 179 mg/L

72-hour LC50 = 179 mg/L

96-hour LC50 = 179 mg/L

The control mortality was 0% at 96 hours.

Test substance : The purity and identification of the test material is not noted. The test 

material was confirmed by the authors to be AMP-95 (2-Amino-2-methyl-1-

propanol).

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (16)

4.3 TOXICITY TO AQUATIC PLANTS E.G. ALGAE

Species : Scenedesmus sp. (Algae)

Endpoint : growth rate

Exposure period : 72 hour(s)

Unit : mg/l

EC50 : ca. 520 

Limit test :

Analytical monitoring : no

Method : OECD Guide-line 201 "Algae, Growth Inhibition Test"

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : The investigations according to the guideline give false results in the case 

of volatile substances due to the decreasing concentration. Closing of the 

test vessel led to growth inhibition or death in the absence of the test 

material. By previous passage of CO2-enriched air and variation of the air 

space in the test vessel, the conditions could be optimized for the growth of 

the algae in the closed vessel during the 96 hour test so that the growth 

rate was comparable to that in an open vessel. 

The chemical was added at increasing concentrations from a test solution 

prepared from a continuously illuminated algae stock culture, prepared with 

nutrient solution, and was placed in front of a light wall. The test vessels 

were shaken slightly from time to time in order to prevent sedimentation of 

the algae. The determination of the algae concentrations was carried out, 

based on a calibration curve and nominal concentrations, by measuring the 

extinction at time 0, 24, 48, 72, 96 hours. The inhibition was calculated 

with the trapezoidal formula in the Guideline. The EC50 after 72 hours was 

determined graphically by plotting the percent inhibition linearly against the 

concentration expressed logarithmically.

Result : No data other than EC50.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (12)
4. Ecotoxicity Id 124-68-5

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4.4 TOXICITY TO MICROORGANISMS E.G. BACTERIA

Type : aquatic

Species : Pseudomonas putida (Bacteria)

Exposure period : 120 hour(s)

Unit : mg/l

EC50 : ca. 101 - 202 calculated

Analytical monitoring : no

Method :

Year : 1986

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : No detailed method information was provided in the report.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.06.2006 (12)

Type : aquatic

Species : other bacteria: activated sludge filtrate

Exposure period : 120 hour(s)

Unit : mg/l

EC50 : ca. 132 

Analytical monitoring : no

Method : other: Sapromat 

Year : 1989

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

19.05.2006

4.5.1 CHRONIC TOXICITY TO FISH

4.5.2 CHRONIC TOXICITY TO AQUATIC INVERTEBRATES

4.6.1 TOXICITY TO SEDIMENT DWELLING ORGANISMS

4.6.2 TOXICITY TO TERRESTRIAL PLANTS

4.6.3 TOXICITY TO SOIL DWELLING ORGANISMS

4.6.4 TOX. TO OTHER NON MAMM. TERR. SPECIES

Species : other avian: Redwinged Blackbird

Endpoint : mortality

Exposure period :

Unit : mg/kg bw
4. Ecotoxicity Id 124-68-5

Date 30.11.2006

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LC50 : ca. 102 measured/nominal

Method :

Year : 1983

GLP : no data

Test substance :

Method : Wild-trapped birds were preconditioned to captivity for 2-6 weeks and were

dosed via gavage with solutions of the test chemical in propylene glycol. 

LD50 values were calculated by the method of Thompson (1948) and 

Thompson and Weil (1952).

Remark : There was no discussion of any in-life observations or pathological 

findings.

Result : The calculated LD50 based on experimental results was 102 mg/kg.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (17)

Species : Musca domestica (arthropod (Diptera))

Endpoint : other: incorporation into phospholipids of larvae

Exposure period :

Unit : other: umol/g

Method :

Year : 1965

GLP : no data

Test substance :

Method : Larvae were grown in diets with and without choline, and growth rate and 

mortality were observed.

Result : When no choline is included in the diet, growth retardation is noted. The 

test material in the diet causes death of the larvae before the sixth day after 

hatching. If choline chloride is added to the diet with the test material, 

growth is normal. 

Decreasing the level of choline in the diet causes an increase by 7-24% (of 

total lipids) in the proportion of phosphatidyl-aminobutanols found in larval 

lipids.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

26.07.2006 (18)

4.7 BIOLOGICAL EFFECTS MONITORING

4.8 BIOTRANSFORMATION AND KINETICS

4.9 ADDITIONAL REMARKS
5. Toxicity Id 124-68-5

Date 30.11.2006

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5.0 TOXICOKINETICS, METABOLISM AND DISTRIBUTION

In Vitro/in vivo : In vivo

Type : Metabolism

Species : rat

Number of animals

 Males : 42

 Females :

Doses

 Males : The test material at a specific activity of 5uCi/umole was delivered via an IP 

dose of 5.1x10^6 counts/minute in 0.2mL water per rat

 Females :

Vehicle : water

Route of administration : i.p.

Exposure time :

Product type guidance :

Decision on results on acute tox. tests :

Adverse effects on prolonged exposure :

Half-lives : 1

st:

2

nd:

3

rd:

Toxic behaviour :

Deg. product : no

Method : other

Year : 1970

GLP : no

Test substance : other TS: 14C-AMP

Method : The 42 rats were divided into 2 equal groups. One group of 50g SpragueDawley rats were given a standard rodent diet, and the other group was 

given a choline-deficient diet (via a supplement of 13.2mL of ADC drops). 

The test material ((3H)2-amino-2-methylpropanol) at a specific activity of 

5uCi/umole was delivered to the rats via one intraperitoneal injection of 

5.1x10^6 counts/min in 0.2mL water. The rats were sacrificed at 30 

minutes, and at 1, 2, 3, 6, 24, 96 hours following dosing.

The rats were sacrificed via decapitation. Serum was stored at -20 and the 

organs and tissues were removed and immediately frozen in tubes and 

immersed in a dry-ice / acetone bath. Urine and feces were collected on 

paper towels and the matter was extracted from the paper using a 95% 

ethanol solution until no more than 5% of the initial radiation on the paper 

remained. The given tissues (0.5-1g each of the brain, heart, kidney, liver, 

intestine, spleen, and skeletal muscle) were homogenized with 3mL of 95% 

ethanol and the homogenate was centrifuged. To extract lipids from the 

brain tissue, the homogenate was was mized with a 2:1 chloroform : 

methanol solution, and the filtrate was stored until use. To fractionate the 

livers and kidneys, the mitochondria were prepared via peer-reviewed 

method (Hogeboom et al.) and extracted using 95% ethanol. Microsomes 

were isolated by centrifugation, and the microsomes and mitochondria 

were washed with sucrose, then repeatedly extracted using ethanol. The 

particulate-free supernatant fluid was extracted reoeatedly with ethanol 

mixtures to insure the maximum recovery possible from the cytosol. 

Determining the radioactivity of the serum was possible using 

trichloroacetic acid to make the serum protein-free, and transferred into an 

ethanol solution. Aliquots of urine and tissue extracts were transferred into 

ethanol and were similarly treated. Isolation and hydrolysis of 

phospholipids of mitochondria and microsomes of the liver was 

accomplished by removing the mitrochondrial and microsomal solvents in 
5. Toxicity Id 124-68-5

Date 30.11.2006

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vacuo, and residues taken up in a chloroform : methanol (2:1) mixture. 

Aliquots from each sample were developed on a silicic acid plate and 

stained with I2. Stained areas were scraped from the plates, and extracted 

with ethanol, then chloroform:methanol. Solvents were removed, and the 

phospholipid residues were hydrolyzed with HCl and stored at 105 degrees 

for 6hr. Petroleum ether extraction removed the fatty acids and 

unhydrolyzed lipids. The aqueous layer was dried, and residues were 

extracted in ethanol. Individual components were separated via paper 

chromatography, and the location of the compound was identified by 

staining them with I2 vapor. The papers were placed in scintillation liquid 

for radioactive determinations.

Remark : Technical experts that reviewed the paper noted that there are 2 main 

deficiencies in the methods employed by the authors. An IP dose, as 

administered in this study, gave the reviewers no data regarding the oral 

bioavailability of AMP, and it is assumed that accidental ingestion is one of 

the most likely routes of exposure to the compound. It is also noted that a 

lack of mass balance determination is a significant methodological 

deficiency, as it is impossible to determine the extent of storage of the test 

material, or the extent of excretion of the material. While the metabolic fate 

of the AMP in the tissues and urine is known (AMP is stored unchanged 

and excreted unchanged), the relative per cent of material stored versus 

excreted cannot be determined due to lack of a mass-balance method. 

The reviewers note that this is a reputable study with acceptable analytical 

and experimental methods except where noted, and is generally a useful 

study to use as a reference.

Result : Serum

Tritium appeared in the serum 30 minutes post-dosing. After an initial 

uptake of the tritium, a large portion disappeared quickly. The radioactivity 

in the serum of rats fed the choline-deficient diet was always lower than 

rats on a normal diet, except at 6 hours, when the levels were about the 

same. 

Urine

The tritium levels in urine (cumulatively) for the normal-diet group was 

greater than the choline-deficient group up to 6 hours, at which time the 

levels were essentially the same. From 6-24 hours, the accrued 

radioactivity levels in the normal-diet group exceeded that of the cholinedeficient group. Data analyses showed that in both groups, the test 

material was excreted in the urine unchanged.

Tissues & Organs

Tissues from the choline-deficient diets had a greater retention of the 

amino alcohol than the normal-diet group. The radioactivity incorporated 

into the mitochondria and microsomal phospholipid fractions of liver from 

choline-deficient rats increased with time, while the radioactivity in the 

corresponding fractions in normal rats decreased with time. The 

distribution of tritium among the liver & kidney fractions was different and 

suggested an incorporation of the test material into various types of 

phospholipids. The livers from the choline-deficient group showed a higher 

level of tritium in all subcellular fractions than the normal-diet group at all 

times. Most of the tritium was found in the cytosol of both liver and kidney. 

While the amount of tritium decreased with time in the mitochondrial and 

microsomal fractions of livers from animals fed normal diet, the amount of 

radioactivity increased with time in the corresponding subcellular fractions 

of the livers from animals receiving the choline-deficient diet.

Test substance : The authors confirm the test substance as 2-amino-2-methylpropanol, but 

do not give purity or lot.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint
5. Toxicity Id 124-68-5

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01.06.2006 (19)

5.1.1 ACUTE ORAL TOXICITY

Type : LDLo

Value : ca. 1000 - 2000 ml/kg bw

Species : rabbit

Strain :

Sex :

Number of animals :

Vehicle :

Doses :

Method :

Year : 1940

GLP :

Test substance : no data

Method : Oral administration was carried out on rabbits, and the test material was 

delivered by stomach tube. The materials were administered in 25% w/v 

aqueous solutions. The solutions were neutralized in repeat experiments 

with HCl due to high alkalinity. Animals were fasted 24 hours prior to 

dosing. Following administration, animals were observed for 2-3 hours 

prior to caging, and were kept for observation more than 5 weeks after 

initial dosing.

Result : The lowest lethal dose was observed to be 1000-2000 mg/kg with both the 

alkaline and neutral solutions. Twenty to 40 minutes following dosing, 

animals exhibited progressive weakness to collapse, unsteadiness and 

incoordination ending in complete ataxia, and changes in respiration first by 

slowing and later by increasingly rapid rate. No deviations in blood findings 

were noted, and no methemoglobin formation. There were no other 

findings in the post-exposure observation period.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

30.11.2006 (20)

Type : LD50

Value : ca. 2150 ml/kg bw

Species : mouse

Strain :

Sex :

Number of animals :

Vehicle :

Doses :

Method : other: Miller and Tainter, Proc.Soc.Exper.Biol. and Med. 57:261. 1944 

Year : 1955

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

30.11.2006 (21)

Type : LD50

Value : = 2175 mg/kg bw

Species : mouse

Strain :

Sex :

Number of animals :
5. Toxicity Id 124-68-5

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Vehicle :

Doses : 1250, 1875, 2500, 3750 mg/kg

Method :

Year : 1976

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : Mice were dosed once at dose levels of 1250, 1875, 2500, or 3750 mg/kg 

AMP. No further information was provided.

Result : All dose levels produced irritation, slowed activity and response to a tail 

pinch. All mice were grossly normal at necropsy.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

30.11.2006 (22)

Type : LD50

Value : = 2400 mg/kg bw

Species : mouse

Strain :

Sex : female

Number of animals :

Vehicle :

Doses : 1875, 1950, 2100, 2400, 3000 mg/kg

Method :

Year : 1976

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : Mice were dosed perorally with doses of 1875, 1950, 2100, 2400, or 3000 

mg/kg AMP-95 (5% added water). No further methods information was 

provided.

Result : The calculated LD50 was 2400 +/- 89 mg/kg.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

30.11.2006 (23)

Type : LD50

Value : ca. 2900 mg/kg bw

Species : rat

Strain : no data

Sex : male

Number of animals : 50

Vehicle : physiol. saline

Doses : 2200, 2400, 2800, 3600, 4000 mg/kg

Method :

Year : 1976

GLP : no data

Test substance : other TS: P1826 (6C29-9B)

Method : The acute oral toxicity of P-1826 was determined using young adult male 

fasted rats. Five groups of 10 animals each were administered orally a 

single dose of P-1826 diluted in saline using equal volumes. Animals were 

observed closely for four hours and daily thereafter for 14 days.

Result : Doses exceeding 2800 mg/kg orally results in rapid absorbtion into the 

circulatory system resulting in gross damage to the liver, kidney, spleen, 

and respiratory system, followed by respiratory collapse. The compound 

produces irritation to the stomach and duodenum at doses of 2800 mg/kg 

and greater. 

In life observations included: traces of blood on the nostrils, labored 

breathing, ataxia, and death due to respiratory collapse.
5. Toxicity Id 124-68-5

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Necropsy findings (animals that died during the observation period): gas in 

stomach, inflamed and gaseous duodenum, liver and spleen dark, blood 

clot in heart.

Necropsy findings (survivors until a scheduled necropsy): No findings in 

dose levels less than 2800 mg/kg. At 2800 mg/kg, 3 were grossly normal 

and 3 had a small amount of gas in the stomach with a slightly inflamed 

duodenum. At 3600 mg/kg, 1 was grossly normal and 1 was grossly 

normal except a stomach adhered to the liver.

The following data are reported:

LD0 = 2200 mg/kg

LD50 = 2900 +/-140 mg/kg

LD100 = 4000 mg/kg

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (24)

5.1.2 ACUTE INHALATION TOXICITY

5.1.3 ACUTE DERMAL TOXICITY

Type : LD50

Value : > 2000 mg/kg bw

Species : rabbit

Strain : no data

Sex : male/female

Number of animals : 12

Vehicle : other: no vehicle

Doses : 1000, 1500, 2000 mg/kg

Method : other: Pharmacology Lab Protocol 

Year : 1980

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : Each group of rabbits was treated with 1000, 1500, or 2000 mg of test 

material per kg body weight (mg/kg). The desired dose was spread over 

the prepared abdominal skin area (abraded or smooth as designated). The 

skin was covered with a gauze and a sheet of impervious rubberized cloth 

to prevent any loss of the test material. The trunk was further enclosed 

with a flexible wire screen held in place by tape. The animals were 

returned to individual cages.

After 24 hours dermally exposed, the bindings and patches were removed, 

the exposed areas gently cleaned, and observed for skin irritancy. The 

animals were observed for another 14 days for any gross symptoms of 

toxicity. At the end of the 14 day observation period, the animals were 

weiged, sacrificed, and the organs examined for gross pathology.

Result : At the end of the 24 hour exposure period, the intact and abraded treated 

skin sites were severely irritated and black in color. The sites became 

necrotic within two to three days and remained necrotic for the 14 days. 

The treated sites had severe eschar formation by the 14th day. The rabbits 

in the three treatment groups lost body weight over the 14 day observation 

period. The animals in all treated groups showed no signs of toxicity or 
5. Toxicity Id 124-68-5

Date 30.11.2006

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abnormal pharmacological behavior. At necropsy, all organs in all rabbits 

were grossly normal. The treated skin sites in all rabbits were necrotic.

Test condition : 12 Rabbits weighing 3.0 +/- 0.5 kg were divided into 3 groups of 4 each, 

and their abdomens were shaved free of hair. The skin of 2 rabbits were 

further prepared by abrasions. The abrasions were made 2-3 cm apart 

over the area of exposure with a blunt hypodermic needle without bleeding.

Conclusion : The acute dermal LD50 for P-1826 for the rabbit was >2000 mg/kg. The 

test material was dermally nontoxic, but was a severe skin irritant.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (25)

5.1.4 ACUTE TOXICITY, OTHER ROUTES

Type : other

Value : 

Species : rat

Strain : Sprague-Dawley

Sex : male

Number of animals :

Vehicle : water

Doses : 0.76-1.52 mmol : 100g body weight

Route of admin. : i.p.

Exposure time :

Method :

Year : 1979

GLP :

Test substance : as prescribed by 1.1 - 1.4

Method : The test material was obtained from Aldrich Chemical Co., Milwaukee, WI. 

The material was used as received, no additional purification. The 

compound was dissolved in distilled water, and neutralized to a pH 7-7.2, 

and injected intraperitoneally. All compounds were freshly prepared, and 

used immediately after neutralization. The compound was tested at 

0.76mmol / 100g body weight. The dosage is equivalent to that used for dsterine in previous experiments, which always resulted in proximal tubular 

necrosis. Evidence of any cellular necrosis was evaluated by light 

microscopic examination of hemotoxylin- and eosin-stained sections of 

kidneys from animals sacrificed at 24 hours after administration of the test 

material.

Result : 2-Amino-2-methyl-1-propanol did not cause noticeable tubular necrosis 

under these test conditions.

Test condition : Male Sprague-Dawley rats (Charles River), 100-120g, were used. The 

animals had free access to feed and water.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (26)

Type : LC50

Value : ca. 325 mg/kg bw

Species : mouse

Strain :

Sex :

Number of animals :

Vehicle :

Doses :

Route of admin. : i.p.
5. Toxicity Id 124-68-5

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Exposure time :

Method : Miller and Tainter, Proc. Soc. Exper. Biol. and Med. 57:261. 1944

Year : 1955

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Source : ANGUS Chemie GmbH Ibbenburen

European Commission - European Chemicals Bureau Ispra (VA)

Reliability : (4) not assignable

4e (documentation insufficient for assessment)

06.03.2006

5.2.1 SKIN IRRITATION

Species : rabbit

Concentration :

Exposure :

Exposure time : 4 hour(s)

Number of animals :

Vehicle :

PDII :

Result : highly irritating

Classification : irritating

Method :

Year : 1940

GLP :

Test substance : as prescribed by 1.1 - 1.4

Method : Animals were prepared by closely clipping the skin over the anterior 

abdominal wall. After securing the animal in the supine position, a 

measured amount of the test material was pipetted onto the surface of the 

skin. The test material was allowed to evaporate in still air, and the animal 

was released to the cage after the skin was dry. The treatments were 

repeated daily until 5 had been made.

Result : No illness resulted from skin applications of the test material, and 

observations were limited to irritation. Two animals showed chemical 

dermititis, infiltration of the skin and subcutaneous tissues, superficial 

redness, and a considerable loss of hair. Burrowing lesions in the 

subcutaneous tissues were produced by the introduction of the test 

material into small wounds on an abraded dermal test site.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, and acceptable for 

assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (20)

5.2.2 EYE IRRITATION

Species : rabbit

Concentration : 100 %

Dose :

Exposure time :

Comment :

Number of animals :

Vehicle : none

Result : highly irritating

Classification : risk of serious damage to eyes

Method :
5. Toxicity Id 124-68-5

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Year : 1975

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : Animals were dosed with the test material, in one study the eyes were 

flushed 15-30 seconds after application, and in the other, they were not. 

No further methods information was given.

Remark : Based on known toxicity and use patterns, it is assumed that the free 

amine was tested in this case and that the high pH was likely the cause of 

the serious eye damage noted.

Result : Unflushed eyes scored a 110 on the grading scale used, the highest 

possible. The test material had destroyed the vision. Flushed eyes scored 

69.3/89.3 when flushed at 15 and 30 seconds, respectively. A score of 16 

or higher is considered a severe irritant.

