U.S. Environmental Protection Agency March 2012

Hazard Characterization Document

SCREENING-LEVEL HAZARD CHARACTERIZATION

OF HIGH PRODUCTION VOLUME CHEMICALS

2-Amino-2-methyl-1-propanol (AMP)

CASRN 124-68-5

The High Production Volume (HPV) Challenge Program1 was conceived as a voluntary initiative 

aimed at developing and making publicly available screening-level health and environmental 

effects information on chemicals manufactured in or imported into the United States in quantities 

greater than one million pounds per year. In the Challenge Program, producers and importers of 

HPV chemicals voluntarily sponsored chemicals; sponsorship entailed the identification and 

initial assessment of the adequacy of existing toxicity data/information, conducting new testing if 

adequate data did not exist, and making both new and existing data and information available to 

the public. Each complete data submission contains data on 18 internationally agreed to “SIDS” 

(Screening Information Data Set1,2) endpoints that are screening-level indicators of potential 

hazards (toxicity) for humans or the environment. 

The Environmental Protection Agency’s Office of Pollution Prevention and Toxics (OPPT) is 

evaluating the data submitted in the HPV Challenge Program on approximately 1400 sponsored 

chemicals by developing hazard characterizations (HCs). These HCs consist of an evaluation of 

the quality and completeness of the data set provided in the Challenge Program submissions. 

They are not intended to be definitive statements regarding the possibility of unreasonable risk of 

injury to health or the environment. 

The evaluation is performed according to established EPA guidance2,3and is based primarily on 

hazard data provided by sponsors; however, in preparing the hazard characterization, EPA 

considered its own comments and public comments on the original submission as well as the 

sponsor’s responses to comments and revisions made to the submission. In order to determine 

whether any new hazard information was developed since the time of the HPV submission, a 

search of the following databases was made from one year prior to the date of the HPV 

Challenge submission to the present: (ChemID to locate available data sources including 

Medline/PubMed, Toxline, HSDB, IRIS, NTP, ATSDR, IARC, EXTOXNET, EPA SRS, etc.), 

STN/CAS online databases (Registry file for locators, ChemAbs for toxicology data, RTECS, 

Merck, etc.) and Science Direct. OPPT’s focus on these specific sources is based on their being 

of high quality, highly relevant to hazard characterization, and publicly available. 

OPPT may not develop HCs for those HPV chemicals which have recently been assessed and 

published internationally through the HPV program of the Organization for Economic 

Cooperation and Development (OECD) and for which Screening Initial Data Set (SIDS) Initial 

Assessment Reports (SIAR) and SIDS Initial Assessment Profiles (SIAP) are available. These 

documents are presented in an international forum that involves review and endorsement by 

 

1 U.S. EPA. High Production Volume (HPV) Challenge Program; http://www.epa.gov/chemrtk/index.htm.

2 U.S. EPA. HPV Challenge Program – Information Sources; http://www.epa.gov/chemrtk/pubs/general/guidocs.htm.

3 U.S. EPA. Risk Assessment Guidelines; http://cfpub.epa.gov/ncea/raf/rafguid.cfm.
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2

governmental authorities around the world. OPPT is an active participant in these meetings and 

accepts these documents as reliable screening-level hazard assessments. HCs may be created if 

new data suggest a need to update the case work where the OECD document will be used as key 

support documentation.

These hazard characterizations are technical documents intended to inform subsequent decisions 

and actions by OPPT. Accordingly, the documents are not written with the goal of informing the 

general public. However, they do provide a vehicle for public access to a concise assessment of 

the raw technical data on HPV chemicals and may provide information previously not readily 

available to the public. 
U.S. Environmental Protection Agency March 2012

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Chemical Abstract Service 

Registry Number

(CASRN)

124-68-5

Chemical Abstract Index 

Name 1-Propanol, 2-amino-2-methylStructural Formula

Summary

2-Amino-2-methyl-1-propanol (AMP) is a solid possessing low vapor pressure and high water 

solubility. It is expected to have high mobility in soil. The rate of volatilization is considered low 

based on its Henry’s Law constant. Under normal environmental conditions, AMP will not 

undergo hydrolysis because there are no hydrolyzable groups in its structure. The rate of 

atmospheric oxidation is negligible. AMP is not readily biodegradable. It is expected to have 

low persistence (P1) in water, soil and air, moderate persistence (P2) in sediment, and low 

bioaccumulation potential (B1).

The acute oral and dermal toxicity of AMP is low in male rats and rabbits (both sexes), 

respectively. In a 90-day repeated dose toxicity study, rats were administered AMP by oral 

gavage at pH 7 and pH 11. At pH 11, mortality was observed at the two high doses; the NOAEL 

was 500 mg/kg-bw/day. The NOAEL for pH 7 could not be determined because information 

was not available on the doses at which effects were observed. In an eight-week dietary study in 

rats with AMP, hepatocyte vacuolation was observed at all doses; the severity increased with 

dose. Based on the hepatic effects, the NOAEL was not established. In a similar dietary study in 

mice, no treatment-related effects were observed at any dose; the NOAEL was 3200 ppm 

(highest dose tested; 14-28 mg/kg-bw/day). In a 90-day dietary study in dogs with AMP, 

findings were largely indicative of the liver as a target organ. Based on increased liver weights 

with associated histopathological findings and clinical chemistry changes at the two higher 

doses, the NOAEL was 25 ppm (~0.9 mg/kg-bw/day). In a one-year dietary dog study using 

AMP, clinical chemistry findings for high-dose males included differences in serum albumin via 

serum electrophoresis, but no related differences were seen by clinical chemistry measurements;

the NOAEL was 110 ppm (highest dose tested; ~3 mg/kg-bw/day).

