ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 

FOR 

DIMETHYL PHOSPHITE 

CAS Reg. No. 868-85-9 

PROPOSED 
DIMETHYL PHOSPHITE Proposed: October, 2009 

2

1 

2 ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 

3 FOR 

4 DIMETHYL PHOSPHITE 

5 CAS Reg. No. 868-85-9 

6 

7 

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9 PROPOSED 

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DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 

2 PREFACE 

3 

4 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 

5 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous 

6 Substances (NAC/AEGL Committee) has been established to identify, review and interpret 

7 relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic 

8 chemicals. 

9 

10 AEGLs represent threshold exposure limits for the general public and are applicable to 

11 emergency exposure periods ranging from 10 minutes to 8 hours. Three levels C AEGL-1, 

12 AEGL-2 and AEGL-3 C are developed for each of five exposure periods (10 and 30 minutes, 1 

13 hour, 4 hours, and 8 hours) and are distinguished by varying degrees of severity of toxic effects. 

14 The three AEGLs are defined as follows: 

15 

16 AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per 

17 cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general 

18 population, including susceptible individuals, could experience notable discomfort, irritation, or 

19 certain asymptomatic, non-sensory effects. However, the effects are not disabling and are 

20 transient and reversible upon cessation of exposure. 

21 

22 AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 

23 which it is predicted that the general population, including susceptible individuals, could 

24 experience irreversible or other serious, long-lasting adverse health effects or an impaired ability 

25 to escape. 

26 

27 AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 

28 which it is predicted that the general population, including susceptible individuals, could 

29 experience life-threatening health effects or death. 

30 

31 Airborne concentrations below the AEGL-1 represent exposure levels that could produce 

32 mild and progressively increasing but transient and nondisabling odor, taste, and sensory 

33 irritation or certain asymptomatic, non-sensory effects. With increasing airborne concentrations 

34 above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity 

35 of effects described for each corresponding AEGL. Although the AEGL values represent 

36 threshold levels for the general public, including susceptible subpopulations, such as infants, 

37 children, the elderly, persons with asthma, and those with other illnesses, it is recognized that 

38 individuals, subject to unique or idiosyncratic responses, could experience the effects described 

39 at concentrations below the corresponding AEGL 

40 

41 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 TABLE OF CONTENTS 

2 PREFACE....................................................................................................................................................3

3 EXECUTIVE SUMMARY ........................................................................................................................6

4 1. INTRODUCTION..............................................................................................................................8

5 2. HUMAN TOXICITY DATA.............................................................................................................8

6 2.1. Acute Lethality...............................................................................................................................8

7 2.2. Nonlethal Toxicity..........................................................................................................................8

8 2.3. Developmental/Reproductive Toxicity.........................................................................................9

9 2.4. Genotoxicity....................................................................................................................................9

10 2.5. Carcinogenicity ..............................................................................................................................9

11 2.6. Summary.........................................................................................................................................9

12 3. ANIMAL TOXICITY DATA............................................................................................................9

13 3.1. Acute Lethality...............................................................................................................................9

14 3.2. Non-lethal Toxicity.........................................................................................................................9

15 3.3. Repeated-Exposure Studies.........................................................................................................10

16 3.4. Developmental/Reproductive Toxicity.......................................................................................11

17 3.5. Genotoxicity..................................................................................................................................11

18 3.6. Chronic Toxicity/Carcinogenicity ..............................................................................................11

19 3.7. Summary.......................................................................................................................................11

20 4. SPECIAL CONSIDERATIONS .....................................................................................................12

21 4.1. Metabolism and Disposition........................................................................................................12

22 4.2. Mechanism of Toxicity ................................................................................................................12

23 4.3. Structure Activity Relationships ................................................................................................12

24 4.4. Other Relevant Information .......................................................................................................12

25 4.4.1. Species Variability...............................................................................................................12

26 4.4.2. Susceptible Populations ......................................................................................................12

27 4.4.3. Concentration-Exposure Duration Relationship..............................................................12

28 4.4.4. Concurrent Exposure Issues ..............................................................................................13

29 5. DATA ANALYSIS FOR AEGL-1 ..................................................................................................13

30 5.1. Summary of Human Data Relevant to AEGL-1 .......................................................................13

31 5.2. Summary of Animal Data Relevant to AEGL-1 .......................................................................13

32 5.3. Derivation of AEGL-1 .................................................................................................................13

33 6. DATA ANALYSIS FOR AEGL-2 ..................................................................................................13

34 6.1. Summary of Human Data Relevant to AEGL-2 .......................................................................13

35 6.2. Summary of Animal Data Relevant to AEGL-2 .......................................................................13

36 6.3. Derivation of AEGL-2 .................................................................................................................13

37 7. DATA ANALYSIS FOR AEGL-3 ..................................................................................................14

38 7.1. Summary of Human Data Relevant to AEGL-3 .......................................................................14

39 7.2. Summary of Animal Data Relevant to AEGL-3 .......................................................................14

40 7.3. Derivation of AEGL-3 .................................................................................................................14

41 8. SUMMARY OF AEGLS .................................................................................................................15

42 8.1. AEGL Values and Toxicity Endpoints.......................................................................................15

43 8.2. Comparison with Other Standards and Guidelines..................................................................15

44 8.3. Data Adequacy and Research .....................................................................................................15

45 9. REFERENCES.................................................................................................................................17

46 APPENDIX A: DERIVATION OF AEGL VALUES...........................................................................19

47 APPENDIX B: DERIVATION SUMMARY FOR DIMETHYL PHOSPHITE AEGLS .................22

48 APPENDIX C: CATEGORY PLOT FOR DIMETHYL PHOSPHITE.............................................25
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 LIST OF TABLES 

2 

3 Table 1. Summary of AEGL Values for Dimethyl Phosphite ....................................................... 7 

4 Table 2. Chemical and physical properties for dimethyl phosphite.............................................. 8 

5 TABLE 3. AEGL-1 values for dimethyl phosphite...................................................................... 13 

6 TABLE 4. AEGL-2 values for dimethyl phosphite...................................................................... 14 

7 TABLE 5. AEGL-3 values for dimethyl phosphite...................................................................... 15 

8 TABLE 6. Summary of AEGL values......................................................................................... 15 

9 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 EXECUTIVE SUMMARY 

2 

3 Dimethyl phosphite (DMP) is a colorless liquid with a mild odor; it is a degradation product 

4 of trimethyl phosphite (TMP). It is used as an intermediate in the manufacture of insecticides 

5 and herbicides. It is also used as a fireproofing agent in the production of textiles. Dimethyl 

6 phosphite is manufactured in a closed system by reacting phosphorus trichloride with methanol 

7 or sodium methoxide, and is listed as a High Production Volume (HPV) chemical. 