Conclusion : The test material is considered to be a severe eye irritant, and there is little 

beneficial effect even when eyes are almost immediately flushed with 

water.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (27)

Species : rabbit

Concentration :

Dose :

Exposure time :

Comment :

Number of animals :

Vehicle : none

Result : highly irritating

Classification : risk of serious damage to eyes

Method :

Year : 1975

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : The data source does not specify other than citing Draize Techniques for 

rabbits.

Remark : Based on known use patterns and toxicity of the compound, it is assumed 

that the serious eye damage noted in this evaluation was due to testing of 

the free amine at a pH~11. The high pH is likely the cause of the eye 

damage.

Result : Animals treated with AMP scored a 110 for eye irritation. It is considered a 

severe eye irritant, with a high potential for eye damage.

Conclusion : The potential for eye damage is high.

Reliability : (4) not assignable

4 (documentation insufficient for assessment)

01.06.2006 (28)

5.3 SENSITIZATION

Type : Patch-Test

Species : guinea pig

Concentration : 1

st: Induction 5 % 

2

nd: Challenge 2.5 % 

3

rd: Challenge 5 % 

Number of animals : 30

Vehicle : water

Result : not sensitizing
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Classification : not sensitizing

Method : other: Buehler 

Year : 1982

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : One group was treated with 0.5mL of 10% P-1826 solution, a negative 

control group was treated with saline, and a positive control group was 

treated with dinitrochlorobenzene (DNCB solubilized in alcohol and made 

to volume with saline). After 24 hours, the patches were removed, and 

sites were cleaned and scored at 24 and 48 hours for erythema and edema 

according to Draize (Draize, JH, "Appraisal of the Safety of Chemicals in 

Foods, Drugs, and Cosmetics". Assoc. of Food and Drug Officials of the 

United States, p. 48, 1957). At 48 hours, the application was repeated with 

each group, and continued 2-3 times per week until 10 applications were 

made. Animals were allowed a 2 week recovery period, and then 

challenged at a virgin site. The test and negative control animals were 

challenged with 0.5mL of 2.5% and 5% solutions of P-1826. Positive and 

negative control animals were also challenged with 0.03% DNCB solution. 

After 24 hours, the test material was cleaned away, depilated, and three 

hours later scored for erythema and edema. Sites were scored again at 48 

hours. 

Test material is considered a sensitizer if the challenge elicits skin 

reactions in a large number of test animals when compared to the negative 

control.

Result : During the induction, the 10% P-1826 solution was found to be mildly 

irritating to all animals in the test group, so the remaining 8 doses during 

the induction were made with a 5% solution. The positive control, DCNB, 

elicited a mild to strong reaction during the 10 applications. There was one 

death in the positive control group, but was deemed not treatment-related 

via necropsy.

At challenge with 2.5% and 5% solutions of P-1826, none of the animals in 

the test or negative control groups showed any skin reactions at 24 hours, 

but the positive control animals showed mild skin reactions at 48 hours.

Nine of ten positive controls when challenged with DNCB at 24 hours 

showed skin reactions, and 7/10 showed reactions at 48 hours. Only 4/10 

negative controls showed reactions when challenged with DNCB at 24 

hours, and none at 48 hours.

Test condition : Thirty male guinea pigs (250-300g each) were divided into 3 groups of 10 

each. The animals' backs and flanks were shaved free of hair. The guinea 

pigs were topically treated with the solutions applied under an occlusive 

patch.

Conclusion : 2-Amino-2-methyl-1-propanol was a non-sensitizer in the topical 

sensitization test in guinea pigs, under these test conditions.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

18.09.2006 (29)

Type : Intracutaneus test

Species : guinea pig

Concentration : 1

st: Induction .1 % 

2

nd: Challenge .05 % 

3

rd: Challenge .01 % 

Number of animals : 30

Vehicle : water

Result : not sensitizing

Classification : not sensitizing
5. Toxicity Id 124-68-5

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Method :

Year : 1982

GLP : no

Test substance : as prescribed by 1.1 - 1.4

Method : One group was treated with 0.05mL of 1% P-1826 solution, a negative 

control group was treated with saline, and a positive control group was 

treated with dinitrochlorobenzene (DNCB solubilized in alcohol and made 

to volume with saline). After 24 hours, sites were cleaned and scored for 

erythema and edema according to Draize (Draize, JH, "Appraisal of the 

Safety of Chemicals in Foods, Drugs, and Cosmetics". Assoc. of Food and 

Drug Officials of the United States, p. 48, 1957). At 48 hours, the 

application was repeated with each group, and continued 2-3 times per 

week until 10 applications were made. Animals were allowed a 2 week 

recovery period, and then challenged at a virgin site. The test and negative 

control animals were challenged with 0.1mL of 0.05% and 0.01% solutions 

of P-1826. Positive and negative control animals were also challenged 

with 0.3% and 0.03% DNCB solution. After 24 hours, they were depilated, 

and three hours later scored for erythema and edema. Sites were scored 

again at 48 hours. 

Test material is considered a sensitizer if the challenge elicits skin 

reactions in a large number of test animals when compared to the negative 

control.

Result : During the induction phase, the first injection at 1% and second injection at 

0.5% P-1826 induced necrotic lesions, so the remaining 8 injections were 

made with 0.1% solutions. The 0.3% DNCB sites were necrotic for the 

entire 10 injections.

At challenge with 0.05% and 0.01% P-1826, one animal in the test group 

showed mild reactions with 0.05%, but none of the negative controls 

challenged with P-1826 showed any reactions at 24 or 48 hours. In the 

repeat challenge, none of the animals in the test group showed any 

reactions with P-1826, but of the negative control group, 4 animals at 

0.05% and 1 animal at 0.01% showed skin reactions at 24 hours.

A challenge with the positive control induced skin reactions in the positive 

control group. The 0.03% solution did not elicit any skin reaction at 48 

hours.

Test condition : Thirty male guinea pigs (250-300g each) were divided into 3 groups of 10 

each. The animals' backs and flanks were shaved free of hair. The guinea 

pigs were intradermally-injected with the solutions.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (30)

5.4 REPEATED DOSE TOXICITY

Type : Sub-chronic

Species : rat

Sex : male/female

Strain : other: CD

Route of admin. : gavage

Exposure period : 13 weeks

Frequency of treatm. : 5 days / week

Post exposure period :

Doses : 0, 500, 750, 1100, 1700 mg/kg at pH of 7 & 11+

Control group : yes, concurrent vehicle
5. Toxicity Id 124-68-5

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LOAEL : < 500 mg/kg

Method :

Year : 1977

GLP : no

Test substance : other TS: P-1826 (assumed to be AMP-Regular)

Method : Dose Preparation

The dose solution for pH=11+ was prepared by adding the neat test 

material to distilled water in order to achieve a concentration adequate to 

dose the animals 1-5mL of dose solution according to the animals' body 

weights and dose group. The dose solution of pH=7 was prepared by 

adding the neat test material to distilled water, neutralizing the solution to 

pH=7. Because the resulting stock solution is purple in color, the solution 

was decolored using activated charcoal. The stock solution was then 

diluted as appropriate to obtain solutions adequate to dose the animals 

with 1-5mL solution according to their body weights and the targeted dose.

Dose Administration

The solutions were administered 5 days per week for 13 weeks, once per 

day by oral gavage. The dose was adjusted to the body weight of the rat 

by administration of different volumes of solution (1-5mL).

In-life Observations & Measures

Animals were observed 5 days/week for pharmacological effects of the test 

material. The observations were general, including signs of altered food 

and water consumption, irritability, sedation, hair and cutaneous 

alterations, external inflammation, hyperventilation, convulsions, 

neuromuscular paralysis, and altered activity. Body weights were recorded 

weekly, and dead animals were recorded and autopsied as soon as 

discovered.

Hematology & Clinical Chemistry Measures

The following blood parameters were measured: hemaglobin, packed cell 

colume (hematocrit), erythrocyte count, leucocyte count, differential count, 

transaminases, glutamic-oxalacetic and glutamic-pyruvic, total protein, 

blood urea nitrogen (BUN), Sodium, Potassium, Chloride, and Creatinine. 

For urine, Ph, protein, occult blood, glucose, bilirubin, sediment, and 

specific gravity were measured.

Pathology

Only gross pathology was reported.

Result : Mortality

A high mortality rate was recorded for animals with the pH=11 doses. No 

treatment-related mortality was noted for the pH=7 groups.

Behavior and Appearance

General observations on the pH=11 groups included hyperventilation and 

respiratory difficulty, neither of which could be confirmed at necropsy. Nontreatment related pneumonia was noted in some rats. Rats generally 

showed hyperirritability and hyperactivity at the time of AMP administration. 

In the pH=11 rats receiving more than 750mg/kg, abdominal swelling, 

nasal and mouth bleeding were noted the first few days of the study. The 

abdominal swelling was always followed by death. Some loss of hair 

around the mouth and face was noted for pH=11 rats, and assumed to be 

treatment-related. General observations for rats receiving the dose at 

pH=7 were hyperventilation (lesser extent than pH=11 rats), and limited 

hyperactivity and hyperirritability. Some of the rats also showed loss of hair 

around the mouth and face. In a few rats, the effect was accompanied by 

skin ulceration due likely to excessive salivation, or a local irritancy by the 

compound.

Body Weight, Food Consumption Trends
5. Toxicity Id 124-68-5

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There was no significant difference in the rate of body weight change 

between all dose groups relative to the controls. Food and water 

consumption were qualitatively noted. Food consumption appeared 

normal, while AMP-administered rats appeared to drink more frequently 

than controls.

Hematology & Clinical Chemistry

Neither the pH=7 or pH=11 females showed significant differences in 

hematocrit, hemoglobin, erythorcyte counts, or leukocytes. The males from 

the pH=11 group in the 1100 mg/kg dose group showed a significant 

decrease in hematocrit, hemoglobin, and red blood cell count due to a loss 

of blood.

 

pH 11 group males

Group HCT HgB RBC(x10^6) WBC

Control (10) 44+-1 16.5+-0.4 7.41+-0.29 8.2+-1.2

500mg/kg (8) 43+-1 16.7+-0.9 6.20+-0.47 13.6+-2.6

750mg/kg (7) 43+-1 16.2+-0.5 6.31+-0.34 9.4+-2.5

1100mg/kg(2) 40+-1 14.9+-0.3 5.94+-0.10 9.0+-1.6

1700mg/kg (none surviving)

 A slight but significant decrease is seen in the RBC of rats receiving 500 

and 750 mg/kg AMP. There was no significant effect on hematocrit at 

these exposure levels. The pH=7 group (only at 1700mg/kg) showed 

significant decreases in hematocrit and hemoglobin.

pH 7 group

Group HCT HgB 

Control (10) 46+-1 17.1+-0.1 

500mg/kg (9) 43+-2 16.4+-0.5 

750mg/kg (10) 42+-1 16.4+-0.6 

1100mg/kg(10) 42+-1 16.4+-0.8 

1700mg/kg (9) 40+-1 15.1+-0.2

No significant differences were measured in Na, K, Cl, Ca, total serum 

protein, BUN, or creatinine for either pH group at any dose level. SGPT 

values were within normal ranges for all dose groups except for pH=7 

females at 1700mg/kg, and pH=7 males at 1000 and 1700 mg/kg, where 

the values were significantly elevated.

Urinalysis

Urinalysis was performed only for the pH=11 groups. The data indicated 

some proteinuria.

Gross Pathology

There were no treatment-related grossly-recognizable changes observed at 

necropsy.

Test condition : CD rats were received from Charles River weighing 90-100g, and were 

acclimated a minimum of one week to the laboratory prior to the 

experimental start. The rats were divided into groups of 10 per sex per 

dose level, for each of 2 pH's. They were housed in groups of 2-3 per 

plastic cage, and fed via overhead racks. Food and water was provided ad 

libitum and animals were housed in rooms with controlled temperature, 

humidity, and photocycles.

Conclusion : LOAEL and NOAEL cannot be established because the authors do not 

specifically state, or provide detailed data regarding the lowest dose level 

at which in-life observations (respiratory difficulty, hyperirritability, 

hyperactivity, etc.) were seen.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint
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01.06.2006 (31)

Type : Sub-chronic

Species : dog

Sex : male/female

Strain : Beagle

Route of admin. : oral feed

Exposure period : 90 days

Frequency of treatm. : continuous

Post exposure period :

Doses : 0, 25, 600, 2500 ppm

Control group : yes, concurrent vehicle

NOAEL : = 25 ppm

LOAEL : = 600 ppm

Method :

Year : 1981

GLP : no

Test substance : other TS: AMP-95/HCl 48.6% ai. Lot 109-1

Method : The AMP was administered orally via the diet as AMP-95/HCl to 32 Beagle 

dogs (4/sex/dose group) at dose levels of 0, 25, 600, and 2500 ppm for a 

three month period. The control animals received an untreated diet. Body 

weights were measured pretest, weekly thereafter, and after fasting at 

termination; food consumption was measured daily and presented at 

weekly intervals. Feed samples of each dose level were assayed for 

homogeneity, stability, and verification of dose concentration. Results were 

presented in a subsequent report from the performing laboratory, and not 

presented in this report. Animals were observed for mortality and gross 

signs of toxicologic or pharmacologic effects twice daily, and dogs were 

given a detailed physical examination pre-test and weekly thereafter. 

Ophthalmoscopic examinations were performed pretest and at termination. 

Hematology, clinical chemistry, and urinalysis parameters were analyzed 

twice pre-test, and Month 1 and 3. Blood was obtained via jugular 

venipuncture. Urine was collected in stainless steel metabolism pans 

attached to each animal's permanent cage. Dogs were fasted overnight 

prior to blood collections, and were not dosed until after samples were 

collected. Hematology parameters evaluated included: hemoglobin, 

hematocrit, erythrocytes, platelets, clotting time, prothrombin time, and total 

and differential leukocytes. Clinical Chemistry parameters included: serum 

glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, 

alkaline phosphatase, lactic acid dehydrogenase, blood urea nitrogen, 

fasting glucose, cholesterol, total protein, albumin, globulin, A/G ratio, total 

bilirubin, direct bilirubin, sodiom, potassium, chloride, and calcium. Urine 

was evaluated for the following: Gross appearance, specific gravity, pH, 

protein, glucose, ketones, bilirubin, occult blood, urobilinogen, and 

microscopic analysis.

On days 96-99, animals were necropsied and tisses were preserved for 

weights (brain, ovaries, pituitary, thyroid, heart, adrenals, spleen, testes, 

kidneys, liver) and microscopic evaluation (the above plus aorta, bone, 

sternum, epididimus, esophagus, eye, colon, duodenum, ileum, lungs, 

mesenteric lymph node, mammary gland, sciatic nerve, pancreas, 

parathyroids, prostate, salivary gland, skeletal muscle, skin, spinal cord, 

stomach, thymus, thyroid, trachea, urinary bladder, and gross lesions). 

Statistical analyses were performed on data collected for body weight, food 

consumption, hematology, clinical chemistry, organ weights, and 

organ:body weight ratios. Mean values of all dose groups were compared 

to control at each time interval (where appropriate). Statistically significant 

differences from the controls are indicated.

Species and strain of test animals, route and method of test substance 
5. Toxicity Id 124-68-5

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administration, and dose levels were established by the sponsor. The 

study was performed at Bio/dynamics, INC.

Remark : Results section references Appendix tables and data, but none is included 

in the Dow Chemical copy of the report. Test material intake, therefore, 

cannot be estimated.

Result : Mortality:

All animals survived the duration of the study.

Physical Observations

Included emesis, loose stool, alopecia, and slight penile or vaginal 

discharge. These findings occurred sporadically in the control and/or 

treated animals and are not considered by the authors to be treatmentrelated.

Ophthalmology

Pretest and terminal examinations revealed no significant ocular changes 

through the study. There is no evidence of compound-induced ocular 

damage.

Body Weight: No statistically-significant differences were found in any dose 

group when compared to animals of the same sex in the control group. 

There was a 10% mean body weight reduction noted in the high dose 

group relative to the control for males and females in latter phases of the 

study, suggesting to the authors a slight compound-related effect.

Food Consumption

There was no treatment-related effect of the test material on food 

consumption at any dose level.

Hematology

Pretest hematology values were within the normal physiological range for 

all animals. There were no statistically-significant differences between the 

control and treated animals at Month 1 testing. At Month 3, there was a 

trend toward reduced prothrombin time observed in the treated males and 

females with statistically significant differences noted in the top two dose 

levels for males only (p<0.01). In addition, a slight trend torward reduced 

hemoglobin concentrations was found in the treated females. Only the 

mean value for the high dose, which was slightly below the normal 

physiological range, was statistically significant (p<0.05). No other 

biologically significant differences were observed in any other hematology 

parameter evaluated.

Clinical Chemistry

Pretest mean clinical chemistry values were within the normal physiological 

range for males and females. At both the Month 1 & 3 evaluations, 

statistically significant elevations in serum glutamic oxaloacetic 

transaminase, serum glutamic pyruvic transaminase, and alkaline 

phosphatase activities occurred in the high dose males and females. The 

magnitude of the increases ranged from 2-4 fold for serum glutamic 

oxaloacetic transaminas, 12-28 fold for serum glutamic pyruvic 

transaminase, and 5-6 fold for alkaline phosphatase. These significant 

increases were limited to the high dose animals only, and were similar at 

months 1 & 3 for both sexes. Other findings included reduced mean 

cholesterol values in both sexes at the above intervals, while direct bilirubin 

concentrations were slightly higher in the treated animals. No other 

toxicologically significant differences occurred in the other clinical chemistry 

parameters evaluated. The above effects observed in the high dose 

animals suggest a high degree of hepatocellular damage in the high dose 

animals with no significant changes in the low or mid dose groups. The 

combination of increased serum glutamic oxaloacetic transaminase and 

serum glutamic pyruvic transaminase levels, both of which are present in 

high concentrations in hepatocytes, are indicative of hepatocellular 

necrosis. The increased alkaline phosphatase and direct bilirubin levels 
5. Toxicity Id 124-68-5

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are suggestive of cholestasis and/or bile duct epithelial necrosis. It

appears, therefore, that the liver is the promary target organ, based on the 

clinical chemistry data, when the test substance is administered via the 

diet.

Urinalysis

There is no evidence of a compound-related effect on any of the urinalysis 

parameters studied.

Organ Weight/ Organ:Body Weight Ratios

A trend towards increased liver and/or liver/body weight rations was 

ovserved in both the mid and high dose male and female dogs. These 

differences were slight but tend to support the conclusion that the liver is 

the principle site of toxic action. Also, mean kidney weights and 

kidney/body weight ratios were increased in the high dose males, and in 

mid and high dose females. Other organ weight and organ/body weight 

differences were marginal and appear unrelated to the administration of the 

test material.

Pathology

Two females and one male from the high dose group were found to have 

tan discoloration and mottling in liver upon gross postmortem evaluations. 

No other such findings were present in any of the other treated or control 

animals. Other gross findings occurred sporadically or were present in the 

treated and control animals to a similar degree. Microscopic findings 

included vacuolization, periportal cirrhosis, and bile duct hyperplasia in the 

liver sections in all high-dose males and females. Lipid deposition within 

the cellular vacuoles was confirmed by staining. The periportal cirrhosis 

was characterized by hepatocellular necrosis and fibrosis. These findings 

were more severe in the high-dose females as compared to the males. In 

addition, one low dose female had liver findings similar to the above, while 

2 mid-dose males exhibited minimal fatty changes in the liver. Other 

microscopic findings occurred sporadically in the treated and/or control 

animals and were not related to the administration of the test material. The 

above microscopic findings correlate well with the clinical chemistry data, 

as both indicate hepatotoxicity induced by the test material in the high dose 

animals. The findings noted in the liver of the one low dose female, in the 

absense of altered clinical chemistry data, as well as the absence of similar 

microscopic findings in the mid dose group, are considered to be of 

uncertain significance (this may represent a response to treatment in an 

unusually sensitive animal, or may be a spontaneous finding).

Test condition : Study was run with Beagle dogs, 4/sex/dose. They were 4.5-5 months of 

age at arrival to the Bio/dynamics laboratory, and 5.5-6 months of age at 

the initiation of the study. Weight range at the start of treatment was 7.7-

9.6kg for males (mean 8.7kg), and was 6.3-9.7 for females (mean 8.1kg). 

The dogs were immunized previously against distemper, hepatitis, 

leptospirosis, and rabies by the supplier. Fecal examinations were 

conducted on all dogs by the performing lab during the one month 

acclimation period. Baseline clinical laboratory tests were also performed. 