In a reproductive/developmental toxicity screening test, dietary exposure of rats to AMP showed 

complete litter resorption (100% post-implantation loss) at 1000 mg/kg-bw/day, and significant 

resorptions at 300 mg/kg-bw/day. Effects associated with, or secondary to the post-implantation 

loss increase at 300 mg/kg-bw/day included decreased litter size, increased mean pup body 

weight, and decreased gestation body weight and body weight gain. In males, liver effects 

(weight changes and microscopic) were observed at 1000 mg/kg-bw/day. The NOAEL for 

systemic toxicity in males was 100 mg/kg-bw/day, but could not be established for females due 

to liver effects in the low dose group; the NOAEL for reproductive/developmental toxicity was 
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4

100 mg/kg-bw/day. In a mechanistic study, the authors suggested that increases in postimplantation loss and liver effects seen at 300 mg/kg-bw/day (67% vs. 7.4% in controls) might 

be a result of decreased phosphocholine. In a prenatal developmental toxicity study, rats 

dermally treated with AMP exhibited irritation at the application site (high incidence of scabbing 

and scaling), particularly at 300 mg/kg-bw/day, but there was no evidence of AMP-related 

systemic maternal or developmental toxicity at any treatment dose. The NOAEL for maternal 

toxicity was 100 mg/kg-bw/day and for developmental toxicity, 300 mg/kg-bw/day (highest dose

tested). AMP did not induce gene mutations in bacteria or mammalian cells in vitro and did not 

induce micronuclei in mice in vivo. AMP is irritating to the skin and the respiratory tract in mice

and a severe irritant to the eyes of rabbits. AMP is not a skin sensitizer in guinea pigs.

For AMP, the 96-h LC50 acute toxicity to fish ranges from 184-190 mg/L (nominal). The acute 

toxicity for aquatic invertebrates 48-h EC50 is 193 mg/L (nominal) and the toxicity to aquatic 

plants 72-h EC50 growth rate is 520 mg/L (nominal). 

No data gaps were identified under the HPV Challenge Program.
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The sponsor, the Dow Chemical Company, submitted a Test Plan and Robust Summaries to EPA 

for 2-amino-2-methyl propanol for consideration in the OECD/ICCA HPV program. On August 

18, 2011, EPA received a written request from the sponsor to move sponsorship of AMP to the 

EPA HPV Challenge Program. EPA posted the submission on the ChemRTK HPV Challenge 

website on November 7, 2011 (http://www.epa.gov/chemrtk/pubs/summaries/2-amino-2-methprop/c16861tc.htm).

1. Chemical Identity

1.1 Identification and Purity

The compound is sold as a reaction product; water is the only additive in the commercial 

product. Although AMP may include up to 8% impurities, analysis of commercial AMP did not 

detect nitrosamines (< 50 ppb) or other compounds (Dow Chemical Company, 2003; Angus 

Chemical Company, 2007; Estrin et al., 1982). 

1.2 Physical-Chemical Properties

The physical-chemical properties of the 2-amino-2-methyl propanol are summarized in Table 1.

Table 1. Physical-Chemical Properties of 2-Amino-2-methyl propanol 1

Property SPONSORED CHEMICAL

2-Amino-2-methyl propanol

CASRN 124-68-5

Molecular Weight 89.14

Physical State Solid crystalline mass or viscous liquid (commercial product)

Melting Point 30 °C (measured)

Boiling Point 165.5 oC at 1013 hPa (measured)

Vapor Pressure 0.45 hPa to 1.33 hPa at 20 oC (measured)

Dissociation Constant (pKa) Not applicable

Henry’s Law Constant 6.57 X 10-5Pa-m

3

/mol (estimated)2

Water Solubility Miscible at 25 oC

Log Kow -0.63 at 20 oC (measured)

1 The Dow Chemical Company Revised Robust Summary. Available online at: 

http://www.epa.gov/chemrtk/pubs/summaries/2-amino-2-meth-prop/c16861tc.htm, November 7, 2011.

2 U.S. EPA. 2011. Estimation Programs Interface SuiteTM for Microsoft® Windows, v4.10. U.S. Environmental 

Protection Agency, Washington, DC, USA. Available online at: 

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm
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2. General Information on Exposure

2.1 Production Volume and Use Pattern

CASRN 124-68-5 had an aggregated production and/or import volume in the United States 

between 10 million and 50 million pounds during calendar year 2005. 

Industrial processing and uses, and commercial and consumer uses for the chemical were 

claimed confidential.

2.2 Environmental Exposure and Fate

The environmental fate properties are provided in Table 2. 

2-Amino-2-methyl propanol does not absorb light at >290 nm, and therefore direct photolysis is not 

possible. However, indirect photolysis (hydroxyl radicals) is possible. The half-life based on hydroxyl 

radical attack of AMP was found to be 4 hours. AMP does not possess a molecular structure that contains 

functional groups subject to hydrolysis under neutral ambient conditions, and is reported to be stable 

indefinitely at <200 oC.