8 

9 Data are insufficient for derivation of AEGL-1 values; therefore AEGL-1 values are not 

10 recommended. Absence of AEGL-1 values does not imply that concentrations below AEGL-2 

11 are without effect. 

12 

13 Clinical signs (labored breathing and ptosis) in mice exposed to 1575 ppm DMP for 6 hours 

14 (Hazleton, 1962) were used as the point-of-departure for AEGL-2 values. Inter- and intraspecies 

15 uncertainty factors of 3 each (total 10) were applied because DMP is irritating, and much of the 

16 toxicity is likely caused by a direct chemical effect on the tissue; this type of portal-of-entry 

17 effect is not expected to vary greatly between species or among individuals. The interspecies 

18 uncertainty factor of 3 is also considered sufficient because no clinical signs were noted in rats or 

19 guinea pigs exposed to 1575 ppm for 6 hours. A modifying factor of 3 was also applied because 

20 of the sparse database and because the point-of-departure is a nominal concentration. The 

21 concentration-exposure time relationship for many irritant and systemically-acting vapors and 

gases may be described by Cn 22 x t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et 

23 al., 1986). To obtain conservative and protective AEGL values in the absence of an empirically 

24 derived chemical-specific scaling exponent, temporal scaling may be performed using n=3 when 

25 extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the 

Cn 26 x t = k equation (NRC, 2001). The 30-minute AEGL-2 value was adopted as the 10-min 

27 value because of the added uncertainty of extrapolating from the 6-hr point-of-departure. 

28 

29 The highest concentration causing no mortality in rats (843 ppm for 6 hr) was used as the 

30 point-of-departure for AEGL-3 (Biodymanics, 1980a). Excessive lacrimation, partially closed 

31 eyes, red nasal discharge, red-brown material around the nares, labored breathing, and 

32 unresponsiveness to sound stimuli were noted in rats exposed to 843 ppm DMP 6 hr/day for 5 

33 days. Death was noted at the next concentration tested (934 ppm) essentially after one exposure 

34 because one rat was killed in extremis after day 1 of the study. Inter- and intrapsecies 

35 uncertainty factors of 3 each (total 10) were applied because DMP is irritating, and much of the 

36 toxicity is likely caused by a direct chemical effect on the tissue; this type of portal-of-entry 

37 effect is not expected to vary greatly between species or among individuals. The concentration38 exposure time relationship for many irritant and systemically-acting vapors and gases may be 

described by Cn 39 x t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al., 1986). 

40 To obtain conservative and protective AEGL values in the absence of an empirically derived 

41 chemical-specific scaling exponent, temporal scaling may be performed using n=3 when 

42 extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the 

Cn 43 x t = k equation (NRC, 2001). The 30-minute AEGL-3 value will also be adopted as the 10-

44 min value because of the added uncertainty of extrapolating from the 6-hr point-of-departure. 

45 

46 The calculated values are listed in Table 1 below. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 

Table 1. Summary of AEGL Values for Dimethyl Phosphite

Classification 10-minute 30-minute 1-hour 4-hour 8-hour Endpoint 

(Reference) 

AEGLB1 

(Nondisabling) NR NR NR NR NR Insufficient data 

AEGLB2 

(Disabling) 

120 ppm 

(540 mg/m3) 

120 ppm 

(540 mg/m3) 

95 ppm 

(430 mg/m3) 

60 ppm 

(270 mg/m3) 

39 ppm 

(180 mg/m3) 

Labored breathing 

and ptosis in mice 

(Hazleton, 1962) 

AEGLB3 

(Lethal) 

190 ppm 

(850 mg/m3

) 

190 ppm 

(850 mg/m3) 

150 ppm 

(670 mg/m3) 

96 ppm 

(430 mg/m3) 

63 ppm 

(240 mg/m3) 

NOEL for mortality 

in rats (Biodynamics, 

1980a) 

2 NR: Not Recommended due to insufficient data. Absence of AEGL-1 values does not imply that concentrations 

3 below AEGL-2 are without effect. 

4 

5 

6 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 

2 1. INTRODUCTION 

3 

4 Dimethyl phosphite (DMP) is a colorless liquid with a mild odor; it is a degradation product 

5 of trimethyl phosphite (TMP). It is used as an intermediate in the manufacture of insecticides 

6 and herbicides. It is also used as a fireproofing agent in the production of textiles. Dimethyl 

7 phosphite is manufactured in a closed system by reacting phosphorus trichloride with methanol 

8 or sodium methoxide, and is listed as a High Production Volume (HPV) chemical. HPV 

9 chemicals were produced or imported into the U.S. in quantities of > 1 million pounds in 1990 

10 and/or 1994; estimated US manufacturing capacity was 1000-5000 tons/year in 2002 (UNEP, 

11 2004). Chemical and physical properties are presented in Table 2. 

12 

13 

Table 2. Chemical and physical properties for dimethyl phosphite

Parameter Value References 

Synonyms 

Dimethyl phosphonate; 

dimethylhydrogen phosphite; DMPH; 

DMP; Phosphonic acid, dimethyl ester; 

Dimethyl phosphonus acid; 

Phosphorus acid dimethyl ester; 

Hydrogen dimethyl phosphite 

UNEP, 2004 

Chemical formula C2H7O3P HSDB, 2009 

Molecular weight 110.05 HSDB, 2009 

CAS Reg. No. 868-85-9 HSDB, 2009 

Physical state Colorless liquid HSDB, 2009 

Solubility in water 

Soluble; >10 g/100 ml at 25oC; 

Decomposes to monomethyl phosphite 

and methanol 

UNEP, 2004 

Vapor pressure 1.5 mm Hg at 20oC HSDB, 2009 

Vapor density (air =1) 7.9 HSDB 2009 

Specific gravity 1.2002 g/cm3 at 20oC HSDB, 2009 

Melting point -60oC HSDB, 2009 

Boiling point 170.5oC UNEP, 2004 

Flash point 70oC HSDB, 2009 

Explosive limits Lower: 5.8%; Upper: 38.1% UNEP, 2004 

Conversion factors 1 ppm = 4.49 mg/m3

1 mg/m3 = 0.22 ppm 

14 

15 2. HUMAN TOXICITY DATA 

16 2.1. Acute Lethality 

17 

18 No information concerning acute lethality was located. 

19 

20 2.2. Nonlethal Toxicity 

21 

22 Albright and Wilson, Inc. (1985) reported the results of an air and health monitoring study on 

23 DMP conducted in a manufacturing facility in Charleston, South Carolina. The maximum partial 

24 shift (approximately 3- to 4-hours) employee exposure to DMP was 1.9 ppm and the average 

25 exposure was 0.22 ppm. The maximum 8-hour TWA concentration was 1.1 ppm and the 

26 average exposure was 0.16 ppm. A single maximum area sample of 3 ppm DMP was reported in 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 the immediate production area. The report did not describe the duration of the monitoring, but 

2 noted that exposure information had been obtained on an “ongoing basis.” It was also stated that 

3 standard practice was to obtain separate employee samples in the morning and afternoon from 

4 which an eight hour time weighted average was determined. Albright and Wilson, Inc. (1985) 

5 reported that medical surveillance of the workers did not indicate any significant adverse health 

6 effects related to historical exposures to DMP at this facility. The report states that respiratory 

7 protection is provided to employees during operations with highest exposure potential, to reduce 

8 actual exposure. 