They were housed in elevated metal grid cages, and fed 400g of Purina 

Canine Meal Diet (#5007) presented for 4.5 hours. Fresh food was 

presented daily. Water was provided ad libitum by an automated water 

system. The dogs were maintained on a 12-hour photocycle, and 

temperature was monitored twice daily.

Dogs were ranked by body weight and distributed into 4 groups of 4/sex so 

that body weights in each group were comparable. Groups were assigned 

to control and dose levels randomly. Each dog was assigned a unique 

identification number on an ear tag and on the animal's cage. In addition, 

each dog had an ear tatoo bearing the USDA number.

Test substance : AMP-95/HCl (48.6% AI). Lot #109-1 (11/14/80) provided by International 

Minerals & Chemical Corporation (the study sponsor).
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Conclusion : The results of this study agree with those from a concurrently-run study 

(Bio/dynamics #80-2503), utilizing the same test material and similar dose 

levels in rats, which also indicated the liver is the principle target organ 

from dietary administration of the test material. The degree of changes in 

the present study clearly indicates that dogs are more sensitive to the 

hepatotoxic effects of the test material.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

01.06.2006 (32)

Type : Chronic

Species : dog

Sex : male/female

Strain : Beagle

Route of admin. : oral feed

Exposure period : 1 year

Frequency of treatm. : continuous

Post exposure period :

Doses : 0, 1.1, 11, 110 ppm

Control group : yes, concurrent vehicle

NOAEL : > 110 ppm

Method :

Year : 1990

GLP : no data

Test substance : other TS: AMP-HCl (47.1% AMP)

Method : Animals were dosed via the diet, which was tested by the supplier (Purina) 

for contaminants. The test article was incorporated into the diet on a 

weight/weight basis using a premix. Fresh food was prepared with the test 

article weekly. The animals were offered 400g of the diets daily. Any 

uneaten food was weighed and recorded. Drinking water was provided 

throughout the study ad libitum. Six males and six females were assigned 

to each of 4 dose groups (0, 1.1, 11, 110 ppm).

Daily observations were made of the general appearance, behavior, the 

presence of any signs of toxicity or pharmacologic effects and mortality. 

Body weights were recorded prior to dosing, and weekly thereafter. The 

fasting terminal body weight was also recorded. While weighing, the 

animals were examined for lesions or other signs of toxicity. Each animal 

had an ophthalmoscopic examination once pre-study, weeks 1, month 

3,6,9,12 by a veterinarian.

Blood samples were obtained pre-study, and at 3, 6, 9, 12 months via 

venipuncture of fasted animals. The following parameters were recorded: 

hematocrit, hemoglobin, erythrocyte count, leukocyte count, platelet count, 

prothrombin time, MCH, MCHC, and MCV, Calcium, Phosphorous, 

Chloride, Sodium, Potassium, glucose, serum alkaline phosphatase, serum 

aspartate aminotransferase, serum analine aminotransferase, gamma 

glutamyl, transpeptidase, blood urea nitrogen, total protein, albumin, 

globulin, creatinine, bilirubin, and serum protein. Urine was examined for 

pH, specific gravity, volume and appearance, protein, glucose, acetone 

bodies, creatinine, and microscopic sediment.

Post-mortem examinations included a complete gross examination of the 

external surfaces, all orifices, the cranial cavity, the external surface of the 

brain, the thoracic, pelvic, and abdominal cavities and their viscera, cervical 

tissues and organs, and the carcass. Two animals per sex per dose were 

sacrificed at 6 months, with the remainder at 12 months. Organ weights 

were recorded for the liver, kidneys, testes, thyroids, adrenals, and brain. 

Tissues that were removed and preserved are the same as current OECD 

guidelines.

Experimental dates: 5/19/1988 to 7/25/1989
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Remark : Test material intake is estimated based on week 36 body weights and food 

consumption.

Males

 estimated (mg/kg/day)

Control 0

1.1ppm .031

11ppm 0.31

110ppm 2.98

Females

 estimated (mg/kg/day)

Control 0

1.1ppm .029

11ppm 0.31

110ppm 2.55

Result : There were no general in-life observations made for any treated or control 

animal. Likewise, there were no ophthalmoscopic observations noted for 

any animal. Neither an ANOVA or a Kruskal-Wallis non-parametric 

ANOVA revealed any statistical significance in food consumption patterns 

for any dose level in either sex. There was no statistically significant 

differences in body weights for any of the animals throughout the study. 

Clinical chemistry findings for males revealed a slight decrease in the low 

and mid-dose groups' albumin-globulin ratio. Since there was no doseresponse (the high dose group was not different than the control), it was 

judged to be a spurious finding and not treatment-related. High-dose 

males at 9 and 12 months showed differences in serum albumin via serum 

electrophoresis, but was not corroborated by actual clinical chemistry 

measurements, and was not considered by the authors to be biologicallysignificant. Throughout the study, findings for females included differences 

in serum sodium, serum ALT, and serum AST, but were transient, did not 

appear dose-related, and were judged by the authors to be not related to 

the administration of AMP. There was no effect of AMP administration on 

hematology, and likewise the urinalysis revealed no treatment-related 

effects. There were no effects on organ weights or organ/body weight 

ratios that were attributed to test material administration by the authors.

At necropsy, evaluation of the tissues revealed several isolated 

observations, none of which were attributed to the administration of the test 

material. There were no neoplastic observations in any of the dogs 

sacrificed at either 6 months or one year of administration in their diets.

Test condition : Twenty nine male and 29 female beagle dogs were received from 

Laboratory Research Enterprises, Kalamazoo, MI, and 25 of the healthiest 

of each sex were used for study. The animals were selected based on 

criteria of the US FDA (1982). The dogs were 4 months of age at arrival to 

the testing laboratory. Animals were identified by an assigned identification 

number on a collar, housed singly for an acclimation period, and were 

examined by a laboratory veterinarian for general health status. Animals 

were stratified by body weight, and assigned randomly to their treatment 

groups.

Test substance : 2-amino-2-methyl-1-propanol supplied by Angus Chemical Co, Northbrook, 

IL. Supplied as an aqueous solution of AMP-HCl. Concentration of AMP in 

the solution was 47.1%.

Conclusion : Based on the findings under these study conditions, there is no effect at 

any dose level on general appearance, behavior, body weight, food 

consumption, ophthalmoscopic exams, clinical chemistry, hematology, 

organ weights, or tissue histopathology. Based on the absence of 

statistically and biologically significant findings in dose-response patterns, 

the No-Observed Effect Level for AMP in the diets of Beagle dogs in 

greater than 110 ppm.

Reliability : (2) valid with restrictions
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2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

Flag : Critical study for SIDS endpoint

05.06.2006 (33)

Type : Sub-acute

Species : rat

Sex : male/female

Strain : Sprague-Dawley

Route of admin. : oral feed

Exposure period : 8 weeks

Frequency of treatm. : continuous

Post exposure period :

Doses : 0, 1000, 2000, 4000, 8000, 16000 ppm

Control group : yes, concurrent vehicle

LOAEL : ca. 1000 ppm

Method :

Year : 1976

GLP :

Test substance : other TS: P-1826 (assumed to be AMP-regular)

Method : The test material was fed in the diet at dosage levels of 1000, 2000, 4000, 

8000, 16000 ppm. Ten male and 10 female rats were used at each dose 

level and also in a control group. The compound was mixed with distilled 

water so that the same total volume of liquid was mixed with the food for 

each group. The compound-water premix was mixed with a small amount 

of diet, and the food premix was mixed with the total diet. Control rats also 

received distilled water in their diet at the same volume as the treated diets. 

Rats were observed daily for changes in general behavior and appearance. 

Individual body weights and sex group food consumption were recorded 

weekly.

At the termination of the study, all surviving rats at the 8000ppm and 

16000ppm doses were necropsied. In addition, 2 males and 2 females at 

each of the other dose levels plus control were likewise necropsied. Livers 

plus any gross lesions from all animals necropsied were paraffin 

embedded, sectioned, and stained and examined microscopically.

Remark : Estimated test material intake on week 4, based on mean body weights 

and food consumption:

MALES

Dose Group Material Intake (mg/kg/day) 

Control 0 

1000ppm 244

2000ppm 474

4000ppm 912

8000ppm 1901

16000ppm 4698

FEMALES

Dose Group Material Intake (mg/kg/day)

Control 0

1000ppm 436

2000ppm 806

4000ppm 1628

8000ppm 3424

16000ppm 7579

Result : In-life observations made beginning week 3 included emaciation, rough 

hair coat, and scattered 1x1mm lesions over the dorsal surfaces of a few 

rats in the 16000ppm group. After week 3, the incidences increased so 
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that all rats in the high dose showed similar clinical signs. Hair loss on the 

dorsal surface was also noted in rats in this group beginning at week 5 and 

continuing thereafter. One female rat at the high dose showed general 

paleness and tremors prior to death at week 2. Two female rats in the 

16000ppm group died during the study.

Rats in the 16000ppm group gained slightly less weight as compared to 

control rats. Gains in the other dose groups were similar to the control. 

Food consumption patterns were similar for all animals. 

At necropsy, all 16000ppm surviving rats, and all rats at the 8000ppm dose 

level were necropsied. Two males and two females from each of the other 

groups were also examined. Alopecia and focal skin erosions and 

ulcerations found in rats at the 16000ppm dose level were viewed as 

possibly compound related. Hepatocyte vacuolation descrived in rats from 

all the treated groups, with increasing severity at the higher dose levels, 

was considered compound related. Microscopic skin lesions found at the 

16000ppm dose level, like the corresponding gross lesions, were viewed 

as possibly compound related.

Test condition : Sixty male (133-183g at study start) and female (115-146g at study start) 

CD rats were received from Charles River Labs, and were housed 

individually in hanging canges, maintained in a temperature and humidity 

controlled room. Purina rodent chow and water were provided to the 

animals ad libitum.

Conclusion : LOAEL = 1000ppm

LOAEL under these test conditions was 1000ppm. Observed effects at 

1000 ppm included alopecia and focal skin erosions.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (34)

Type : Sub-acute

Species : mouse

Sex : male/female

Strain : CD-1

Route of admin. : oral feed

Exposure period : 8 weeks

Frequency of treatm. : continuous

Post exposure period :

Doses : 0, 200, 400, 800, 1600, 3200 ppm

Control group : yes, concurrent vehicle

NOAEL : > 3200 ppm

Method :

Year : 1976

GLP :

Test substance : other TS: P-1826 (assumed to be AMP-regular)

Method : The test material was fed in the diet at dosage levels of 200, 400, 600, 800, 

1600, 3200 ppm. Ten male and 10 female mice were used at each dose 

level and also in a control group. The compound was mixed with distilled 

water so that the same total volume of liquid was mixed with the food for 

each group. The compound-water premix was mixed with a small amount 

of diet, and the food premix was mixed with the total diet. Control mice 

also received distilled water in their diet at the same volume as the treated 

diets. 

Mice were observed daily for changes in general behavior and appearance. 

Individual body weights and sex group food consumption were recorded 

weekly.

At the termination of the study, all surviving mice at the 3200ppm dose 
5. Toxicity Id 124-68-5

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were necropsied. In addition, 2 males and 2 females at each of the other 

dose levels plus control were likewise necropsied. Livers plus any gross 

lesions from all animals necropsied were paraffin embedded, sectioned, 

and stained and examined microscopically.

Remark : Estimated test material intake for the animals were calculated based on 4 

week body weight and food consumption:

MALES 

 Estimated mg/kg/day 

Control 0

200ppm 1.244

400ppm 2.088

800ppm 3.360

1600ppm 8.950

3200ppm 14.380

FEMALES

 Estimated mg/kg/day 

Control 0

200ppm 1.600

400ppm 3.146

800ppm 6.070

1600ppm 12.870

3200ppm 27.742

Result : No changes considered to be related to compound were seen in the 

general behavior and appearance. There was no treatment-related 

mortality. Increases in body weight over the course of the study were 

comparable for control and all treated animals. Food consumption values 

were also similar for the control and treated animals.

There were no compound-related gross lesions observed in any of the 

necropsied mice. There were likewise no microscopic lesions that were 

considered treatment-related in the livers of any mice necropsied.

Test condition : Sixty male (20-31g at study start) and female (18-27g at study start) CD-1 

mice were received from Charles River Labs, and were housed individually 

in hanging canges, maintained in a temperature and humidity controlled 

room. Purina rodent chow and water were provided to the animals ad 

libitum.

Conclusion : The NOAEL for CD-1 mice under these conditions is >3200ppm.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (35)

Type : Sub-acute

Species : dog

Sex : male/female

Strain : Beagle

Route of admin. : oral feed

Exposure period : 4 weeks

Frequency of treatm. : continuous

Post exposure period :

Doses : 0, 600, 1800, 5400, 16200 ppm

Control group : yes, concurrent vehicle

NOAEL : ca. 600 ppm

Method :

Year : 1976

GLP :

Test substance : other TS: P-1826 (lot 6C29-9B), purity not given, supplied by the study 

sponsor
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Method : P-1826 was administered in the diet at doses 600, 1800, 5400, and 16,200 

ppm. One male and one female was assigned to each dose level. The 

compound was mixed with distilled water and a small amount of chow to 

create a premix. The premix was used to mix the total diets at each dose 

level. Dogs were observed daily for changes in general behavior and 

appearance. Individual body weights and food consumption were recorded 

weekly. Blood and urine was collected pre-study and at week 4. 

Hematology studies included hemoglobin, hematocrit, total erythrocyte 

count, total and differential leukocyte counts and erythrocyte sedimentation 

rate. Clinical chemistry parameters included: fasting glucose, urea 

nitrogen, serum glutamic oxalacetic and pyruvic transaminase activities, 

serum alkaline phosphatase activity, total protein and albumin. Albumin to 

globulin ratios were calculated. Urinalysis included description of color and 

appearance, measurement of volume, pH, specific gravity, occult blood, 

and microscopic examination of the sediment.

Remark : Estimated test material intake was calculated based on week 2 body 

weights and food consumption data:

Males

Control estimated (mg/kg/day)

600ppm 21.9

1800ppm 59.6

5400ppm 25.37 (food consumption extremely low)

16200ppm (1 gram of food consumption reported)

FEMALES

Control estimated (mg/kg/day)

600ppm 19.0

1800ppm 70.86

5400ppm 198.0 

16200ppm 168.8 (food consumption low)

Result : Soft stool and/or diarrhea frequently were noted for the female dog at 

5400ppm, and for both dogs at 1800 and 16200 ppm. A dry nose and 

mouth were noted the second week of study for both dogs at the 16200 

ppm. There was no mortality during the study. Marked losses in body 

weight were seen for the male dog at the 5400ppm dose level and for both 

dogs at the 1800 and 16200 ppm dose levels. All other dogs maintained or 

showed gains in body weight. A marked decrease in food consumption 

was noted for the male dog at the 5400ppm dose level, and almost total 

anorexia was noted for both dogs at the 16200ppm dose level. Slightly 

elevated hemoglobin, hematocrit, and erythrocyte count were noted for the 

female high-dose female at 4 weeks. Also at 4 weeks, a slight neutropenia 

for the male dog at the 5400 and 16200 ppm dose levels was noted. No 

other changes were seen in hematological studies. At the 600ppm dose 

level, the female showed a slight increase in SGPT activity. Moderate to 

marked increases were seen in alkaline phosphatase and SGPT activity for 

all dogs at the 1800, 5400, and 16200ppm dose levels. Slight to moderate 

increases in SGOT activity also were seen for all dogs at the 5400 and 

16200ppm dose levels. No other changes were seen in clinical chemistry 

parameters. There were no unusual values seen in urinalyses. There 

were no compound related gross pathologic lesions observed at necropsy 

in any dog. There appeared to be a compound related decrease in 

absolute liver weights at 5400 and 16200 ppm and several dogs also had 

decreases in relative liver weights as compared to values from untreated 

dogs of similar age and weight. Microscopically, all dogs except the male 

at 600ppm had evidence of toxic liver injury, characterized by hepatocyte 

vacuolation, necrosis of scattered individual hepatocytes and 

accumulations of a greenish-brown pigment in Kuppfer cells. Sinusoids in 
5. Toxicity Id 124-68-5

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the centrolobular areas of some livers appeared dilated, suggesting that 

atrophy of some liver parenchymal tissue had occurred. Decreased liver 

weight noted in some dogs would be consistent with atrophy of hepatic 

parenchymal tissue; with only one dog of each sex, the authors had 

difficulty assessing such. Microscopic lesions in tissues other than the liver 

were those which commonly occur spontaneously in dogs and were not 

considered significant.

Test condition : Four male and four female beagle dogs (6.9-10 kg) were housed 

individually in metal metabolism cages, maintained in a temperature and 

humidity controlled room, and offered Purina dog chow and water ad 

libitum.

Test substance : P-1826 (lot 6C29-9B) purity not given, supplied by the study sponsor

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (36)

Type : Sub-acute

Species : rat

Sex : male/female

Strain : Long-Evans

Route of admin. : gavage

Exposure period : 5 days

Frequency of treatm. : once per day

Post exposure period :

Doses : 0, 500, 1000, 2500 mg/kg

Control group : yes

NOAEL : ca. 500 - 1000 mg/kg

LOAEL : ca. 1000 - 2500 mg/kg

Method :

Year : 1977

GLP :

Test substance : as prescribed by 1.1 - 1.4

Method : Four groups of rats were gavaged daily for 5 days with AMP in distilled 

water at dose levels of 0, 500, 1000, 2500 mg/kg. These were 

administered from stock solutions at a rate of 1mL/100g body weight. The 

pH's of the dosing solutions all exceeded 11. The rats were observed daily 

and body weights were taken through the 5 days of dosing and up to the 

15th day of the study. The survivors were sacrificed and necropsied on the 

15th day. Tissues were taken for further study. Body weights and organ 

weights were measured for livers and kidneys. Representative samples of 

livers and kidneys were selected for microscopic examination.

Result : Mortality

All five males at 2500mg/kg were dead by test day 3. Two females died by 

test day 11 at 1000mg/kg, and all five females at 2500mg/kg were dead by 

test day 3.

Bodyweight

There were slight decreases in bodyweight noted for surviving rats in all 

dose groups, relative to the controls. There were no statistically significant 

findings.

Necropsy

All livers of the surviving rats looked normal grossly. Upon further 

examination of tissues, there was no data presented in the report that 

suggest a harmful effect of the compound under these experimental 

conditions. The gross and microscopic findings represent the usual profile 

of spontaneous diseases that occur in rats. There were no significant 

findings in kidney and liver organ weights or organ:body weight ratios for 

any dose level relative to the controls.

Source : Albany Medical College, unpublished data. FOI# F86-38214.
5. Toxicity Id 124-68-5

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Test condition : Forty Long-Evans rats (90-100g), 5/sex/dose, were acclimated to the lab 

for more than one week. Rat chow and water were provided ad libitum.

Conclusion : In general, no dose-related pathological effects were seen in the livers of 

rats. The mortality of the higher dose animals appeared to be associated 

with GI tract effects. The clinical chemistry studies show significant 

changes in some of the parameters, and cannot be disregarded. There 

exists, however, a strong possibility that the clinical chemical differences as 

well as GI tract pathology is associated with the strong alkalinity (pH>11) of 

the dose preparation, rather than an effect of the AMP alone.

Under conditions of this study, the following LOAEL and NOAEL are noted:

Males 

LOAEL = 2500 mg/kg

NOAEL = 1000 mg/kg

Females

LOAEL = 1000 mg/kg

NOAEL = 500 mg/kg

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

19.05.2006 (37)

Type : Sub-acute

Species : monkey

Sex : female

Strain : other: Rhesus

Route of admin. : drinking water

Exposure period : 5 days

Frequency of treatm. : once daily

Post exposure period :

Doses : 500, 1000 mg/kg

Control group : no

Method :

Year : 1977

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Method : The monkeys were dosed with AMP in distilled water at dose levels of 500 

and 1000 mg/kg. Dosing continued for 5 days or until the higher dose 

monkey died. Body weights were taken daily. The low dose monkey was 

observed for 14 days prior to necropsy on the 15th day, and the high dose 

monkey was necropsied at the time of death. Hematology and clinical 

chemistry parameters were evaluated, and animals were examined at 

necropsy for gross and microscopic findings.