AMP is not “readily biodegradable” as indicated in a closed bottle test. However, some degradation has 

been shown to occur under favorable conditions based on measured mineralization in soil and activated 

sludge. The bioconcentration factor of 14C-AMP was determined experimentally in Golden orfe

(Leuciscus idus), and was reported to be less than 1. Bioaccumulation is not expected based on the 

partition coefficient and very high water solubility. 

At environmental pH (typically pH 8) AMP is highly water soluble and hygroscopic, and in water is 

present primarily protonated (as an ammonium ion), with chloride, hydroxide or other available 

environmental anion as the counter ion. AMP is also known to readily form carbonate salts by reacting 

with carbon dioxide in the air. It would be expected that much of the AMP would ionize to form salts in 

the environment.

Table 2. Environmental Properties of 2-Amino-2-methyl propanol 1

Property SPONSORED CHEMICAL

2-Amino-2-methyl propanol

CASRN 124-68-5

Photodegradation Half-life 4 hours (measured)

Hydrolysis Half-life Contains no functional groups subject to hydrolysis 

under neutral ambient conditions; stable at < 200 oC

Biodegradation 40% degradation in 28 days (Not readily

biodegradable – OECD TG 301D);

89.3% degradation in 28 days (Readily 

biodegradable – OECD TG 301F)

Bioaccumulation Factor 0.9 (estimated)2

Log Koc 2.54 (estimated)2
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Table 2. Environmental Properties of 2-Amino-2-methyl propanol 1

Property SPONSORED CHEMICAL

2-Amino-2-methyl propanol

Fugacity

(Level III Model)2

Air (%)

Water (%)

Soil (%)

Sediment (%)

0.0146

36.2

63.7

0.07

Persistence3P1 (Not persistent in water, soil or air)

3

P2 (Moderately persistent in sediment) 3

Bioaccumulation3 B1 (Not bioaccumulative) 3

1 The Dow Chemical Company Revised Robust Summary. Available online at: 

http://www.epa.gov/chemrtk/pubs/summaries/2-amino-2-meth-prop/c16861tc.htm, November 7, 2011.

2 U.S. EPA. 2011. Estimation Programs Interface SuiteTM for Microsoft® Windows, v4.10. U.S. Environmental 

Protection Agency, Washington, DC, USA. Available online from: 

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm

3

Persistence and bioaccumulation estimations and criteria are available in the PBT Profiler website, available online 

at: http://www.pbtprofiler.net [See Appendix]

Conclusion: 2-Amino-2-methyl-1-propanol (AMP) is a solid possessing low vapor pressure and 

high water solubility. It is expected to have high mobility in soil. The rate of volatilization is 

considered low based on its Henry’s Law constant. Under normal environmental conditions, 

AMP will not undergo hydrolysis because there are no hydrolyzable groups in its structure. The 

rate of atmospheric oxidation is negligible. AMP is not readily biodegradable. It is expected to 

have low persistence (P1) in water, soil and air, moderate persistence (P2) in sediment, and low 

bioaccumulation potential (B1).

3. Human Health Hazard

A summary of health effects data submitted for SIDS endpoints is provided in Table 3.

Acute Oral Toxicity

AMP was administered as a single dose in physiological saline to young male rats (10/dose) at 

2200-4000 mg/kg. Rats were observed for 14 days. Signs of acute toxicity included labored 

breathing, ataxia, and death due to respiratory collapse. There was grossly observable damage 

noted to the liver, kidney, spleen, and respiratory system, and doses greater than 2800 mg/kg 

produced irritation to the stomach and duodenum. Upon necropsy, a dark clot was seen in the 

heart. An oral LD50 of 2900 mg/kg was determined.

LD50 (male) = 2900 mg/kg
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Acute Dermal Toxicity

Undiluted AMP was applied to intact and abraded rabbit (male and female/4 animals/dose) skin

at 1000, 1500 or 2000 mg/kg for 24 hours under occluded dressings and observed for 14 days. 

There were no signs of systemic toxicity. However the treatment sites were necrotic within 2-3 

days, and remained so at study termination. AMP was considered to be a severe skin irritant. 

Treated groups exhibited a loss in body weight over the 14-day post-treatment period. The LD50

was reported to be greater than 2000 mg/kg. 

LD50 > 2000 mg/kg

Repeated-Dose Toxicity

(1) In a 90-day oral gavage repeated-dose study, CD rats (male and female) were gavaged with 

0, 500, 750, 1100 or 1700 mg/kg-bw/day AMP for 5 days/week at both pH 7 and 11. At pH 11, 

decreased survival was seen at all doses, and no animals survived at 1700 mg/kg-bw/day. 

