                                      P-14-0321/0323
              Office of Chemical Safety and Pollution Prevention
United States
Environmental Protection Agency
 





MEMORANDUM

SUBJECT:	Risk Assessment on P-14-0323 and P-14-0321

FROM:		[ 
		                               ]
		Risk Assessment Division (7403M)
		Office of Pollution Prevention and Toxics

THRU		[
                  ]
		Risk Assessment Division (7403M)
      Office of Pollution Prevention and Toxics

TO:		[                             ]
		Chemical Control Division
		Office of Pollution Prevention and Toxics


This document is a human health risk assessment on P-14-0321 and P-14-0323 based upon toxicology data submitted by [                     ] and revised worker and population exposures.

TABLE OF CONTENTS
1	PMN CHEMICALS	4
1.1	P-14-0321	4
1.1.1	Structure:	4
1.1.2	Names:	4
1.2	P-14-0323	4
1.2.1	Structure:	4
1.2.2	Names:	4
2	HEALTH EFFECTS TOXICITY DATA	5
2.1	P-14-0321	5
2.1.1	Toxicology Data Summary on P-14-0321	5
2.2	P-14-0323	5
2.2.1	Toxicology Data Summary on P-14-0323	5
2.3	Synopsis of Toxicity Data on P-14-0321; P-14-323 and [                         ] Product	7
3	EXPOSURE TO P-14-0321/0323	7
3.1	Occupational Exposure	7
3.2	General Population Exposures	10
3.2.1	P-14-0321	11
3.2.2	P-14-0323	12
4	RISK ASSESSMENT	15
4.1	Human Health Risk Discussion	15
4.1.1	Effects Levels Used to Determine Non-cancer Risk for Single Exposure Effects	15
4.1.1.1	P-14-0321	15
4.1.1.2	P-14-0323	16
4.1.1.3	Benchmark MOE Determination	17
4.1.2	Occupational Risk Discussion	17
4.1.2.1	MOE Calculations P-14-0321 - Worker	18
4.1.2.2	MOE Calculations P-14-0323 - Worker	18
4.1.2.3	Risk Discussion - Worker	18
4.1.3	General Population Risk Discussion	19
4.1.3.1	MOE Calculations P-14-0321 - Population	19
4.1.3.2	MOE Calculations P-14-0323 - Population	19
4.1.3.3	Risk Discussion - Population	20
4.1.4	Uncertainties in Risk Assessment  -  Focus on P-14-0323	20
4.1.4.1	Endpoint	20
4.1.4.1.1	MOE Calculations are for 1 Exposure/Day	20
4.1.4.2	Worker Exposure	21
4.1.4.2.1	Worker Exposure Chemical Used for Estimate	21
4.1.4.2.2	Workplace Activity	21
4.1.4.2.3	Duration of Operator Exposure	22
4.1.4.3	General Population Exposures	22
5	Human Health Recommendations	22
5.1	Worker - Sampling	22
5.2	Worker - Laboratory Analysis	22
5.3	Population Risk	22
REFERENCES	23
Appendix A	POINT OF DEPARTURE CALCULATIONS	23
LIST OF TABLES
Table 2-1 Comparative toxicity of PMNs in different species	7
Table 3-1 Occupational Inhalation Exposures from EPA Initial Review Engineering Report (IRER) using ChemSTEER for P-14-0321 & 0323	9
Table 3-2 Occupational Inhalation Exposures from Monitoring Data Provided by [         ] on [        ]	9
Table 3-3 P-14-0321. General Population Exposures Using a Distance of 500 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	11
Table 3-4 P-14-0321. General Population Exposures Using a Distance of 500 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency Efficiency for Fugitive Emissions	11
Table 3-5 P-14-0321. General Population Exposures Using a Distance of 50 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	12
Table 3-6 P-14-0321. General Population Exposures Using a Distance of 50 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	12
Table 3-7 P-14-0323. General Population Exposures Using a Distance of 500 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	13
Table 3-8 P-14-0323. General Population Exposures Using a Distance of 500 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	13
Table 3-9 P-14-0323. General Population Exposures Using a Distance of 50 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions for Fugitive Emissions	14
Table 3-10 P-14-0323. General Population Exposures Using a Distance of 50 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions	14
Table 4-1 P-14-0321 Occupational MOE Calculations for Single Exposures	18
Table 4-2 P-14-0323 Occupational MOE Calculations for Single Exposures	18
Table 4-3 P-14-0321 General Population MOE Calculations for Single Exposures	19
Table 4-4 P-14-0323 General Population MOE Calculations for Single Exposures	20

LIST OF FIGURES
Figure 1-1 P-14-0321 Structure	4
Figure 1-2 P-14-0323 Structure	4
Figure 2-1 [                        ] = end product of P-14-0321 & 0323 Reactions	7
Figure 4-1 Point of Departure Calculations P-14-0321  -  See Appendix A for Formulas and Constants	16
Figure 4-2 Point of Departure Calculations P-14-0323  -  See Appendix A for Formulas and Constants	17

ADDENDUM: ECOTOXICITY ESTIMATES FOR P-14-0321 AND P-14-0323 ....................................................27



PMN CHEMICALS
P-14-0321
Structure:

                                      CBI
Figure 1-1 P-14-0321 Structure
MW = [           ]
Names:
   * CBI
P-14-0323

Structure:

                                      CBI
Figure 1-2 P-14-0323 Structure
MW = [               ]
Names:
   * CBI


HEALTH EFFECTS TOXICITY DATA
P-14-0321
Toxicology Data Summary on P-14-0321
   * Summary: Rat 4 hour acute toxicity. Two separate studies.
         o       The PMN is not lethal with 4 hours exposure to 11, 537 ppm and 52,538 ppm. 
         o       The PMN is not lethal with 4 hours exposure to 96,936 ppm. At necropsy both males and females exhibited gray discoloration of the lungs (3 total) and petechiae on one or more lung lobes (5 animals total). The report notes that "These gross lesions were considered to be related to the exposure."
   * Acute toxicity studies: Rats were exposed in two separate studies for a single 4 hour exposure to concentrations of 11,537 ppm 52,538 ppm and 96,936 ppm.
   * RCCHan:WIST rats, 2 male and 2 female, were exposed nose-only to a target concentration of 50,000 ppm for 4 hours and observed for 14 days. Animals were exposed in a four armed plethysmograph. No controls were run. In a first experiment the target concentration was not reached and the nominal concentration was determined to be 11,537 ppm. For that reason a second experiment was performed and the nominal concentration was 52,538 ppm. 

At 11,537 ppm clinical observations included shallow breathing, decreased frequency and dyspnoea, piloerection. No effects were seen from 2 days after exposure to the end of the 14 day observation period. No abnormalities were seen at necropsy. Males showed body weight loss one day after exposure but gained weight thereafter. The weight loss may have been due to restraint used during exposure. No weight loss was observed in females. All animals gained weight after the first day.
      
      At 52,538 ppm clinical signs included decreased breathing frequency. After exposure no signs were noted. No abnormalities were seen at necropsy. Males showed body weight loss one day after exposure but gained weight thereafter. The weight loss may have been due to restraint used during exposure. No weight loss was observed in females. All animals gained weight after the first day.
   * Wistar outbred rats, 3 males and 3 females, were exposed nose only to a target concentration of 100,000 ppm for 4 hours and observed for 14 days. The analytical concentration using a total carbon analyzer was 96,936 ppm. No control animals were used.
      All animals exhibited shallow breathing, dyspnoea and altered breathing rate that increased in frequency and severity during exposure. They resolved shortly after exposure. Animals showed a slight weight loss after day 1 of exposure. The animals exhibited normal growth after the first week post-exposure. The authors considered this be partially due to restraints used during exposure. No animals died. At necropsy both males and females exhibited gray discoloration of the lungs (3 total) and petechiae on one or more lung lobes (5 animals total). The report notes that "These gross lesions were considered to be related to the exposure."
      
