### SIAM 29, 20

- 22 October 200 9 UK/ICCA

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this document are intended to be mutually supportive, and should be understood and interpreted together. 

### SIDS INITIAL ASSESSMENT PROFILE

CAS Numbers and Chemical Names 63449

- 39

- 8 Paraffin waxes and hydrocarbon waxes, chloro
85535

- 86

- 0 Alkanes, C 18

- 28 

### , chloro
85422

- 92

- 0 Paraffin oils, chloro

Example Structural Formulae C n 

### H 2n+2

- y 

### Cl y 

### , where n = 18 to 30 and y = ~4 to ~30

SUMMARY CONCLUSIONS OF THE SIAR
Analogue/Category Justification The Long

- Chain Chlorinated Paraffins (LCCP) category contains complex commercial substances whose chemical components are predominantly in the range of carbon c hain lengths from C 18 to C 30 with chlorine content in the range of approximately 35

- 72% by weight. Chlorinated paraffins (CP) are derived from the chlorination of straight

- chain hydrocarbon substances (i.e., n

- paraffins, n

- alkanes) and are generally divid ed into three categories based on their carbon chain

- length:

• Short

- Chain Chlorinated Paraffin (SCCP): C 10 to C 13

• Mid

- Chain Chlorinated Paraffin (MCCP): C 14 to C 17

• Long

- Chain Chlorinated Paraffin (LCCP): C 18 to C 30 For purposes of this assessme nt, the LCCPs are being divided into 3 subgroups to reflect differences in carbon chain length (those derived from the C 18 - C 20 hydrocarbon feedstock and those from the C 20 - C 30 hydrocarbon feedstock), and physical state (as a result of degree of chlorinatio n). Both factors have an influence on use pattern, which adds to the usefulness of this approach. These subgroups are:

- C 18 - C 20 LCCPs: ca. 40

– 52% Cl (liquid)

- C 20 - C 30 LCCPs: ca. 40

– 54% Cl (liquid)

- C 20 - C 30 LCCPs: ca. 70% Cl (solid) LCCP purity is related to the purity of the n

- paraffin feedstock. In North America and Western Europe, n

- paraffin feedstocks contain no more than 1

- 2% isoparaffins and <100 ppm (<0.01%) aromatics (which are specifically removed from the paraffins feedstock by hydrodesulfurisat ion). The feedstocks may contain n

- alkanes beyond the nominal or predominant carbon number range reported for the feedstock. The carbon number range (C 18 - C 30 ) of the LCCP category is generally fully encompassing of the main commercial products, though some C 18

- 20 products may contain a significant (10

- 20%) amount of C 17 chlorinated alkane. The substances in this category have a predictable range of physico

- chemical properties and physical forms. As chain length and degree of chlorination increases, pour (m elting) points and octanol

- water partition coefficients increase and water solubilities decrease. W hile there are ranges to the physico

- chemical properties, LCCPs all still display similar characteristics

– very low water solubility, very low vapour press ure, and high K ow values. Environmental fate modelling indicates that all LCCPs are anticipated to partition almost entirely to the soil or sediment, depending on release patterns, indicating that fate and behaviour are likely be very similar for all LCCP s. Data from the related substance MCCPs, which have similar physico

- chemical properties, are structurally analagous and, where known, have a similar toxicological profile to C 18

- 20 LCCPs, are used to address human health hazards for C 18

- 20 LCCPs, includin g acute toxicity, irritation, repeated dose toxicity, toxicity for reproduction (effects on fertility) and developmental

### SIAM 29, 20

- 22 October 200 9 UK/ICCA

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this document are intended to be mutually supportive, and should be understood and interpreted together. toxicity. Data from liquid C20

- 30 LCCPs is read across to solid C20

- 30 LCCPs for acute Daphnia magna toxicity. Physico

- chemical Propert ies Measured data for commercial LCCPs usually give a range of values for single endpoints owing to the complex nature of the substance. Estimated values have been predicted using representative individual structures. LCCPs can vary from free

