## Update on the Human Health Assessment of Long-Chain
Chlorinated Alkanes

Health Canada

May 2012ii SYNOPSIS

Chlorinated paraffins (CPs) were included in 1989 on the Priority Substances List under the 1988 Canadian Environmental Protection Act (CEPA 1988) for assessment of potential risks to the envir onment and human health.

The use of the term paraffins to identify th ese substances was recently changed to alkanes to harmonize with more current nomenclature that is recognized by other jurisdictions
and international bodies.

CPs are chlorinated alkanes that have car bon chain lengths ranging from 10 to 38 with varying degree of chlorination. They are subdivided into three groups: short-chain chlorinated paraffins with 10-13 carbon at oms (SCCPs), medium-chain chlorinated paraffins with 14-17 carbon atoms (MCCPs) a nd long-chain chlorinated paraffins with 18 to 38 carbon atoms (LCCPs).

In 1993, Environment Canada and Health Canada published an assessment report that concluded SCCPs constitute or may constitute a danger to human health or life according to the criteria described in the CEPA 1988. Ho wever, available data at that time were considered insufficient to conclude whethe r short-, medium- or long-chain chlorinated paraffins were harmful to the environment or whether medium- or long-chain chlorinated paraffins were considered a danger to human health.

After addressing the critical data gaps identified in the 1993 assessment report, a draft follow-up report was published in 2005, which was followed by a 60-day comment period. The final follow-up report was publishe d in 2008 with the conclusion that all CPs are harmful to human health under paragraph 64( c ) of CEPA 1999 and CPs containing up to 20 carbon atoms are harmful to environment under paragraph 64( a ) of CEPA 1999.

In 2009, the Environment Agency of United Kingdom published an environmental risk assessment report on LCCPs and this new in formation informed an update to the exposure characterization for various human subpopulations for LCCPs.

There were no new critical health effects id entified for LCCPs. Therefore, the tolerable daily intake (TDI) (i.e., the level of intake to which it is believed that a person may be exposed daily over a lifetime without dele terious effects) of 71 μg/kg-bw per day, derived for non-neoplastic eff ects in the follow-up assessmen t in 2008, was used for risk characterization.

Upper-bounding estimates of daily intakes of LCCPs by the general population of Canada are well below the established TDI, and th erefore, it is concl uded that long-chain chlorinated alkanes that have the molecular formula C n H
x Cl (2n+2-x) in which 18 ≤ n ≤ 38 are not harmful to human health as defined in paragraph 64( c ) of CEPA 1999.INTRODUCTION

Chlorinated paraffins (CPs) are chlorinate d alkanes that have carbon chain lengths ranging from 10 to 38. They are subdivided in to three groups: shor t-chain chlorinated paraffins with 10-13 carbon atoms (SCCP), me dium-chain chlorinated paraffins with 14- 17 carbon atoms (MCCP) and long-chain chlori nated paraffins with 18 to 38 carbon atoms (LCCP).

CPs were included in 1989 on the Priori ty Substances List under the 1988 Canadian
Environmental Protection Act (CEPA 1988) for assessment of potential risks to the environment and human health. In 1993, Environment Canada and Health Canada published an assessment report that concluded that SCCPs constitute or may constitute a danger to human health or life according to th e criteria described in the CEPA. However, available data at that time were consider ed insufficient to conclude whether short-, medium- or long-chain chlorinated paraffins we re harmful to the environment or whether medium- or long-chain chlorinated paraffins were considered a da nger to human health.

Following the publication of the assessment report, research to address data gaps relevant to the assessment of impacts of CPs on the environment was undertaken. Furthermore, an industry survey on the manufacture, import a nd uses of CPs in Canada was conducted for the years 2000 and 2001 through a Canada Gazette Notice issued pursuant to section 71 of CEPA 1999. Finally, the scie ntific literature wa s reviewed to identify new exposure and toxicological data.