P-14-0323
Toxicology Data Summary on P-14-0323
   * Rat acute toxicity.
         o The PMN is not lethal with 4 hours exposure to 20,516 ppm.
      Wistar outbred rats were exposed nose only to target concentrations of 5,000, 20,000 and 100,000 ppm of the PMN for different durations. Analytical concentrations were determined by a total carbon analyzer and were 4,922, 20,516, and 98,184 ppm. At each exposure concentration/duration 2 male and 2 female rats were exposed. Durations for the 4,922 ppm exposure were 60, 85 230, 170 and 240 minutes. Durations for the 20,516 ppm exposure were 15, 30, 60, 120, and 240 minutes. Durations for the 98,184 ppm exposure were 9, 17, 32, and 60 minutes.
   
      No animals died at any of the exposure/duration concentrations tested. The report states "Exposure to 2-chloro-3,3,3-trifluoropropene induced respiratory abnormalities such as a decreased breathing frequency, irregular breathing, shallow breathing and sniffing. Behavioural abnormalities included lethargy, muscle weakness, excessive grooming and hunched posture. Animals showed a body weight loss on the day after exposure, but had gained weight again on day 3 and in all but a few cases had gained weight on day 7 compared to their pre-exposure weight. At necropsy, exposure related abnormalities were not seen."
   
      In the 4,922 ppm exposure group the breathing irregularities disappeared 4 days after exposure.
   
      In the 20,516 exposure group breathing irregularities persisted for 12 days in males exposed for 120 minutes and longer. In females the breathing irregularities persisted for 9 days in animals exposed for 30 minutes or longer. Muscle weakness was observed in males and females exposed for 30 minutes or longer. The frequency of this response was higher in the females.
   
      In the 98,184 ppm exposure group breathing irregularities were observed at durations of 17 minutes and longer in males and females. They persisted longer in females (3-5 days) than in males (1-4 days). Although lethargy and muscle weakness was observed in this group the effects did not persist as long as they did in the 20,516 ppm exposure group.

   * Mouse acute toxicity.
         o Male/Female 4 hour LC50 = 479/402
         o Male/Female 1 hour LC50 = 6,098/5,123
      
      Mice (2 male and 2 female) were exposed to concentrations between 2,500 ppm and 20,000 ppm for durations between 13 and 240 minutes. Durations varied according to the concentration tested with lower concentrations tested for longer durations and vice-versa.
      o Using the data generated the submitter calculated an n of 0.545 in the equation C[n] * t = k where C = exposure concentration, t = duration, n = exponent and k = constant. The one and four hour LC50 values were estimated to be 6,098 and 479 ppm for males and 5,123 and 402 ppm for females respectively. The value of n in the equation is very low. Typically n varies between 1 and 3 and may approach infinity for chemicals that equilibrate rapidly and act through peak blood levels (NRC, 2001). In the history of the AEGL program that has looked at hundreds of chemicals no value of n has been so low. Given the structure of the experiment (2 animal per sex per dose/concentration combination), lack of precision and the AEGL Program experience, the value of n is probably close to 1 or greater. There is uncertainty about the LC50 values.


   0.1 Synopsis of Toxicity Data on P-14-0321; P-14-323 and [          ] Product
Below is a brief overview of toxicity and studies available on the chemicals. The reaction sequence is P-14-323 + HF -> P-14-321 -> [             ]. 

CBI

Figure 2-1 [                              ] = end product of P-14-0321 & 0323 Reactions

Table 2-1 Comparative toxicity of PMNs in different species
PMN
Acute Tox^
Repeat tox^

Mouse
Rat
Rabbit
Mouse
Rat
Rabbit
P-14-0321
ND
low
ND
ND
ND
ND
P-14-0323
high
low
ND
ND
ND
ND
[               ]
low
low
low
ND
low
moderate
[               ]
low
low
ND
low
low
ND
^	ND = No Data
	Qualitative toxicity values assigned per US EPA, 2011
       low = Relatively non-toxic  -  Acute LC50 >20,000 mg/m[3]; 28 day repeated dose NOAEL <600 mg/m[3]
      moderate = Relatively toxic  -  Acute LC50 >10,000-20,000 mg/m[3]; 28 day repeated dose NOAEL 600-3,000 mg/m[3]
      high = Relatively toxic  -  Acute LC50 >2,000-10,000 mg/m[3]; 28 day repeated dose NOAEL <600 mg/m[3]
Note  -  this is a gross oversimplification and is meant only to give a relative picture of what is, and is not, known about toxicity in these chemicals

EXPOSURE TO P-14-0321/0323

The Initial Review Engineering Report (IRER) reports on P-14-0321 and P-14-0323 show the same basis and occupational exposure levels so they are combined below in the description of exposure.
Occupational Exposure
Background
Both PMNs are site-limited intermediates and will be used and consumed in one plant. Both PMNs are consumed in manufacturing [                           ], a [                                              ]. Use of [             ] will likely expand to include all forms of [                   ] applications. It has a low global warming potential and is an ultimate replacement for global warming [                   ] chemicals. [                ] met with the Agency on May 27, 2015. They discussed the manufacturing process and controls for P-14-0321/0323. [                    ] stated that worker exposures could occur during sampling, line breaking and laboratory analysis. They did not discuss procedures in the laboratory when the samples are analyzed. [                    ] submitted operator and laboratory worker exposure data for [                         ]. These data were used to calculate worker exposures in the IRER.
   * Sampling  -  The sampling process involves connecting the sampling device to the PMN process line. There is a valve between the vessel and the sampling device that is closed when the connection is made. To sample, valves are then opened between the PMN vessel and sampling device to collect the sample. The valves are then closed and the sampling device removed. The only opportunity for exposure is when the sampling device is disconnected and involves the amount of PMN left in the dead space. The duration of exposure should be less than a minute per sampling event. There are 8 samples taken per 12-hour shift.
   * Line breaking  -  The lines may be broken for maintenance. Before this is done, the vessel and lines are purged with nitrogen and other documented standard operating procedures (verbally communicated from [                      ]). Because of purging with nitrogen, vacuum treatment, etc. exposures due to line breaking are not expected.
   * Laboratory analysis of sample  -  [                    ] presented monitoring data for [                ], another fluorochemical with similar pchem properties.

IRER Worker Exposure Report Dated 2016-04-27
All worker exposures are by inhalation. All exposure values have been recalculated as ppm so they can be more transparently compared with the toxicity data. The worker exposure Potential Dose Rate (PDR) was presented as mg/day in the IRER. The exposure calculations were based on the submitter-provided average and the high-end airborne concentrations (monitoring data) for structure operators (0.136 ppm and 5.2 ppm respectively) and laboratory technicians (0.654 ppm and 10 ppm respectively).



Table 3-1 Occupational Inhalation Exposures from EPA Initial Review Engineering Report (IRER) using ChemSTEER for P-14-0321 & 0323
Process
# sites
Activity
# sites
 # workers
 # days/yr
Scenario
Potential Dose Rate
--------------------------------------------------------------------------------
Exposure per day*
8 hour TWA
Exposure - calculated
8 hr TWA in ppm**
Total exposure duration per day
Manufacturing
1 site
Sampling PMN
@ 1 site


250
3 workers  -  12 hour shift
--------------------------------------------------------------------------------
40 mg
4.0 mg/m[3] 
 0.75 ppm
8 minutes




3 workers  -  12 hour shift
--------------------------------------------------------------------------------
610 mg
61 mg/m[3] 
11 ppm
8 minutes
Manufacturing
1 site
Laboratory analysis of sample @ 1 site


250
8 hour shift
--------------------------------------------------------------------------------
40 mg
4.0 mg/m[3] 
 0.75 ppm
8 hours




8 hour shift
--------------------------------------------------------------------------------
610 mg
61 mg/m[3] 
11 ppm
8 hours
* For risk calculations, TWA values are expressed as 8 hour values. It should be noted that the submitter provided 8-hour TWA monitoring data for structure operators and laboratory technicians. However, the structure operators are expected to work 12-hour shifts and the laboratory technicians are expected to work 8-hour shifts based on submitter data.
** ppm values are calculated for P-14-0323 [                   ]. Values for P-14-0321 will be slightly lower [                        ].