9 

10 2.3. Developmental/Reproductive Toxicity 

11 

12 No human developmental/reproductive data were located. 

13 

14 2.4. Genotoxicity 

15 

16 No human genotoxicity data were located. 

17 

18 2.5. Carcinogenicity 

19 

20 No human carcinogenicity data were located. 

21 

22 2.6. Summary 

23 

24 Human data are limited to one workplace monitoring report where an average exposure of 

25 0.22 ppm did not show health effects. No other human data were located. 

26 

27 3. ANIMAL TOXICITY DATA 

28 3.1. Acute Lethality 

29 

30 A 1-hour rat LC50 of >5112 ppm was reported (Albright and Wilson, Inc., 1985). No other 

31 details were reported.

32 

33 3.2. Non-lethal Toxicity 

34 

35 Groups of ten male Swiss albino mice, ten male Wistar rats, and ten male English short-hair 

36 guinea pigs were exposed to a “mean theoretical concentration” of 1575 ppm DMP for 6 hours 

37 (Hazleton, 1962). Concentrations were calculated from air flow and net loss of test material. 

38 Exposures were conducted in a 500 liter stainless steel chamber with one or two fritted-disc glass 

39 bubblers at the inlet containing the DMP. A glass trap was placed between the vapor generator 

40 and chamber to collect liquid. Air flow was 18 L/minute with one bubbler and 35 L/min with 

41 two bubblers. Animals were observed continually during exposure for signs of toxicity and 

42 mortality. At the end of the seven day observation period, animals were sacrificed and 

43 necropsies were performed. There were no deaths during exposure or during the 7-day 

44 observation period. There were no clinical signs in rats or guinea pigs. Two mice had labored 

45 breathing after 1 hr- 50 min of exposure, and all mice had ptosis after 5 hours exposure. No 

46 other clinical signs were noted. Necropsies showed only lung congestion with pulmonary 

47 hemorrhage in rats and small hemorrhagic areas on the lungs of two guinea pigs. 

48 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 

2 3.3. Repeated-Exposure Studies 

3 

4 In a range-finding study, groups of five male and five female Sprague-Dawley rats were 

5 repeatedly exposed to 0, 431, 843, or 934 ppm DMP for six hours per day for five consecutive 

6 days (Biodymanics, 1980a). Animals were exposed in one cubic meter stainless steel and glass 

7 dynamic chambers, with an airflow of 83 L/min. The test atmosphere was generated by passing 

8 a nitrogen stream through a bubbler containing the DMP, varying the amount of nitrogen to 

9 volatilize the appropriate amount of test material. Test atmospheres were sampled four times per 

10 exposure (at 1, 2.5, 4, and 5.5 hours) for infrared analysis. Mortality was observed only in the 

11 934 ppm group. None of the female rats in the 934 ppm group survived beyond day three of 

12 exposure (1 was killed in extremis on day one, 3 died on day two, and 1 died on day three). 

13 Two males died and one was killed in extremis on day three, while one died and another was 

14 killed in extremis on day 4 prior to exposure. Clinical signs were observed in all DMP-exposed 

15 animals at all exposure levels. Excessive lacrimation, partially closed eyes, red nasal discharge, 

16 labored breathing, and unresponsiveness to sound stimuli were recorded during exposure in all 

17 treated groups. The time to observation of effects decreased with exposure concentration; effects 

18 were noted on day 1 for the 934 ppm group, day 2 for the 843 ppm group, and day 4 for the 431 

19 ppm group. On day 3, swelling of the limbs with red discoloration, fresh or dried ocular or nasal 

20 discharge, and dull, dry and/or cloudy corneal surfaces were observed in animals exposed to 431 

21 and 843 ppm, with the incidence of these effects increasing until termination. The authors 

22 suggested that the degradation of DMP to phosphorus acid was likely responsible for the irritant 

23 effects observed. Body weight loss or decreased body weight gain were noted in both sexes in 

24 the 843 and 934 ppm groups. Increased absolute and relative lung weights were noted in males 

25 from all treatment groups. Lung discoloration was noted in both sexes at all treatment levels, 

26 and congestive changes were noted only in high-concentration animals. 

27 

28 

29 Groups of twenty male and twenty female Sprague-Dawley rats were exposed to 0, 12, 35, 

30 119, or 198 ppm DMP 6 h/d, 5 d/wk, for up to 4 wks, followed by a 4-week follow-up period 

31 (Biodymanics, 1980b). Exposure methods were similar to those described above (Biodymanics, 

32 1980a). Up to five rats/sex/concentration were sacrificed 2, 4, and 6 weeks after the start of 

33 exposure, with the remaining survivors being sacrificed after 8 weeks. Lethality occurred at 

34 concentrations of 119 and 198 ppm. In the 198-ppm group, 13 males and 14 females died or 

35 were killed in extremis before day 27; in the 119-ppm group, one male died on day 23 and one 

36 female died on day 14. Neurological impairment, which was usually reversed by the following 

37 morning, was noted in the rats exposed to 119 and 198 ppm. Physical signs of irritation of the 

38 skin, mucous membranes, eyes, eyelids, and conjunctiva, and inflammation of the cornea 

39 (keratitis) were noted at concentrations of 35 ppm and above during clinical observation periods, 

40 and signs of respiratory irritation (rales) occurred at 119 ppm and above. Body weight reduction 

41 (8%) was reported for both male and female rats at concentrations of 119 and 198 ppm for much 

42 of the study period. Hemoglobin and hematocrit were decreased in males at 119 and 198 ppm 

43 and in females at 198 ppm. Increased SGPT, alkaline phosphatase, and urea levels were noted in 

44 males and females at 198 ppm, and increased SGPT (males) and decreased glucose concentration 

45 (males and females) were also noted at 119 ppm. Irritation of superficial ocular structures was 

46 observed in all treatment groups, and was associated with inflammatory changes of intraocular 

47 structures. Lenticular opacities were observed at concentrations of 35 ppm and above, and 

48 progressed to cataracts in the 119 and 198 ppm groups during the post-exposure period. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 Increased absolute and relative kidney weights were observed in all treatment groups. Red 

2 discoloration of the lungs and nasal turbinates and involution of the thymus were seen in 

3 decedents at 198 ppm. An increased incidence of hypospermatogenesis (decreased epididymal 

4 sperm content) was also reported in the two highest concentration groups. 