On June 11, 2005, the Ministers of the E nvironment and of Health published the summary of the scientific results of the follow-up assessment on CPs in the Canada Gazette , Part I for a 60-day public comment pe riod. At the same time, a statement outlining the proposed risk management measure - a prohibition regulation - was also published. Comments were subsequently received from industry and industry associations. The draft follow-up assessment report was revised based on these comments and the final was published on August 30, 2008. The final follow-up assessment report concluded that CPs containing between 10 and 38 carbon atoms are harmful to human health under paragraph 64( c ) of CEPA 1999 and CPs containing up to 20 carbon atoms are harmful to the environment under paragraph 64( a ) of CEPA 1999.

In 2011, Health Canada made a decision to update the human health assessment of LCCPs based on new information relevant to exposure characterization for the general population in Canada.

This Update on the Human Health Assessment of Long-Chain Chlorinated Alkanes

, which was built upon the final follow-up asse ssment report published in 2008, was prepared by staff in the Existing Substances Program at Health Canada and incorporates input from other programs with in the department. The external peer review of exposure assessment was conducted by WECC Wania E nvironmental Chemists Corp., Toronto, Canada. The draft Update on the Human Health Assessm ent of Long-Chain Chlorinated
Alkanes that was published in September 2011 wa s subject to a 60-day public comment

1period. Although external comments were taken into consideration, the final content and outcome of this assessment report remain the responsibility of Health Canada.

SUMMARY OF INFORMATION CRITICAL TO THE ASSESSMENT UNDER
CEPA 1999

In the 2008 follow-up assessment, upper-boundi ng intake estimates for long-chain chlorinated paraffins (LCCPs) were calculated using concentrations in a limited number of foodstuffs in the United Kingdom (Cam pbell and McConnell 1980). Furthermore, concentrations in foods were represented by th e limits of detection for five of eight food groups in the calculation of da ily intake. The confidence in exposure was low because of high uncertainty in estimating to tal daily intakes of LCCPs fr om drinking water, food and soil. For the general population, none of those intakes exceeded the TDI (71 μg/kg bw/day). However, for infants, non-formula fed, the total daily intake of LCCPs of 16 μg/kg bw/day was within the same order of magnitude. It was on this basis that LCCPs were concluded to be harmful to human health as defined in paragraph 64( c ) of the Canadian Environmental Protection Act, 1999 (CEPA 1999).

Since then, in 2009, the United Kingdo m Environment Agency published an environmental risk assessment report on LCCPs (Environment Agency 2009). In the absence of monitoring data, envi ronmental concentrations of three main types of LCCPs,
C 18-20 liquid, C >20 liquid and C >20 solid, were predicted using European Union System for the Evaluation of Substances (EUSES) modelli ng based on physical chemical properties. Furthermore, EU release volume for the se lective types of LCCPs was used as no UK release data was identified.

Health Canada has updated its assessment of LCCPs, informed by the United Kingdom Environment Agency report. As there is no Canadian release data for LCCPs, an EU release value of 140,000 kg/year is used in the prediction. This value is considered conservative as chlorinated paraffins are no longer produced in Canada. Use volume in Canada in 2001 was approximately 200,000 kg with no reportable releases identified to the National Pollutants Release Inventory (NPRI) as of 2009 (NPRI 2009). Exposure estimates from the environment and food for C 18-20 and C >20 liquid LCCPs are estimated using a Farfield Human Exposure model (FHX 2008). Analytical methods currently available for LCCPs do not routinely differentiate the types of chlorina ted paraffins either in terms of chlorine content or chain length distribution. The FHX model, developed by the Centre for Environmental Modelling and Ch emistry of Trent University for Health Canada, brings together information on chemical partitioning, degradation, environmental fate and transport and food web bioaccumulation for assessing human ageclass-specific exposure from chemicals rele ased to the environment. The FHX model calculates steady-state c oncentrations in the multi-media co mpartments such as air, water and soil and various food groups, including fru its, vegetables, milk, dairy, fish, and meats based on the unit emission rate. The EP Isuite v.4.0 predicted physical chemical properties (MW, VP, water solubility, log Ko w and half-lives in air, water, soil and sediment, in fish ) (EPIsuite 2008) for C 18 H 37 Cl 1 (CAS 106232-85-3), C 18 H 22 Cl 16 and

2C 18 H 30 C l8 of the C 18-20 alkanes group and C 22 H 45 Cl 1 (CAS 85535-86-0) of the C >20 alkane group were used in the FHX model (Appendix 1).