Result : The high dose female died 2 hours after the 3rd dose. Cause of death was 

recorded as gastrointestinal hemorrhaging. Both monkeys showed an 

approximately 10% decrease in body weight from the first to last 

measurement.

Hematology results showed no significant changes in RBC, HgB, or Hct 

and only a slight increase in WBC counts. In the surviving monkey, 

significant differences in Ca++, BUN, Creatinine, SGPT, CPK, and OCT 

were seen.

The liver in both the low and high dose animals, upon necropsy evaluation, 

were found to be grossly and microscopically within normal limits.

Source : Albany Medical College, unpublished data. FOI #F86-38214.

Test condition : Two Rhesus monkeys were acclimated to the conducting laboratory for 

over one week. Baseline values for clinical chemistry, hematology, and 

urinalysis were performed prior to dosing.

Conclusion : In general, no dose-related pathological effects were seen in the livers of 
5. Toxicity Id 124-68-5

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monkeys. The mortality of the high dose animal appeared to be associated 

with GI tract effects. The clinical chemistry studies show significant 

changes in some of the parameters, and cannot be disregarded. There 

exists, however, a strong possibility that the clinical chemical differences as 

well as GI tract pathology is associated with the strong alkalinity (pH>11) of 

the dose preparation, rather than an effect of the AMP alone.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

19.05.2006 (37)

Type : Sub-acute

Species : mouse

Sex : male

Strain : Swiss Webster

Route of admin. : inhalation

Exposure period : 180 minutes

Frequency of treatm. : once

Post exposure period : 20 minute recovery in room air

Doses : 185-1160 mg/m3

Control group : yes

Method :

Year : 1996

GLP : no data

Test substance : as prescribed by 1.1 - 1.4

Method : The method of aerosol generation for AMP is not specified in detail. The 

animals were placed in plethysmographs attached to the generation 

apparatus such that their heads were extended into the interior of the 

chamber. A latex collar served as a seal around the neck of the mouse 

and held its head in place. Pressure transducers permitted the 

measurement of pressure changes created by mice during inhalation and 

exhalation. Relative tidal volume changes and respiratory frequency were 

measured. Each experiment consisted of a 20 minute control period in air 

alone, exposed to air (sham exposed), or exposed to the test material for 

180 minutes. A 20-minute recovery period was given immediately following 

exposure. Animals were observed for 1 week for any mortality.

Using the breathing patterns measured during the experiment by the 

plethysmograph, sensory irritation and pulmonary irritation can be 

identified.

Remark : The article failed to cite detailed atmosphere generation methods. The 

atmosphere concentration is reported only as a range of 185-1160 mg/m3; 

the absence of a time-weighted average concentration makes 

interpretation of the results difficult, as the actual dose to the animal is not 

known. The analysis of the atmosphere by Miran IR does not preclude the 

possibility aerosol exposure at a higher concentration than reported.

Result : In general, exposure to the test material resulted in immediate sensory 

irritation, and persisted throughout the 3 hour exposures. The test material 

also produced pulmonary irritation, but the effect was not immediate (2-3 

hour delay in onset). Animals exposed to AMP failed to return to control 

levels during the 20 minute recovery period following exposure, thus 

recovery was considered poor. The test material is considered moderate in 

potency relative to other test materials tested concurrently under these test 

conditions.

Test substance : Supplied to the conducting lab by the United Auto Workers and General 

Motors Corporation National Joint Committee om Health and Safety.

Conclusion : AMP may be considered a sensory and pulmonary irritant at the 

concentration range tested in mice under these study conditions.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)
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01.06.2006 (38)

Type : Sub-chronic

Species : rat

Sex : male/female

Strain : Sprague-Dawley

Route of admin. : oral feed

Exposure period : 3 months

Frequency of treatm. :

Post exposure period :

Doses : 0, 25, 150, 250, 2500 ppm in feed

Control group : yes, concurrent vehicle

LOAEL : = 2500 ppm

Method :

Year : 1981

GLP : no

Test substance : other TS: AMP-95/HCl 66.1ai (Lot 109-1)

Method : Appropriate amounts of test material were mixed with standard lab rodent 

diet weekly, to provide 0, 25, 150, 250, or 2500 ppm to the animals. The 

animals received the test material continuously in the diet for 90-92 days 

prior to necropsy. Homogeneity of the test material in the feed was

assayed by sampling all dose levels (from the top, middle, and bottom of 

the containers). Samples from all dose levels were assayed for stability in 

the feed at day 0, 3, 4, 7, 10, and 14. Concentration of the test material in 

the feed was analyzed for all dose levels on test weeks 1, 2, 3, 4, 6, 8, 12, 

and 13.

Animals were observed twice daily for mortality and gross signs of 

toxicologic or pharmacologic effects. A detailed physical examination for 

signs of local or systemic toxicity, pharmacologic effects, and palpable 

masses was performed weekly. Ophthalmoscopic examinations were 

performed pretest and at the end of month 1 and 3. Body weights were 

recorded twice pretest, weekly during treatment, and terminally after 

fasting. Food consumption was recorded weekly beginning the week prior 

to study start, and test material was calculated from food consumption data 

based on nominal concentration of the test material in the feed.

Blood was analyzed for the following parameters (pretest, month 1 & 3): 

hemoglobin, hematocrit, erythrocytes, platelets, total & differential 

leukocytes, erythrocyte morphology, serum glutamic oxaloacetic 

transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, 

blood urea nitrogen, fasting glucose, total protein, albumin, globulin, A/G 

ratio, cholesterol, sodium, potassium, calcium, total bilirubin, and lactic 

acid dehydrogenase.

Urine was analyzed at month 1 and 3, and gross appearance, specific 

gravity, pH, protein, glucose, ketones, bilirubin, occult blood, urobilinogen, 

and microscopic analysis were evaluated.

Animals dying spontaneously received a gross postmortem exam. All 

others surviving to necropsy were euthanized under anesthesia, underwent 

a gross postmortem exam, and select tissues were weighed and/or 

preserved for examination. Organ weight was collected for adrenals, brain, 

gonads, heart, kidneys, liver, pituitary, and spleen and they were also 

preserved for examination. In addition, the following were preserved: 

aorta, blood smear, bone and bone marrow, epididymus, eye, cecum, 

ileum, duodenum, jejunum, lungs, mesenteric & mediastinal lymph nodes, 

mammary glands, sciatic nerve, pancreas, parathyroid, prostate, salivary 

gland, seminal vesicle, skeletal muscle, skin, spinal cord, stomach, thymus, 

thyroid, trachea, bladder, uterus, gross lesions, and tissue masses.
5. Toxicity Id 124-68-5

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Statistical analysis included body weight, food consumption, hematology, 

and clinical chemistry parameters, organ weights and organ:body weight 

ratios. Mean values of all dose groups were compared to control at each 

time interval where appropriate. Statistically significant differences from 

control are indicated in appendices.

Remark : Results & methods sections referenced appendix data, which is not 

provided in Dow's copy of the report. As such, test material intake 

(mg/kg/day) could not be estimated.

Result : Mortality

All animals survived the test material administration, with the exception of 2 

females- one died following Month 1 blood collection, and the other was 

sacrificed on test day 18 due to poor food consumption, constipation, 

lethargy, and swollen abdomen. The condition was not considered due to 

the test material.

Physical Observations

All observations noted were interpreted by the author to be related to a viral 

infection (sialdacryoadenitis) in all dose groups at approximately the same 

frequency, primarily in males except where noted, and included: alopecia, 

swollen salivary glands (both sexes), opacities, excessive lactimation, and 

chromodacryorrhea. 

Ophthalmoscopic Examinations

Pretest exams revealed no notable abnormalities. At months 1 & 3, a 

significant increase in a variety of lesions, which appeared to be infectious 

in origin, were noted. The observations were likely secondary to the 

sialodacryoadenitis infection which can lead to opacity and other ocular 

lesions. The incidence of the abnormalities was similar in all dose groups 

and both sexes, and therefore does not appear to be treatment-related.

Body Weight

Body weight differences between the treated and control animals of both 

sexes were slight during the course of the study. No consistent pattern 

related to the administration of the test substance was evident. It is 

concluded by the authors that the dose levels selected did not affect body 

weights significantly.

Food Consumption

Among treated males, slight reductions in food consumption were evident 

during weeks 1-3 as compared to the control. Thereafter, mean food 

consumption values were comparable in all groups. Mean food 

consumption values tended to be slightly higher in the treated females as 

compared to the controls during the course of the study. The increases 

were slight and are not considered to be of toxicological significance.

Test Substance Intake

Test substance intake values based on nominal dietary concentrations 

were approximately proportional to the dietary concentrations. Test 

substance intakes were highest for all groups during the early phase of the 

study and gradually declined reaching a plateau by approximately week 10. 

Since the females consumed more feed on a body weight basis, their test 

substance intake calues were highter as compared to the males within a 

given group.

Hematology

Pretest hematology values were within normal limits for both sexes. 

Occasional statistically significant differences were noted in the group 

mean hematology data for the treated animals as compared to the control 

groups, for both males and females. However, as all means were 

generally within the normal physiological range and no consistent 

treatment-related pattern evident, it was concluded by the authors that the 

administration of the test material did not significantly alter the hematology 
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parameters evaluated.

Clinical Chemistry

Pretest values were normal for both sexes. At month 1, total bilirubin 

values were significantly decreased in the 2 highest dose groups while total 

protein and globulin levels were significantly increased in only the highest 

dose group. Among the females, month 1 alkaline phosphatase was 

slightly elevated in all but the control and low dose groups. Statistical 

significance was noted for only the 250ppm group. At Month 3, a trend 

toward increased SGOT levels was found among the treated males, while 

BUN levels tended to be lower in dosed animals as compared to the 

controls. In addition, LDH was significantly increased in the high dose only. 

Among the females, SGOT, SGPT, and LDH were significantly elevated in 

the high dose only. In addition, total protein and globulin values were 

significantly decreased in the high dose. Other significant differences were 

noted in both sexes at the 1 and 3 month evaluations. However, these 

differences were generally slight and the values within the normal 

physiological range for animals of this species and strain. The combination 

of increases in SGOT, SGPT, and LDH in the males and decreased BUN in 

the females at Month 3 suggest that the liver may be a target organ. The 

magnitude of these differences was slight and generally confined to the 

high dose group. Therefore any alterations in liver function would be 

expected to be minimal in degree. 

Urinalysis

There were no effects on urinalysis parameters noted in any animal over 

the course of the study.

Organ Weight and Organ:Body weight ratios

Among the males, the high dose kidney/body weight ratio was increased, 

while the absolute liver weights were decreased in the 150 and 250 ppm 

groups. Among the females, the absolute and relative liver and spleen 

weights were significantly increased in the 25 and 2500 ppm groups, 

respectively. The changes were slight and appear due to biological 

variation as no dose-response pattern emerged. The possible exception is 

the tendency toward increased liver weights in the treated females. As 

previously discussed, the clinical biochemistry values suggest the liver as a 

target organ for the test material. Frequently, liver weight changes are 

secondary to biochemical altherations in liver morphology and/or function.

Pathology

Gross post-mortem examinations revealed no significant compound-related 

abnormalities. Lesions noted occurred sporadically and/or were found in 

both the control and treated animals at approximately the same incidence. 

Microscopic evaluations revealed patchy hepatocellular vacoulization in the 

livers of 3/20 males and 4/20 females in the high dose group This finding 

ranged from nomimal to moderate in degree. These vacuoles, presumably 

containing lipid, suggest that the liver may be a target organ for the test 

compound, as the clinical chemistry evaluations showed increased serum 

concentrations of hepatic enzymes.

Test condition : Male and female Sprague-Dawley rats were received from Charles River 

Breeding Laboratories and were 4 weeks of age at arrival to the 

Bio/dynamics Lab. They were allowed to acclimate to the laboratory for a 

minimum of 14 days, and were housed individually in elevated stainless 

steel cages. They were fed Purina Certified Lab Chow (#5002) ad libitum, 

and fresh food was presented weekly. Water was provided ad libitum via 

an automated water system. Photocycle was 12 hours light per 24 hour 

cycle, and temperature was monitored twice daily. They were 

approximately 7.5 weeks of age at the start of treatment. Animals were 

given a pre-assignment physical examination and unsuitable animals were 

excluded from assignment to test groups. The animals were assigned 

randomly to groups (20/sex/dose), and were identified with an numeric 
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metal ear tag.

Reliability : (3) invalid

3 (methodological deficiencies, high incidence of viral infection in test 

animals)

01.06.2006 (39)

5.5 GENETIC TOXICITY ‘IN VITRO‘

Type : Bacterial reverse mutation assay

System of testing : S. typhimurium (tester strains TA98, TA100, TA1535, TA1537) and E.coli 

(tester strain WP2 uvrA)

Test concentration : 100, 333, 1000, 3333, 5000 ug per plate

Cycotoxic concentr. :

Metabolic activation : with and without

Result : negative

Method : OECD Guide-line 471

Year : 1996

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : Positive controls, appropriate to the given tester strains, were used as 

follows:

All strains, activated - 2-aminoanthracene

WP2uvrA, nonactivated - methyl methanesulfonate

TA98, nonactivated - 2-nitrofluorene

TA100, TA1535, nonactivated - sodium azide

TA1537, nonactivated - 9-aminoacridine

The concentration varied according to positive control compound. The 

sterility of the test article was verified.

Preliminary Toxicity Assay

Ten dose levels of the test article were plated, one plate per dose, with 

overnight cultures of TA100 and WP2 uvrA on selective minimal agar in the 

presence and absence of rat liver S9 activation.

Mutagenicity Assay

An initial and confirmatory assay was used to evaluate the mutagenic 

potential of the test material. A minimum of 5 dose levels of the test article, 

with vehicle and positive controls, were plated with tester strains in the 

presence and absence of rat liver S9 activation. All dose levels of test 

article, vehicle controls, and positive controls were plated in triplicate. The 

test systems were exposed to the test article via the plate incorporation 

methodology described by Ames, et.al.( (1975) and updated by Maron and 

Ames (1983). Plates were coded according to the testing laboratory's 

standard procedures. Plates were incubated for 48-72 hours at 35-39C. 

Plates not counted immediately following the incubation period were stored 

at 2-6C until the colonies could be counted.

Toxicity and degree of precipation were scored relative to the vehicle 

control plate using a well-defined 9-point scale. Colonies were counted 

either by an automated colony counter or by hand unless the assay was 

preliminary or the plate exhibited toxicity. Plates exhibiting test article 

precipitate that interferes with an automated colony counter were counted 

by hand.

Mean and standard deviation of the number of revertants per plate were 

calculated and reported. For a positive finding, the test material must 

cause a dose-related increase in mean revertants per plate of at least one 

tester strain with a minimum of 2 increasing concentrations of test article. 
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Positive finding for TA1535 and TA1537 is an increase in mean revertants 

at the peak of dose-response greater than, or equal to, 3x mean control 

value. Positive finding for TA98, TA100, WP2 uvrA is an increase in mean 

revertants at the peak of dose-response greater than, or equal to, 2x mean 

control value.

Remark : GLP's were followed except for the following exceptions:

1. The identity, strength, purity, and composition or other characteristics to 

define the test or control article were not determined by the testing facility.

2. Analyses to determine the uniformity, concentration, or stability of the 

test or control mixtures were not performed by the testing facility.

3. The stability of the test or control article under the test conditions was 

not determined by the testing facility.

Result : Water was selected as the solvent of choice. The test material was soluble 

in water at approximately 100ug.mL, the maximum concentration tested. 

Preliminary Toxicity Assay

The maximum dose tested was 5000ug/plate, achieved by using a 

concentration of 100mg/mL and a 50uL plating aliquot. Based on the 

findings, the maximum dose plated in the mutagenicity assay was 

5000ug/plate. Neither precipitate nor appreciable toxicity was observed.

Mutagenicity Assay

Neither precipitate nor appreciable toxicity was observed in the initial or 

confirmatory assays. In neither the initial nor confirmatory assay was there 

a positive response with any of the tester strains at any dose level, in the 

presence or absence of S9 activation. The mean of each positive control 

exhibited at least a 3-fold increase in the number of revertants over the 

mean value of the respective vehicle control, indicating a valid test.

Test condition : Salmonella tester strains were recieved directly from Dr. Bruce Ames, 

University of California, Berkeley, and the E.coli was received from the 

National Collection of Industrial and Marine Bacteria, Aberdeen, Scotland.

Tester strains TA98 and TA1537 are reverted from histidine dependence 

(auxotrophy) to histidine independence (prototrophy) by frameshift 

mutagens. Tester TA1535 is reverted by mutagens that cause basepair 

substitutions. Tester TA100 is reverted by mutagens that cause both 

frameshift and basepair substitution mutations. Specificity of the reversion 

mechanism in E.coli is sensitive to basepair substitution mutations, rather 

than frameshift mutations.

To assure that cultures were harvested in late log phase, the length of 

incubation was controlled and monitored. Each culture wasmonitored 

spectrophotometrically for turbidity and was harvested at a percent 

transmittance yielding a titer of approximately 10^9 cells per milliliter.

Acoclor 1254-induced rat liver S9 was used for the metabolic activation 

system. The S9 was prepared from male Sprague-Dawley rats induced 

with a single IP injection of Acroclor 1254, 500mg/kg, five days prior to 

sacrifice. Each batch was assayed for its ability to metabolize.

Conclusion : The results of this study indicate that, under the conditions of this study, the 

test material did not cause a positive response with any of the tester strains 

in the presence and absence of Acrclor-induced rat liver S9.

Reliability : (1) valid without restriction

1 (guideline, GLP study)

Flag : Critical study for SIDS endpoint

01.06.2006 (40)

Type : Mammalian cell gene mutation assay

System of testing : L5178Y/TK+- Mouse Lymphoma

Test concentration : 0.5, 1.5, 5.0, 15, 50, 150, 500, 1500, 5000 ug/mL

Cycotoxic concentr. :

Metabolic activation : with and without
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Result : negative

Method : OECD Guide-line 476

Year : 1996

GLP : yes

Test substance : other TS: AMP-95

Method : Aroclor 1254-induced rat liver S9 was used as the metabolic activation 

system. 

A preliminary toxicity assay was used to establish the optimal dose levels 

for the mutagenesis assay. L5178Y cells were exposed to the vehicle 

alone and to concentrations of the test article ranging from 0.5-5000 uL in 

both the absence and presence of S9-activation. Cell population density 

was determined at 24 and 48 hours after exposure to the test article. 

Toxicity was measured as suspension of growth relative to the growth of 

the solvent controls. The mutagenesis assay, initial and independent 

repeat, was used to evaluate the mutagenic potential of the test article. 

L5178Y mouse lymphoma cells were exposed to the vehicle alone and 10 

concentrations of the test article in both the absence and presence of S9. 

Positive controls, with and without S9, were tested concurrently.

Tubes containing L5178Y/TK+- cells with F0P medium or S9 activation 

mixture, and 100uL of test solution at concentrations of 0.5, 1.5, 5.0, 15, 

50, 150, 500, 1500, 5000 ug/mL were prepared. Positive controls treated 

with MMS and 7,12-DMBA were also prepared. Treatment tubes were 

gassed with CO2 and incubated in the dark for 4 hours. Cells were 

washed twice, resuspended, gassed with CO2 in air again, and placed on a 

roller. Cells were counted, and numbers were adjusted if necessary. For 

expression of TK+- cells, cells were placed in a cloning meduim of 

granulated agar, mixed with Trifluorothymidine (TFT) or viable count, 

prewarmed and filled with cloning media. The tubes were centrifuged, 

supernatant decanted, and cells resuspended in cloning media. Tests were 

conducted in duplicate. TFT or Viable Count were added to the flask and 

placed on a shaker. The suspension was placed in petri dishes, placed in 

cold storage for 30 minutes, then incubated for 10-14 days.

Diameters and numbers of colonies were recorded, and analyzed relative 

to positive and solvent controls. Previous published data indicates that the 

large colony mutants received localized damage, likely in the form of a 

point mutation or small deletion within the TK locus, and small colony 

mutants received damage to collateral loci concordant with the loss of TK 

activity.

Remark : Study followed GLP's except for the following:

1. The identity, strength, purity, and composition or other characteristics to 

define the test or control article were not determined by the testing facility.

2. Analyses to determine the uniformity, concentration, or stability of the 

test or control mixtures were not performed by the testing facility.