5 

6 

7 

8 3.4. Developmental/Reproductive Toxicity 

9 

10 No inhalation studies designed specifically to look at reproductive or developmental toxicity 

11 in animals were located. However, hypospermatogenesis was observed in 3/20 and 4/19 rats 

12 exposed via inhalation to 119 and 198 ppm DMP, respectively, for 6 hr/d, 5 d/wk for 4 weeks 

13 (Biodymanics, 1980b). 

14 

15 

16 3.5. Genotoxicity 

17 

18 Dimethyl phosphite was not mutagenetic in Salmonella typhimurium strains TA98, 

19 TA100, TA1535, or TA1537 in the presence or abcence of exogenous metabolic activation 

20 (NTP, 1985). DMP was positive with metabolic activation and negative without metabolic 

21 activation in the L5178Y tk+/- mouse lymphoma cell forward mutation assay (McGregor et al., 

22 1988). DMP caused chromosomal aberrations and sister chromatid exchanges in the Chinese 

23 hamster ovary assay with and without metabolic activation (Tennant et al., 1987). DMP was 

24 positive in a mouse bone marrow micronucleus test (Shelby et al., 1993). DMP did not induce 

25 sex linked recessive lethals in Drosophila melanogaster (NTP, 1995; Woodruff, 1985). 

26 

27 

28 3.6. Chronic Toxicity/Carcinogenicity 

29 

30 No inhalation data were located. Dimethyl phosphite was administered for 103 weeks by 

31 gavage in corn oil to groups of 50 male F344/N rats and groups of 50 male and 50 female 

32 B6C3F1 mice at doses of 0, 100, or 200 mg/kg (NTP, 1985; Dunnick et al., 1986). Groups of 50 

33 female F344/N rats were administered 0, 50, or 100 mg/kg. Dose-related toxicity was noted in 

34 the lungs of treated male and female rats, with lung lesions being most prevalent in high-dose 

35 male rats. Lung lesions included alveolar epithelial hyperplasia, chemical pneumonia, 

36 alveolar/bronchiolar adenoma and carcinoma, and squamous cell carcinoma. Neoplastic and 

37 non-neoplastic lesions were noted in the forestomachs of male and female rats, with males more 

38 severely affected. Mineralization of the cerebellum in male rats and focal calcification of the 

39 testes in male mice were also noted. 

40 

41 3.7. Summary 

42 

43 Animal inhalation data are limited. Clinical signs from both acute and repeated-exposure 

44 studies suggest that DMP is an irritant; effects included lacrimation, exophthalmos, respiratory 

45 distress, ocular opacities, cataracts, and pulmonary congestion. Genotoxicity testing yielded 

46 both positive and negative results. Hypospermatogenesis was noted in rats repeatedly exposed to 

47 DMP for 4-weeks. No inhalation data on chronic toxicity/carcinogenicity were located. 

48 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 4. SPECIAL CONSIDERATIONS 

2 4.1. Metabolism and Disposition 

3 

4 Studies in rats and mice suggest that DMP is oxidatively demethylated to monomethyl 

5 hydrogen phosphite and the methanol formed is further oxidized via formaldehyde to CO2. 

Nomeir and Matthews (1997) administered 10-200 mg/kg 14C 6 -labeled DMP to male F-344/N 

7 rats and male B6C3F1 mice. The compound was readily and essentially completely absorbed 

8 from the GI tract of both rats and mice and was eliminated primarily as expired CO2 (44-57%) 

9 and urine (28-49%). Only 1-2% was collected from feces and only 2-3% as volatile organics. 

10 Radioactivity was primarily distributed to the liver, kidneys, spleen, lungs and forestomach. 

11 Absorption, metabolism, and disposition were linear in both species. The clearance rate was two 

12 times faster in the mouse than in the rat. The monomethyl hydrogen phosphite metabolite was 

13 excreted in the urine of both species and suggests that DMP is demethylated in vivo. In vitro 

14 studies suggest that DMP is metabolized to formaldehyde in the liver, lung, kidney, forestomach 

15 and stomach of rats (Nomeir and Matthews, 1997). 

16 

17 4.2. Mechanism of Toxicity 

18 

19 Information concerning the mechanism of toxicity of DMP was not located; however, 

20 repeated-exposure studies in rats suggest that it is an irritant when inhaled. Clinical signs noted 

21 in rat inhalation studies include lacrimation, exophthalmos, respiratory distress, ocular opacities, 

22 cataracts, and pulmonary congestion. 

23 

24 

25 4.3. Structure Activity Relationships 

26 

27 DMP is structurally similar to organophosphate insecticides that inhibit cholinesterase 

28 activity; however, DMP does not appear to be a cholinesterase inhibitor. Repeated-exposure 

29 inhalation studies in rats (Biodymanics, 1980a,b) did not indicate systemic or cumulative toxic 

30 effects suggesting cholinesterase inhibition, but suggested the effects were indicative of local 

31 irritation. 

32 

33 4.4. Other Relevant Information 

34 

35 

36 

37 4.4.1. Species Variability 

38 

39 Data are not sufficient for determining species sensitivity. However, because DMP is an 

40 irritant via the inhalation route, little interspecies variability is expected. 

41 

42 4.4.2. Susceptible Populations 

43 

44 No information was available on populations especially sensitive to DMP toxicity. However, 

45 because DMP is an irritant via the inhalation route, little intraspecies variability is expected. 

46 

47 4.4.3. Concentration-Exposure Duration Relationship 

48 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 The concentration exposure time relationship for many irritant and systemically acting 

vapors and gases may be described by Cn 2 x t = k, where the exponent ranges from 0.8 to 3.5 (ten 

3 Berge et al. 1986). In lieu of a definitive data set allowing empirical derivation of the exponent 

4 n, temporal scaling was performed, using n = 3 when extrapolating to shorter time points and n = 

1 when extrapolating to longer time points using the Cn 5 x t = k equation (NRC, 2001). 

