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Description of key information

Absorption of LCCPs via the oral and inhalation routes are predicted to be about 50 per cent of the administered dose.  Absorption via the dermal route is predicted to be much lower (about 1 per cent of administered dose).

Key value for chemical safety assessment

Absorption rate - oral (%):
50
Absorption rate - dermal (%):
1
Absorption rate - inhalation (%):
50

Additional information

Basic Toxicokinetics

Limited toxicokinetic information is available for the LCCP products. The information available for LCCPs, as well as information available for intermediate length chlorinated paraffins (MCCP), have been reviewed by authorities (IPCS EHC 181, 1996; UK Environment Agency, 2009; OECD SIDS Dossier, 2009). These reviews predicted that absorption of LCCPs via the oral and inhalation routes will be significant (about 50 per cent of the administered dose).Absorption via the dermal route is predicted to be lower (about 1 per cent ofadministered dose). Absorption decreases with increasing carbon chain lengthand degree of chlorination.

Toxicokinetic information is available for a liquid grade C22–26, 43% chlorination LCCP product anda solid grade C22–26, 70% chlorination LCCP product. In conjunction with a standard 13-week repeated dose toxicity study, 18 rats of eachgender received a single dose of a radiolabelled C22–26, 43% chlorinated LCCP by theoral (gavage) route at 100 or 3,750 mg/kg (IRDC, 1984b). The animals were dosedeither after having received the respective dose level of unlabelled LCCP daily for 13weeks or having previously not been exposed to LCCP. Radioactivity in faeces andurine was monitored during the first seven days after radiolabelled LCCP dosing. Threeanimals per gender per group were killed at 0.5, 1, 2, 7, 28 and 90 days for collection oftissue and/or blood samples for radioactivity measurement.It was found that between 82 and 95 per cent of the administered radioactivity wasrecovered in the faeces during the seven-day collection period, most of which wasrecovered during the first two days. Between 0.1 and 0.8 per cent of the radiolabel wasexcreted in the urine. Blood concentrations of radioactivity in animals from the two dosegroups were very similar. Also, the inter-group differences in the concentration ofradioactivity for any given tissue were much less than the differences between theadministered dose. Tissue radioactivity levels were initially greatest in the liver but by90 days a redistribution to adipose tissue had occurred. This study suggests thatabsorption of the LCCP product may be saturable, but the extent of systemicabsorption and systemic elimination of LCCP could not be determined from this study.

Toxicokinetics of a C22–26, 70% chlorination product were investigated in a study ofidentical design (IRDC, 1984a). It was found that between 61 per cent and 88 per centof the administered radioactivity was recovered in the faeces during the seven-daycollection period. Only a very small proportion of the radioactivity (<0.1–1 per cent) wasexcreted in the urine. The highest levels of radioactivity were found in the liver, gonadsand adipose tissue seven days after dosing, with lower levels being found in the brain,kidney, blood and heart. As was the case with the C22–26, 43% chlorination LCCP study,the extent of systemic absorption and systemic elimination could not be determined.

A 14C-labelled chlorinated paraffin, C18; 50-53% Cl (CP-LH), was administered by gavage as a single dose of 500 mg/kg to three female Sprague-Dawley rats (Yang et al., 1987). After 24 h, 1% of the radioactive dose was recovered in the urine, 1.5% in the expired air and 22% in the faeces. After 96 h, 1.9% of the radioactive dose was recovered in the urine, 3.3% in the expired air, 5% in body tissue and 76% in the faeces.

Dermal Absorption

Chlorinated paraffins are slowly absorbed by the dermal route in Sprague-Dawley rats (Yang et al., 1987). Two 14C-labelled chlorinated paraffins, C18;50-53% Cl (CP-LH) and C28;47% Cl (CP-LL), were applied to rat skin (5-7 animals of each sex) at a concentration of 66 mg/cm2, approximately equivalent to 2000 mg/kg body weight. Only 0.7% (males) and 0.6% (females) of the C18 dose was absorbed after 96 h. Only 0.02% of the C28 dose was absorbed in males whereas in females the level was not detectable. This indicates that increasing chain length leads to decreased permeability. Of the absorbed C18 dose, 40% was exhaled as 14C-labelled CO2, and 20% was excreted in urine and 20% in faeces.

Theseresultsindicatethatratskinactsasaneffective barrier to chlorinatedparaffinscontainingeighteenormorecarbonsandmorethan40%chlorinebyweight.ThedermalabsorptionoftheCl8chlorinatedparaffinwasestimatedtobenearly100timeslessthantheoralabsorption.

Basedoncurrenttoxicityresultsfromrodentexperimentsandthesepresentfindings,chlorinatedparaffinsofthetypetestedwouldbeexpectedtohavelittleornoeffectinanimalsasa resultofdermalexposure.Ina review of limited comparativein vivodatafrom man and rat,(Wester andMaibach(1983)notedthatpercutaneousabsorptionisgenerallygreaterintherat.Thus,itis reasonabletosuggestthatchlorinatedparaffinsareunlikelytobesystemicallytoxictohumansbyskincontactunder normalconditions ofproductionand use.

 

References

International Programme on Chemical Safety Environmental Health Criteria #181, Chlorinated Paraffins, 1996.

UK Environment Agency (EA, of England and Wales) (2009). Environmental Risk Evaluation Report: Long-Chain Chlorinated Paraffins. January 2009.

OECD SIDS Assessment Report,Long Chain Chlorinated Paraffins (LCCPs).October, 2009

WESTER,R.C.andMAIBACH, H.J.(1983).Invivopercutaneous absorption. In:Dermatotoxicology(F.N. Marzulliand H.I.Maibach,eds.),pp. 131-146.Hemisphere,NewYork.