Abdominal swelling was seen in pH 11 rats at 1100 and 1700 mg/kg-bw/day; all these rats later 

died. No treatment-related mortality was seen in the pH 7 rats. Clinical signs of toxicity (e.g. 

hyperventilation, hyperirritability, hyperactivity, convulsions, and neuromuscular paralysis) were 

noted largely in the animals given pH 11 AMP, but to a lesser extent in pH 7 AMP as well. Skin 

exfoliation and some ulceration as well as hair loss were seen. Nasal and mouth bleeding was 

also noted. The lowest dose(s) at which these symptoms were observed were not stated. There 

were no significant differences in body weights. AMP-administered rats appeared to drink more 

frequently than controls. Neither the pH 7 nor the pH 11 females showed significant differences 

in hematocrit, hemoglobin, erythrocyte counts, or leukocytes. The males from the pH 11 group 

in the 1100 mg/kg dose group showed a significant decrease in hematocrit and hemoglobin, and 

red blood cell count due to a loss of blood; red blood cell counts were also decreased at all other 

pH 11 doses but statistical significance was not stated. pH 11 rats showed increased white blood 

cells without a clear dose response. In the pH 7 rats, decreased hematocrit and hemoglobin was 

seen at 1700 mg/kg-bw/day. Also at pH 7, alanine aminotransferase was increased at 1100 

mg/kg-bw/day (males) and 1700 mg/kg-bw/day (both sexes). Urinalysis was conducted only for 

the pH 11 rats. Some proteinuria was seen, but doses were not noted. There were no treatmentrelated grossly-recognizable changes observed at necropsy. Because the authors do not state 

doses at which other effects were observed, the LOAEL and NOAEL could not be determined 

for the pH 7 groups.

LOAEL = 500 mg/kg-bw/day (based on mortality)

NOAEL = Not established

(2) In a 90-day oral repeated-dose study, beagle dogs (4/sex/dose) were fed 25, 600 or 2500 ppm 

(approximately 0.9, 22, and 90 mg/kg-bw/day) AMP in the diet (Parekh, 1981). Body weight 

was decreased by 10% at the highest dose, although the change was not statistically significant. 

Decreased hemoglobin was seen in females at the highest dose (p < 0.05) with similar trend at 

lower doses and decreased prothrombin time was seen in males at the mid and high doses 

(p < 0.01). The authors noted clinical chemistry changes (higher bilirubin, lower cholesterol, and 

elevations of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase), 

increased liver weights, and histopathologic findings (vacuolization, periportal cirrhosis, and bile 

duct hyperplasia) at the 2500 ppm dose level in the diet (approximately 90 mg/kg-bw/day) that 
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are indicative of the liver as a target organ. At the mid and high dose, increased relative and 

absolute kidney weights were seen but without accompanying changes in urinalysis. 

LOAEL = 600 ppm (22 mg/kg-bw/day; based on prothrombin time in males, increased liver 

and/or liver:body weight ratios in both sexes, and minimal fatty changes in the liver)

NOAEL = 25 ppm (0.9 mg/kg-bw/day)

(3) In an eight-week oral repeated-dose study, Sprague-Dawley rats (10/sex/dose) were fed 0, 

1000, 2000, 4000, 8000 or 16,000 ppm AMP (mixed with distilled water) in the diet. The 

corresponding approximate doses by body weight (males/females) were determined to be 0, 

244/436, 474/806, 912/1628, 1901/3424, and 4698/7579 mg/kg-bw/day, respectively. Rats were 

observed for changes in general behavior and appearance each day, and body weights and food 

consumption were recorded weekly. All control rats, surviving rats at the top two doses and two 

rats/sex at each of the other doses were necropsied at the end of the study. Livers and gross 

lesions were examined microscopically. At the high dose, several effects were seen in rats. 

Rough hair coat, emaciation, and scattered lesions over the dorsal surfaces of a few rats were 

seen at week three, with all rats showing similar clinical signs after the third week. Dorsal hair 

loss was seen starting at week five. Two female rats died during the study; one of these 

exhibited tremors and paleness. These rats gained slightly less weight compared to controls. At 

necropsy, alopecia and focal skin erosions and ulcerations as well as microscopic skin lesions 

were viewed as possibly compound related. In all treatment groups, hepatocyte vacuolation was 

seen in rats, with increasing severity at the higher doses. 

LOAEL = 100 ppm (244/436 mg/kg-bw/day in males/females; based on hepatocyte vacuolation 

seen at all doses)

NOAEL = Not established

(4) In a similar eight-week oral repeated-dose study, CD-1 mice (10/sex/dose) were fed 0, 200, 

400, 800, 1600 or 3200 ppm AMP (mixed with distilled water) in the diet. These doses 

corresponded to approximate doses by body weight (males/females), of 0, 1.2/1.6, 2.1/3.1, 

3.4/6.1, 9.0/13, and 14/28 mg/kg-bw/day. Mice were observed for changes in general behavior 

and appearance, body weights and food consumption. All surviving mice at the 3200 ppm dose 

and 2 rats per sex at each of the other doses and in controls were necropsied at the end of the 

study. Livers and gross lesions were examined microscopically. No compound-related changes 

were seen at any treatment dose. 

NOAEL = 3200 ppm (14-28 mg/kg-bw/day; based on no treatment-related effects observed at 

highest dose tested)

(5) In a one-year oral repeated-dose study, beagle dogs were treated with AMP in the diet at 0,

1.1, 11 and 110 ppm (approximately 0.029/0.031, 0.31/0.31, and 2.6/3.0 mg/kg-bw/day in 

females/males). General behavior, appearance, and body weight was recorded, and 

ophthalmoscopic examinations were conducted. Full clinical chemistry, hematology, urinalysis 

and pathological examinations were conducted. Clinical chemistry findings for males revealed a 

slight decrease in the low and mid-dose groups' albumin-globulin ratio. Since there was no clear 

dose-response in any clinical chemistry finding (the high dose group was not different than the 

control), the findings were judged to be spurious findings and not treatment-related. At 9 and 12 

months, high-dose males exhibited differences in serum albumin via serum electrophoresis, but 

clinical chemistry measurements did not show differences, and was not considered by the authors 
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10

to be biologically-significant. Throughout the study, findings for females included differences in 

serum sodium, serum alanine aminotransferase, and serum aspartate aminotransferase, but were 

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

administration of AMP. 