Table 3-2 Occupational Inhalation Exposures from Monitoring Data Provided by [                     ] on [                  ]
Process
# sites
Activity
# sites
 # workers
 # days/yr
Scenario
8 hour TWA
Total exposure duration per day
Manufacturing
1 site
Operator PMN
@ 1 site


250
Average of range - 
3 workers  -  12 hour shift
0.136 ppm
8 minutes




High end of range  -  
3 workers  -  12 hour shift
5.2 ppm
8 minutes
Manufacturing
1 site
Laboratory analysis of sample @ 1 site


250
Average of range - 
8 hour shift
0.654 ppm
8 hours




High end of range - 
8 hour shift
10 ppm
8 hours

General Population Exposures
The [                     ] site is located in [                           ] and site specific model inputs were provided by [                      ] and incorporated into EPA's air modeling.  Stack and fugitive height of releases, efficiency, and distance were considered. A distance of 500 meters was selected to better represent near facility general population for this site.  A distance of 50 meters was selected to better represent bystander, visitor, and worker exposure near the building. EPA's standard default is 100 meters. At a distance of 500 meters, 24 hour estimated air concentrations range from 33 to 222 ug/m3. At a distance of 50 meters, 24 hour estimated air concentrations range from 102 to 939 ug/m3.  Fugitive emissions are the major source of airborne emissions, >95 %, far exceeding any other source. Information was provided on the efficiency of fugitive releases for the company's existing Title V of the Clean Air Act  (Title V - Permits; CAA Sections 501-507; USC Sections 7661-7661f) air permit and technology used to control and repair leaks. Using available information, EPA assessed 0% and 90% efficiency although there is uncertainty as to what the actual percent efficiency could be. The 24 hour duration is used for the airborne concentration because the plant runs for 24 hours.


P-14-0321

Table 3-3 P-14-0321. General Population Exposures Using a Distance of 500 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                             39
                                                                         0.0039
                                                                              3
10 m
                                                                       3.55E-06
--------------------------------------------------------------------------------
0.02
                                                                         9.3E-6
                                                                       2.47E-09
Fugitive
                                                                            90%
                                                                            9.6
                                                                           0.96
                                                                            279
4 m
                                                                       3.84E-03
--------------------------------------------------------------------------------
21.00
                                                                         3.4E-3
                                                                       9.76E-05
Stack
                                                                             0%
                                                                            5.7
                                                                            5.7
                                                                            279
50 ft.
                                                                       1.94E-03
--------------------------------------------------------------------------------
10.60
                                                                         1.7E-3
                                                                       1.25E-04
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       4.74E-07
--------------------------------------------------------------------------------
0.0026
                                                                         4.2E-7
                                                                       3.07E-08
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       2.25E-04
--------------------------------------------------------------------------------
1.23
                                                                         2.0E-4
                                                                       1.46E-05
                             Total Manufacturing 
                                                                       6.01E-03
--------------------------------------------------------------------------------
32.85
                                                                         5.3E-3
                                                                       2.37E-04

Table 3-4 P-14-0321. General Population Exposures Using a Distance of 500 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                             39
                                                                         0.0039
                                                                              3
10 m
                                                                       3.55E-06
--------------------------------------------------------------------------------
0.02
                                                                         3.2E-6
                                                                       2.47E-09
Fugitive
                                                                             0%
                                                                            9.6
                                                                            9.6
                                                                            279
4 m
                                                                       3.84E-02
--------------------------------------------------------------------------------
210.00
                                                                         3.4E-2
                                                                       9.76E-04
Stack
                                                                             0%
                                                                            5.7
                                                                            5.7
                                                                            279
50 ft.
                                                                       1.94E-03
--------------------------------------------------------------------------------
10.60
                                                                         1.7E-3
                                                                       1.25E-04
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       4.74E-07
--------------------------------------------------------------------------------
0.0026
                                                                         4.2E-7
                                                                       3.07E-08
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       2.25E-04
--------------------------------------------------------------------------------
1.23
                                                                         2.0E-4
                                                                       1.46E-05
                             Total Manufacturing 
                                                                       4.06E-02
--------------------------------------------------------------------------------
221.85
                                                                         3.6E-2
                                                                       1.12E-03



Table 3-5 P-14-0321. General Population Exposures Using a Distance of 50 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                             39
                                                                         0.0039
                                                                              3
10 m
                                                                       4.08E-06
--------------------------------------------------------------------------------
0.02
                                                                         3.3E-6
                                                                       2.83E-09
Fugitive
                                                                            90%
                                                                            9.6
                                                                           0.96
                                                                            279
4 m
                                                                       1.70E-02
--------------------------------------------------------------------------------
93.00
                                                                         1.5E-2
                                                                       4.42E-04
Stack
                                                                             0%
                                                                            5.7
                                                                            5.7
                                                                            279
50 ft.
                                                                       1.69E-03
--------------------------------------------------------------------------------
9.21
                                                                         1.5E-3
                                                                       1.09E-04
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       5.44E-07
--------------------------------------------------------------------------------
0.0030
                                                                         4.9E-7
                                                                       3.52E-08
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       4.26E-05
--------------------------------------------------------------------------------
0.23
                                                                         3.7E-5
                                                                       2.76E-06
                             Total Manufacturing 
                                                                       1.87E-02
--------------------------------------------------------------------------------
102.47
                                                                         1.7E-2
                                                                       5.54E-04

Table 3-6 P-14-0321. General Population Exposures Using a Distance of 50 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                             39
                                                                         0.0039
                                                                              3
10 m
                                                                       4.08E-06
--------------------------------------------------------------------------------
0.02
                                                                         3.3E-6
                                                                       2.83E-09
Fugitive
                                                                             0%
                                                                            9.6
                                                                            9.6
                                                                            279
4 m
                                                                       1.70E-01
--------------------------------------------------------------------------------
930.00
                                                                         1.5E-1
                                                                       4.42E-03
Stack
                                                                             0%
                                                                            5.7
                                                                            5.7
                                                                            279
50 ft.
                                                                       1.69E-03
--------------------------------------------------------------------------------
9.21
                                                                         1.5E-3
                                                                       1.09E-04
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       5.44E-07
--------------------------------------------------------------------------------
0.0030
                                                                         4.9E-7
                                                                       3.52E-08
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       4.26E-05
--------------------------------------------------------------------------------
0.23
                                                                         3.7E-5
                                                                       2.76E-06
                             Total Manufacturing 
                                                                       1.72E-01
--------------------------------------------------------------------------------
939.47
                                                                         1.5E-1
                                                                       4.53E-03


The 24 hour total manufacturing emissions TWA concentration of 32.85, 221.85, 102.47 and 939.47 ug/m[3] or 0.0053, 0.036, 0.017 and 0.15 ppm will be used in population exposure calculations.
P-14-0323