3. The stability of the test or control article under the test conditions was 

not determined by the testing facility.

Result : Sterile distilled water was the solvent of choice. The test material was 

miscible in water at 500 mg/mL, the maximum tested concentration.

Preliminary Toxicity Assay

The high dose tested was 5000ug/mL. Osmolality of the solvent control 

was 300mmol/kg and of the highest dose was 396mmol/kg. Suspension 

growth relative to the solvent control was 13% at 5000ug/mL without S9 

activation, and 31% with S9 activation. Based on these results, the dose 

levels chosen for the mutagenesis assay ranged from 500-5000ug/mL for 

both the non-activated and S9-activated cultures.

Mutagenesis Assay

In the non-activated system, cultures treated with 1000-500ug/mL were 
5. Toxicity Id 124-68-5

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cloned and produced a range in suspension growth of 11-55%. In the S9-

activated system, cultures treated with 500-5000ug/mL were cloned and 

produced a range in suspension growth of 9-98%.

No treated cultures exhibited mutant frequencies more than 55 mutants per 

10^6 clonable cells over the solvent control. A dose-response trend was 

not observed in either the activated or non-activated systems. Over the 

concentration ranges, total growth for the non-activated cultures ranged 

from 12-60%, and 10-137% for the S9-activated cultures. Results of the 

independent repeat assay are similar (12-62% and 32-124% for nonactivated and S9-activated system suspension growth, respectively; 14-

67% and 29-191% for non-activated and S9-activated system total 

growths, respectively). There was likewise no increase in mutant 

frequencies over the solvent control. Colony sizing for the positive control 

yielded the expected increase in small colonies, thereby verifying the 

methods used to detect small colony mutants.

Conclusion : The results of the L5178Y/TK+- Mouse Lymphoma Mutagenesis Assay 

indicate that, under the conditions of this study, 2-amino-2-methyl-1-

propanol did not cause a positive response in the non-activated and S9-

activated systems, and was concluded to be negative.

Reliability : (1) valid without restriction

1 (guideline, GLP study)

Flag : Critical study for SIDS endpoint

27.07.2006 (41)

Type : Ames test

System of testing : S.cerevisiae (D-4) and S.typhimurium (TA98, TA100, TA1535, TA1537, 

and TA1538)

Test concentration : 0.01, 0.1, 1.0, 5.0 microliters per plate

Cycotoxic concentr. :

Metabolic activation : with and without

Result : negative

Method :

Year : 1976

GLP : no

Test substance : other TS:Referred to as P-1826 (AMP) Lot #6029-9B. No purity 

information was included in the final report.

Method : P-1826 was evaluated for its potential mutagenic effect using the microbial 

procedure of Ames, et.al. Saccharomyces cerevisiae D-4 and five strains 

of Salmonella typhimurium (TA98, TA100, TA1535, TA1537, and TA1538) 

were used for the evaluation in which the reaction mixture was tested with 

and without rat liver cell 9000Xg supernate metabolic activation.

Male rats were euthanized and the organs were immediately dissected and 

placed in cold sucrose buffered solution with TRIS at a pH of 7.4. The 

organs were washed twice with the buffered solution and homogenized. 

The homogenate was centrifuged, the supernatant was extracted, and 

retained in cold storage, and were used for the activation study.

Approximately 10^9 cells from a log phase culture of each indicator strain 

were added to test tubes containing 2mL of molten agar supplemented 

biotin and histidine. For non-activation tests, the four dose levels of the 

test compound were added to the contents of the appropriate tubes and 

poured over the surfaces of selected agar plates. In activation tests, the 

tissue supernatant and required cofactors were added to the overlay tubes. 

Four dose levels of the test chemical were added to the appropriate tubes, 

which were then mixed and the contents poured over the surface of a 

minimal agar plate and allowed to solidify. Plates were incubated for 48 to 

72 hours at 37C, and scored for colonies. Positive (nonactivated assay 

methylnitrosoguanidine, 2-nitrofluorene, quinacrine mustard; activated 

assay 2-anthramine, 2-acetylaminofluorene, 8-aminoquinoline, 

dimethylnitrosamine) and solvent controls (water, DMSO, or saline 
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depending on the positive control used) were run with each assay.

The numbers of colonies on each plate were counted and recorded. The 

positive and the solvent controls are provided as reference points.

Result : The test compound, P-1826, was examined for mutagenic activity in a 

series of in vitro microbial assays employing Salmonella and 

Saccharomyces indicator organisms. The compound was tested directly

and in the presence of liver microsomal enzyme preparations from Aroclorinduced rats. The appropriate positive controls for each system and strain 

elicited a strongly-positive result in all cases, validating the assay. 

The compound was tested over a series of concentrations such that there 

was either quantitative or qualitative evidence of some chemically-induced 

physiological effects at the high dose level. The low dose in all cases was 

below a concentration that demonstrated any toxic effect. The dose range 

employed for the evaluation of the compound was from 0.01uL to 5uL per 

plate.

The results of the tests conducted on the compound in the absence of a 

metabolic system were all negative.

The results of the tests conducted on the compound in the presence of the 

rat liver activation system were all negative as well.

Test substance : Referred to as P-1826 (AMP) Lot #6029-9B. No purity information was 

included in the final report.

Conclusion : The test compound did not demonstrate mutagenic activity in any of the 

assays conducted in this evaluation and was considered not mutagenic 

under these test conditions.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (42)

5.6 GENETIC TOXICITY ‘IN VIVO‘

Type : Micronucleus assay

Species : mouse

Sex : male/female

Strain : ICR

Route of admin. : i.p.

Exposure period : 1 ip injection

Doses : vehicle control, 16, 30, 60 mg/kg, and positive control CP (50mg/kg)

Result : negative

Method : OECD Guide-line 474 "Genetic Toxicology: Micronucleus Test"

Year : 1998

GLP : yes

Test substance : other TS: AMP-95 (lot 35662)

Method : In each the Pilot & Toxicity Studies (designed to set appropriate dose 

levels for the micronucleus assay), and the Micronucleus Assay, mice were 

weighed immediately prior to dose administration and the dose volume was 

based on individual body weights. They were observed after dosing, and 

daily thereafter for 3 days for clinical signs of chemical effects. Body 

weights were recorded prior to dose administration and 1 and 3 days after 

dosing. Mice were given a single IP injection of the test article in water, the 

vehicle alone, or the positive control substance.

Pilot Study: 2 male mice were dosed with 1, 10, 100, or 1000 mg test 

material /kg body weight, and 5 males and 5 females were dosed with 2000 

mg/kg. 
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Toxicity Study:

5 male and 5 female mice were dosed with 200, 400, 600, 800 mg/kg.

Based on the results of the pilot and toxicity studies, the high dose for the 

micronucleus test was set at 60 mg/kg, which was estimated to be 

approximately 80% of the LD50/3.

Micronucleus Assay:

Male and female mice were dosed with the positive control (5/sex/dose), 

vehicle control (5/sex/dose), 16 mg/kg (5/sex/dose), 30 mg/kg (5/sex/dose), 

or 60 mg/kg (5/sex/dose with an additional 5/sex/dose in the event of 

mortality) via a single IP injection of the test material or the positive control 

(cyclophosphamide). At the scheduled sacrifice times (24 and 48 hours), 

up to 5 mice / sex / dose were sacrificed, the femurs exposed, and bone 

marrow aspirated into a syringe of fetal bovine serum. The bone marrow 

cells were pelleted by centrifugation and the supernatant drawn off. The 

cells were resuspended and a small amount of suspension spread onto a 

glass slide. Two to four slides were prepared per animal. The slides were 

fixed in methanol, stained, and permanently mounted. Slides were coded 

and scored blindly. Using oil immersion, 2000 polychromatic erythrocytes 

were scored for the presence of micronuclei. The number of 

micronucleated normochromatic erythrocytes in the field of 2000 

polychromatic erythrocytes was enumerated. The proportion of 

polychromatic erythrocytes to total erythrocytes was also recorded per 

1000 erythrocytes. Statistical significance was determined using the 

Kastenbaum-Bowman tables which are based on the binomial distribution. 

The test article was considered to induce a positive response if a doseresponsive increase in mocronucleated polychromatic erythrocytes was 

observed and one or more doses were statistically-elevated relative to the 

vehicle control (p>0.05) at any sampling time. If a single dose group was 

significantly elevated without a dose-response trend, the assay was 

considered a suspect or unconfirmed positive and a repeat assay 

recommended. The test article would be considered negative if no 

statistically significant increase in micronucleated polychromatic 

erythrocytes above the concurrent vehicle control was observed at any 

sampling time.

Remark : Exceptions to GLP's included:

1. The identity, strength, purity, and composition or other characteristics to 

define the test or control article were not determined by the testing facility.

2. Analyses to determine the uniformity, concentration, or stability of the 

test or control mixtures were not performed by the testing facility.

3. The stability of the test or control article under the test conditions was 

not determined by the testing facility.

Result : Pilot:

Mortality occurred within 4 hours following dosing: 5/5 males and 5/5 

females at 2000 mg/kg, and 2/2 males at 1000 mg/kg. There were no 

clinical observations noted.

Toxicity:

Mortality occurred within 3 days of dosing: 5/5 males and 5/5 females at 

400, 600, and 800 mg/kg, and 3/5 males and 5/5 females at 200 mg/kg. 

Clinical signs included: lethargy in males and females at all dose levels, 

piloerection in males and females, and crusty eyes in males at 200 mg/kg. 

The LD50/3 was calculated by probit analysis to be approximately 73.7 

mg/kg for male and female mice. 

Micronucleus Assay:

There was no treatment-related mortality at any dose level. Clinical signs 

noted on the day of dosing included: lethargy in males and females at 60 

mg/kg (highest dose). All other mice treated with test material and control 
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articles appeared normal during the study. The number of micronucleated 

polychromatic erythrocytes per 2000 polychromatic erythrocytes in test 

article-treated groups was not statistically increased relative to their 

respective vehicle control in either male of female mice, regardless of dose 

level or bone marrow collection time.

Test condition : ICR mice from Harlan Sprague-Dawley, INC, were 6-8 weeks old at study 

initiation. For the pilot, toxicity, and MNT assay, males ranged in weight 

from 27.4g to 31.9g, and females ranged from 23.0g to 28.0g. After arrival 

to the lab, the animals were monitored for parasites and infections, and 

were quarantined a minimum of 5 days. They were observed daily for 

general health, food and water consumption patterns, and other conditions. 

The animals were deemed healthy prior to placement on study.

Mice were housed in an AALAC-accredited facility with appropriate 

temperature, humidity, and photocycle for the species. They were housed 

up to 5 per cage, and given food and water ad libitum. The feed and water 

contained no contaminants that influenced the study.

The mice were randomized and placed into assigned dose groups, and 

were identified by a uniquely numbered ear tag.

Conclusion : Under the conditions of the assay described in this report, 2-amino-2-

methyl-1-propanol did not induce a sugnificant increase in the incidence of 

micronucleated polychromatic erythrocytes in bone marrow, and was 

concluded to be negative in the micronucleus test using male and female 

ICR mice.

Reliability : (1) valid without restriction

1 (guideline, GLP study)

Flag : Critical study for SIDS endpoint

01.06.2006 (43)

5.7 CARCINOGENICITY

5.8.1 TOXICITY TO FERTILITY

Type : other: OECD 421

Species : rat

Sex : male/female

Strain : other: CD

Route of admin. : oral feed

Exposure period : 2 weeks before breeding through postpartum day 4

Frequency of treatm. : continuous

Premating exposure period

 Male : 2 weeks

 Female : 2 weeks

Duration of test : Approximately 7 weeks

No. of generation 

studies

:

Doses : 0, 100, 300, 1000 mg/kg/day

Control group : yes, concurrent vehicle

other: NOEL (repro 

effects)

: = 100 mg/kg bw

other: NOEL (males, 

toxicity)

: = 300 mg/kg bw

other: NOEL (females, 

toxicity)

: < 100 mg/kg bw

Result : No effects on mating or conception. Liver effects in females at 100 

mg/kg/day and higher, increased post-implantation loss at 300 mg/kg/day 

and higher.
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Method : OECD Guide-line 421 

Year : 2005

GLP : yes

Test substance : other TS: AMP-HCl

Method : CD (Crl:CD(SD)IGSBR) rats were obtained from a commercial supplier and 

were approximately eight weeks of age at the time of study initiation. Each 

animal was evaluated by a laboratory veterinarian or a trained 

animal/toxicology technician, under the direct supervision of a lab 

veterinarian to determine their general health status and acceptability for 

study purposes upon arrival at the laboratory. The animals were housed 2-

3 per cage in stainless steel cages, in rooms designed to maintain 

adequate conditions (temperature, humidity, and photocycle), and 

acclimated to the laboratory for approximately two weeks prior to the start 

of the study. They were offered a commercial diet and water ad libitum. 

During the study, animals were housed one per cage (prebreeding) or two 

per cage (one male and one female during breeding) in stainless steel 

cage in rooms designed to maintain adequate conditions (temperature, 

humidity, and photocycle). Dams were housed one per cage (with their 

litter) in plastic cages provided with corn cob nesting material from 

approximately day 19 of gestation and throughout the lactation phase of 

the study. 

Animals were stratified by body weight and then randomly assigned to 

treatment groups using a computer program designed to increase the 

probability of uniform group mean weights and standard deviations at the 

start of the study. Animals placed on study were uniquely identified via 

subcutaneously implanted transponders (BioMedic Data Systems, Seaford, 

Delaware) which were correlated to unique alphanumeric identification 

numbers. 

Groups of 12 male and 12 female CD rats were fed diets supplying 0 

(control), 100, 300, or 1000 mg/kg/day of AMP. Males were exposed for at 

least two weeks prior to breeding and continuing throughout breeding for 

37 days. The females were exposed for two weeks prior to breeding, 

continuing through breeding (up to two weeks), gestation (three weeks), 

and lactation (four days). Effects on gonadal function, mating behavior, 

conception, development of the conceptus, parturition, litter size, pup 

survival, sex, pup body weight and the presence of gross external 

morphological alterations were assessed. In addition, a gross necropsy 

and histopathology of the adults was conducted with an emphasis on 

organs of the reproductive system. Males were dosed via the diet for at 

least 14 days prior to mating, continuing throughout mating, for 37 days. 

Females were dosed by dietary exposure for 14 days prior to breeding, and 

continuing through breeding (up to two weeks), gestation (three weeks), 

and lactation (four days).

Representative samples from the test diets were evaluated concurrently 

with the concentration verification analyses (see below) to ensure 

homogeneous distribution of the test material at the lowest and highest 

concentrations in the feed at least once during the study. Preliminary 

stability analyses of the test material in rodent diets at concentrations of 

0.0005% and 0.005% and 5.0% were initiated prior to the start of the 

range-finding study. Analysis of all test diets from the first mix of the main 

study were initiated prior to the start of dosing using gas chromatographymass spectrometry (GC-MS) incorporating an internal standard to 

determine target concentrations. 

Breeding Procedure

Breeding of the adults commenced after approximately two weeks of 

treatment. Each female was placed with a single male from the same dose 

level (1:1 mating) until pregnancy occurred or two weeks had elapsed. 
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During the breeding period, daily vaginal lavage samples were evaluated 

for the presence of sperm as an indication of mating. The day on which 

sperm were detected or a vaginal copulatory plug was observed in situ was 

considered day 0 of gestation. The sperm or plug-positive (presumed 

pregnant) females then were separated from the male and returned to their 

home cages. If mating did not occur after two weeks, the animals were 

separated without further opportunity for mating.

Daily Observations

A cage-side examination was conducted twice daily, designed to detect 

significant clinical abnormalities that were clearly visible upon a limited 

examination, and to monitor the general health of the animals for all males 

pre-exposure and weekly throughout the study. Clinical examinations were 

conducted on all females pre-exposure and weekly throughout the prebreeding and breeding periods. Mated (sperm-positive or plug-positive) 

females received clinical examinations on GD 0, 7, 14 and 20. Females 

that delivered litters were subsequently evaluated on LD 0, 1 and 4, and on 

additional days if warranted by observations made during daily cage-side 

examinations. Females that failed to mate or deliver a litter were examined 

weekly. Clinical observations included a careful, hand-held examination of 

the animal with an evaluation of abnormalities in the eyes, urine, feces, 

gastrointestinal tract, extremities, movement, posture, reproductive system, 

respiration, skin/hair-coat, and mucous membranes, as well as an 

assessment of general behavior, injuries or palpable mass/swellings. 

Body Weights/Body Weight Gains

Body weights for males were recorded on test days -1, 1, 4, 7, and weekly 

thereafter. Females were weighed on test days 1, 4, 7, and 14 during the 

pre-breeding period. During gestation, females were weighed on GD 0, 7, 

14, and 20. Females that delivered litters were weighed on LD 1 and 4. 

Females that failed to mate or deliver a litter were not weighed during the 

gestation or lactation phases. Body weight gains were determined for the 

following intervals: GD 0-7, 7-14, 14-20, 0-20, and LD 1-4.

Feed Consumption

Feed consumption for all animals was measured on test days 1, 4, 7 and 

14 during the pre-breeding period by weighing feed containers at the start 

and end of a measurement cycle. During breeding, feed consumption was 

not measured in males or females due to co-housing. Following breeding, 

feed consumption was measured weekly for males. For mated females, 

feed consumption was measured on GD 0, 7, 14, and 20. For females 

delivering litters, feed consumption was measured on LD 1 and 4. Feed 

consumption was not recorded for females that failed to mate or deliver a 

litter. 

Litter Data

Females were observed for signs of parturition beginning on or about GD 

20. In so far as possible, parturition was observed for signs of difficulty or 

unusual duration. The day of delivery was recorded as the first day the 

presence of the litter was noted and was designated as LD 0. Litters were 

examined as soon as possible after delivery. The following information 

was recorded on each litter: the date of parturition, litter size on the day of 

parturition (day 0), the number of live and dead pups on LD 0, 1, and 4, 

and the sex and the weight of each pup on LD 1 and 4. Any visible 

physical abnormalities or demeanor changes in the neonates were

recorded as they are observed during the lactation period. Any pups found 

dead or sacrificed in moribund condition were sexed and examined grossly, 

to the extent possible, for external and visceral defects and discarded.

Adult Necropsy

A complete necropsy of all the adults was performed. All males were 

necropsied on test day 38, while females that delivered litters were 
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necropsied on LD 4. Females that did not deliver a litter were necropsied 

at least 24 days after the last day of the mating period. In all cases, dosing 

continued until the day prior to sacrifice at which time the animals were 

fasted overnight. Fasted adult rats submitted alive for necropsy were 

anesthetized by the inhalation of carbon dioxide, weighed, and their 

tracheas exposed and clamped. The animals were then euthanized by 

decapitation.

A complete necropsy was conducted on all animals by a veterinary 

pathologist assisted by a team of trained individuals. The necropsy 

included an examination of the external tissues, and all orifices. The head 

was removed, the cranial cavity opened and the brain, pituitary and 

adjacent cervical tissues were examined. The eyes were examined in situ 

by application of a moistened microscope slide to each cornea. The nasal 

cavity was flushed via the nasopharyngeal duct and the lungs were 

distended to an approximately normal inspiratory volume with neutral, 

phosphate-buffered 10% formalin using a hand-held syringe and blunt 

needle. The skin was reflected from the carcass, the thoracic and 

abdominal cavities were opened and the viscera examined. All visceral 

tissues were dissected from the carcass, re-examined and selected tissues 

were incised. The uteri of all females were stained with a 10% solution of 

sodium sulfide stain for approximately two minutes and were examined for 

the presence and number of implantation sites (Kopf et al., 1964). After 

evaluation, the uteri were gently rinsed with saline and preserved in neutral 

phosphate 10% formalin. Weights of the epididymides, kidneys, liver, and 

testes were recorded, and organ:body weight ratios calculated. 

Offspring Necropsy

All pups surviving to LD 4 were euthanized by oral administration of sodium 

pentobarital solution, examined for gross external alterations, and then 

discarded. Any pups found dead were examined to the extent possible.

Histopathology

Tissues with relevant gross lesions was conducted on all adult rats from 

the control and high-dose groups. The histopathological examination of the 

testes included a qualitative assessment of stages of spermatogenesis. 