There were no new critical health effects id entified for LCCPs. Therefore, the tolerable daily intake (TDI) (i.e., the level of intake to which it is believed that a person may be exposed daily over a lifetime without dele terious effects) of 71 μg/kg-bw per day, derived for non-neoplastic eff ects in the follow-up assessment in 2008 was used for risk characterization. This TDI value was base d on the lowest dose of LCCP (LowestObserved-Adverse-Effect Level [LOAEL] = 100 mg/kg-bw per day) at which adverse effects (diffuse lymphohistiocytic inflammati on in the liver and in the pancreatic and mesenteric lymph nodes in female rats) were observed, in a carci nogenicity bioassay in which an adequate range of endpoints had been examined (NTP, 1986; Bucher et al

., 1987), divided by an uncertainty factor of 1000 (×10 for intraspecies variation; ×10 for interspecies variation; ×10 for use of a LOAEL rather than a NOAEL) and multiplied by 5/7 (for conversion of 5 days/week administ ration to daily exposure) (Health Canada, 2008).

Intake of C 18 H 37 Cl 1 with its upper bounding intake estimates ranging from 0.007 μg per kg-bw per day for 60+ age group to 0.024 μg per kg-bw per day for 0.5-4 years age group, is the highest among the three substances within C 18-20 alkanes group. These intake estimates are 10000 and 3000 times lower, respectiv ely, than the tolerable daily intake of 71 μg per kg-bw per day (Appendix 2). Th e intake estimates for the other two representative substances in the C 18-20 substances, C 18 H 22 Cl 16 and C 18 H 30 C l8 , were found at an order of magnitude lower than C 18 H 37 Cl 1 . This could possibly be due to the higher vapour pressure and water solubility of the latter substance. The estimated upper bound intakes of the C >20 type is predicted to range from 0.013 μg per kg-bw per day for 60+ age group to 0.040 μg per kg-bw per day fo r 0.5-4 years age group, which are 5500 and 1800 times lower, respectively, than the tolerable daily intake.

As these estimates are well below than the de rived TDI, it is concluded that LCCPs are not harmful to human health as defined in paragraph 64( c ) of the Canadian Environmental Protection Act, 1999

.

Uncertainties in Evaluation of Risk to Human Health

There is high degree of confidence in the database of toxicol ogical studies upon which the TDI for LCCPs is based as the database is complete, including a well documented carcinogenicity bioassay in rat and mice.

The commercial products in the C 18-20 and C >20 liquid groups contain a mixture of many components with different carbon chain length and various chlo rine weight content which can range from a low of 20% to a high of 70%. The upper bounding exposure estimates
of C 18-20 and C >20 LCCPs are based on the predicted phys ical chemical properties of the specific C 18-20 and C >20 liquid compounds with different ch lorine content. There is considerable uncertainty over the physica l chemical properties chosen for the environmental modelling and the bioconcentration factor used to estimate the uptake

3from soil into root crops, from air into leaf crops and the subsequent transfer into the food chain. However, given the very conservative input values of the predicted physical chemical, confidence is high that estimated exposure to LCCPs from the environment and food for different age class of the general popu lation are considerably lower than the TDI of 71 μg/kg bw/day.

CONCLUSION

Based on the information presented, it is concluded that LCCP s (i.e., chlorinated paraffins with 18 to 38 carbon atoms) are not entering the e nvironment in a quantity or concentration or under conditions that may cons titute a danger to human life or health as defined in the paragraph 64( c ) of CEPA 1999.