6 

7 4.4.4. Concurrent Exposure Issues 

8 

9 No concurrent exposure issues were identified. 

10 

11 5. DATA ANALYSIS FOR AEGL-1 

12 5.1. Summary of Human Data Relevant to AEGL-1 

13 

14 No human data relevant to development of AEGL-1 values were identified. 

15 

16 5.2. Summary of Animal Data Relevant to AEGL-1 

17 

18 No animal data relevant to development of AEGL-1 values were identified. 

19 

20 5.3. Derivation of AEGL-1 

21 

22 Data are insufficient to derive AEGL-1 values for dimethyl phosphite. Therefore, AEGL-1 

23 values are not recommended (Table 3). 

24 

TABLE 3. AEGL-1 values for dimethyl phosphite

10-minute 30-minute 1-hour 4-hour 8-hour 

NR NR NR NR NR 

25 NR: Not Recommended due to insufficient data. Absence of AEGL-1 values does not imply that concentrations 

26 below AEGL-2 are without effect. 

27 

28 

29 6. DATA ANALYSIS FOR AEGL-2 

30 6.1. Summary of Human Data Relevant to AEGL-2 

31 

32 No human data relevant to development of AEGL-2 values were identified. 

33 

34 6.2. Summary of Animal Data Relevant to AEGL-2 

35 

36 Mice exposed to 1575 ppm DMP for 6 hrs exhibited labored breathing and ptosis. No 

37 clinical signs were noted in rats and guinea pigs similarly exposed (Hazleton, 1962). 

38 

39 Irritation of superficial ocular structures associated with inflammatory changes of intraocular 

40 structures was observed in rats exposed to 12 ppm DMP 6 hr/day, 5 days/week for 4-weeks 

41 (Biodynamics, 1980b). 

42 

43 6.3. Derivation of AEGL-2 

44 

45 The clinical signs (labored breathing and ptosis) in mice exposed to 1575 ppm DMP for 6 
DIMETHYL PHOSPHITE Proposed: October, 2009 

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1 hours (Hazleton, 1962) will be used as the point-of-departure for AEGL-2 values. Inter- and 

2 intraspecies uncertainty factors of 3 each (total 10) will be applied because DMP is irritating, and 

3 much of the toxicity is likely caused by a direct chemical effect on the tissue; this type of portal4 of-entry effect is not expected to vary greatly between species or among individuals. The 

5 interspecies uncertainty factor of 3 is also considered sufficient because no clinical signs were 

6 noted in rats or guinea pigs exposed to 1575 ppm for 6 hours. A modifying factor of 3 will also 

7 be applied because of the sparse database and because the point-of-departure is a nominal 

8 concentration. The concentration-exposure time relationship for many irritant and systemicallyacting vapors and gases may be described by Cn 9 x t = k, where the exponent, n, ranges from 0.8 

10 to 3.5 (ten Berge et al., 1986). To obtain conservative and protective AEGL values in the 

11 absence of an empirically derived chemical-specific scaling exponent, temporal scaling may be 

12 performed using n=3 when extrapolating to shorter time points and n = 1 when extrapolating to 

longer time points using the Cn 13 x t = k equation (NRC, 2001). The 30-minute AEGL-2 value 

14 will also be adopted as the 10-min value because of the added uncertainty of extrapolating from 

15 the 6-hr point-of-departure. AEGL-2 values are presented in Table 4, and calculations are 

16 presented in Appendix A.

17 

TABLE 4. AEGL-2 values for dimethyl phosphate 

10-minute 30-minute 1-hour 4-hour 8-hour 

120 ppm 

(540 mg/m3) 

120 ppm 

(540 mg/m3) 

95 ppm 

(430 mg/m3) 

60 ppm 

(270 mg/m3) 

39 ppm 

(180 mg/m3) 

18 

19 

20 7. DATA ANALYSIS FOR AEGL-3 

21 7.1. Summary of Human Data Relevant to AEGL-3 

22 

23 No human data relevant to development of AEGL-3 values were identified. 

24 

25 7.2. Summary of Animal Data Relevant to AEGL-3 

26 

27 A 1-hr rat LC50 of >5112 ppm was reported (Albright and Wilson Inc., 1985). 

28 

29 Excessive lacrimation, partially closed eyes, red nasal discharge, labored breathing, and 

30 unresponsiveness to sound stimuli were noted in rats exposed to 843 ppm DMP 6 hr/day for 5 

31 days (Biodymanics, 1980a). Swelling of the limbs with red discoloration, fresh or dried ocular 

32 or nasal discharges, and dull, dry and/or cloudy corneal surfaces were also noted as was 

33 decreased body weight gain. Death was noted at the next highest concentration tested (934 ppm) 

34 as one rat was killed in extremis after day 1 of exposure. 

35 

36 

37 7.3. Derivation of AEGL-3 

38 

39 The highest concentration causing no mortality in rats (843 ppm for 6 hr) will be used as 

40 the point-of departure for AEGL-3 (Biodymanics, 1980a). Excessive lacrimation, partially 

41 closed eyes, red nasal discharge, red-brown material around the nares, labored breathing, and 

42 unresponsiveness to sound stimuli were noted in rats exposed to 843 ppm DMP 6 hr/day for 5 

43 days. Death was noted at the next concentration tested (934 ppm) essentially after one exposure 

44 because one rat was killed in extremis after day 1 of the study. Inter- and intraspecies 
DIMETHYL PHOSPHITE Proposed: October, 2009 

15

1 uncertainty factors of 3 each (total 10) will be applied because DMP is irritating, and much of the 

2 toxicity is likely caused by a direct chemical effect on the tissue; this type of portal-of-entry 

3 effect is not expected to vary greatly between species or among individuals. The concentration4 exposure time relationship for many irritant and systemically-acting vapors and gases may be 

described by Cn 5 x t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al., 1986). 

6 To obtain conservative and protective AEGL values in the absence of an empirically derived 

7 chemical-specific scaling exponent, temporal scaling may be performed using n=3 when 

8 extrapolating to shorter time points and n = 1 when extrapolating to longer time points using the 

Cn 9 x t = k equation (NRC, 2001). The 30-minute AEGL-3 value will also be adopted as the 10-

10 min value because of the added uncertainty of extrapolating from the 6-hr point-of-departure. 

11 AEGL-3 values are presented in Table 5, and calculations are presented in Appendix A.

12 

TABLE 5. AEGL-3 values for dimethyl phosphate 

10-minute 30-minute 1-hour 4-hour 8-hour 

190 ppm 

(850 mg/m3) 

190 ppm 

(850 mg/m3) 

150 ppm 

(670 mg/m3) 

96 ppm 

(430 mg/m3) 

63 ppm 

(240 mg/m3) 

13 

14 The AEGL-3 values are considered protective. Dividing the 1-hr rat LC50 of >5112 ppm 

15 (Albright and Wilson Inc., 1985) by 3, yields an estimated 1-hr lethality threshold of >1701 ppm. 