Examination of tissues from the remaining groups was limited to the liver 

(males and females), cervix, ovaries, oviducts, uterus, vagina, and relevant 

gross lesions. The histopathological examination of the testes included a 

qualitative assessment of stages of spermatogenesis. The presence and 

integrity of the 14 stages of spermatogenesis was qualitatively evaluated 

following the criteria and guidance of Russell et al. (1990). Microscopic 

evaluation included a qualitative assessment of the relationships between 

spermatogonia, spermatocytes, spermatids, and spermatozoa seen in 

cross sections of the seminiferous tubules. The progression of these 

cellular associations defined the cycle of spermatogenesis. In addition, 

sections of both testes were examined for the presence of degenerative 

changes (e.g., vacuolation of the germinal epithelium, multinucleated giant 

cells, a decrease in the thickness of the germinal epithelium, a 

preponderance of Sertoli cells, sperm stasis, inflammatory changes, 

mineralization, and fibrosis). 

Selected histopathologic findings were graded to reflect the severity of 

specific lesions to evaluate: 1) the contribution of a specific lesion to the 

health status of an animal, 2) exacerbation of common naturally occurring 

lesions as a result of the test material, and 3) dose-response relationships 

for treatment related effects. Very slight and slight grades were used for 

conditions that were altered from the normal textbook appearance of an 

organ/tissue, but were of minimal severity and usually with less than 25% 

involvement of the parenchyma. This type of change would not be 

expected to significantly affect the function of the specific organ/tissue nor 

have a significant effect on the overall health of the animal. A moderate 

grade was used for conditions that were of sufficient severity and/or extent 

(up to 50% of the parenchyma) that the function of the organ/tissue may 
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have been adversely affected, but not to the point of organ failure. The 

health status of the animal may or may not have been affected, depending 

on the organ/tissue involved, but generally lesions graded as moderate 

would not be life threatening. A severe grade was used for conditions that 

were extensive enough to cause significant organ/tissue dysfunction or 

failure. This degree of change in a critical organ/tissue may be life 

threatening.

The above grading criteria were not sufficiently flexible to accurately 

characterize the liver microscopic vacuolization consistent with fatty 

change found in this study. Therefore, the following criteria were applied 

only to the observation of "liver vacuolization, consistent with fatty change, 

hepatocyte, multifocal": grade 1 - infrequently observed, grade 2 -

occasionally observed, and grade 3 - readily observed.

STATISTICS AND CALCULATIONS

Parental body weights and gestation and lactation body weight gains, litter 

mean body weights, feed consumption, and organ weights were first 

evaluated by Bartlett's test for equality of variances ( = 0.01; Winer, 1971). 

Based upon the outcome of Bartlett's test, either a parametric or 

nonparametric analysis of variance (ANOVA) was performed. If the 

ANOVA was significant at alpha = 0.05, a Dunnett's test or the Wilcoxon 

Rank-Sum test with Bonferroni's correction (Miller, 1966) was performed 

(experiment-wise alpha = 0.05). Statistical outliers were identified by a 

sequential test at alpha = 0.02 (Grubbs, 1969), and were excluded only for 

documented scientifically sound reasons. Feed consumption values were 

excluded from analysis if the feed had been spilled or scratched.

Gestation length, average time to mating (precoital interval) and litter size 

were analyzed using a nonparametric ANOVA (Hollander and Wolfe, 

1973). If the ANOVA was significant at alpha=0.05, the Wilcoxon RankSum test (Hollander and Wolfe, 1973) with Bonferroni's correction was 

performed at experiment-wise alpha = 0.05, two-sided. The mating, 

conception, fertility and gestation indices (defined below) were analyzed by 

the Fisher exact probability test (Siegel, 1956) with Bonferroni's correction 

at experiment-wise alpha=0.05, two-sided. Evaluation of the neonatal sex 

ratio on postnatal day 1 was performed by the binomial distribution test 

(Steel and Torrie, 1960) at alpha = 0.05, two-sided. Gender was 

determined for pups born dead on postnatal day 0 and these data were 

included in sex ratio calculations. Post-implantation loss, pup survival 

indices and other incidence data among neonates were analyzed using the 

litter as the experimental unit by a censored Wilcoxon test (alpha = 0.05; 

Hollander and Wolfe, 1973) as modified by Haseman and Hoel (1974) with 

Bonferroni's correction. Non-pregnant females, females with resorptions 

only, or females found to be pregnant after staining of their uteri were 

excluded from the appropriate analyses. Both the Dunnett's test and 

Bonferroni's correction correct for multiple comparisons to the control to 

keep the experiment-wise error rate at 0.05. Both were reported at the 

experiment-wise alpha level. Because numerous measurements were 

statistically compared in the same group of animals, the overall false 

positive rate (Type I errors) was greater than the nominal alpha levels. 

Therefore, the final toxicologic interpretation of the data considered other 

factors, such as dose-response relationships, biological plausibility and 

consistency, and historical control values.

Calculation of Reproductive Indices 

Reproductive indices were calculated for female and male mating indices, 

male conception index, female and male fertility indices, gestation index, 

gestation survival index, post-implantation loss, and days 1 and 4 pup 

survival indices.

Result : All animals survived until scheduled termination. No treatment-related 

effects on behavior or demeanor were observed at any dose level during 

the treatment-period.
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There were no treatment related differences in the amount of feed 

consumed by any of the treated males or females when compared to their 

respective controls throughout the study. Gestation feed consumption of 

dams given 1000 mg/kg/day could not be compared due to a lack of viable 

litters at this dose level.

No significant differences in body weights were observed for males at any 

dose level tested. Pre-mating body weights of treated females were not 

different from controls. Dams given 300 mg/kg/day exhibited a nonstatistically significant decrease (5.5%) in gestation day 20 body weight, 

and a statistically significant decrease in body weight gain between GD 14 

and 20. This also led to a slight decrease (not statistically identified) in 

body weight gain for the GD 0-20 interval. The mean GD 14-20 body 

weight gain in the 300 mg/kg/day group was 40% less than the control 

body weight gain during this period, which correlated closely with an 

approximate 50% reduction in mean litter sizes observed in this group. 

Gestation body weights and body weight gains of dams given 100 

mg/kg/day were not different from controls. Gestation body weights and 

body weight gains of females given 1000 mg/kg/day could not be 

compared due to a lack of viable litters at this dose level. There were no 

treatment-related differences in body weight or body weight gains during 

the lactation phase of the study.

There were no treatment-related effects at any dose level on mating, 

conception, fertility, time to mating, gestation length or sex ratio. However, 

a marked increase in percent post-implantation loss (embryo resorption) 

occurred in the 300 and 1000 mg/kg/day group females, with both the 

incidence, severity and likely timing of this effect being dose-related. In the 

1000 mg/kg/day group, all twelve pregnant females showed evidence of 

complete litter resorption. In the 300 mg/kg/day group, four of twelve 

females exhibited complete litter loss, with the remaining eight females 

showing partial litter losses to varying degrees. Judging from the gross 

and microscopic appearance of the resorbed implantation sites, as well as 

the pattern of individual animal body weight gains during gestation, it is 

estimated that the embryonic deaths occurred sometime toward the end of 

the second week of gestation (implantation is completed on GD 6; full term 

is 21-22 days), with some of the high dose animals perhaps occurring 

slightly earlier. In the 100 mg/kg/day group, all reproductive parameters 

including percent postimplantation loss were comparable to control values. 

One of 12 females in the 100 mg/kg/day group was initially considered nonpregnant based on the absence of implantation sites following sodium 

sulfide staining at necropsy. However, histological examination of the 

uterus revealed a very small amount of hemosiderin pigment in only one 

implantation site, suggesting that an embryo had implanted and then was 

resorbed almost immediately. This single case of very early resorption 

does not fit with the timing of resorption seen in the 300 and 1000 

mg/kg/day group, which occurred somewhat later. As pregnancies are not 

normally diagnosed histologically, there are no historical control data to 

directly address the significance of this observation. However, the 

likelihood that this was a spurious finding is supported by the fact that 

isolated occurrences of females that mate, but do no show evidence of 

embryo implantation following sodium sulfide staining are commonly 

encountered in reproductive toxicity studies. Considering this, and the fact 

that all reproductive parameters in this group were unaffected by treatment, 

this single incident of litter resorption in the low dose group was considered 

spurious and unrelated to treatment 

Observations recorded in the offspring occurred at low frequency and bore 

no relationship to treatment. There were no visible external morphologic 

alterations noted in any of the offspring delivered. There were no 

treatment-related effects on litter size in dams given 100 mg/kg/day. In the 

300 mg/kg/day group, there were statistically identified decreases in mean 
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number of pups born live, and mean number of pups on day 1 and 4 

postpartum. These decreases in litter size were a function of the increase 

in post-implantation loss, as noted previously. No litters were produced by 

the 1000 mg/kg/day group females. 

There were no treatment-related effects on mean pup body weights in the 

100 mg/kg/day group. Mean pup body weights in the 300 mg/kg/day group 

were increased on days 1 and 4 postpartum, with the male mean pup 

weights identified as statistically different. These increases were most 

likely due to the decreased litter size at this dose level, as pup body weight 

varies inversely with litter size (Agnish and Keller, 1997). Mean pup body 

weights of dams given 1000 mg/kg/day could not be evaluated due to a 

lack of viable litters.

In the 1000 mg/kg/day males, mean body weight was increased 

approximately 5% when compared to the control group. Although not 

statistically identified, it was associated with statistically identified increases 

in absolute and relative liver and kidney weight. Similar body or organ 

weight effects were not observed in any of the female groups. However, it 

should be noted that terminal body weight and organ weight data from the 

1000 mg/kg/day group were excluded from analysis because they did not 

produce any viable litters and, therefore, could not legitimately be 

compared to the controls, which were in a post-partum state. Also 

excluded from analysis were four females in the 300 mg/kg/day group and 

one in the 100 mg/kg/day group which did not produce viable litters. The 

increased absolute and relative liver and kidney weights of the 1000 

mg/kg/day males were statistically identified and were outside of the 

historical control range for several studies, suggesting a treatment related 

effect. 

There were no treatment-related gross pathologic observations. All 

animals survived to the scheduled termination of the in-life phase of the 

study. 

Males given 1000 mg/kg/day and females given 100 mg/kg/day had 

treatment-related liver effects. Hepatocellular changes in 12/12 males of 

the 1000 mg/kg/day group were characterized by very slight, diffuse, 

cytoplasmic microvacuolization of periportal hepatocytes. In general, the 

very slight effect was present in most of the periportal hepatocytes; 

however, in the three liver sections examined from different lobes (left 

lateral, middle, and right lateral), one was generally more noticeably

affected. In general, the left and right lateral lobes were more affected than 

the middle lobe. The gradation of the effect was based upon the most 

severely affected lobe. The livers of a few male rats in the control, low and 

middle dose group were also affected. It is likely the microscopic 

hepatocellular change in the 1000 mg/kg/day males was related to the 

significantly increased absolute and relative liver weight observed in this 

group. 

There were 3/12 female control rats, and nearly all treated female rats with 

a similar microscopic hepatic effect. In addition to the aforementioned 

microscopic liver change in the various groups, another observation 

characterized by individual hepatocytes with vacuolated cytoplasm, 

suggestive of fatty change, was noted. The fatty change generally involved 

either the left or right lateral lobe most extensively. In no case was the 

middle lobe the most severely involved. In rats with a grade 2 or 3 

involvement of hepatocytes with fatty change, the effect extended from the 

periportal region to the midzone of the lobule. Even in the most severely 

affected livers of either sex, the hepatocytes surrounding the central vein 

were microscopically normal. The fatty change in livers of 1000 mg/kg/day 

males was observed at a higher frequency and severity when compared to 

lower dose groups and their respective control group. In the female rats of 

all treated groups, the incidence and severity of hepatic fatty change was 
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increased compared to their respective controls. 

In the female rats of all treated groups, the incidence and severity of 

hepatocellular fatty change was increased compared to their respective 

controls. The number of female rats in the 100 and 300 mg/kg/day groups 

was more frequently affected with a grade 2 and 3 hepatocellular fatty 

change in the 1000 mg/kg/day group. This may be due to the fact no litters 

were being nursed in the highest dose group. A clear dose response for 

the hepatic effect was not present in female 100 and 300 mg/kg/day 

groups. The preferential involvement of the left and right lateral lobes 

verses the middle lobe, in hepatocellular fatty change, may be due to 

normal variation in portal blood flow and/or normal variation in metabolic 

enzymes involved in lipid and triglyceride metabolism. The 

microvacuolization and the fatty change in hepatocytes of even the most 

severely affected rats were not associated with evidence of increased 

hepatocellular necrosis or death. The observed microscopic hepatic 

effects were interpreted as reversible.

In the 1000 mg/kg/day male rats the microscopic liver effects observed 

were associated with increased absolute and relative liver weights. 

However, in the female rat livers of all dose levels were affected, despite 

the absence of an increased liver weight in this sex. 

The microscopic hepatic fatty change was noted in essentially all 1000 

mg/kg/day males and all treated groups of females; because a low 

incidence was observed in controls of both sex, and low and middle dose 

males, it may represent normal variation associated with fasting. The 

microscopic vacuolization in the periportal hepatocytes seen in various 

groups of rats of both sexes may also be partially attributable to a variable 

degree of fasting prior to necropsy. The normal activity of coprophagy in 

the rat could also contribute to periportal hepatocellular vacuolization. 

Therefore, greater amounts of glycogen would still remain in the periportal 

hepatocytes. Whether the effects within the livers of male and female rats 

can be totally attributed to indirect nutritional effects is uncertain. It is likely 

that the response in the liver was due to nutritional considerations and the 

test chemical. The presence of the test chemical in their feed likely 

accentuated this effect in high dose males, and all dose group of females, 

with subsequent fatty change also being observed. 

An alternative explanation for the observed liver fatty change is related to 

the known potential of a number of aliphatic alcoholic amines to cause a 

deficiency in the nutrient choline in rats and mice. AMP has been shown to 

disrupt phospholipid synthesis (Cosmetic Ingredient Review, 1990). As 

reviewed by Zeisel et al. (1995), choline requirements of pregnant rats in 

particular are substantially increased as the developing fetus is dependent 

upon maternal supplies of choline. The latter would explain the observed 

sensitivity of pregnant females to the liver fatty change relative to males. 

AMP-induced choline deficiency may also have accounted for the 

increased incidence of fetal resorbtions in the present study consistent with 

findings of resorptions in mice fed choline-deficient diets.

There were no histopathological lesions per se in the uterus. However, in 

light of the aforementioned effect on post-implantation loss, four sections of 

uterus were microscopically examined from each female rat to ascertain 

the presence of one or more implantation sites. In the control, low, and 

middle dose animals which delivered a litter, the uterus contained small 

numbers of individual pigment laden macophages within the deep layer of 

the endometrial stroma and the myometrium, with a large aggregation of 

these pigmented cells in the myometrium associated with the mesometrial 

attachment. This is the normal appearance of a post-partum uterus. In the 

remaining middle and high-dose females which had totally resorbed litters, 

the uteri did not have the typical microscopic findings of an implantation 

site usually located in the region of the myometrium associated with the 

mesometrial attachment. However, a clearly recognizable change was 
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present in the endometrium likely associated with a previous implantation. 

Immediately beneath the uterine mucosa, within the endometrial stroma, 

there were increased numbers of pigment laden macrophages. In five 

high-dose females, the pregnancies were detected by microscopic 

examination of the uterus. Overall, the microscopic uterine findings in rats 

that did not litter were consistent with embryonic death and subsequent 

resorption. 

Normal estrous cyclic activity in all the control and all treated female rats 

was observed microscopically in the tissues examined. Microscopic 

findings in the tissues examined from the adults did not reveal a likely 

mechanism for the observed effects on post-implantation loss. However, 

the fatty changes in the liver of all dose levels of female rats and the 1000 

mg/kg/day males does suggest a possible effect on normal lipid and 

triglyceride metabolism. Whether similar effects may have been present in 

tissues of the rapidly developing fetus or involved in the normal formation 

of the placenta to maintain pregnancy was not determined in this study. 

Certainly the normal metabolism of lipids and triglycerides is a critical 

function for cellular membrane synthesis, and could have affected fetal 

viability. Endocrine glands were not microscopically examined in this study 

to determine whether a morphologic change was present.

Male reproductive organs and their accessory sex glands were unaffected 

by treatment. The microscopic observations in tissues other than liver and 

uterus, were not interpreted to be due to treatment with the test chemical.

Conclusion : Dietary exposure of male rats to 1000 mg/kg/day of AMP caused increases 

in absolute and relative liver weights, accompanied by a very slight degree 

of microvacuolization of periportal hepatocytes, with or without 

vacuolization of hepatocytes consistent with fatty change. Females in all 

treatment groups exhibited similar histopathological changes in the liver, 

but in the absence of an organ weight change. Absolute and relative 

kidney weights were increased in the 1000 mg/kg/day males, but these 

were not considered toxicologically significant due to the absence of 

histopathological changes. AMP had no effect on mating performance or 

conception, but caused marked, dose-related increases in postimplantation loss (embryo resorption). At the high dose level, all 12 

pregnant females showed evidence of complete litter resorption (100% 

post-implantation loss), while at 300 mg/kg/day, post-implantation loss was 

70% (vs. 10% in controls). Effects associated with, or secondary to the 

post-implantation loss increase at 300 mg/kg/day included decreased litter 

size, increased pup body weight, and decreased gestation body weight and 

body weight gain. There were no treatment related effects on reproductive 

performance in the 100 mg/kg/day group.

The no-observed effect level (NOEL) for general toxicity in males was 300 

mg/kg/day, while the general toxicity NOEL for females could not be

determined, based upon the presence of very slight microscopic liver 

effects. The NOEL for reproductive effects was considered to be 100 

mg/kg/day.

Reliability : (1) valid without restriction

1 (GLP, guideline study)

Flag : Critical study for SIDS endpoint

18.09.2006 (44)

5.8.2 DEVELOPMENTAL TOXICITY/TERATOGENICITY

Species : rat

Sex : female

Strain : other: CRL:CD(SD)

Route of admin. : dermal

Exposure period : Gestation Day 6-20
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Frequency of treatm. : 6 hours per day

Duration of test : 15 days

Doses : 0, 30, 100, 300 mg/kg/day

Control group : yes, concurrent vehicle

NOAEL maternal tox. : = 100 

other: NOEL 

(developmental tox)

: = 300 

Method : OECD Guide-line 414 "Teratogenicity"

Year : 2006

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : Groups of 26 time-mated female Crl:CD(SD) rats were administered AMP 

once daily by the dermal route at dose levels of 0, 30, 100, or 300 

mg/kg/day for approximately 

6 hours from GD 6-20. Dose solutions were prepared in deionized water at 

concentrations of 30, 100, and 

300 mg/ml and pH adjusted to approximately 9.5 with HCl. The solutions 

were administered at a dose volume of 1 ml/kg body weight in order to 

achieve the targeted dose levels. Dose volumes were adjusted daily based 

on individual body weights. Dose solutions were prepared weekly during 

the course of the study. Homogeneity and stability were determined prior 

to study initiation, and concentration of the dose suspensions was 

determined from the first mix.

Time-mated female rats were obtained from a commercial supplier. 

Sexually mature adult rats were 10-11 weeks of age and weighed 

approximately 200-250 grams at study start.

Each animal was evaluated by the laboratory veterinarian to determine the 

general health status and acceptability for study purposes upon arrival at 

the laboratory. Rats were housed one per cage in stainless steel cages, in 

rooms designed to maintain adequate conditions (temperature, humidity, 

and photocycle) and acclimated for at least three days. Prior to dosing 

animals were acclimated to the wrapping material for approximately 2, 4, 

and 6 hours on GD 3, 4, and 5, respectively.

Animals were housed one per cage in stainless steel cages in rooms 

designed to maintain adequate environmental conditions for the species. 

Animals were provided feed and municipal water ad libitum. Rats were 

stratified by GD 0 body weight and then randomly assigned to treatment 

groups using a computer program designed to increase the probability of 

uniform mean group weights and standard deviations at the start of the 

study. Animals that were placed on study were uniquely identified via 

subcutaneously implanted transponders (BioMedic Data Systems, Seaford, 

Delaware) that were correlated to unique alphanumeric identification 

numbers. 

Sexually mature, adult virgin females were naturally mated with males of 

the same strain at the supplier's facility. Females were checked for in situ 

copulation plugs the following morning and those found with such a plug 

were removed from the males' cages. The day on which a vaginal plug 

was detected was considered GD 0. GD 0 body weights were provided by 

the supplier, and maintained in the study record. Rats arrived in the testing 

laboratory on GD 1 or 2.