- flowing mobil e liquids, through highly viscous glassy liquids, to waxy solids and powders. Distinct melting points are not evident; liquid LCCPs generally exhibit pour points (approximate range

- 30 to 10 °C ) and solid LCCPs softening points (103

– 115  C). H igher value s correspond with a greater degree of chlorination. LCCPs decompose at temperatures above 210 °C before boiling occurs. Vapour pressures range from 1. 4 x 10 - 1 5 to 5.3 x 10 - 4 P a (estimated at 25 °C) for C 20

- 30 (ca. 70% Cl) and C 18

- 20 (ca. 40% Cl), respecti vely. Estimated octanol

water partition coefficients (log K ow ) range from 7.5

– 11.5 for C 18

- 20 , from 7.6

- 17.5 for liquid C 20

- 30 and from 16.9

– 20.1 for solid C 20

- 30 LCCPs. The estimated water solubility ranges from 1.6  10 - 11

– 6.6 μg/L at 20 °C for L CCPs.
Human Health Toxicokinetics, metabolism and distribution
No information was available on the metabolism of the LCCPs. Ninety

- day studies, in which 14 C radio

- labelled LCCPs were administered orally to rats, showed that an average of 77% of the adminis tered radio

- activity was excreted in the faeces within seven days. Less than 1% was excreted in urine or expired air. This suggests that the compound was either poorly absorbed or that a significant quantity was excreted in the bile, either unchanged or as a metabolite. Up to about 4% remained in the tissues, mainly the liver. There have been no studies on absorption through the skin. It is known that both SCCPs and MCCPs are absorbed via this route to only a very small extent (~0.7 % for MCCPs). It is anticipated that based on the larger molecule size of LCCPs, they would be less likely than MCCPs to be absorbed through the skin. Similarly, there are no studies on the absorption of LCCPs through the respiratory tract, either as vapour, aerosol or dust, although it is reasonable to assume that absorption via the lungs is unlikely to be higher than the assumed rate of oral absorption, i.e. 50%. Acute toxicity There is adequate data to assess the acute toxicity of LCCPs. C 20

- 30 LCCPs (both solid and liquid) are of very low acute toxicity, having oral LD 50 values in excess of 5.0 g/kg bw in the rat and other species. MCCPs are also of very low acute toxicity, with oral LD 50 >2.0 g/kg bw in the rat. As such it is likely that C 18

- 20 liquid grade LCCPs are of ve ry low acute toxicity. There are no data on the acute toxicity of LCCPs following dermal administration. However, as it is anticipated that they would not be absorbed to any significant extent via this route, it is considered unnecessary to conduct such te sts. Similarly, there are no data on the acute toxicity of LCCPs following inhalation.
Irritation There is adequate data to assess the irritant potential of LCCPs. In a study of liquid C 20

- 30 LCCPs, 0.5 ml neat LCCP, which included several stabilisers, wa s applied as a single occlusive application for 24 hours to abraded and non

- abraded skin of rabbits . Erythema and oedema was scored after 24 and 72 hours. Slight erythema was observed on both the abraded and non

- abraded skin in two out of six rabbits at 24 hours. In another study, up to 6 applications of 0.1ml of either liquid or solid LCCPs, either neat or in a non

- irritating vehicle, were applied to the shorn back of three female rats on alternate 24

- hour periods. It was concluded that these test materia ls were non

- irritant. Single exposure to MCCPs also caused slight irritation in standard tests, but somewhat more pronounced irritation has been reported following repeated exposure, presumably due to the defatting properties of MCCPs

. There are no data on respiratory irritation of LCCPs, Overall the only concern regarding skin irritant properties of LCCPs relates to read across data from MCCPs which may be applicable to C 18

- 20 LCCPs. C 20

- 30 LCCPs d o not possess irritating properties.
Sensitisation
Valid s kin sensitisation studies on LCCPs in guinea pigs have shown no evidence of sensitising potential. These findings, together with the lack of sensitisation activity shown by SCCPs and MCCPs, support the conclusion that LCCPs are unlikely to have any signifi cant potential to sensitise the skin. Repeat