Table 3-7 P-14-0323. General Population Exposures Using a Distance of 500 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                            200
                                                                           0.02
                                                                              6
10 m
                                                                       1.82E-05
--------------------------------------------------------------------------------
0.10
                                                                         1.9E-5
                                                                       2.53E-08
Fugitive
                                                                            90%
                                                                            6.2
                                                                           0.62
                                                                            268
4 m
                                                                       2.38E-03
--------------------------------------------------------------------------------
13.00
                                                                         2.4E-3
                                                                       6.13E-05
Stack
                                                                             0%
                                                                            2.3
                                                                            2.3
                                                                            268
50 ft.
                                                                       7.80E-04
--------------------------------------------------------------------------------
4.26
                                                                         8.0E-4
                                                                       4.85E-05
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       1.28E-07
--------------------------------------------------------------------------------
0.0007
                                                                         1.3E-7
                                                                       7.90E-09
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       6.00E-05
--------------------------------------------------------------------------------
0.33
                                                                         6.2E-5
                                                                       3.72E-06
                             Total Manufacturing 
                                                                       3.24E-03
--------------------------------------------------------------------------------
17.69
                                                                         3.3E-3
                                                                       1.14E-04

Table 3-8 P-14-0323. General Population Exposures Using a Distance of 500 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                            200
                                                                           0.02
                                                                              6
10 m
                                                                       1.82E-05
--------------------------------------------------------------------------------
0.10
                                                                         1.9E-5
                                                                       2.53E-08
Fugitive
                                                                             0%
                                                                            6.2
                                                                            6.2
                                                                            268
4 m
                                                                       2.38E-02
--------------------------------------------------------------------------------
130.00
                                    2.4E-2
                                                                       6.13E-04
Stack
                                                                             0%
                                                                            2.3
                                                                            2.3
                                                                            268
50 ft.
                                                                       7.80E-04
--------------------------------------------------------------------------------
4.26
                                                                         8.0E-4
                                                                       4.85E-05
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       1.28E-07
--------------------------------------------------------------------------------
0.0007
                                                                         1.3E-7
                                                                       7.90E-09
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       6.00E-05
--------------------------------------------------------------------------------
0.33
                                                                         6.2E-5
                                                                       3.72E-06
                             Total Manufacturing 
                                                                       2.47E-02
--------------------------------------------------------------------------------
134.69
                                                                         2.5E-2
                                                                       6.65E-04



Table 3-9 P-14-0323. General Population Exposures Using a Distance of 50 Meters from the Source and 90% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm 
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                            200
                                                                           0.02
                                                                              6
10 m
                                                                       2.09E-05
--------------------------------------------------------------------------------
0.11
                                                                         2.1E-5
                                                                       2.91E-08
Fugitive
                                                                            90%
                                                                            6.2
                                                                           0.62
                                                                            268
4 m
                                                                       1.10E-02
--------------------------------------------------------------------------------
60.00
                                                                         1.1E-2
                                                                       2.74E-04
Stack
                                                                             0%
                                                                            2.3
                                                                            2.3
                                                                            268
50 ft.
                                                                       6.79E-04
--------------------------------------------------------------------------------
3.71
                                                                         7.0E-4
                                                                       4.23E-05
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       1.46E-07
--------------------------------------------------------------------------------
0.0008
                                                                         1.5E-6
                                                                       9.06E-09
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       1.14E-05
--------------------------------------------------------------------------------
0.06
                                                                         1.1E-5
                                                                       7.08E-07
                             Total Manufacturing 
                                                                       1.17E-02
--------------------------------------------------------------------------------
63.89
                                                                         1.2E-2
                                                                       3.17E-04


Table 3-10 P-14-0323. General Population Exposures Using a Distance of 50 Meters from the Source and 0% LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Fugitive or Stack
Efficiency
kg/site/day pre-treatment
kg/site/day post-treatment
Days
Height of release
ADR mg/kg/day
--------------------------------------------------------------------------------
24 hr concentration ug/m[3]
ppm
LADD mg/kg/day
Stack
                                                                         99.99%
                                                                            200
                                                                           0.02
                                                                              6
10 m
                                                                       2.09E-05
--------------------------------------------------------------------------------
0.11
                                                                         2.1E-5
                                                                       2.91E-08
Fugitive
                                                                             0%
                                                                            6.2
                                                                            6.2
                                                                            268
4 m
                                                                       1.10E-01
--------------------------------------------------------------------------------
600.00
                                                                         1.1E-1
                                                                       2.74E-03
Stack
                                                                             0%
                                                                            2.3
                                                                            2.3
                                                                            268
50 ft.
                                                                       6.79E-04
--------------------------------------------------------------------------------
3.71
                                                                         7.0E-4
                                                                       4.23E-05
Stack
                                                                         99.99%
                                                                            5.2
                                                                        0.00052
                                                                            279
10 m
                                                                       1.46E-07
--------------------------------------------------------------------------------
0.0008
                                    1.5E-6
                                                                       9.06E-09
Stack
                                                                             0%
                                                                            1.2
                                                                            1.2
                                                                            279
75 ft.
                                                                       1.14E-05
--------------------------------------------------------------------------------
0.06
                                                                         1.1E-5
                                                                       7.08E-07
                             Total Manufacturing 
                                                                       1.11E-01
--------------------------------------------------------------------------------
603.89
                                                                         1.1E-1
                                                                       2.78E-03

Fugitive emissions are the major source of airborne emissions, >95%, far exceeding any other source. The 24 hour total manufacturing emissions TWA concentration of 17.69, 134.69, 63.89 and 603.89 ug/m[3] or 0.0033, 0.025, 0.012 and 0.11 ppm will be used in population exposure  calculations.
RISK ASSESSMENT
Human Health Risk Discussion
Effects Levels Used to Determine Non-cancer Risk for Single Exposure Effects
P-14-0321
The only toxicity data on P-14-0321 is a rat acute toxicity study. The PMN is not lethal with 4 hours exposure to 96,936 ppm. At necropsy both males and females exhibited gray discoloration of the lungs (3 total) and petechiae on one or more lung lobes (5 animals total). This was considered to be treatment related. At 11,537 ppm and 52,538 ppm males showed body weight loss one day after exposure but gained weight thereafter. The weight loss may have been due to restraint used during exposure. No weight loss was observed in females. All animals gained weight after the first day. In addition, clinical observations indicated breathing difficulties at all doses. No controls were run in any of the studies. The necropsy observations are considered compound related. Thus the NOAEC for acute effects is 52,538 ppm from 4 hours of exposure.

This value is scaled to 8 hours using Haber's Rule (C*t=k where C=concentration, t=duration, and k=constant) to compare with the 8 hours TWA exposure values when calculation and MOE. The 8 hour NOAEC for single exposure effects is 26,269 ppm.

The 8 hour NOAEC is further adjusted to reflect a higher breathing rate in workers. Population exposure estimates in the New Chemicals program use an adult general population inhalation rate of 0.61 m[3]/hr = 14.7 m[3]/day or 4.9 m[3]/8 hr. This value is taken from the US EPA Exposure Factors Handbook 2011 as the average of the mean long-term exposure values for inhalation for males and females combined (all age ranges 21-81+ yrs). This will be considered to be the resting default breathing rate. The working breathing rate is 10 m[3] (Engineering report default) per 8 hour working day. The 8 hour NOAEC of 26,269 ppm corrected for the difference in default and worker breathing rates is 12,872 ppm.

Acute NOAEC POD for 8 hours population exposure (CSCENARIO-8) = 26,269 ppm. Adjusted for 24 hours CSCENARIO-24 = 8756 ppm.
Acute NOAEC POD for 8 hours adjusted worker exposure to P-14-0321 (CSCENAIRO-ADJ-8) = 12,872 ppm.


Figure 4-1 Point of Departure Calculations P-14-0321  -  See Appendix A for Formulas and Constants

P-14-0323
Data on P-14-0323 include acute lethality studies in rats and mice. The PMN is not lethal to rats at concentrations of 20,516 ppm (109,503 mg/m[3]) exposure for 4 hours. The estimated mouse LC50 for 1 hour in the female (most sensitive sex) is 5,123 ppm (27,344 mg/m[3]) and for 4 hours exposure it is 402 ppm (2,146 mg/m[3]).