NOAEL = 110 ppm (2.6-3.0 mg/kg-bw/day; based on no treatment-related effects observed at 

highest dose tested) 

Reproductive Toxicity

In a combined reproductive/developmental toxicity guideline study, CD rats (12/sex/dose) were 

fed diets supplying 0 (control), 100, 300 or 1000 mg/kg-bw/day 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 

behaviour, conception, development of the conceptus, parturition, litter size, pup survival, sex, 

pup body weight, pup gross external morphological alterations, and pathology of adult gonads 

were assessed. At 1000 mg/kg-bw/day, increases in absolute and relative liver weights, 

accompanied by a very slight degree of microvacuolization of periportal hepatocytes, with or 

without vacuolization of hepatocytes were noted in males. Females in all treatment groups 

exhibited similar histopathological changes in the liver with greater frequency, but in the absence 

of an organ weight change. AMP had no effect on mating performance or conception, but 

caused marked, dose-related increases in post-implantation loss (embryo resorption). At the 

highest dose, all 12 pregnant females showed 100% post-implantation loss, while at 300 mg/kgbw/day, post-implantation loss was 70% (vs. 10% in controls). Effects associated with, or 

secondary to the increase in post-implantation loss increase at 300 mg/kg-bw/day included 

decreased litter size, increased mean pup body weight, and decreased gestation body weight and 

body weight gain in dams. There were no treatment related effects on reproductive performance 

in the 100 mg/kg-bw/day group. 

LOAEL (male systemic toxicity) = 1000 mg/kg-bw/day (based on liver effects)

NOAEL (male systemic toxicity) = 300 mg/kg-bw/day 

LOAEL (female systemic toxicity) = 100 mg/kg-bw/day (based on the presence of 

microscopic liver effects at all doses)

NOAEL (female systemic toxicity) = Not established

LOAEL (reproductive toxicity) = 300 mg/kg-bw/day (based on post-implantation loss)

NOAEL (reproductive toxicity) = 100 mg/kg-bw/day
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Developmental Toxicity

(1) In the combined reproductive/developmental toxicity study in rats, described above, post 

implantation loss was observed at doses of 300 mg/kg-bw/day and above. Liver effects were 

observed in dams at all doses.

LOAEL (maternal toxicity) = 100 mg/kg-bw/day (based on the presence of microscopic liver 

effects at all doses)

NOAEL (maternal toxicity) = Not established

LOAEL (developmental toxicity) = 300 mg/kg-bw/day (based on post-implantation loss)

NOAEL (developmental toxicity) = 100 mg/kg-bw/day

(2) In a prenatal developmental toxicity study, pregnant rats were exposed 6 hours daily via the 

dermal route to 0, 30, 100, or 300 mg AMP/kg-bw/day from gestation days (GD) 6-20. Rats 

were sacrificed on GD 21, and subjected to a pathological examination including external tissues 

and all orifices, stomach, liver, kidneys, and uterine findings. The first four presumed pregnant 

females from each dose group were selected for blood collection on GD 20. Dermal 

administration of 300 mg/kg-bw/day of AMP produced significant effects at the test site, as 

evidenced by scabbing and moderate to severe scaling. The dermal finding of slight scaling at 

30 and 100 mg/kg-bw/day was not considered adverse, as the observation was transient in nature 

and low in incidence. There was no evidence of test article-related systemic maternal or 

developmental toxicity at any dose tested. The NOAEL for maternal toxicity was 100 mg/kgbw/day. The NOAEL for developmental toxicity was 300 mg/kg-bw/day (highest dose 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.

LOAEL (maternal toxicity) = 300 mg/kg-bw/day (based on high incidence of scabbing and 

scaling at test site)

NOAEL (maternal toxicity) = 100 mg/kg-bw/day

NOAEL (developmental toxicity) = 300 mg/kg-bw/day (based on no adverse treatment-related 

effects at the highest dose tested)

Genetic Toxicity – Gene Mutation

In vitro

(1) In a bacterial reverse mutation assay using the plate incorporation method, Salmonella 

typhimurium strains TA98, TA100, TA1535, TA1537 and E. coli (WP2 uvrA) were treated with 

up to 5000 μg/plate AMP (Wagner, 1996). Initial and confirmatory assays were used to evaluate 

the mutagenic potential of the test material. In triplicate tests, a minimum of 5 doses of the test 

article, with vehicle (water) and positive controls, were plated with tester strains in the presence 

and absence of metabolic (rat liver S9) activation. 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. 

AMP was not mutagenic in this assay.
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(2) In a bacterial reverse mutation assay using S. typhimurium strains TA98, TA100, TA1535, 

TA1537 and TA1538 and Saccharomyces cerevisiae (D-4) at test concentrations of 0.01 to 5.0 

μL/plate in both the presence and absence of metabolic activation, AMP was negative for gene 

mutations. A negative (solvent control) was also run. Positive controls were used and showed 

appropriate responses.

AMP was not mutagenic in this assay.