- dose toxicity
There are valid oral 90

- day repeat dose toxicity studies in the rat on a C 23(average) , 43%Cl LCCP, a C 22

- 26 , 43 % Cl LCCP (both liquid grades) and a C 22

- 28 , 70% Cl LCCP (a solid grade) which have been conducted to protocols which are broadly consistent with modern guidelines. There are also a valid oral 90

- day repeat dose toxicity stud y in the mouse and valid 2

- year repeat dose studies in both the rat and the mouse on the C 23(average) , 43%Cl LCCP.
Studies in rats : The principal target organ in the rat for 90

- day and 2

- year studies was the liver, with the lymphatic system and kidneys in male rats and the haematological system in female rats also identified as target organs. The

### SIAM 29, 20

- 22 October 200 9 UK/ICCA

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this document are intended to be mutually supportive, and should be understood and interpreted together. female rat was the mos t sensitive sex and species

. In the 90

- day study of C 22

- 28 , 70% Cl solid LCCP, the NOAEL for both male and female rats was 900 mg/kg bw/day based on hepatotoxicity at 3750 mg/kg bw/day (LOAEL). In a 90

- day study of C 23(average) , 43%Cl LCCP, no significant adverse effects were observed in the male rats (NOAEL =3750 mg/kg bw/day), but effects in the liver (granulomatous inflammation) were observed in all dose groups for the females (LOAEL of 235 mg/kg bw/day). In a 90

- day study of C 22

- 26 , 43 % Cl liquid LCC P
, there was evidence of liver toxicity in all exposed females (increased absolute liver weight, dose

- dependent multifocal granulomatous hepatitis accompanied by an increase in the intensity of ORO staining, a slight increase in microsomal Lowry protein an d a concomitant increase in microsomal enzyme levels). There were no effects in the livers of treated male rats, although trace/mild nephrosis was reported in male rats receiving 3750 mg/kg/day. The NOAEL for male rats from this study was 900 mg/kg bw/day and the LOAEL for female rats was 100 mg/kg bw/day (no NOAEL could be established). In the 2

- year study of rats with C 23(average) , 43%Cl LCCP, i ncreased liver weights were seen in both male and female rats, the effect being seen after 6 months dosing in female rats and after 12 months dosing in male rats. The effects were accompanied by a slight elevation in several serum enzyme levels and, in females only, variations in haematological parameters. The primary pathological lesion reported was a diffuse lym phohistiocytic inflammation of the liver and the pancreatic and mesenteric lymph nodes. The LOAEL for effects in the liver was 1875 mg/kg bw/day in male rats and 100 mg/kg bw/day in female rats.
Studies in mice : In the mouse, oral administration of the C 2 3 (average) , 43 % Cl LCCP for either 90

- days or 2

- years caused no effects on body or organ weights, no clinical signs of toxicity and no treatment

- related histopathological effects (90

- day NOAEL = 7500 mg/kg bw/day; 2

- year NOAEL= 5000 mg/kg bw/day).
The LO AEL for C 20

- 30 LCCPs in 90 day and 2 year studies in the rat was 900 mg/kg bw/day in males and 100 mg/kg bw/day in females, based on hepatotoxicity. The NOAEL for males in the 90 day study was 300 mg/kg bw/day, but no NOAEL was obtained for females.
There was no valid repeat

- dose toxicity study on a C 18

- 20 liquid grade LCCP, though available data on MCCPs, C 14

- 17 , was used for read across purposes. In a 90

- day rat dietary study, using MCCP, decreased plasma triglycerides and cholesterol, and increased kidn ey weights were observed at 222 mg/kg bwt/day, and the NOAEL was 23 mg/kg bw/day. This NOAEL can be read across to C 18