The relevant species for human risk calculations is unknown so the most susceptible species, the mouse, is used in risk calculations. The 4 hour mouse female LC50 is 402 ppm. If one assumes the non-lethal level is 1/3 the LC50 (NRC, 2001) then the 4 hour non-lethal exposure becomes 134 ppm. This is a threshold for lethality but the experience in the AEGL Program (NRC, 2001) was that frank toxic effects were seen at this exposure (1/3 LC50). Therefore, 134 ppm exposure for 4 hours is considered a LOAEC for toxic effects. The 4 hour mouse LOAEC for single exposure toxicity is estimated to be 134 ppm.

The 4 hour mouse LOAEC of 134 ppm is time scaled to 8 hours using Haber's Rule (C*t=k where C=concentration, t=duration, and k=constant) to compare with the 8 hours TWA exposure values when calculating the MOE. Using this rationale the extrapolated 8 hour mouse LOAEC is 67 ppm. Risks from repeated exposure cannot be calculated because there are no repeat exposure data on the PMNs.

The 8 hour NOAEC has been further adjusted to reflect a higher breathing rate in workers. Population exposure estimates in the New Chemicals program use an adult general population inhalation rate of 0.61 m[3]/hr = 14.7 m[3]/day or 4.9 m[3]/8 hr. This value is taken from the US EPA Exposure Factors Handbook 2011 as the average of the mean long-term exposure values for inhalation for males and females combined (all age ranges 21-81+ yrs). This will be considered to be the resting default breathing rate. The working breathing rate is 10 m[3] (Engineering report default) per 8 hour working day. The 8 hour NOAEC of 67 ppm corrected for the difference in default and worker breathing rates is 33 ppm.
 
Acute LOAEC POD for 8 hours population exposure (CSCENARIO-8) = 67 ppm. Adjusted for 24 hours (CSCENARIO-24) = 22 ppm.
Acute LOAEC POD for 8 hours adjusted worker exposure to P-14-0323 (CSCENAIRO-ADJ-8) = 33 ppm.


Figure 4-2 Point of Departure Calculations P-14-0323  -  See Appendix A for Formulas and Constants

Benchmark MOE Determination
Benchmark MOE for P-14-0321
The mode of action of the toxicity seen in P-14-0321 is unknown. Therefore default interspecies and intraspecies uncertainty factors of 10 are used. The benchmark MOE for P-14-0321 = 10 * 10 = 100. 

Benchmark MOE for P-14-0323
The mode action of the toxicity seen in P-14-0323 is unknown. Therefore default interspecies and intraspecies uncertainty factors of 10 will be used. The POD values for worker and population exposures are the threshold for lethality. The POD will be considered a LOAEC because at this exposure it is likely that the animals will experience adverse toxic effects. An additional uncertainty factor of 10 to account for differences between the LOAEC and NOAEC is applied. The benchmark MOE for P-14-0323 = 10 * 10* 10 = 1,000.
Occupational Risk Discussion
The worker exposures were expressed as total exposure for 8 hours of exposure. This was converted to an 8 hour TWA assuming workers breathe 1.25 m[3] per hour. The 8 hour PODs were divided by the 8 hour TWAs to calculate the MOE values.
MOE Calculations P-14-0321 - Worker
The MOE calculations are for a single exposure only because there are no data for repeated exposures. Endpoints discussed in Section 4.1.1.1.

Acute lethal NOAEC POD for 8 hours exposure to P-14-0321 = 26,269 ppm. Adjusted for higher breathing rates in workers, the NOAEC POD for 8 hours exposure is 12,872 ppm.

Table 4-1 P-14-0321 Occupational MOE Calculations for Single Exposures
MOE  = (NOAEC for lethality of 12,872 ppm for 8 hours)/(Exposure)
Benchmark MOE = 100
Estimate source
Activity
8 hour TWA
MOE
IRER
Sampling PMN  -  Low end
 0.75 ppm
17,163

Sampling PMN - High end
11 ppm
1,170

Laboratory analysis
 0.75 ppm
17,163

Laboratory analysis
11 ppm
1,170
[                  ] monitoring data
Operator
0.136 ppm
94,647

Operator 
5.2 ppm
2,475

Laboratory analysis
0.654 ppm
19,681

Laboratory analysis
10 ppm
1,287

MOE Calculations P-14-0323 - Worker
The MOE calculations are for a single exposure only because there are no data for repeated exposures. Endpoints discussed in Section 4.1.1.2.

Acute lethal LOAEC POD for 8 hours exposure to P-14-0323 = 67 ppm. Adjusted for higher breathing rates in workers, the LOAEC POD for 8 hours exposure is 33 ppm.

Table 4-2 P-14-0323 Occupational MOE Calculations for Single Exposures
MOE  = (LOAEC for lethality of 33 ppm for 8 hours)/(Exposure)
Benchmark MOE = 1,000
Estimate source
Activity
8 hour TWA
MOE
IRER
Sampling PMN  -  Low end
 0.75 ppm
44

Sampling PMN - High end
11 ppm
3.0

Laboratory analysis
 0.75 ppm
44

Laboratory analysis
11 ppm
3.0
[                  ] monitoring data
Operator
0.136
240

Operator
5.2
6.3

Laboratory analysis
0.654 ppm
50

Laboratory analysis
10 ppm
3.3

--------------------------------------------------------------------------------
Risk Discussion - Worker
P-14-0321
All estimates of MOE values are above 1,000, well above the benchmark value of 100. Risk from single exposures is not supported.

P-140-0323
   * Sampling PMN activities
All of the MOE values are below the benchmark MOE of 1,000. The estimated exposures are 8 hour TWA values whereas the real workplace exposures are from sampling 8 times a day where each sampling event would be 1 minute exposure or less. This introduces uncertainties into the sampling exposure estimates. However, with the data available the MOE values are significantly below the benchmark MOE and risk for single exposures is supported.
   * Laboratory analysis activities
All laboratory analysis MOE values are below the benchmark MOE of 1,000. Adjusting the Point of Departure (POD) for differences in breathing rates for a laboratory worker is probably unnecessary because the laboratory worker breathing rate is probably close to the default human breathing rate. However, this consideration would only double the MOE values and would still be well below the benchmark MOE of 1,000.
General Population Risk Discussion
MOE Calculations P-14-0321 - Population
The MOE calculations are for a single exposure only because there are no data for repeated exposures. Population exposure is by inhalation only. The major fraction of the exposure, >95%, is from fugitive releases.  

Acute NOAEC POD for 8 hours population exposure (CSCENARIO-8) = 26,269 ppm. Adjusted for 24 hours CSCENARIO-24 = 8756 ppm.

Table 4-3 P-14-0321 General Population MOE Calculations for Single Exposures
MOE  = (24 hour POD NOAEC from an acute lethality study = 8,756 ppm)/(Exposure)
Benchmark MOE = 100
Distance from the source
LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Total 24 hour TWA exposure
MOE
500 meters
90%
5.3E-3
1,7000,000
500 meters
0%
3.6E-2
240,000
50 meters
90%
1.7E-2
520,000
50 meters
0%
1.5E-1
58,000

All calculated MOE values are well above the benchmark MOE of 100. There is no identifiable risk to the population from single exposures to P-14-0321
MOE Calculations P-14-0323 - Population
The MOE calculations are for a single exposure only because there are no data for repeated exposures. Population exposure is by inhalation only. The major fraction of the exposure, >95%, is from fugitive releases.  