16 Applying a total uncertainty factor of 10, yields a value of 170 ppm; this concentration is 

17 consistent with the derived 1-hr AEGL-3 value. 

18 

19 8. SUMMARY OF AEGLS 

20 8.1. AEGL Values and Toxicity Endpoints 

21 

22 AEGL values are summarized in Table 6. AEGL-1 values are not recommended due to 

23 insufficient data. AEGL-2 values are based on labored breathing and ptosis in mice exposed to 

24 DMP for 6-hr. AEGL-3 values are based on the highest concentration causing no mortality in 

25 rats exposed to DMP for 6-hr. 

26 

TABLE 6. Summary of AEGL values 

Exposure Duration Classification 

10-minute 30-minute 1-hour 4-hour 8-hour 

AEGL-1 

(Nondisabling) NR NR NR NR NR 

AEGL-2 

(Disabling) 

120 ppm 

(540 mg/m3

) 

120 ppm 

(540 mg/m3) 

95 ppm 

(430 mg/m3) 

60 ppm 

(270 mg/m3) 

39 ppm 

(180 mg/m3) 

AEGL-3 

(Lethal) 

190 ppm 

(850 mg/m3

) 

190 ppm 

(850 mg/m3) 

150 ppm 

(670 mg/m3) 

96 ppm 

(430 mg/m3) 

63 ppm 

(240 mg/m3) 

27 NR: Not Recommended due to insufficient data. Absence of AEGL-1 values does not imply that concentrations 

28 below AEGL-2 are without effect. 

29 

30 

31 8.2. Comparison with Other Standards and Guidelines 

32 

33 No other standards or guidelines were located for dimethyl phosphite. 

34 

35 8.3. Data Adequacy and Research 
DIMETHYL PHOSPHITE Proposed: October, 2009 

16

1 

2 Human and animal data are both limited. Human data are limited to one workplace 

3 monitoring report. Acute animal inhalation data are limited to studies with nominal 

4 concentrations. Repeated-exposure analytical data are available. Additional acute inhalation 

5 toxicity studies would be helpful. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

17

1 

2 9. REFERENCES 

3 

4 

5 Albright and Wilson, Inc. 1985. Chemical Hazard Information File. Dimethyl Hydrogen 

6 Phosphite (DMHP) with 4 attachments. OTS05850379. 

7 

8 Biodynamics, 1980a. A five day inhalation toxicity study of MCTR-174-79 in the rat. Project 

9 No. 79-7344. March 4, 1980. 

10 

11 Biodynamics, 1980b. A four week inhalation toxicity study of MCTR-242-79 in the rat with 

12 pathology report and cover letter dated 122281. Project No. 79-7328. OTS02048661. 

13 

14 Dunnick, J.K., G.A. Boorman, J.K. Haseman, J. Langlos, R.H. Cardy, and A.G. Manus. 1986. 

15 Lung Neoplasms in Rodents after Chronic Administration of Dimethyl Hydrogen Phosphite. 

16 Cancer Res. 46: 264-270. 

17 

18 Hazleton, 1962. Initial Submission: Letter submitting acute inhalation exposure in mice, rat, 

19 and guinea pigs, on hexachloro-2-cyclopentanone (final report) with attachments. Hazelton 

20 Laboratories, Inc. Falls Church, VA. November 1, 1962. OTS0537047. 

21 

22 HSDB (Hazardous Substances Data Bank). 2009. Dimethyl Phosphite. [Online] Available. 

23 http://toxnet.nlm.nih.gov/ [02/09/2009]. TOXNET, Toxicology Data Network. US. Natl. Library 

24 of Medicine. 

25 

26 McGregor, D.B., Brown, A., Cattanach, P., Edwards, I., McBride, D. and Caspary, W.J. 1988. 

Responses of the L5178Y tk+

/tk- 27 mouse lymphoma cell forward mutation assay II: 18 coded 

28 chemicals. Environ. Mol. Mutagen. 11:91-118. 

29 

30 Nomeir, A.A. and Matthews, H.B. 1997. Metabolism and disposition of dimethyl hydrogen 

31 phosphite in rats and mice. J. Toxicol. Environ. Health. 51: 489-501. 

32 

33 NTP (National Toxicology Program). 1985. Toxicology and Carcinogenesis Studies of 

34 Dimethyl Hydrogen Phosphite in F344/N Rats and B6C3F1 Mice. Technical Report Series 

35 No. 287. Available online at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr287.pdf. 

36 

37 NRC (National Research Council). 2001. Standing operating procedures for developing acute 

38 exposure guideline levels for hazardous chemicals. Committee on Toxicology, Board on 

39 Toxicology and Environmental Health Hazards, Commission on Life Sciences, National 

40 Research Council. National Academy Press, Washington, DC. 

41 

42 Shelby, M.D., G.L. Erexson, G.J. Hook, and R.R. Tice. 1993. Evaluation of a Three-Exposure 

43 Mouse Bone Marrow Micronucleus Protocol: Results with 49 Chemicals. Environ. Mol. 

44 Mutagen. 21: 160-179. 

45 

46 ten Berge, W.F., A. Zwart, and L.M. Appelman. 1986. Concentration-time mortality response 

47 relationship of irritant and systemically acting vapours and gases. J. Hazard. Materials: 13: 

48 301-309. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

18

1 

2 Tennant, R.W., Spalding, J.W., Stasiewicz, S., Caspary, W.D., Mason, J.M. and Resnick, M.A. 

3 1987. Comparative evaluation of genetic toxicity patterns of carcinogens and noncarcinogens: 

4 strategies for predictive use of short-term assays. Environ. Health Perspect. 75: 87-95. 

5 

6 UNEP (United Nations Environmental Program Publications). 2004. Dimethyl Phosphonate. 

7 CAS No. 868-85-9. OECD SIDS Initial Assessment Report. 

8 

9 Woodruff, R.C., Mason, J.M., Valencia, R., and Zimmering, S. 1985. Chemical mutagenesis 

10 testing in Drosophila. V. Results of 53 coded compounds tested for the National Toxicology 

11 Program. Environ. Mutagen. 7: 677-702. 

12 

13 
DIMETHYL PHOSPHITE Proposed: October, 2009 

19

1 

2 APPENDIX A: Derivation of AEGL Values

3 

4 Derivation of AEGL-1 

5 

6 

7 AEGL-1 values are not recommended due to insufficient data. Absence of AEGL-1 values does 

8 not imply that concentrations below AEGL-2 are without effect.
DIMETHYL PHOSPHITE Proposed: October, 2009 

20

1 Derivation of AEGL-2 

2 

3 Key Study: Hazleton, 1962. Initial Submission: Letter submitting acute inhalation exposure 

4 in mice, rat, and guinea pigs, on hexachloro-2-cyclopentanone (final report) with 

5 attachments. Hazelton Laboratories, Inc. Falls Church, VA. November 1, 1962. 