A cage-side examination was conducted twice daily, at approximately the 

same time each day to detect significant clinical abnormalities that were 

clearly visible upon a limited examination, and used to monitor the general 

health of the animals. The animals were not hand-held for these 

observations unless deemed necessary. In addition, all animals were 

observed for morbidity, mortality, and the availability of feed and water at 

least twice daily. 
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Following removal of the wrapping material at the end of each daily sixhour exposure period, the test sites were graded for erythema, edema, 

scaling, and fissuring. 

Body weights were recorded on GD 0 by the supplier, and daily during the 

dosing period, and at necropsy (GD 21). 

Feed consumption were measured and statistically analyzed for the 

following intervals: GD 3-6, 6-9, 9-12, 12-15, 15-18, and 18-21. 

On GD 21, all surviving females (not fasted) were euthanized by carbon 

dioxide inhalation and a limited gross pathologic examination (necropsy) 

was performed. The sequence of the maternal necropsies was 

counterbalanced across groups (e.g., control, high, middle, low) to control 

for potential confounding influences of timing on fetal growth and skeletal 

ossification. The maternal necropsy included an examination of the 

external tissues and all orifices. The stomach, liver, and kidneys were 

dissected from the carcass and were incised. Any obvious gross 

pathologic alterations were recorded, and the weight of the liver, kidneys, 

and gravid uterus were recorded. The ratios of liver and kidney weights to 

terminal body weight were calculated. Representative sections of liver, 

kidneys, and gross lesions were preserved in neutral, phosphate-buffered 

10% formalin. Microscopic examination of tissues was not conducted. 

A detailed examination of the reproductive tract was performed and the 

number and position of implantations, viable fetuses, dead fetuses, and 

resorptions were recorded. Resorptions were classified as either "early" or 

"late" based on the presence (late resorption) or absence (early resorption) 

of grossly recognizable embryonic/fetal form, while a "dead fetus" would 

indicate a very recent death as evidenced by a lack external degenerative 

changes. For females with one or more viable fetuses, the number of 

ovarian corpora lutea were counted. The uteri of females lacking visible 

implantations were stained with a 10% aqueous solution of sodium sulfide 

(Kopf et al., 1964) and examined for evidence of early resorptions in order 

to verify pregnancy status. 

The sex of all fetuses was determined and the body weight of all viable 

fetuses recorded. All fetuses were given an external examination that 

included observations on body proportions, the head and face (including 

closure of the palate), abdomen, spine, extremities, genitalia, rectum, and 

tail. At least one half of all the fetuses in each litter were chosen randomly 

via computer for visceral examination conducted by dissection under a low 

power stereomicroscope for evidence of visceral alterations. The visceral 

examination included observation of the thymus, trachea, esophagus, 

lungs, great vessels, heart (external and internal), liver, gastrointestinal 

tract, pancreas, spleen, kidney (sectioned), adrenal glands, ureters, 

bladder, and reproductive organs. The heads of these fetuses were 

removed, placed in Bouin's fixative and serially sectioned to allow for 

inspection of the eyes, brain, nasal passages and tongue. The remaining 

fetuses not selected for visceral examination were then skinned, 

eviscerated, preserved in alcohol and double stained with Alcian Blue and 

Alizarin Red S for cartilage and bone. After staining, skeletons were 

macerated and cleared. A thorough evaluation of the fetal skeleton was 

conducted on the remaining fetuses not selected for visceral examination. 

All fetal alterations were classified as a variation or malformation. A 

variation is defined as a divergence beyond the normal range of structural 

constitution that may not adversely affect survival or health. A 

malformation is defined as a permanent structural change that may 

adversely affect survival, development or function and/or which occurs at a 

relatively low incidence in the specific species/strain. The fetal 

examinations were conducted such that investigators were blind to 

treatment group assignment.
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Toxicokinetic Subgroup

The first four presumed pregnant females from each dose group were 

selected for blood collection to evaluate systemic exposure following 

dermal administration of AMP. On the last day of dosing (GD20), following 

approximately three hours of dermal exposure, the designated animals 

were anesthetized using isoflurane and blood was collected from the orbital 

sinus. Approximately 0.5 ml of blood from each animal was collected into 

heparinized tubes. The samples were submitted to the analytical chemistry 

department for analysis and were stored frozen at approximately -80 C. 

AMP present in the blood was derivatized with pentafluorobenzoyl chloride 

under basic conditions and extracted in toluene. Quantitation was 

performed utilizing an isotopically labeled internal standard (D6-AMP) and 

matrix standards prepared in control blood. The limit of quantitation was 15 

ng/g blood AMP.

STATISTICS AND CALCULATIONS

Maternal body weights, maternal body weight gains, organ weights 

(absolute and relative), fetal body weights, and feed consumption were 

evaluated by Bartlett's test (alpha = 0.01; Winer, 1971) for equality of 

variances. Based on the outcome of Bartlett's test, a parametric (Steel and 

Torrie, 1960) or nonparametric (Hollander and Wolfe, 1973) analysis of 

variance (ANOVA) was performed. If the ANOVA was significant at alpha 

= 0.05, analysis by Dunnett's test (alpha = 0.05; Winer, 1971) or the 

Wilcoxon Rank-Sum test (alpha = 0.05; Hollander and Wolfe, 1973) with 

Bonferroni's correction (Miller, 1966) were performed, respectively. Feed 

consumption values were excluded from analysis if the feed was spilled or 

scratched. 

Frequency of pre- and post-implantation loss (calculations shown below), 

and fetal alterations were analyzed using a censored Wilcoxon test 

(Haseman and Hoel, 1974) with Bonferroni's correction. The number of 

corpora lutea, implantations, and litter size were evaluated using a 

nonparametric ANOVA (alpha = 0.05) followed by the Wilcoxon Rank-Sum 

test (alpha = 0.05) with Bonferroni's correction. Pregnancy rates were 

analyzed using the Fisher exact probability test (alpha = 0.05; Siegel, 

1956) with Bonferroni's correction. Fetal sex ratios were analyzed using a 

binomial distribution test. Females lacking visible implantations at the 

scheduled necropsy were excluded from the appropriate analyses. 

Statistical outliers were identified, using a sequential method (alpha = 0.02; 

Grubbs, 1969), and if excluded, were excluded for sound scientific reasons. 

Both Dunnett's test and Bonferroni's correction correct for multiple 

comparisons to the control group to keep the experiment-wise alpha at 

0.05. Both were reported at the experiment-wise alpha level.

Because numerous measurements were statistically compared in the same 

group of animals, the overall false positive rate (Type I errors) was greater 

than the nominal alpha levels. Therefore, the final interpretation of the data 

will consider statistical analyses along with other factors, such as doseresponse relationships and whether the results are consistent with other 

biological and pathological findings and historical control values.

Remark : Test material was utilized at a pH of approximately 9.5, reflecting the 

highest pH of most personal care and industrial formulations containing 

AMP. The test material represents an equilibrium between the HCl salt of 

AMP and the nonionized base ("AMP-base"). As AMP-base is expected to 

be the primary form absorbed by skin, the test material in this study reflects 

the form of the material resulting in maximal exposure of humans from 

dermal contact with an AMP-containing product.

Result : In-Life Observations

Examinations performed on all animals during the course of the study 

revealed no treatment-related clinical findings. Dermal grading of the test 

site revealed a pattern of localized effects most pronounced in the 300 

mg/kg/day dose group. The 300 mg/kg/day females showed significant 

dermal effects during the grading period, as compared to the other 
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treatment groups. One 300 mg/kg/day female was found with very slight 

edema from GD 9-13. This finding was not observed in any other dose 

group. Almost all of the 300 mg/kg/day females (92%) were observed with 

slight scaling, with nine animals (36%) progressing to moderate to severe 

scaling during the last half of the dosing period. One, two, and seven 

females at 0, 30, and 100 mg/kg/day, respectively, were also found with 

slight scaling, but this was not considered adverse, as the incidence was 

relatively low, as compared to the 300 mg/kg/day group and the finding 

resolved prior to necropsy in three of the seven 100 mg/kg/day animals. In 

addition, no animals at the 30 and 100 mg/kg/day groups showed any 

signs of moderate to severe scaling. Scabbing was mainly observed at the 

300 mg/kg/day dose level. Twenty 300 mg/kg/day females (77%) were 

noted with scabs at up to 25% of the test site. Over time, these the scabs 

progressed to include ever increasing areas of the test site, with one 

animal showing scabs covering most of the test site for the last week of 

dosing. The initial occurrence of scabbing varied considerably among the 

females, but there was a tendency for animals showing the greatest 

amount of scabs to have developed these lesions earlier. With the 

exception of one control animal, no other females were observed with any 

scabbing. 

Overall, the dermal grading procedures revealed a treatment-related effect 

at the high-dose level of 300 mg/kg/day. The slight, transient scaling seen 

at lower dose levels was not considered to be toxicologically significant.

Body Weights/Body Weight Gains

There were no statistically identified differences in the mean gestation body 

weight for females at any dose level. 

Feed consumption was increased at 100 mg/kg/day during GD 3-9 interval. 

These statistically identified parameters were not considered treatment 

related, but attributed to relatively low control values.

There were no statistically identified differences in mean terminal body 

weight, mean liver and kidney weights, or relative liver and kidney to body 

weight ratios in the treatment groups, as compared to the control. Gross 

pathological findings were spurious in nature and not attributed to 

treatment.

There were no significant treatment related effects on pregnancy rate, litter 

size, numbers of corpora lutea or implantations, percent preimplantation 

loss, fetal sex ratios, fetal body weights, or gravid uterine weights at any 

dose level. Mean percent postimplantation loss was statistically decreased 

in the 300 mg/kg/day group, but this was not considered to be test articlerelated, as the value was lower than seen in the control group. One female 

in the 30 mg/kg/day group was found to be non-pregnant, as confirmed by 

ammonium sulfide staining.

There were no statistically significant differences in the incidence of any 

fetal alteration (malformation or variation) in any of the treated groups, as 

compared to the control. There were no external fetal alternations 

observed. Any reported findings were sporadic in nature, and were not 

considered toxicologically relevant or treatment related. 

Toxicokinetic Subgroup

Blood samples were obtained from four presumed pregnant females on the 

last day of dosing following approximately three hours of dermal 

application. The results indicate dermal absorption of AMP in a doseresponsive manner. The disproportionately higher mean blood 

concentration of AMP at 300 mg/kg/day may have been the result of a 

compromised skin barrier, as evidenced by significant dermal effects 

(scabbing and scaling) at the test site for that group. At this dose level, one 

female (animal # 7169) was noted with a blood value approximately three 

times that of the others. The increase in the blood value for this animal is 
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likely the result of a greater degree of compromise to the skin barrier, as 

evidenced by a greater degree of scabbing (up to 50%) at the test site on 

the day of blood collection, as compared to the other animals in the group.

Conclusion : Dermal administration of 300 mg/kg/day of AMP produced significant 

effects at the test site, as evidenced by scabbing (77% affected) and 

moderate to severe scaling (35% affected). The dermal finding of slight 

scaling at 30 and 100 mg/kg/day was not considered adverse, as the 

observation was transient in nature and relatively low in incidence. There 

was no evidence of test article related systemic maternal or developmental 

toxicity at any dose level tested. Under the conditions of this study, the 

NOAEL for maternal toxicity based on dermal effects was 100 mg/kg/day. 

The NOEL for developmental toxicity was 300 mg/kg/day, the highest dose 

level tested. Analyses of blood samples confirmed systemic exposure to 

AMP in a dose-responsive manner, although the study was not designed to 

quantify percent absorption.

Reliability : (1) valid without restriction

1 (GLP, guideline study)

Flag : Critical study for SIDS endpoint

07.09.2006 (45)

Species : rat

Sex : female

Strain : Sprague-Dawley

Route of admin. : dermal

Exposure period : GD 6-20

Frequency of treatm. : daily

Duration of test : 6 hours per day

Doses : 0, 100, 300 or 400 mg/kg/day

Control group : yes, concurrent vehicle

Method :

Year : 2005

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : The purpose of this study was to make a preliminary evaluation of the 

maternal toxicity and embryo/fetal lethality potential of 2-methyl-2-

aminopropanol hydrochloride (AMP-HCl) in Crl:CD(SD) rats following 

repeated dermal administration. Groups of eight time-mated female rats 

received AMP-HCl by occluded dermal application, six hours/day at 

targeted dose levels of 0, 100, 300 or 400 mg/kg/day on gestation days 

(GD) 6-20. In-life parameters evaluated for all groups included clinical 

observations, body weight, body weight gain, feed consumption, and 

dermal grading of the test site. Blood samples were collected 

approximately three hours after dermal application, from 2-3 rats/group on 

GD 20 to evaluate dermal absorption of AMP-HCl. On GD 21, all surviving 

rats were euthanized and examined for gross pathologic alterations. Liver 

and kidney weights, the number of corpora lutea, implantations, 

resorptions, and live/dead fetuses were recorded.

Result : Dermal administration of AMP-HCl at dose levels of 100, 300 and 400 

mg/kg/day resulted in no maternal toxicity and no indication of adverse 

embryo/fetal effects. Administration of the test material by the dermal route 

was well tolerated by all animals, without significant adverse dermal 

effects. Analyses of blood samples taken on the last day of dosing 

indicated a dose-responsive increase in systemic exposure, although the 

study was not designed to quantify percent absorption. Based on these 

results, the no-observed-effect level (NOEL) for maternal and embryo/fetal 

development was 

400 mg/kg/day, which was the highest dose level tested. 

As no significant adverse dermal effects were noted in the developmental 

toxicity probe study, a two-week dermal follow-up study using male and 

non-pregnant female rats was initiated (Phase II). Solubility issues were 

encountered with AMP-HCl when it was prepared again using the 
5. Toxicity Id 124-68-5

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hydrochloride salt. As a result, the base form of AMP was used in the 

prepration of the dose formulations for this study, and this alleviated the 

difficulties with solubility. AMP base (pH 9.5) at 300, 400 and 500 

mg/kg/day was administered once daily, by the dermal route to the 

animals. Significant adverse dermal effects (scabbing, redness, 

tenderness to touch) were noted at the two highest dose levels (400 and 

500 mg/kg/day) after a few days of dosing. This resulted in the immediate 

termination of treatment to these two dose groups. However, the low-dose 

of 300 mg/kg/day showed only slight dermal effects after 11 days of dosing 

and was, therefore, used as the high-dose level for the definitive 

developmental toxicity study.

Based on the results obtained from this follow-up work and the 

developmental toxicity probe study, dose levels of 0, 30, 100, or 300 

mg/kg/day of AMP base were selected for a definitive dermal 

developmental toxicity study in rats.

Reliability : (1) valid without restriction

1 (GLP study of acceptable quality with documentation sufficient for 

assessment)

07.09.2006 (46)

5.8.3 TOXICITY TO REPRODUCTION, OTHER STUDIES

Type : other: dietary toxicity

In vitro/in vivo : In vivo

Species : dog

Sex : male/female

Strain : Beagle

Route of admin. : oral feed

Exposure period : 1 year

Frequency of treatm. : continuous

Duration of test :

Doses : 0, 1.1, 11.0, 110.0 ppm

Control group : yes, concurrent vehicle

Result : No effect on reproductive organs

Method :

Year : 1990

GLP :

Test substance : as prescribed by 1.1 - 1.4

Result : There were no general in-life observations made for any treated or control 

animal. There is no statistically significant differences in body weights for 

any of the animals throughout the study. 

There were no effects on organ weights or organ/body weight ratios that 

were attributed to test material administration by the authors. Reproductive 

organs that were examined included: testes, ovaries, and uteri.

At necropsy, evaluation of the tissues revealed isolated observations, none 

of which were attributed to the administration of the test material. There 

were no neoplastic observations in any of the dogs sacrificed at either 6 

months or one year of administration in their diets.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (33)

Type : other: dietary toxicity

In vitro/in vivo : In vivo

Species : dog

Sex : male/female
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Strain : Beagle

Route of admin. : oral feed

Exposure period : 90 days

Frequency of treatm. : continuous

Duration of test : 90 days

Doses :

Control group :

Method :

Year : 1981

GLP :

Test substance : as prescribed by 1.1 - 1.4

Result : Physical Observations

Included emesis, loose stool, alopecia, and slight penile or vaginal 

discharge. These findings occurred sporadically in the control and/or 

treated animals and are not considered by the authors to be treatmentrelated.

Urinalysis

There is no evidence of a compound-related effect on any of the urinalysis 

parameters studied.

Reproductive organs evaluated: Testes (without epididimus), ovaries, and 

uterus.

Organ Weight/ Organ:Body Weight Ratios

Organ weight and organ/body weight differences were marginal and 

appear unrelated to the administration of the test material.

Pathology

There were no observations noted in any reproductive organ upon gross 

and microscopic evaluation.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (39)

Type : other: dietary toxicity

In vitro/in vivo : In vivo

Species : rat

Sex : male/female

Strain : other: CD

Route of admin. : oral feed

Exposure period : 8 weeks

Frequency of treatm. : continuous

Duration of test : 8 weeks

Doses : 1000, 2000, 4000, 8000, 16000 ppm

Control group : yes, concurrent vehicle

Method :

Year : 1976

GLP :

Test substance : as prescribed by 1.1 - 1.4

Result : Rats in the 16000ppm group gained slightly less weight as compared to 

control rats. Gains in the other dose groups were similar to the control. 

Food consumption patterns were similar for all animals. 

At necropsy, all 16000ppm surviving rats, and all rats at the 8000ppm dose 

level were necropsied. Two males and two females from each of the other 

groups were also examined. Alopecia and focal skin erosions and 

ulcerations found in rats at the 16000ppm dose level were viewed as 

possibly compound related. Hepatocyte vacuolation descrived in rats from 
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all the treated groups, with increasing severity at the higher dose levels, 

was considered compound related. Microscopic skin lesions found at the 

16000ppm dose level, like the corresponding gross lesions, were viewed 

as possibly compound related.

There were no gross or microscopic observations noted in epididimus, 

uteri, ovaries, or testes.

Reliability : (2) valid with restrictions

2e

01.06.2006 (34)

5.9 SPECIFIC INVESTIGATIONS

Endpoint : Mechanistic Studies

Study descr. in chapter :

Reference :

Type : other: In vitro using Chinese hamster ovary cells

Species :

Sex :

Strain :

Route of admin. :

No. of animals :

Vehicle :

Exposure period :

Frequency of treatm. :

Doses : 0.8, 4, 8, 16, 24, and 32 mM (100, 500, 1000, 2000, 3000, and 4000 mg/L, 

respectively) in the first Trial and 0.8, 4, 8, 16, 32, 48, and 80 mM (100, 

500, 1000, 2000, 4000, 6000, and 10000 mg/L, respectively) in the second 

trial

Control group :

Observation period :

Result :

Method :

Year : 2006

GLP :

Test substance : as prescribed by 1.1 - 1.4

Method : The potential of AMP·HCl to inhibit the uptake of the essential nutrient 

choline in cultured mammalian cells was determined. Effects of AMP upon 

choline uptake by CHO cells were evaluated in actively growing cultures 

exposed to 3H-choline and a range of concentrations of AMP·HCl (0-32 

mM; 0-4000 mg/L) for approximately 

10 minutes. Concentrations of AMP·HCl used were based upon the results 

of a cytotoxicity assay and encompassed concentrations ranging from 

nontoxic to moderately toxic following 48 hours exposure. The pH of all 

dosing solutions was adjusted to that of the culture medium. Following 

treatment, cells were harvested, washed and lysed. The protein 

concentration of the lysate and 3H content were determined. Choline 

uptake as 3H activity was calculated on a per mg protein basis and treated 

and control data were compared statistically. In addition, the approximate 

effective concentration eliciting a 50% inhibition of uptake (EC50) was 

calculated and compared with that of several other alcohol amines.

Descriptive statistics (means and standard deviations) for choline uptake 

were reported as total 3H counts per mg protein. Control and treated 

values for choline uptake were evaluated by Bartlett's test (alpha=0.01; 

Winer, 1971) for equality of variances. Exploratory data analysis was 

performed by a parametric analysis of variance (ANOVA) (alpha=0.05; 

Steel and Torrie, 1960) and followed, if significant, by Dunnett's test 

(alpha=0.05; Winer, 1971). Dunnett's test corrects for multiple 
5. Toxicity Id 124-68-5

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comparisons to the control and the experiment-wise alpha level was 

reported. Statistical outliers were identified by a sequential test 

(alpha=0.02; Grubbs, 1969).