Acute NOAEC POD for 8 hours population exposure (CSCENARIO-8) = 67 ppm. Adjusted for 24 hours (CSCENARIO-24) = 22 ppm.

Table 4-4 P-14-0323 General Population MOE Calculations for Single Exposures
MOE = (LOAEC for lethality of 22 ppm for 24 hours)/(Exposure).
Benchmark MOE = 1,000
Distance from the source
LDAR (Lead Detection Repair Program) Efficiency for Fugitive Emissions
Total 24 hour TWA exposure
MOE
500 meters
90%
3.3E-3
6,700
500 meters
0%
2.5E-2
880
50 meters
90%
1.2E-2
1,800
50 meters
0%
1.1E-1
200

The MOE calculations are averaged over one day only because there are no data for repeated exposures. Population exposure is by inhalation only. Over 95% of emissions are from fugitive releases. The 24 hour TWA exposure from total air releases is 0.16 ppm. Note, that fugitive releases are based on all VOC releases from sampling as reported.  It is unknown what percent of total releases are comprised of the PMN substance.  It is unknown what the exact efficiency of the Leak Detection and Repair Program (LDRP) will be.
Risk Discussion - Population
P-14-0321
MOE values are all 58,000 or greater, well above the benchmark value of 100. There is no identifiable population risk from single exposures to this PMN.

P-14-0323
The benchmark MOE from single exposures is 1,000. MOE values for population exposures at 500 and 50 meters from the source are 6,700 and 1,800 respectively with 90% efficiency. Thus a concern for single exposures to P-14-0323 is not supported in this scenario. However, it is important to note that repeated exposure data will become available in the future. This may result in risk being identified when these data become available.

The MOE values at 500 and 50 meters with 0% efficiency are 880 and 200. These values are below the benchmark MOE of 1,000. In this scenario there would be concern for risk from single exposures.
Uncertainties in Risk Assessment  -  Focus on P-14-0323
This section focuses on P-14-0323 because MOE values below the benchmark MOE were calculated for this PMN but not P-14-0321.
Endpoint
The MOE calculations are for a single exposure only because there are no toxicity data for repeated exposures.
MOE Calculations are for 1 Exposure/Day
The MOE calculations are for 1 exposure per day. The worst case scenario is 8 exposures per day. The question of acute toxicity is complicated because the impact of multiple single exposures per day is unknown and the impact of short exposures over a period of days is unknown  -  e.g. are the exposures essentially independent or does one exposure increase the toxicity of subsequent exposures.
Worker Exposure
Worker Exposure Chemical Used for Estimate
EPA used exposure data from [                    ] on [                   ] for its worker exposure estimates. Venting of ozone-depleting [                    ] was banned July 1, 1992 and ozone-depleting [                           ] were required to be recovered on June 14, 1993.
   * [                      ] estimate
         o This chemical does not contain HF.
         o Not an ozone-depleter  -  will be limited to [                       ] in future
         o The WEEL 8 hour TWA is [              ]
         o Toxicity
               # Acute rat 4 hour LC50 = >200,000 ppm
               # Acute mouse 4 hour LC50 = >100,000 ppm
               # Subchronic 28 day inhalation NOEL rat = 500 ppm

The chemical used to estimate exposure to the PMNs is an end product. It is relatively non-toxic with a workplace exposure limit of [                  ] The PMNs are intermediates in the production of the ultimate [                         ]. The PMNs are site limited intermediates that are consumed in the manufacturing process. P-14-0321 has a 4 hour LC50 > 96,936. P-14-0323 has a 4 hour rat LC50 > 20,516 ppm; an estimated 1 hour female mouse LC50 of 5,123 ppm and 4 hour mouse LC50 of 402 ppm. The biggest concern in the manufacturing process is the presence of hydrogen fluoride in both PMN streams. HF is much more acutely toxic than P-14-0323. The 1 hour LC50 ranges for HF in the mouse are 342-501 ppm; 10 times lower than the acute toxicity of P-14-0323 in the mouse. HF is very irritating and exposures to HF are tightly controlled.

For the reasons stated in the above paragraph, exposure estimates based upon non-toxic end products with high workplace exposure values are of limited utility and introduce great uncertainty for estimates of exposure to an intermediate with tightly controlled exposure procedures and highly toxic components. The operations for the two types of chemicals (final non-toxic end product vs highly toxic site-limited closed system intermediate) are very different. A better assessment of exposure would be to obtain exposure estimates for chemicals with toxicities, chemical properties and processes similar to the PMN.
Workplace Activity
Sampling: Whether the workplace activities for [                      ] encompass all activities (potentially sampling/maintenance/processing/drumming/etc.) is not characterized so it is not known how well they relate to PMN exposures. The current monitoring data are likely to overestimate exposure because they reflect exposure to relatively non-toxic chemicals with high allowable exposure limits. Because they are the end product, many of the activities are probably related to routine transfer of material to shipping containers. Conversely, exposures to the PMNs are to a site-limited intermediate where exposures are to short duration sampling activity and analysis in the laboratory. Lab handling could be longer than sampling.
Laboratory: The [                  ] estimate for laboratory workers may more relevant to the PMN chemical. It is important to determine whether different procedures are used when the PMN is analyzed compared to what may have been done with [                    ]. If exposures to the PMN are more controlled (for example; use of a hood; number of samples analyzed per day; ambient background levels in the plant that are independent of the analysis activities) than were used for [                 ] analysis, exposures to the PMN could be much lower.
Duration of Operator Exposure
Sampling: For calculation convenience, the operator exposure is assumed to be a total of 8 minutes. It should actually be much less so any assessment is an overestimate.
Laboratory: The duration of exposure may be more relevant. The contribution of ambient levels of [                  ] in the plant to the exposure experienced by the laboratory workers is unknown. 
General Population Exposures
There is uncertainty regarding the actual fugitive emissions. Fugitive emissions from leaks are likely to be short-lived spikes in exposure until the leak is repaired.  Monitoring data provided by the company indicates that over a three month period, approximately 1/3 of the readings were less than 1 ppm for total VOC, another (1/2) of readings were between 1 and 10 ppm for total VOC, and the remaining 10% were above ppm ranging up to >1000 ppm. If leaks were not repaired in a timely manner, more readings would have been reported at higher levels. It is difficult to interpret this data as is since it is for total VOC instead of specific to this chemical, since this is within the facility rather than outdoor air monitoring data near the facility, and it only covers a three month period. However, this information generally indicates that existing leak control technology is able to reduce emitted total VOCs below the allowable levels in the Title V of the Clean Air Act  (Title V - Permits; CAA Sections 501-507; USC Sections 7661-7661f) air permit. However, the exact percent of VOCs that will be comprised of the PMN substance and the percent efficiency removed due to implementation of LDRP remains uncertain and could change depending on site specific conditions such as upkeep and maintenance over time.
Human Health Recommendations
All recommendations should be tempered by the fact they are for single exposure scenarios. When data become available on repeated exposures, the MOE values will likely be lower.
Worker - Sampling
Workers should wear inhalation protective gear with an APF of 1,000. The lowest MOE is 3.0. This is likely an overestimate of exposure during sampling activities because the basis for the model is from exposures to an operator not restricted to sampling activities over an 8 hour exposure TWA, and the exposure experienced during the entire 8 hour period in the IRER basis is presumed to occur in 8 minutes. If [                  ] can provide exposure data from sampling activities for similar chemicals that better reflect the operation and duration of sampling activities with the PMN the MOE values would probably increase markedly.
Worker - Laboratory Analysis
Workers should wear inhalation protective gear with an APF of 1,000. The lowest MOE is 3.0. If [               ] can provide information about how the activities associated with laboratory analysis of the PMN differ from those used as the basis in the exposure assessment the MOE calculations can be revisited. The current basis is from data submitted by [                     ] on [                     ].
Population Risk
The analysis in Section 4.1.3.3 did not identify a risk from single exposures at 500 and 50 meters from the source with 90% efficiency LDAR (Lead Detection Repair Program) efficiency for fugitive emissions. However, with 0% efficiency a risk was identified. To ensure the 90% efficiency goal is met, monitoring for P-14-0323 releases is recommended to ensure at least 90% efficiency.