4

### References

Bucher, J.R., R.H. Alison, C.A. Montgomery, J. Huff, J.K. Haseman, D. Farnell, R. Thompson and J.D. Prejean. 1987. Comparative toxicity and carcinogenicity of two chlorina ted paraffins in F344/N rats and B6C3F1 mice. Fundam. Appl. Toxicol. 9: 454–468.

Campbell, I. and G. McConnell. 1980. Chlorinated paraffins and the environment. 1. Environmental occurrence. Environ. Sci. Technol. 14(10): 1209–1214.

Canada 1993. Priority Substances List Assessment Report – Chlorinated Paraffins

Canada, Dept. of the Environment. 2005. Canadian Environmental Protection Act, 1999: Notice with respect to chlorinated paraffins. Canada Gazette. Part 1, Vol. 139 No. 24, pg 2046-2050. Available at: http://gazette.gc.ca/archives /p1/2005/index-eng.html

Environment Agency UK. 2009. Environmental risk assessment: long chain chlorinated paraffins science report – Environment Agency, UK. Jan. 2009

[EPIsuite] Estimation Programs Inte rface Suite for Microsoft Windows [E stimation Model]. 2008. Version 4.00. Washington (DC): U.S. Environmental Protectio n Agency, Office of Pollutio n Prevention and Toxics; Syracuse (NY): Syracuse Research Corporation. Available from: www.epa.gov/oppt/exposure/pubs/episuite.htm

FHX 2008 Farfield Human Exposure. The Canadian Centre for Environment Modelling Trent University

Health Canada. 1998. Exposure factors for assessing total daily intake of priority substances by the general population of Canada. Unpublished report. Ottawa (ON): Health Canada, Environmental Health Directorate.

Health Canada, 2008. Follow-up report on PSL1 substa nce for which there was insufficient information to conclude whether the substance constitutes a danger to the environment and to the Human Health.

IRDC (International Research and Development Corporation). 1981. Teratology Study in Rabbits With Chlorinated Paraffin: 43% Chlorination of Long Ch ain Length n-paraffin, Studies conducted for the Working Party of the Chlorinated Paraffin Manufact urers Toxicology Testing Consortium, Report Number
438-030.

IRDC (International Research and Development Corporation). 1982. Teratology Study in Rabbits With Chlorinated Paraffin: 70% Chlorination of Long Ch ain Length n-paraffin, Studies conducted for the Working Party of the Chlorinated Paraffin Manufact urers Toxicology Testing Consortium, Report Number
438-039.

IRDC (International Research and Development Corporation). 1983a. Teratology Study in Rats With Chlorinated Paraffin: 43% Chlorination of Long Ch ain Length n-paraffin, Studies conducted for the Working Party of the Chlorinated Paraffin Manufact urers Toxicology Testing Consortium, Report Number
438-015.

IRDC (International Research and Development Corporation). 1983b. Teratology Study in Rats With Chlorinated Paraffin: 70% Chlorination of Long Ch ain Length n-paraffin, Studies conducted for the Working Party of the Chlorinated Paraffin Manufact urers Toxicology Testing Consortium, Report Number
438-045.

[NPRI] National Pollutant Release Inventory. 2009. Gatineau (QC): Environment Canada Available from: HThttp://www.ec.gc.ca/pdb/querysite/query_e.cfm

5NTP (National Toxicology Program). 1986. NTP technical report on the toxicology and carcinogenesis studies of chlorinated paraffins (C 23 , 43% chlorine) (CAS No. 63449-39-8) in F344/N rats and B6C3F 1 mice (gavage studies). National Institutes of Health, Rese arch Triangle Park, North Carolina (NTP TR 305; NIH Publication No. 86-2561).

Serrone, D.M., R.D.N. Birtley, W. Weigand, and R. Millischer. 1987. Toxicology of Chlorinated Paraffins. Food Chem. Toxicol., 25(7):553-562.