Result : A dose-response in cell viability versus concentration of AMP·HCl was 

observed in both toxicity trials. Survival relative to untreated controls 

ranged from 100+% to 61-68% over a concentration range of 0.04-32 mM. 

A 29% and 5.5% survival was noted at 48 and 80 mM, respectively, in trial 

II. The positive control consisting of 5% ethanol resulted in a survival of 

only 28-36% of untreated controls in both trials. No effects upon pH or 

osmolarity of the treated cultures were observed. Based upon these 

findings, a concentration range of 0.4 to 32 mM AMP·HCl was evaluated 

for effects upon 3H-choline uptake by CHO cells.

Uptake of 3H-Choline

There were no significant differences in protein content between treated 

and control cultures indicating no significant loss of cells in the 10-minute 

dosing period, including the high dose which resulted in cell numbers 61-

68% of controls following 48 hours treatment. AMP·HCl was found to 

cause a dose-related decrease in 3H-choline uptake over the 40 to 80 fold 

concentration ranges examined; 0.8-32 mM in Choline Trial I and 0.4-32 

mM in Choline Trial II. A statistically significant decrease in the uptake of 

3H -choline was achieved at concentrations of 4 mM (65-81% of control) to 

32 mM (30-36% of control) in both Trials. AMP·HCl appears to be a 

relative weak inhibitor of choline uptake in vitro with an approximate EC50 

of 8.71-14.79 mM. It is approximately 10-17 fold less active than 

triethanolamine (EC50 ~0.89 mM), approximately 17-28 fold less active 

than diisopropanolamine (EC50 ~0.52 mM), and approximately 44-74 fold 

less active than diethanolamine (EC50 ~0.20 mM) in the same CHO cell 

based in vitro assay.

Conclusion : It was concluded that AMP·HCl has the potential to inhibit uptake of the 

essential nutrient choline in cultured CHO cells in the absence of significant 

toxicity. This activity, however, is relatively weak when compared to 

several other alcohol amines under similar assay conditions.

Reliability : (1) valid without restriction

1 (meets generally accepted scientific standards and is described in 

sufficient detail)

02.06.2006 (47)

Endpoint : Mechanistic Studies

Study descr. in chapter :

Reference :

Type : other: in vivo

Species : rat

Sex : female

Strain : Sprague-Dawley

Route of admin. : dietary

No. of animals :

Method :

Year : 2006

GLP : yes

Test substance : as prescribed by 1.1 - 1.4

Method : The potential of dietary HCl salt of 2-amino-2-methyl-1-propanol (AMP-HCl) 

to depress hepatocellular levels of the essential nutrient choline in pregnant 

rats was evaluated. Two groups of 6 female Crl:CD(SD) rats each were 

fed diets containing 0 (control) or 300 mg/kg/day of AMP-HCl for 

approximately two weeks prior to breeding, continuing throughout breeding 

(up to two weeks), and two weeks into gestation (GD 0-13). Clinical 

observation, body weight, and feed consumption data were collected. On 

GD 14, the females were euthanized and samples of liver were excised 

and frozen in liquid nitrogen or saved in 10% formalin. Uteri were 

examined and the number of live implants and resorptions were 
5. Toxicity Id 124-68-5

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determined. Formalin fixed liver underwent histopathological examination 

following standard hematoxylin and eosin staining and osmium tetroxide 

treatment for identification of lipid. Frozen liver was analyzed for levels of 

choline (Cho), betaine, glycerophosphocholine (GPCho), phosphocholine 

(PCho), phosphatidyl choline (PtdCho), and sphingomyelin (SM).

Result : Dietary administration of 300 mg/kg/day of AMP-HCl resulted in no adverse 

clinical observations, mean body weight, or feed consumption effects. 

However, AMP-HCl ingestion caused an increased postimplantation loss 

(67.0% in treated versus 7.4% in control rats), and a slight increase in 

hepatic lipid vacuolation relative to controls. These changes to varying 

degrees, correlated with an approximately 20-25% statistically identified 

decrease in hepatic levels of PCho which is the primary storage pool of 

choline. Levels of GPCho, indicative of conversion of PtdCho to Cho, were 

elevated 2-3 fold relative to control dams. Hepatic levels of remaining 

metabolites were either unchanged or minimally changed relative to 

controls.

Conclusion : The results of this study, when combined with the known choline 

depression caused by pregnancy, suggest that previous findings of lipid 

accumulation and elevated resorptions in an OECD-421 study of AMP-HCl 

in rats (Carney et al., 2005) may be a consequence of, and secondary to, 

PCho deficiency, respectively.

Reliability : (1) valid without restriction

1 (GLP study, based in part on standard test methods, well-documented 

and acceptable for assessment)

16.10.2006 (48)

5.10 EXPOSURE EXPERIENCE

Type of experience : Human

Method : Skin prick tests and patch tests with the test material and common inhalant 

allergens were performed on all subjects. AMP-100 was dissolved in both 

water and ethyl alcohol separately at 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20%. 

Patch tests were applied on the back and read at 48 and 72 hours. 

Positive results were recorded for erythema, oedema, and blisters.

Result : The prick and patch tests were all negative except for one positive reaction 

to Dermatophagoides pteronyssinus in a worker on a different production 

line. All patch tests carried out with substances used in the production line 

proved negative except for AMP-100 at 10% and 20% dilutions in water 

and ethyl alcohol. All positive results manifested as erythema with oedema 

without blistering. 

Positive results at 10% and 20% may be considered as irritative responses. 

There was lack of response to the lower doses (that would have been 

considered allergenic responses) noted in both the asymptomatic and 

symptomatic subjects.

Test condition : Two cases of airborne contact dermititis were noted in a cosmetic company 

during the hair dye production using AMP-100. Subjects suffered for 

months from periorbital oedema and facial erythema which worsened 

during work hours and improved with time away from work. Eight 

additional asymptomatic workers from the same company were studied 

concurrently.

Conclusion : The authors conclude that under these conditions, AMP-100 causes 

airborne irritative contact dermatitis, favored in this study by elevated 

production temperatures and high ambient humidity.

Reliability : (2) valid with restrictions

2 (meets generally accepted scientific standards, well-documented, and 

acceptable for assessment)

01.06.2006 (49)
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5.11 ADDITIONAL REMARKS
6. Analyt. Meth. for Detection and Identification Id 124-68-5

Date 30.11.2006

81 / 89

6.1 ANALYTICAL METHODS

6.2 DETECTION AND IDENTIFICATION
7. Eff. Against Target Org. and Intended Uses Id 124-68-5

Date 30.11.2006

82 / 89

7.1 FUNCTION

7.2 EFFECTS ON ORGANISMS TO BE CONTROLLED

7.3 ORGANISMS TO BE PROTECTED

7.4 USER

7.5 RESISTANCE
8. Meas. Nec. to Prot. Man, Animals, Environment Id 124-68-5

Date 30.11.2006

83 / 89

8.1 METHODS HANDLING AND STORING

8.2 FIRE GUIDANCE

8.3 EMERGENCY MEASURES

8.4 POSSIB. OF RENDERING SUBST. HARMLESS

8.5 WASTE MANAGEMENT

8.6 SIDE-EFFECTS DETECTION

8.7 SUBSTANCE REGISTERED AS DANGEROUS FOR GROUND WATER

8.8 REACTIVITY TOWARDS CONTAINER MATERIAL
9. References Id 124-68-5

Date 30.11.2006

84 / 89

(1) The Merck Index (Eleventh Edition). Merck & Co., INC. Rahway, NJ, USA. 1989.

(2) Budavari, S. (1989) The Merck Index (Eleventh Edition).

Merck & Co., INC. Rahway, NJ, USA.

Not GLP, Published

(3) Wilson, L., Morrison, R., and Olson, J. (2005) The Vapor Pressure of 2-amino-2-methyl-1-

propanol (AMP) at 20 Deg.C.

The Dow Chemical Company Report No: SC AL SC-2005-000140

Not GLP / Unpublished

(4) Howard, P.H. and Meylan, W.M. (1997) Handbook of Physical Proporties of Organic 

Chemicals. 

Environmental Sciences Center, Syracuse Research Corp. Lewis Publishers, New York, 

NY, USA.

Not GLP / Published

(5) Lhotak, H. (1996) Determination of Partition Coefficient Pow (Octanol/Water) According to 

OECD Method 107 of Six Angus Products. 

The Dow Chemical Company Report No: DR-0366-3498-013

Not GLP / Unpublished

(6) Howard, P.H. and Meylan, W.M. (1997) Handbook of Physical Proporties of Organic 

Chemicals. Environmental Sciences Center, Syracuse Research Corp. Lewis Publishers, 

New York, NY, USA.

Not GLP / Published

(7) Lewis, G.E. (1993) Determination of Basicity of 2-Amino-2-methyl-1-propanol (AMP+), 

Ethyl-1,3-Propanediol (AEPD+), 2-Amino-1-butanol, Tris(Hydroxymethyl)Animomethane, 

and 3-Amino-1,2-Propanediol. 

The Dow Chemical Company Report No: 933420 

Not GLP / Unpublished

(8) Littel et.al. (1990) Dissociation Constants of Some Alkanolamines at 293, 303, 318, and 

333K. 

J. Chem. Eng. Data 35:276-277.

Not GLP / Published

(9) Gonsior, S. (2006) Prediction of the Environmental Distribution and Transport Between 

Environmental Compartments for 2-amino-2-methyl-1-propanol Using Level I and Level III 

Fugacity Models. 

Report DR-0001-9476-004 of the Dow Chemical Company.

Not GLP / Unpublished

(10) Harris, G.W. and Pitts, J.N. (1983) Rates of Reaction of Hydroxyl Radicals with 2-

(Dimethylamino)ethanol and 2-Amino-2-methyl-1-propanol in the Gas Phase at 300+-2K.

Environ. Sci. Technol. 17:50-51.

Not GLP / Published

(11) Larson, R.A. and Weber, E.J. (1994) Reaction Mechanisms in Environmental Organic 

Chemistry. Lewis Publishers, CRC Press, INC., Boca Raton, FL, USA.

Not GLP / Published

(12) Freitag, D. and Korte, F. (1989) Investigations of the Ecotoxicological Behavior of AMP 

90, Tris Nitro, Amine CS-1246 and Alkaterge T. 

Technical University Munich, Department of Ecological Chemistry.

The Dow Chemical Company Report No: (not assigned)

Not GLP / Unpublished
9. References Id 124-68-5

Date 30.11.2006

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(13) Parekh, C. (1980) Acute Toxicity Effects of AMP-95 on Bluegill Sunfish, Ninety-six Hour 

LC50. 

Analytical Bio Chemistry Laboratories

The Dow Chemical Company Report No: DR-0309-4391-002

GLP / Unpublished

(14) Young, B.E. and Tapp, J.F. (1983). The Toxicity of AMP 95 to the brown shrimp (Crangon 

crangon) and plaice (Pleuronectes platessa).

Imperial Chemical Industries, PLC. 

The Dow Chemical Company Report No: DR-0309-4391-001

Not GLP / Unpublished

(15) Parekh, C. (1980) AMP-95 Acute Toxicity Effects on Daphnia, 48 Hr LC50. 

Analytical Bio Chemistry Laboratories

The Dow Chemical Company Report No: DR-0309-4391-003

GLP / Unpublished

(16) Young, B.E. and Tapp, J.F. (1983). The Toxicity of AMP 95 to the brown shrimp (Crangon 

crangon) and plaice (Pleuronectes platessa). 

Imperial Chemical Industries, PLC. 

The Dow Chemical Company Report No: DR-0309-4391-001

Not GLP / Unpublished

(17) Schafer, et.al. (1983) The Acute Oral Toxicity, Repellency, and Hazard Potential of 998 

Chemicals to One of More Species of Wild and Domestic Birds. 

Arch. Environ,. Contam. Toxicol. 12:355-382.

Not GLP / Published

(18) Bridges, R.G. and Ricketts, J. (1965). The Incorporation of 1-aminobutanols into the 

Phospholipids of Housefly (Musca domestica) Larvae. 

J. Insect Physiol. 11: 225.

Not GLP / Published

(19) Yue, K.T., Mulford, D.J., and Russell, P.J. (1970). The Metabolism of 2-Amino-2-

methylpropanol in Young Rats. 

The Department of Biochemistry, University of Kansas Medical Center, Kansas City, 

Kansas, USA. 

The Archives of Biochemistry and Biophysics (136:47-53).

Not GLP / Published

(20) Machle et.al. (1940) The Physiological Response of Animals to Some Simple 

Mononitroparaffins and to Certain Derivatives of These Compounds. 

Journal of Industrial Hygiene and Toxicology V22, No8 (315-332)

Not GLP / Published

(21) Hill Top Research (1955) Acute Toxicities of Amines.

Hill Top Research Co.

The Dow Chemical Company Report No: DR-0309-4391-015

Not GLP / Unpublished

(22) Commercial Solvents Corporation (1975) Bioassay Report, Pharmacology Laboratories 

Research and Development Number 8945.

Commercial Solvents Corporation

The Dow Chemical Company Report No: DR-0001-9476-006

Not GLP, Unpublished

(23) IMC (1976) P-1826

International Minerals Corporation

The Dow Chemical Company Report No: DR-0001-9476-005

Not GLP, Unpublished
9. References Id 124-68-5

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(24) Power, C. (1976) Acute Oral Toxicity of P-1826 (AMP) in the Rat. 

Pharmacology Laboratories, Animal Science Research

The Dow Chemical Company Report No: DR-0309-4391-014

Not GLP / Unpublished

(25) Parekh, C. (1980) Dermal Toxicity of P-1826 (AMP). 

Pharmacology Laboratories Animal Science Research

The Dow Chemical Company Report No: DR-0309-4391-011

GLP / Unpublished

(26) Kaltenbach, J.P., Ganote, C.E., and Carone, F.A. (1979) Renal Tubular Necrosis Induced 

by Compounds Structurally Related to D-Sterine. 

Experimental and Molecular Pathology, 30(2):209-214.

Not GLP / Published

(27) Power, C. (1975). AMP Regular and AMP-95- Eye Irritation Tests- Rabbits. 

Commercial Solvents Corporation 

The Dow Chemical Company Report No: DR-0.09-4391-013

Not GLP / Unpublished

(28) Sausaman, D. (1975) Skin and Eye Irritation Data for AMP, AMP-95, and AEPD.

The Dow Chemical Company Report No: DR-0309-4391-012

Not GLP / Unpublished

(29) Parekh, C. (1982) Topical Sensitization Potential of AMP (P-1826). 

Bio/dynamics, Inc.

The Dow Chemical Company Report No: DR-0309-4391-010

Not GLP / Unpublished

(30) Parekh, C. (1982) Intradermal Sensitization Potential of AMP (P-1826). 

Bio/dynamics, Inc.

The Dow Chemical Company Report No: DR-0309-4391-009

Not GLP / Unpublished

(31) Pittz, E. (1977) A 90-Day Safety Evaluation Study of 2-Amino-2-methyl-1-propanol (AMP) 

in Rats. 

The Institute of Comparative and Human Toxicology, Albany Medical College, Albany, NY.

The Dow Chemical Company Report No: DR-0309-4391-023

Not GLP / Unpublished

(32) Parekh, C. (1981) A Three Month In Diet Toxicity Study of 2-Amino-2-methyl-1-propanol in 

Dogs. 

Bio/dynamics, Inc.

The Dow Chemical Company Report No: DR-0309-4391-017

Not GLP / Unpublished

(33) Griffin, T. (1990) A One-Year Oral Toxicity Study of AMP in Dogs (Amended by the original 

author on April 20, 1993). 

Coulston Research Incorporated, Alamogordo, NM. 

The Dow Chemical Company Report No: DR-0309-4391-004

Not GLP (contains an audit certificate) / Unpublished

(34) Goldenthal, E. (1976) Eight Week Tolerance Study in Rats.

(conducting lab>>)

The Dow Chemical Company Report No: DR-0309-4391-022

Not GLP / Unpublished

(35) Goldenthal, E. (1976) Eight Week Tolerance Study in Mice. (conducting lab>>)

The Dow Chemical Company Report No: DR-0309-4391-018

Not GLP / Unpublished
9. References Id 124-68-5

Date 30.11.2006

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(36) Goldenthal, E. (1976) Twenty Eight Day Dietary Range Finding Study in Dogs. 

(conducting lab>>)

The Dow Chemical Company Report No: DR-0309-4391-020

Not GLP / Unpublished

(37) Pittz, E. (1977) A Study on the Toxic Effects of 2-amino-2-methyl-1-propanol in Rats and 

Monkeys. A report of the Institute of Comparative and Human Toxicology, Center of 

Experimental Pathology and Toxicology, Albany Medical College, Albany, NY.

(38) Detwiler-Okabayashi, K. and Shaper, M. (1996) Respiratory Effects of a Synthetic 

Metalworking Fluid and its Components. 

Arch. Toxicol. (1996) 70:195-201.

Not GLP / Published

(39) Parekh, C. (1981) A Three Month In Diet Toxicity Study of 2-Amino-2-methyl-1-propanol in 

Rats. 

Bio/dynamics Inc, East Millstone, NJ. 

The Dow Chemical Report No: DR-0309-4391-021

Not GLP / Unpublished

(40) Wagner, V. (1996) Salmonella/Escherichia Coli Plate Incorporation Mutagenicity Assay 

with a Confirmatory Assay.

Microbiological Associates, INC.

The Dow Chemical Company Report No: DR-0309-4391-008

GLP / Unpublished

(41) San, R. and Clark, J. (1997) In Vitro Mammalian Cell Gene Mutation Test with an 

Independent Repeat Assay.

Microbiological Associates, INC.

The Dow Chemical Company Report No: DR-0309-4391-005

GLP / Unpublished

(42) Baldwin, R. (1976) Mutagenicity Evaluation of P-1826 (AMP). 

Litton Bionetics, INC, 

The Dow Chemical Company Report No: DR-0309-4391-007

Not GLP / Unpublished

(43) Gudi, R. (1998) Mammalian Erythrocyte Micronucleus Test (2-amino-2-methyl-1-propanol). 

MA Bioservices, INC.

The Dow Chemical Company Report No: DR-0309-4391-006

GLP / Unpublished

(44) Carney, E.W., Quast, J.F., and Zablotny, C.L. (2005) 2-Methyl-2-Aminopropanol 

Hydrochloride: A Reproductive / Developmental Toxicity Screening Test in CD Rats. 

The Dow Chemical Company Report No: DR-0038-3186-001

GLP / Unpublished

(45) Carney, E.W. and Thorsrud, B. (2006) AMP: Dermal Developmental Toxicity Study in 

CRL:CD(SD) Rats. 

The Dow Chemical Company Report No: DR-0399-3940-001

GLP / Unpublished

(46) Carney, E.W., Tornesi, B., and Yano, B.L. (2005) AMP-HCl: Dermal Developmental 

Toxicity Probe Study in CD Rats.

The Dow Chemical Company Report No: 051051

GLP, Unpublished

(47) Stott, W.T. and Kan, H.L. (2006) 2-Methyl-2-aminopropanol (AMP): Effects Upon Choline 

Uptake in Chinese Hamster Ovary Cells.

The Dow Chemical Company Report No: DR-0038-3186-002

Not GLP / Unpublished
9. References Id 124-68-5

Date 30.11.2006

88 / 89

(48) Stott, W.T., Zablotny, C.L., and Thomas, J. (2006) Potential of AMP-HCl to Alter Hepatic 

Choline and Phospholipid Synthesis in Pregnant CRL:CD(SD) Rats When Administered by 

the Dietary Route.

The Dow Chemical Company Report No: 050541

GLP, Unpublished

(49) Cipolla et.al. (1997) Airborne Contact Dermatitis from 2-Amino-2-methyl-1-propanol in a 

Cosmetic Company. 

Arh. hig. rada. toksikol 48:205-209.

Not GLP / Published
10. Summary and Evaluation Id 124-68-5

Date 30.11.2006

89 / 89

10.1 END POINT SUMMARY

10.2 HAZARD SUMMARY

10.3 RISK ASSESSMENT