It is important to note that repeated exposure data will become available in the future from testing requested. This may change the risk calculations when these data become available.
 REFERENCES

NRC, 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. National Academy Press. 202 pp.

US EPA, 2011. Design for the Environment Program Alternatives Assessment Criteria for Hazard Evaluation. https://epa.gov/sites/production/files/2014-01/documents/aa_criteria_v2.pdf

POINT OF DEPARTURE CALCULATIONS
Equations for estimating  human inhalation exposures for specific exposure scenarios 
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>
1. Adjust for Differences in Blood:Gas Partition Coefficients
US EPA (2011a) states: "In the RfC Methods, the DAF derivation for ER effects is based more on science policy than on an empirical procedure. Further, this policy is bi-level; (1) where if Hb/g values are unknown the default value for (Hb/g)A / (Hb/g)H = 1; (2) if (Hb/g)A is greater than (Hb/g)H then a default value of 1 is also used." See also Appendix C
 
If the human and animal blood:gas partition coefficients are known the animal POD can be adjusted by Equation 2 to account for differences in the coefficients between animals and humans and estimate the human POD. However, if the (Hb/g )A is greater than the (Hb/g )H the Dosimetry Adjustment Factor (DAF) is set to a default of 1. If the blood:gas partition coefficients are not known the DAF is 1 and no correction is made.
Equation 1 Calculation of DAF
𝐷𝐴𝐹=(𝐻_(𝑏/𝑔) )𝐴/(𝐻_(𝑏/𝑔) )𝐻 
 
Equation 2 Correction for blood:gas partition coefficient differences
〖(𝐶〗_(𝑃𝑂𝐷−𝐻𝑈𝑀𝐴𝑁))=(𝐶_(𝑃𝑂𝐷−𝐴𝑁𝐼𝑀𝐴𝐿) )x𝐷𝐴𝐹 
 
If Blood:Gas Partition Coefficient is Not Known
If the animal and human blood:gas partition coefficients are not known the DAF is 1 and no correction is made.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 
2. Adjust the Human POD to Correspond to the Exposure Scenario Parameters (Days/Hours) 
The Human POD calculated above represents the exposure duration parameters of the animal experiment in terms of hours/day and days/week. When calculating MOE values, adjustments need to be made to the Human POD to correspond to the human exposure parameters (days/week and hours/day of exposure).
............................................................................................................................................................
2.a. Adjust for Differences of Days/Week Exposure
Typical animal experiments are for 5 days per week for subchronic and chronic studies and 7 days/week for developmental and reproductive effects studies. Typical human exposures for PMNs are for 5 days/week exposure or less. The (CPOD-HUMAN) that was determined from the animal study must be adjusted to the human exposure scenario under consideration so the days of exposure are the same and a direct comparison can be made.
Equation 3 Adjust Human POD for differences in days of exposure/week in animals and humans
𝐶_(𝑃𝑂𝐷−𝐷𝐴𝑌)=𝐶_(𝑃𝑂𝐷−𝐻𝑈𝑀𝐴𝑁)x((𝐷𝐴𝑌𝑆_𝐴𝑁𝐼𝑀𝐴𝐿)/(𝐷𝐴𝑌𝑆_𝐻𝑈𝑀𝐴𝑁 )) 
 
Note that if the animal and human scenario exposure days/week is the same that CPOD-DAY = CPOD-HUMAN.
 ............................................................................................................................................................ 
2.b. Adjust for Differences in Hours/Day of Exposure
Typical animal exposure durations are 4-6 hours per day and typical human exposures are 8-24 hours/day. The CPOD-DAY determined above is for the hours/day the animal was exposed. In order to compare with the human exposure values appropriate for the scenario under consideration, the CPOD-DAY needs be converted to the hours used in the exposure scenario under consideration. This is the CSCENARIO. This is done using Haber's rule.
 
Haber's rule can be expressed as C x t = k (C=concentration; t=time; k=constant; Equation 1-4). It is important to understand that each concentration has a duration component. For example, if the NOAEC for a typical subchronic study is 50 ppm, the 50 ppm is for 6 hours exposure. If the exposure were for 8 hours, then the NOAEC would be 37.5 ppm (figure it out using C x t = k).
 
Equation 4 Haber's Rule
𝐶x𝑡=𝐶𝑃𝑂𝐷−𝐷𝐴𝑌x𝑡𝑃𝑂𝐷−𝐴𝑁𝐼𝑀𝐴𝐿= 𝑘 
 
Once k has been determined the concentration for the duration under consideration can be determined with Equation 1-5.
 
Equation 5 Calculate CSCENARIO-t 
𝐶_(𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂−𝑡)=𝑘/𝑡_𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂 
 
Example
Assume the exposure/duration values for humans are the same as the exposure parameters for the animal. For example an animal NOAEC of 50 ppm for 6 hours of exposure for 5 days a week would translate to a human NOAEC concentration of 50 ppm for 6 hours of exposure for 5 days. In this example the NOAEC in a rat subchronic study was 50 ppm. Exposure was for 6 hours/day and 5 days a week. Assume the CPOD-HUMAN is 50 ppm for 6 hours/day exposure, 5 days/week. Since the number of days per week exposure in the animal study and human exposure scenario are the same no correction has to be made for differences in days/week exposure. The value for k is 300 ppm-hr (Equation 1-6).
 
Equation 6 Example Calculate Value for k
𝑘=50 𝑝𝑝𝑚 x6 ℎ𝑟=300 𝑝𝑝𝑚−ℎ𝑟 
 
If the exposure scenario for a human is 8 hours the concentration for an 8 hour exposure is CSCENARIO-8 .
Using Equation 7 CSCENARIO-8 can be calculated.
 
Equation 7 Example Calculate CSCENARIO 
𝐶_(𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂−8)=(300 𝑝𝑝𝑚−ℎ𝑟)/(8 ℎ𝑟)=37.5 𝑝𝑝𝑚 
 
Thus the 6 hour POD of 50 ppm adjusted for an 8 hour human exposure is CSCENARIO-8 or 37.5 ppm.
 ............................................................................................................................................................ 
2.b. Adjust for Differences in Human Breathing Rates 
Determine CSCENARIO for Different Breathing Rates
Oh dear. You thought you were finished. 
The CPOD-HUMAN assumes a similar breathing rate pattern for the animal and human. Breathing rates in animals and humans will vary depending on activity levels. For example, US EPA (2011b) presents breathing rates for different age groups and levels of activity. If you look at the 21 - <31 years group (males and females combined) the mean m[3]/day breathing rate per day can vary between 6.2 m[3] when the activity is sleeping to 72 m[3] for high intensity activity. 
Population exposure estimates in the New Chemicals program use an adult general population inhalation rate of 0.61 m[3]/hr = 14.7 m[3]/day or 4.9 m[3]/8 hr (Appendix F-3).  This value is taken from the Exposure Factors Handbook 2011 as the average of the mean long-term exposure values for inhalation for males and females combined (all age ranges 21-81+ yrs). This will be considered to be the resting default breathing rate RESPDEFAULT. For the purposes of generic assessments the CPOD-HUMAN will be assumed to represent a breathing rate of 14.7 m[3] per day. 
  
It is important to note that if the CPOD-HUMAN assumes a breathing rate of 14.7 m3/day or 4.9 m3/ 8 hours, it has to be converted to the concentration that would give the same dose for workers breathing at 10 m[3]/8 hours (this value is used in the worker exposure reports). 
  