(3) In a mammalian cell gene mutation assay, L5178Y mouse lymphoma cells were exposed to 

the vehicle alone and solutions of AMP at concentrations of 0.5, 1.5, 5.0, 15, 50, 150, 500, 1500, 

5000 μg/mL prepared in both the absence and presence of S9 (San and Clark, 1997). Positive 

controls, with and without S9, were tested concurrently following a preliminary assay. No 

treated cultures exhibited mutant frequencies more than 55 mutants per 106clonable cells over 

the solvent control. A dose-response trend was not observed in either the activated or nonactivated systems, and the independent repeat of the assay showed similar results. 

AMP was not mutagenic in this assay.

Genetic Toxicity – Chromosomal Aberrations

In vivo

In a mouse micronucleus assay, ICR mice (5/sex/dose) received a single IP injection of 16, 30 or 

60 mg/kg AMP; the positive control (cyclophosphamide) was administered in the same manner 

concurrently. At the scheduled sacrifice times (24 and 48 hours), marrow from the femurs was 

extracted and slides were prepared of the bone marrow cells. 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. There was no treatment-related mortality at any dose level. 

Clinical signs noted on the day of dosing were limited to lethargy in males and females at 60 

mg/kg (highest dose). 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 or female mice.

AMP did not induce micronuclei in mice in this assay.

Additional Information 

Skin Irritation

Rabbits were administered AMP on the clipped abdominal skin daily (and allowing the skin to 

dry) for 5 days. It was found to be highly irritating. Two animals had dermatitis, infiltration of 

skin and subcutaneous tissues, superficial redness, and loss of hair. “Burrowing” lesions were 

noted when applied to wounds on abraded skin sites.

AMP was highly irritating to rabbit skin.
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Eye Irritation

Rabbits were treated in the eye with an unknown amount of undiluted test substance. In one 

study, eyes were flushed 15-30s after application and in the other they were not. Unflushed eyes 

scored the highest possible grade (110) and the flushed eyes scored 69.3 (15 sec) and 89.3 (30 

sec); a score of 16 is considered a severe irritant. The damage was not mitigated even with an 

immediate flushing of the eyes. AMP was found to cause serious damage to the eyes and 

destroyed the vision when applied to rabbits. 

AMP was severely irritating to rabbit eyes.

Respiratory Irritation

Restrained Swiss Webster mice were head-only exposed to 0.185 to 1.16 mg/L aerosolized AMP 

for 3 hours followed by a 20 minute recovery period and observed for 1 week for mortality. No 

deaths were recorded but sensory and pulmonary irritation of mice was noted. Pulmonary 

irritation exhibited a delayed onset by 2-3 hours and didn’t fully recover 20 minutes after 

exposure ceased. The authors suggested AMP caused moderate irritation.

AMP was moderately irritating to rabbit eyes.

Sensitization

(1) Guinea pigs were treated topically with 0.5 mL of a 10% AMP solution; after 24 hours, sites 

were cleaned and scored for erythema and edema according to the method of Draize. At 48 

hours, AMP application was repeated, and continued 2-3 times per week until 10 applications 

were made; after 2 applications the concentration was lowered to 5% due to mild irritation 

observed at the 10% applications. Animals were allowed a 2 week recovery period, and then 

challenged at a virgin site with 2.5% and 5% solutions of AMP (contact for 24 hours). Sites 

were scored again at 3 and 48 hours. Negative and positive controls were also used. None of the 

animals induced with AMP or the vehicle control exhibited a positive response when challenged 

with AMP.

AMP was not a dermal sensitizer in guinea pigs.

(2) Guinea pigs were administered intradermal injections during induction and challenge (0.05

mL of a 1, 0.5 and 0.1% AMP solution for inductions and 0.1mL of 0.05% and 0.01% for 

challenge). During the induction phase, the first injection at 1% and second injection at 0.5% 

AMP induced necrotic lesions, so the remaining 8 injections (administered 2-3 times/week) were 

made with 0.1% solutions. The challenge injections occurred after a 2-week recovery period. 

Negative and positive controls were also used. During the challenge period, one animal in the 

test group showed mild reactions with 0.05%. In a repeat challenge, none of the animals in the 

test group showed any reactions with AMP, so the material was considered to be non-sensitizing 

following intradermal application.

AMP was not an intradermal sensitizer in guinea pigs.
U.S. Environmental Protection Agency March 2012

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14

Toxicokinetics, Metabolism and Distribution

In vitro

AMP was evaluated with model human and rat skin sebum using different concentrations of 

AMP (4 and 40%) and formulations (e.g., aqueous, lotion). At 24 hours, 6-17% was absorbed 

through human skin versus 30-51% through rat skin. A significant portion was lost from skin 

due to evaporation. 

In vivo

(1) The metabolism and distribution of AMP has been studied in vivo in Sprague-Dawley rats. 

Rats were administered test material (3H-AMP) at a specific activity of 5μCi/μmol via one 

intraperitoneal injection and subsequently sacrificed at 30 minutes, and at 1, 2, 3, 6, 24, 96 hours 

following dosing. Serum, urine, and feces were collected for analysis. Brain, heart, kidney, 

liver, intestine, spleen, and skeletal muscle were homogenized and analyzed for radioactivity. 