- 20 LCCPs. Mutagenicity There is adequate data to assess the mutagenic potential of LCCPs. LCCPs, like the SCCPs and the MCCPs, do not ind uce mutations in bacteria. There is some evidence of weak clastogenic potential in vitro in mammalian cells, with chromosomal aberrations observed in CHO cells (with metabolic activation) and also sister chromatid exchanges (at 5

- 5000 μ g/mL with and withou t activation); however, no evidence of chromosomal aberrations was seen in a well

conducted in vivo study in rat bone marrow cells, in which the rats received doses of up to 5000 mg/kg bw/day for 5 days by gavage. There was also a negative mouse lymphoma assay conducted by the NTP on C 23(average) liquid LCCP. Taking all of the data on LCCPs into account and considering what is known about shorter chain CPs, it is concluded that LCCPs, as a group, are without significant genotoxic potential. Carcinogenicity There are valid studies on the carcinogenic effects of a C 23(average) 43%Cl LCCP in rats and mice. The only convincing evidence of carcinogenicity was an increased incidence of malignant lymphoma in male mice reported at the highest dose of 5000 mg/kg bw/ day. Marginal increases in the incidence of adrenal medullary phaeochromocytomas were observed in female rats from 100 to 5000 mg/kg bw /day and in hepatocellular carcinomas in female mice at 5000 mg/kg bw /day. These changes were only observed at exposur e levels that are so high (5000 mg/kg bwt/day) that the relevance of this property to a human health is doubtful

. There is no information on the carcinogenic potential of C 18

- 20 LCCPs or C 20

- 30 solid grade LCCPs. However, given the results on the studies in rats and mice on the C 20

- 30 liquid grade LCCP and the fact that CPs, in general, are without significant genotoxic potential
, it is considered that LCCPs present a low carcinogenic potential for humans. Toxicity for Reproduction Effects on Fertility : There are no fertility studies available, conducted with the LCCPs. No evidence of toxicity to the reproductive organs has been found in standard repeated dose studies conducted with LCCPs. In addition, no evidence of an adverse effect on fertility ( sta ndard reproductive/fertility parameters were unaffected) has been found in a well

conducted fertility study conducted oral gavage study of MCCPs. However, in this study
, MCCPs did cause maternal deaths around the time of parturition, and neonatal mortalit ies from internal hemorrhaging as a consequence of reduced maternal vitamin K levels; it is possible that similar effects could be observed with LCCPs. These changes in vitamin K levels were only observed at doses of 74 mg/kg bw /day and above, which is si gnificantly greater than the NOAEL of 43 mg/kg bw /day iden t ified for repeated dose effects established for the MCCPs. Overall
, it is anticipated that the LCCPs are unlikely to pose a hazard to fertility.

### SIAM 29, 20

- 22 October 200 9 UK/ICCA

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this document are intended to be mutually supportive, and should be understood and interpreted together. Developmental Toxicity : There are valid oral gava ge developmental toxicity studies on both solid and liquid grade C 20

- 30 LCCP . There is no evidence that these grades of LCCP cause developmental effects in either rats or rabbits; NOAELs for developmental toxicity range from >1000 to >5000 mg/kg bw/day). T here was some evidence that these grades of LCCP might impact on implantation and foetal survival in the rabbit in the absence of overt maternal toxicity, although the effect was not toxico logically significant even at 5000 mg/kg bw/day, the highest dose t ested.
There was no valid developmental toxicity study on a C 18

- 20 liquid grade LCCP. However, given the results of the studies on the C 20

- 30 LCCPs and the fact that MCCPs have shown no adverse effects in prenatal developmental toxicity studies, it is conc luded that the C 18

- 20 liquid grade LCCP s are also likely to be devoid of developmental toxic effects. Overall, the LCCPs are not considered to be developmental toxicants. LCCPs possess properties indicating a hazard for human health (repeated dose toxici ty and for C 18

- 20 LCCPs, potential for skin irritation ). Adequate screening

- level data are available to characterise the hazard to human health for the purposes of the OECD HPV Chemicals Programme for C 20

- 30 LCCPs and read across data from MCCPs were used to characterise missing SIDS endpoints for the C 18

- 20 LCCPs.