6Appendix 1: Predicted physical/ chemical properties of the C 18-20 and C >20 alkane

group

Parameter C 18 H 37 Cl 1 C 18-20 alkanes

group C 18 H 22 Cl 16 C 18-20 alkanes

group C 18 H 30 C l8 C 18-20 alkanes

group C 22 H 45 Cl 1 C >20 alkane

group Molecular Weight 288.95 530.06 805.6 345.06

Vapour Pressure (Pa) 3.79E-01 3.32E-06 6.43E-11 9.7E-04

Solubility (g/m 3 ) 1.4E-04 3.87E-07 3.39E-10 1.4E-06

Log Kow 9.36 10.6 12.07 11.2

Half-life in air (day) 0.51 0.94 5.45 0.41

Half-life in water (days) 38 180 180 15

Half-life in soil (days) 75 360 360 30

Half-life in sediment (days) 337 1620 1620 135

Metabolic half-life in fish (days) 1 143 811 6440 495

Metalic half-life in avian and mammals (days) 143 811 6440 495

1 Calculated from first order rate constant value for 1 kg fish -BCFBAF (EPISuite 2008)

78 Appendix 2: Predicted upper-bounding daily intakes of C 18 H 37 Cl 1 for the general population in Canada

Estimated intake ( μ g/kg-bw per day) of C 18-20 LCCPs by various age

groups
0–6 months 1, 2, Route of

exposure

formula
fed not formula
fed 0.5–4

years 3 5–11

years 4 12–19

years 5 20–59

years 6 60+

years 7

Ambient
air 1.92x10 -6 4.12x10 -6 3.21x10 -6 1.83x10 -6 1.57x10 -6 1.36x10 -6

Indoor air 1.35x10 -5 2.88x10 -5 2.25x10 -5 1.28x10 -5 1.10x10 -5 9.54x10 -6
Drinking

water 8.49x10 -8

. 9.58x10 -8 7.53x10 -8 4.29x10 -8 4.49x10 -8 4.72x10 -8

Food and beverages 8 2.26x10 -7 0.018 0.024 0.017 0.010 0.009 0.007

Soil NA NA NA NA NA NA

Total intake <0.01 0.018 0.024 0.017 0.010 0.009 0.007
Abbreviation: NA, not available.

1 Assumed to weigh 7.5 kg, to breathe 2.1 m 3 of air per day, to drink 0.8 L of water per day (formulafed) or 0.3 L/day (not formula fed) and to ingest 30 mg of soil per day (Health Canada 1998). Formulafed infants are assumed to consume no other foods.

2 For exclusively formula-fed infants, intake from water is synonymous with intake from food. The concentration of LCCPs in water used to reconstitute formula was based on predicted water concentration. data.. Approximately 50% of infants are introduced to solid foods by 4 months of age and 90% by 6 months of age (NHW 1990).

3 Assumed to weigh 15.5 kg, to breathe 9.3 m 3 of air per day, to drink 0.7 L of water per day and to ingest 100 mg of soil per day (Health Canada 1998).

4 Assumed to weigh 31.0 kg, to breathe 14.5 m 3 of air per day, to drink 1.1 L of water per day and to ingest 65 mg of soil per day (Health Canada 1998).

5 Assumed to weigh 59.4 kg, to breathe 15.8 m 3 of air per day, to drink 1.2 L of water per day and to ingest 30 mg of soil per day (Health Canada 1998).

6 Assumed to weigh 70.9 kg, to breathe 16.2 m 3 of air per day, to drink 1.5 L of water per day and to ingest 30 mg of soil per day (Health Canada 1998).

7 Assumed to weigh 72.0 kg, to breathe 14.3 m 3 of air per day, to drink 1.6 L of water per day and to ingest 30 mg of soil per day (Health Canada 1998).

8 The food group includes fruits, vegetables, dairy, fish and meats based on mechanistic mass bioaccumulation models that include biotransformation loss