Although a mass balance wasn’t used to determine distribution of AMP, qualitative information 

can be obtained from the study. Tritium appeared in the serum 30 minutes post-dosing, and the 

authors noted that a large portion disappeared quickly from serum after initial uptake. Low 

levels remained in the liver (greatest retention), skeletal muscle, heart muscle, intestines, spleen 

and kidneys. Hepatic radioactivity was found to be incorporated into the mitochondria and 

microsomal phospholipid fractions of liver and decreased with time. A majority of AMP was 

excreted in urine (as unchanged AMP), and levels of radioactivity in urine as well as blood 

decreased to near background by 96 hours post dosing.

(2) In a mechanistic study, two groups of six female Sprague-Dawley rats were fed diets with 0 

or 300 mg/kg-bw/day of AMP-HCL for two weeks before breeding, throughout breeding, and 

two weeks into gestation (GD 0-13). An increase in post-implantation loss was seen in the dosed 

group compared with controls (67% vs. 7.4%). The dams also showed slight increased hepatic 

lipid vacuolation. The changes correlated with 20-25% statistically-decreased liver 

phosphocholine, the primary storage for choline. Two- to three-fold increases in 

glycerophosphoholine (which indicates conversion of phosphatidyl choline to choline) were seen 

in the liver. The authors note that liver and post-implantation loss effects may be a result of 

decreased phosphocholine.

Conclusion: The acute oral and dermal toxicity of AMP is low in male rats and rabbits (both 

sexes), respectively. In a 90-day repeated dose toxicity study, rats were administered AMP by 

oral gavage at pH 7 and pH 11. At pH 11, mortality was observed at the two high doses; the 

NOAEL was 500 mg/kg-bw/day. The NOAEL for pH 7 could not be determined because 

information was not available on the doses at which effects were observed. In an eight-week 

dietary study in rats with AMP, hepatocyte vacuolation was observed at all doses; the severity 

increased with dose. Based on the hepatic effects, the NOAEL was not established. In a similar 

dietary study in mice, no treatment-related effects were observed at any dose; the NOAEL was 

3200 ppm (highest dose tested; 14-28 mg/kg-bw/day). In a 90-day dietary study in dogs with

AMP, findings were largely indicative of the liver as a target organ. Based on increased liver 

weights with associated histopathological findings and clinical chemistry changes at the two 

higher doses, the NOAEL was 25 ppm (~0.9 mg/kg-bw/day). In a one-year dietary dog study 

using AMP, clinical chemistry findings for high-dose males included differences in serum 

albumin via serum electrophoresis, but no related differences were seen by clinical chemistry 

measurements; the NOAEL was 110 ppm (highest dose tested; ~3 mg/kg-bw/day).
U.S. Environmental Protection Agency March 2012

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15

In a reproductive/developmental toxicity screening test, dietary exposure of rats to AMP showed 

complete litter resorption (100% post-implantation loss) at 1000 mg/kg-bw/day, and significant 

resorptions at 300 mg/kg-bw/day. Effects associated with, or secondary to the post-implantation 

loss increase at 300 mg/kg-bw/day included decreased litter size, increased mean pup body 

weight, and decreased gestation body weight and body weight gain. In males, liver effects

(weight changes and microscopic) were observed at 1000 mg/kg-bw/day. The NOAEL for 

systemic toxicity in males was 100 mg/kg-bw/day, but could not be established for females due 

to liver effects in the low dose group; the NOAEL for reproductive/developmental toxicity was 

100 mg/kg-bw/day. In a mechanistic study, the authors suggested that increases in postimplantation loss and liver effects seen at 300 mg/kg-bw/day (67% vs. 7.4% in controls) might 

be a result of decreased phosphocholine. In a prenatal developmental toxicity study, rats 

dermally treated with AMP exhibited irritation at the application site (high incidence of scabbing 

and scaling), particularly at 300 mg/kg-bw/day, but there was no evidence of AMP-related 

systemic maternal or developmental toxicity at any treatment dose. The NOAEL for maternal 

toxicity was 100 mg/kg-bw/day and for developmental toxicity, 300 mg/kg-bw/day (highest dose 

tested). AMP did not induce gene mutations in bacteria or mammalian cells in vitro and did not 

induce micronuclei in mice in vivo. AMP is irritating to skin and eyes of rabbits and the 

respiratory tract in mice. AMP is not a skin sensitizer in guinea pigs.
U.S. Environmental Protection Agency March 2012

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Table 3. Summary Table of the Screening Information Data Sets Submitted under the U.S. 

HPV Challenge Program – Human Health Data

Endpoint SPONSORED CHEMICAL

2-Amino-2-methyl propanol

Acute Oral Toxicity

LD50 (mg/kg) > 2000

Acute Dermal Toxicity

LD50 (mg/kg) > 2000

Repeated-Dose Toxicity

NOAEL/LOAEL 

Oral (mg/kg-bw/day)

(rat, 90-day, pH11)

NOAEL = not established

 LOAEL = 500

(rat, 8-week)

NOAEL = not established

 LOAEL = 244/436 (males/females)

(mouse, 8-week)

NOAEL = 14-28 (highest dose tested)

(dog, 90-day)

NOAEL = 0.9

LOAEL = 22

(dog, 1-year)

NOAEL = 2.6-3.0 (highest dose tested)

Reproductive Toxicity

NOAEL/LOAEL 

Oral (mg/kg-bw/day)

NOAEL=100

LOAEL=300

Developmental Toxicity

NOAEL/LOAL

Oral (mg/kg-bw/day)

Maternal Toxicity

Developmental Toxicity

NOAEL=Not Established

LOAEL=100

NOAEL=100

LOAEL =300

Developmental Toxicity

NOAEL/LOAL

Dermal(mg/kg-bw/day)

Maternal Toxicity

Developmental Toxicity

NOAEL=100

LOAEL=300

NOAEL=300 (not established)

Genetic Toxicity – Gene Mutation

In vitro Negative

Genetic Toxicity – Chromosomal Aberrations

In vivo Negative

Additional Information

Skin Irritation

Eye Irritation

Skin Sensitization

Highly irritating

Severely irritating

Not sensitizing

Measured data in bold
U.S. Environmental Protection Agency March 2012

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17

4. Hazard to the Environment

A summary of aquatic toxicity data submitted for SIDS endpoints is provided in Table 4. 