6 OTS0537047. 

7 

8 Toxicity endpoint: Labored breathing and ptosis in mice exposed to 1575 ppm DMP for 6 

9 hours. 

10 

11 Uncertainty factors: Interspecies: 3, DMP is irritating, and much of the toxicity is likely caused 

12 by a direct chemical effect on the tissues; this type of portal-of-entry effect 

13 is not expected to vary greatly between species. The interspecies 

14 uncertainty factor of 3 is also considered sufficient because no clinical 

15 signs were noted in rats or guinea pigs exposed to 1575 ppm for 6 hours. 

16 

17 Intraspecies: 3, DMP is irritating, and much of the toxicity is likely caused 

18 by a direct chemical effect on the tissues; this type of portal-of-entry effect 

19 is not expected to vary greatly among individuals. 

20 

21 Modifying factor: 3: Sparse data base and nominal concentration for point-of-departure 

22 

Time scaling: C3 23 x t = k (30-min, 1-hr, 4-hr) 

1575 ppm 3 x 6 hr = 2.34 x 1010 ppm3 24 -hr 

25 

C1 26 x t = k (8-hr) 

27 1575 ppm x 6 hr = 9450 ppm-hr 

28 

29 10-minute AEGL-2: 30-min value adopted as 10-min value = 120 ppm 

30 

30-minute AEGL-2: C3

 x 0.5 hr = 2.34 x 1010 ppm3 31 ·hr 

 C3 = 4.68 x 1010 32 ppm 

33 C = 3604 ÷ 30 = 120 ppm 

34 

1-hour AEGL-2: C3

 x 1 hr = 2.34 x 1010 ppm3 35 ·hr 

 C3 = 5.85x 109 36 ppm 

37 C = 2860 ÷ 30 = 95 ppm 

38 

4-hour AEGL-2: C3

 x 4 hr = 2.34 x 1010 ppm3 39 ·hr 

 C3

 = 5.85 x 109 40 ppm 

41 C = 1802 ÷ 30 = 60 ppm 

42 

8-hour AEGL-2: C1

 x 8 hr = 9450 ppm3 43 ·hr 

 C1 44 = 1181 ppm 

45 C = 1181 ÷ 30 = 39 ppm 

46 

47 
DIMETHYL PHOSPHITE Proposed: October, 2009 

21

1 

2 Derivation of AEGL-3 

3 

4 Key Study: Biodynamics, 1980a. A five day inhalation toxicity study of MCTR-174-

5 79 in the rat. Project No. 79-7344. March 4, 1980. 

6 

7 Toxicity endpoint: Highest concentration causing no mortality in rats (843 ppm for 6 hr). 

8 Excessive lacrimation, partially closed eyes, red nasal discharge, red9 brown material around the nares, labored breathing, and unresponsiveness 

10 to sound stimuli were noted in rats exposed to 843 ppm DMP 6 hr/day for 

11 5 days. Death was noted at the next concentration tested (934 ppm) 

12 essentially after one exposure because one rat was killed in extremis after 

13 day 1 of the study. 

14 

15 Uncertainty factors: Interspecies: 3, DMP is irritating, and much of the toxicity is likely caused 

16 by a direct chemical effect on the tissues; this type of portal-of-entry effect 

17 is not expected to vary greatly between species. 

18 

19 Intraspecies: 3, DMP is irritating, and much of the toxicity is likely caused 

20 by a direct chemical effect on the tissues; this type of portal-of-entry effect 

21 is not expected to vary greatly among individuals. 

22 

23 Modifying factor: None 

24 

Time scaling: C3 25 x t = k (30-min, 1-hr, 4-hr) 

843 ppm 3 x 6 hr = 3.59 x 109

 ppm3 26 -hr 

27 

C1 28 x t = k (8-hr) 

29 843 ppm x 6 hr = 5058 ppm-hr 

30 

31 10-minute AEGL-3: 190 ppm: 30-min value adopted as 10-min value 

32 

30-minute AEGL-3: C3

 x 0.5 hr = 3.59 x 109 ppm3 33 ·hr 

 C3

 = 7.18 x 109 34 ppm 

35 C = 1929 ÷ 10 = 190 ppm 

36 

1-hour AEGL-3: C3

 x 1 hr = 3.59 x 109 ppm3 37 ·hr 

 C3 = 3.59 x 109 38 ppm 

39 C = 1531 ÷ 10 = 150 ppm 

40 

4-hour AEGL-3: C3

 x 4 hr = 3.59 x 109 ppm3 41 ·hr 

 C3

 = 8.98 x 108 42 ppm 

43 C = 964 ÷ 10 = 96 ppm 

44 

8-hour AEGL-3: C1

 x 8 hr = 5058 ppm3 45 ·hr 

 C1 46 = 632 ppm 

47 C = 632 ÷ 10 = 63 ppm 
DIMETHYL PHOSPHITE Proposed: October, 2009 

22

1 

2 

3 APPENDIX B: Derivation Summary for Dimethyl Phosphite AEGLs 

4 

5 

6 AEGL-1 VALUES 

10-minute 30-minute 1-hour 4-hour 8-hour 

NR NR NR NR NR 

Key Reference: 

Test Species/Strain/Number: 

Exposure Route/Concentrations/Durations: 

Effects: 

Endpoint/Concentration/Rationale: 

Uncertainty Factors/Rationale: 

Total uncertainty factor: 

Interspecies: 

Intraspecies: 

Modifying Factor: NA 

Animal to Human Dosimetric Adjustment: NA 

Time Scaling: 

Data Adequacy: Not Recommended due to insufficient data. Absence of AEGL-1 values does not imply that 

concentrations below AEGL-2 are without effect. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

23

1 

2 AEGL-2 VALUES 

10-minute 30-minute 1-hour 4-hour 8-hour 

120 ppm 

(540 mg/m3) 

120 ppm 

(540 mg/m3) 

95 ppm 

(430 mg/m3) 

60 ppm 

(270 mg/m3) 

39 ppm 

(180 mg/m3) 

Key Reference: Hazleton, 1962. Initial Submission: Letter submitting acute inhalation exposure in mice, rat, and 

guinea pigs, on hexachloro-2-cyclopentanone (final report) with attachments. Hazelton Laboratories, Inc. Falls 

Church, VA. November 1, 1962. OTS0537047. 

Test Species/Strain/Number: Mouse/Swiss albino/10 males 

Exposure Route/Concentrations/Durations: Inhalation/1575 ppm/6-hr 

Effects: Labored breathing (2/10) and ptosis (10/10). 