Environment LCCPs have very low volatility and water solubility. LCCPs are hydrolytically stable as they contain no hydrolysable functional groups. Based on Mackay Level III fugacity modelling, i n the environment LCCPs are expected to remain almost entirely in the soil when released to soil and migrate to the sediment when released to water. This is also supported by the high Kow values for LCCP, which suggest a strong affinity for soil and sedim ent. Estimated Koc values for LCCPs range between 2.93 x 10 6 and 1 x 10 10 L/kg (the upper limit of the model). Any limited amount of LCCPs in the air may adsorb to particulates or aerosols. Unsorbed LCCPs in air would break down via photooxidation, mediat ed primarily by hydroxyl radicals with a calculated degradation half

- life range of 18 to 112 hours (based on a 12

- hour day and a hydroxyl radical concentration of 5x10 5 • OH/cm 3 ). Data indicate some potential for biodegradation with acclimated microorganis ms, though limited biodegradation in non

- acclimated organisms. The potential for biodegradation appears to increase with decreasing chlorine content. There is also information to suggest that biodegradation of LCCPs may occur under anaerobic conditions. H owever LCCPs are not considered to be readily biodegradable. LCCPs do not appear to be toxic to microorganisms in the available study data. Studies performed mostly in excess of water solubility have shown LCCPs to bioaccumulate in fish and mussels; it is not possible to obtain a reliable BCF value from these data. The potential for uptake and accumulation of LCCPs by fish and other aquatic and terrestrial organisms appears to decrease with increasing carbon chain length and increasing degree of chlorinati on. Model estimated BCFs in fish are as follows based on representative log Kow values ( EU Technical Guidance Document parabolic equation, applicable for substances with log Kow >6 and molecular weight < 700 g/mol: log BCF =

- 0.2 x(log Kow) 2 + (2.74 x log Kow

– 4.72)) :

C 18

- 20 liquid LCCP BCF = 1,096 L/kg (based on log Kow 9.7)
C 20

- 30 liquid LCCP BCF = 192 L/kg (based on log Kow 10.3)
C 20

- 30 solid LCCP BCF <1 L/kg (based on log Kow 17) Results of dietary exposure studies in fish show that uptake from food occurs in the laboratory, and that this uptake in some cases can be significant. The degree of uptake appears to be highest for the C 18

– 20 LCCPs, but uptake of C 20

- 30 LCCPs has also been demonstrated. The uptake of the highly chlorinated C 20

- 30 s olid LCCPs from food appears to be minimal. There is a relatively large amount of aquatic toxicity data available for LCCPs. Aquatic toxicity testing is problematic due to the very low water solubility of LCCPs. In many instances
, it is uncertain whether s aturated test solutions contained undissolved test substance. It is likely that the methods used in some tests (e.g., water accommodated fraction) to prepare test solutions may result in the more soluble components (ie those with shorter chain lengths) pre sent in the commercial LCCP being preferentially represented in the resultant solution. These, and the fact that any effects observed were near the limit of water solubility, complicate interpretation of test results. The substances in the category general ly show little or no toxicity at concentrations well in excess of their water solubility in acute tests. Available acute test re sults are as follows.
C 18

- 20 LCCPs Fish (96h): no effects at limit of solubility

. Daphnia magna (48

- h): no effects at solubility limit in one of two studies; 15% immobilisation in another study in a saturated solution (400

– 500 ug/l, measured).
C 20

- 30 liquid LCCPs Fish (96

- h): no effects at limit of solubility

.