Acute Toxicity to Fish

Bluegill sunfish (Lepomis macrochirus) were exposed to 32-560 mg/L (nominal concentrations) 

AMP under static conditions. Concentrations for the 96-h study were based on a 72-h range

finding test using 1, 10, 100, 560 or 1000 mg/L AMP. No sublethal effects were reported.

96-h LC50 = 190 mg/L (nominal)

European Plaice (Pleuronectes platessa; 20 per dose level) were exposed to 100, 320, 560, 1000 

mg/L (nominal concentrations) of AMP under semi-static conditions. Nominal temperature of 

the test solution was 15°C (14.4-15°C 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 and salinity was 34.76-34.82 ‰

96-h LC50 = 184 mg/L (nominal)

Acute Toxicity to Aquatic Invertebrates

(1) Daphnia magna (10/concentration) were exposed to 0, 100, 180, 320, 560 or 1000 mg/L 

AMP under static conditions at 19-20 oC. 

48-h LC50 = 193 mg/L (nominal)

(2) Sand shrimp (Crangon crangon) were exposed to 0, 56, 100, 320 or 560 mg/L AMP under 

semi-static conditions for 96 hours. The control mortality was 0% at 96 hours.

48-h LC50 = 179 mg/L

96-h LC50 = 179 mg/L

Toxicity to Aquatic Plants

Algae (Scenedesmus sp.) was exposed to AMP (concentrations not stated) using closed vessels. 

Passage of CO2-enriched air and variation of the air space in the test vessel allowed the 

optimization of growth comparable to that of an open vessel.

72-h EC50 (growth rate) = 520 mg/L (nominal)

Conclusion: For AMP, the 96-h LC50 acute toxicity to fish ranges from 184-190 mg/L (nominal). 

The acute toxicity for aquatic invertebrates 48-h EC50 is 193 mg/L (nominal) and the toxicity to 

aquatic plants 72-h EC50 growth rate is 520 mg/L (nominal). 
U.S. Environmental Protection Agency March 2012

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Table 4. Summary of the Screening Information Data Set under the U.S. HPV Challenge 

Program - Aquatic Toxicity Data

Endpoint SPONSORED CHEMICAL

2-Amino-2-methyl propanol

Fish

96-h LC50

(mg/L)

184-190 (nominal)

Aquatic Invertebrates

48-h LC50

(mg/L)

193 (nominal)

Aquatic Plants

72-h EC50 (growth rate) 

(mg/L)

520 (nominal)

Bold = derived from experimental data

5. References

Angus Chemical Company. Information about impurities in aminomethyl propanol and 

aminomethyl propanediol. 2007. Unpublished data submitted by CTFA. Cited in: Burnett, 

C.L., Bergfeld, W.F., Belsito, D.V., Klaassen, C.D., Marks Jr, J.G., Shank, R.C., Slaga, T.J., 

Snyder, P.W., and Andersen, F.A. (2009) Cosmetic Ingredient Review Expert Panel. Final 

Amended Report on Safety Assessment on Aminomethyl Propanol and Aminomethyl 

Propanediol. International Journal of Toxicology, 28 (6) 141S-161S.

Estrin NF, Haynes CR, Whelan JM. (1982). CTFA Specifications Spectra. Washington, DC: 

Cosmetic, Toiletry, and Fragrance Association. Cited in: Burnett, C.L., Bergfeld, W.F., Belsito, 

D.V., Klaassen, C.D., Marks Jr, J.G., Shank, R.C., Slaga, T.J., Snyder, P.W., and Andersen, 

F.A. (2009) Cosmetic Ingredient Review Expert Panel. Final Amended Report on Safety 

Assessment on Aminomethyl Propanol and Aminomethyl Propanediol. International Journal of 

Toxicology, 28 (6) 141S-161S.

Dow Chemical Company (2003). Material Safety Data Sheet.
U.S. Environmental Protection Agency March 2012

Hazard Characterization Document

19

Appendix

PBT profiler output

Results

Orange or red highlights indicate that the EPA criteria have been exceeded. 

Black-and-white version

Persistence Bioaccumulation Toxicity

124-68-5 1-Propanol, 2-amino-2-methylPBT Profiler Estimate = PBT

Media

Half-Life

(days) 

Percent in

Each Medium BCF

Fish ChV

(mg/l) 

Water 15 39% 3.2 9.5

Soil 30 61%

Sediment 140 0%

Air 0.62 0%

Developed by the Environmental Science Center under contract to the Office of Chemical Safety 

and Pollution Prevention , U.S. Environmental Protection Agency

Computer Resources Donated by SRC, Inc. Ver 1.301 Last Updated November 1, 2010