Endpoint/Concentration/Rationale: Labored breathing and ptosis/1575 ppm 

Uncertainty Factors/Rationale: 

Total uncertainty factor: 10 

Interspecies: 3 

Intraspecies: 3 

DMP is highly irritating, and much of the toxicity is likely caused by a direct chemical effect on the tissue; this type 

of portal-of-entry effect is not expected to vary greatly between species or among individuals. The interspecies 

uncertainty factor of 3 is also considered sufficient because no clinical signs were noted in rats and guinea pigs 

exposed to 1575 ppm for 6 hr. 

Modifying Factor: 3: Sparse data base and nominal concentration point-of-departure 

Animal to Human Dosimetric Adjustment: NA 

Time Scaling: Cn x t = k. To obtain conservative and protective AEGL values in the absence of an empirically 

derived chemical-specific scaling exponent, temporal scaling was performed using n=3 when extrapolating to 

shorter time points and n = 1 when extrapolating to longer time points using the Cn

 x t = k equation (NRC, 2001). 

The 30-min AEGL-2 value was adopted as the 10-min value because the point-of-departure is 6-hr. 

Data Adequacy: Sparse data set. 

3 
DIMETHYL PHOSPHITE Proposed: October, 2009 

24

1 

2 

3 AEGL-3 VALUES 

4 

5 

10-minute 30-minute 1-hour 4-hour 8-hour 

190 ppm 

(850 mg/m3

) 

190 ppm 

(850 mg/m3) 

150 ppm 

(670 mg/m3) 

96 ppm 

(430 mg/m3) 

63 ppm 

(240 mg/m3) 

Key Reference: Biodynamics, 1980a. A five day inhalation toxicity study of MCTR-174-79 in the rat. Project No. 

79-7344. March 4, 1980. 

Test Species/Strain/Number: Rat/Sprague-Dawley/ 5/sex/group 

Exposure Route/Concentrations/Durations: Inhalation/ 431, 843, 934 ppm/6-hr for up to five days 

Effects: All Concentration Groups: Excessive lacrimation, partially closed eyes, red nasal discharge, red-brown 

material around the nares, labored breathing, and unresponsiveness to sound. 

 

934 ppm: Mortality. One rat killed in extremis on day 1, 8/9 remaining rats died before study termination. 

Endpoint/Concentration/Rationale: Highest concentration causing no mortality in rats. Death was noted at the next 

concentration tested (934 ppm) essentially after one exposure because one rat was killed in extremis after day 1 of 

the study. /843 ppm for 6-hr

Uncertainty Factors/Rationale: 

Total uncertainty factor: 10 

Interspecies: 3 

Intraspecies: 3 

DMP is highly irritating, and much of the toxicity is likely caused by a direct chemical effect on the tissue; this type 

of portal-of-entry effect is not expected to vary greatly between species or among individuals. 

Modifying Factor: NA: 

Animal to Human Dosimetric Adjustment: NA 

Time Scaling: Cn x t = k. To obtain conservative and protective AEGL values in the absence of an empirically 

derived chemical-specific scaling exponent, temporal scaling was performed using n=3 when extrapolating to 

shorter time points and n = 1 when extrapolating to longer time points using the Cn

 x t = k equation (NRC, 2001). 

The 30-min AEGL-3 value was adopted as the 10-min value because the point-of-departure is 6-hr. 

Data Adequacy: Sparse data set. However, the AEGL-3 values are considered protective. Dividing the 1-hr rat 

LC50 of >5112 ppm (Albright and Wilson Inc., 1985) by 3, yields an estimated 1-hr lethality threshold of >1701 

ppm. Applying a total uncertainty factor of 10, yields a value of 170 ppm; this concentration is consistent with the 

derived 1-hr AEGL-3 value. 
DIMETHYL PHOSPHITE Proposed: October, 2009 

25

1 

2 APPENDIX C: Category Plot for Dimethyl Phosphite 

3 

4 

5 

1 

10 

100 

1000 

10000 

ppm

0 60 120 180 240 300 360 420 480 

Minutes

Human - No Effect

Human - Discomfort

Human - Disabling

Animal - No Effect

Animal - Discomfort

Animal - Disabling

Animal - Partially Lethal

Animal - Lethal

AEGL

Chemical Toxicity

 Dimethyl Phosphite

AEGL-2

6 

7 

8 

9 

10 Note: Animal partially lethal data points at 360 minutes are from repeated exposure studies. Lethality was 

11 not noted until after 14-27 days of exposure.
DIMETHYL PHOSPHITE Proposed: October, 2009 

26

1 Category Plot Data 

2 

3 

Source Species Sex # Exposures ppm Minutes Category Comments 

NAC/AEGL-1 NR 10 AEGL 

NAC/AEGL-1 NR 30 AEGL 

NAC/AEGL-1 NR 60 AEGL 

NAC/AEGL-1 NR 240 AEGL 

NAC/AEGL-1 NR 480 AEGL 

 

NAC/AEGL-2 120 10 AEGL 

NAC/AEGL-2 120 30 AEGL 

NAC/AEGL-2 95 60 AEGL 

NAC/AEGL-2 60 240 AEGL 

NAC/AEGL-2 39 480 AEGL 

 

NAC/AEGL-3 190 10 AEGL 

NAC/AEGL-3 190 30 AEGL 

NAC/AEGL-3 150 60 AEGL 

NAC/AEGL-3 96 240 AEGL 

NAC/AEGL-3 63 480 AEGL 

 

 Rat 1 5112 60 pl free standing LC50 >5112 ppm 

 Rat 1 1575 360 0 no clinical signs 

 Gp 1 1575 360 0 no clinical signs 

 Mouse 1 1575 360 2 labored breathing (1/10), ptosis (10/10) 

 Rat 5 431 360 2 lacrimation, nasal discharge, labored breathing, 

unresponsive to sound, corneal effects 

 Rat 5 843 360 2 lacrimation, nasal discharge, labored breathing, 

unresponsive to sound, corneal effects, 

increased lung weight 

 Rat 5 934 360 3 10/10 mortality, days 1-4 of 5 day exposure 

protocol 

 Rat 20 12 360 1 Irritation of superficial ocular structure 

 Rat 20 35 360 1 skin, mucous membrane, ocular irritation 

 Rat 20 119 360 pl 2/40 mortality days 14-23; signs of irritation, 

rales, decreased BW, hematological effects, 

ocular opacity, cataract 

 Rat 20 198 360 pl 27/40 mortality before day 27; 

signs of irritation, rales, decreased BW, 

hematological effects, ocular opacity, cataract 

4