 Equation 8 Adjust CSCENARIO for differences in breathing rates between the human default breathing rate and the specific scenario breathing rate 
𝐶_(𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂−𝐴𝐷𝐽−𝑡)=𝐶_(𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂−𝑡)x(𝑅𝐸𝑆𝑃_𝐷𝐸𝐹𝐴𝑈𝐿𝑇)/(𝑅𝐸𝑆𝑃_𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂 ) 
  
Example 
Using the example in Equation 7 the CSCENARIO-8 is 37.5 ppm. This represents a POD of 37.5 ppm for a human breathing at the default breathing rate of 4.9 m[3]/8 hours. However, a worker is assumed to breathe 10 m[3]/8 hours. Since the worker has a higher breathing rate than a default human, the POD will be lower because the dose/unit time will be greater. Therefore it is necessary to convert the POD of 37.5 ppm to a value that corresponds to worker at a higher breathing rate. In the example below RESPDEFAULT = 4.9 m[3]/8 hours and RESPSCENARIO = 10[3]/8 hours. 
  
Equation 9 Example Adjust CSCENARIO for differences in breathing rates between the human default breathing rate and the specific scenario breathing rate
𝐶_(𝑆𝐶𝐸𝑁𝐴𝑅𝐼𝑂−𝑡−𝐴𝐷𝐽)=37.5 𝑝𝑝𝑚x  (4.9 𝑚^3  𝑝𝑒𝑟 8 ℎ𝑜𝑢𝑟𝑠)/(10 𝑚^3  𝑝𝑒𝑟 8 ℎ𝑜𝑢𝑟𝑠)=18.4 𝑝𝑝𝑚 
 
Thus the POD for a human breathing at the default rate (4.9 m[3]/8 hours) over an 8 hour period is 37.5 ppm and the POD for a human worker breathing at an elevated rate (10m[3]/8 hours) is 18.4 ppm.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 
Definition of Variables
C = Concentration in ppm or mg/m[3]. Use same units throughout calculations.
CPOD-ANIMAL = Animal POD exposure concentration.
CPOD-HUMAN = Human POD exposure concentration adjusted from the animal inhalation concentration as appropriate (e.g. blood-gas partition coefficient).
CPOD-DAY = Human POD exposure concentration adjusted to the same number of days per week exposure as the animal study.
CSCENARIO-t = The CPOD-DAY converted to the hours being considered in the specific human exposure scenario.
CSCENARIO-ADJ-t = The CSCENARIO adjusted for the human breathing rate in the specific exposure scenario. 
DAF = Dosimetric Adjustment Factor.
DAYSANIMAL = Days of week the animal was exposed.
DAYSHUMAN = Days of week a human is exposed in the specific exposure scenario being assesssed.
(Hb/g )A = Blood gas partition coefficient animal.
(Hb/g )H = Blood gas partition coefficient human.
k = Constant in Haber's rule equation of C * t = k. Note that the C used in the equations is adjusted for differences between animal and human blood:gas airc coefficients and days per week exposure. The value for t was the hours of exposure used in the animal experiment. 
RESPDEFAULT = Default human respiratory rate. For PMNs this will be 14.7 m[3]/day (see above)
RESPSCENARIO = Respiratory rate in a human in the scenario under consiseration.
t = Duration of exposure in minutes or hours. Use same units throughout calculations.
tPOD-ANIMAL = Animal POD exposure duration.
tSCENARIO = The duration of the human exposure scenario under consideration.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 
>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> 
References 
Haber, F. 1924. Zur Geschichte des Gaskrieges. Pp. 76-92 in Fünf Vorträge aus den Jahren 1920-1923. Berlin: Springer-Verlag.
 
NRC. 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels
for Hazardous Chemicals. National Academy Press, Washington, DC.
 
US EPA. 1991. Chemical Engineering Branch Manual for the Preparation of Engineering Assessments. IT Environmental Programs, Inc.
 
US EPA. 1993. Draft Guidance on LADDs and APDRs. Memorandum from Becky Brown date June 21, 1993.
 
US EPA. 1994. Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry. EPA/600/8-90/066F.
 
US EPA. 2009. Risk Assessment Guidance for Superfund Volume I: Human Health Evaluation Manual (Part F, Supplemental Guidance for Inhalation Risk Assessment). EPA-540-R-070-002;
OSWER 9285.7-82; January 2009
 
US EPA. 2011a. STATUS REPORT: Advances in Inhalation Dosimetry for Gases with Lower Respiratory Tract and Systemic Effects. EPA/600/R-11/067.
 
US EPA. 2011b. HIGHLIGHTS of the Exposure Factors Handbook. EPA/600/R-10/030 October 2011.
 
US EPA. 2013. Vocabulary Catalogue. http://www.epa.gov/iris/help_gloss.htm#f 


 ADDENDUM - ECOTOXICITY ESTIMATES FOR P-14-0321 AND P-14-0323

P-14-0321:

                                 Test Organism
                                   Test Type
                                 Test End Point
                                   
Predicted
                                   
Measured
                                   
Comments
 Fish
                                     96-h 
 LC50
 15
 
 
 Daphnid
                                      48-h
 LC50
 9.4
 
 
 Green algae
                                      96-h
 EC50
 10.3
 
 
 Fish
                                       --
 Chronic Value
 1.6
 
 
 Daphnid
                                       --
  Chronic Value
 1.2
 
 
 Green algae
                                       --
 Chronic Value
 3.3
 
 
 Sewage sludge
                                      3-h
 EC50
                                       --
 
 
 Sewage sludge
                                       --
 Chronic Value
                                       --
 
 

Ecotox Value Comments:
Predictions are based on SARs for neutral organics;  SAR chemical class = neutral organics;  MW 151; solid; S = 420 mg/L at 25 C (P); gas;  pH7;  effective concentrations based on 100% active ingredients and mean measured concentrations;  hardness <150.0 mg/L as CaCO3;  and TOC <2.0 mg/L;

                                     Factors
                                      Values
                                    Comments
 Assessment Factor
 10
 
Concentration of Concern (ppb) - Acute Value


 Concentration of Concern (ppb) - Chronic Value
 120
 
 SARs
 Neutral Organics
 
 SAR Class
 Neutral Organics
 
TSCA New Chemical Category
Neutral Organics




P-14-0323:

                                 Test Organism
                                   Test Type
                                 Test End Point
                                   
Predicted
                                   
Measured
                                   
Comments
 Fish
                                     96-h 
 LC50
 7.4
 
 
 Daphnid
                                      48-h
 LC50
 6.2
 
 
 Green algae
                                      96-h
 EC50
 10.7
 
 
 Fish
                                       --
 Chronic Value
 2.1
 
 
 Daphnid
                                       --
  Chronic Value
 0.081
 
 
 Green algae
                                       --
 Chronic Value
 3.0
 
 
 Sewage sludge
                                      3-h
 EC50
                                       --
 
 
 Sewage sludge
                                       --
 Chronic Value
                                       --
 
 

Ecotox Value Comments:
Predictions are based on SARs for vinyl/allyl halides;  SAR chemical class = vinyl/allyl halides;  MW 131; gas; S = 570 mg/L at 25 C (P); gas; pH7;  effective concentrations based on 100% active ingredients and mean measured concentrations;  hardness <150.0 mg/L as CaCO3;  and TOC <2.0 mg/L;

                                     Factors
                                      Values
                                    Comments
 Assessment Factor
 10
 
Concentration of Concern (ppb) - Acute Value


 Concentration of Concern (ppb) - Chronic Value
 8
 
 SARs
 vinyl/allyl halides
 
 SAR Class
 vinyl/allyl halides
 
TSCA New Chemical Category
None