### SIAM 29, 20

- 22 October 200 9 UK/ICCA

This document may only be reproduced integrally. The conclusions and recommendations (and their rationale) in this document are intended to be mutually supportive, and should be understood and interpreted together. Daphnia magna (48h): no effects at limit of solubility

. C 20

- 30 solid LCCPs Fish (96

- h): no effects at limit of solubility No study is available for C 20

- 30 solid LCCPs, but no effects are expected given no effects were seen with C 20

- 30 liquid LCCPs. No valid algal study exists for any of the LCCPs, but data from related chl orinated paraffins (SCCPs and MCCPS) suggest that LCCPs would show no effects on algae. The overall toxicity profile of these substances (SCCP, MCCP, LCCPs) suggest that filling this data gap is not critical for the environmental assessment.
Chronic stud ies in fish are available for C 20

- 30 liquid and solid LCCPs. No effects were seen in the tests (NOECs equating to the highest concentrations tested were reported: 4 mg/l nominal and 3.8 mg/l nominal). The results may be read across to C 18

- 20 LCCPs. Daphni a magna has been identified as the most sensitive species for chlorinated paraffins as a substance class. Two studies are available which investigated chronic toxicity to Daphnia magna from C 18

- 20 LCCPs. One showed no effects at a saturation limit of 2 ug /L (measured) and the other, which followed a water

- accommodated fraction technique, showed effects at 58

- 65 μg/L and no effects at 29

– 32 ug/L (measured). Based on these data, the worst case assumption is that the NOEC for C 18

- 20 LCCPs for Daphnia magn a is 29 μg/L (which is above many estimates of water solubility for LCCPs). Available chronic studies with C 20

- 30 liquid LCCPs in Daphnia magna indicate no effects are observed below the limit of water solubility; the same conclusion can be read across to C 20

- 30 solid LCCPs. Upon release into the environment
, the substances are likely to partition to sediment in the aquatic compartment and bind to soil in the terrestrial environment; no data for sediment

- or soil

- dwelling organisms were available. LCCPs ge nerally show little acute aquatic toxicity at concentrations at or above water solubility. Given the complexity of the substances and their very low solubility interpretation of test results is not straight forward. C 18

- 20 liquid LCCPs possess properties i ndicating a hazard for the environment (chronic toxicity to invertebrates). Based on the available data C 20

- 30 liquid and solid LCCPs appear to present a low hazard for the environment. LCCPs are not readily biodegradable, and may have a potential for bioa ccumulation. Use/Exposure The total EU usage of LCCPs was in the range of 5,000

- 10,000 tonnes/year from 1998

- 2004. The main areas of use for LCCPs are as a flame retardant in rubber and textiles, and as a plasticiser/flame retardant in sealants/adhesives and paints. LCCPs may also be used to a lesser extent as a secondary plasticiser in PVC, as an extreme pressure additive in metal cutting/working fluids (oil

- and/or water

- based) and as a component of leather fat liquoring treatments (leather is treated with a fat liquor as the last step in its preparation; the fat liquor improves the feel and suppleness of the leather). Occupational exposure to LCCPs may occur during their manufacture, their incorporation into downstream products (PVC, metal working fl uids, sealants, rubber, leather fat liquors, paints, textiles) and their processing, especially at high temperatures and during the use of these products. Occupational exposure may occur via dermal contact, though workers are generally advised to wear pr otective clothing and avoid skin contact. Exposure by inhalation is not expected to be a likely source of exposure due to the very low volatility of LCCPs, though there is the potential for aerosols to form during the use of liquid products such as metal

- working fluids or by inhalation of dusts from applications using the solid grades. Consumer exposure may occur through use of the substance as a plasticiser or flame retardant in consumer goods. Exposure would primarily be via the dermal route given the su bstance's physico

- chemical properties. No information on migration of the substance from articles containing it is available. The concentrations of the substance used in articles are typically <1

- 6% in PVC, and most rubber and paints. In exceptional cases , up to 15% is used in cabling materials and in some rubbers. Coatings that contain LCCPs are typically only used in occupational settings (e.g., roadway paint). Releases to the environment could occur during production, the processing steps for the ident ified uses of the substance, use of articles containing the substance, and at end of life disposal. However, exposure is expected to be low from the majority of these releases . Depending on the waste disposal practices followed for water

based emulsions fo r metal working fluids that may contain the substance, release of the substance to the environment may occur. However, the use of LCCPs in metal working fluids is expected to be minor compared to other applications.