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Description of key information

In well reported studies (Hoechst AG, 1986, 1983) conducted according to modern standards, C10-13 chlorinated paraffins (59 and 70% chlorination) have the potential to produce, at most, mild irritation when applied under a semi-occlusive dressing to the shaven skin of rabbits for 4 h. More pronounced irritation can occur following repeated exposure, and is probably due to a defatting mechanism. Limited information in humans indicates that SCCPs do not cause skin irritation. No corrosion has been reported. 
There is no information from humans on the potential for SCCPs to cause eye irritation. However, the information from animals indicates that C10-13 chlorinated paraffins (40 to 63% chlorination) produce only mild eye irritation in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

In well reported, unpublished studies (Hoechst AG, 1986, 1983) conducted according to modern standards, three rabbits were treated, dermally, with 0.5 ml of undiluted SCCPs applied under a semi-occlusive dressing to the shaven skin for 4 h. In the later study, no signs of skin irritation were seen for up to 72 h after removal of the C10-13 chlorinated paraffin (59% chlorination) (Hoecsht AG, 1986). In the earlier study, very slight oedema (grade 1) was noted in two of the animals for up to 24 h following skin application of a C10-13 chlorinated paraffin (70% chlorination). One rabbit showed clearly defined erythema (grade 2 on a scale of 0-4) at 48 and 72 h, while "slightly noticeable" erythema (grade 1) was seen in the other two animals. All signs of irritation were completely resolved by day 7 (Hoechst AG, 1983).

SCCPs were also investigated in several other unpublished studies, although (according to the final RAR (EU, 2000)) these were not conducted according to modern protocols and were less well, and often only briefly reported. All studies were conducted using rats. In most studies, six 24

hour applications of 0.1 or 0.2 mL of chlorinated paraffin was applied to shaven skin, under occlusive dressings. Treatment periods were separated by 24-hour treatment-free periods. The samples of chlorinated paraffin were usually undiluted but contained low percentages of epoxy

stabilisers and/or various additives. Two studies investigated C10-13, 70% chlorinated paraffin. In the more recent study, no signs of irritation were noted throughout the study following repeated application of the chlorinated paraffin which contained 0.1 or 2% benzoyl peroxide initiator. In the earlier study the chlorinated paraffin contained 1 or 2% of an epoxised vegetable oil stabiliser with and without additives (0.1% oxalic acid or 0.05% benzotriazole). Very mild to mild desquamation was only noted following the applications of chlorinated paraffins which contained the additives. The reactions were described as occasional, transient and inconsistent. It was not stated how many applications were made before these reactions were seen. Another two studies investigated the effects of three C10-13, 63% chlorinated paraffins, containing up to 3% epoxy soya oil stabilisers or other unspecified additives. Erythema was usually noted following 2 to 4 applications of all three paraffins, although on one occasion erythema was noted in 1/3 animals after only one application. The severity of the reactions were not described. Desquamation was also noted following 3 or 4 applications and increased in severity with further treatments. In theolder study (with 0.7% epoxy carboxylate stabiliser) the desquamation was described as severe following the fourth application when the study was terminated.

Several studies have been conducted using C10-13 paraffins which were 48, 50, 52 or 55% chlorinated. In most studies the paraffins contained 0.2 or 2% epoxy stabilisers. In one study with 48 or 55% chlorinated paraffins, containing 0.2% epoxy octyl stearate stabiliser, no signs of irritation

were noted throughout the study (unpublished reference, 52, 1969). In the other studies results were as above with mild or slight erythema to erythema and mild desquamation usually being noted following the second or third application. In one study, testing a 52% chlorinated

paraffin with 2% epoxised octyl oleate stabiliser, erythema was noted following the first application, although the severity of the reactions were not discussed. It was noted in 4/5 of the studies that the reactions did not worsen following further applications, although in one study (testing a 52% chlorinated paraffin with unspecified additives), slight erythema, noted after the second application worsened to severe erythema

with slight necrosis after the third, when the study was terminated. An unspecified volume of a C10-13, 40% chlorinated paraffin, containing 1% epoxy soya oil stabiliser, produced slight desquamation following the second application and mild erythema after the third (unpublished reference 57, 1966). This condition persisted throughout the remaining applications until the end of the study when small scattered ulcers developed.

Several or all of the above studies have been summarised in less detail in a published report (Birtley et al., 1980).

Two unpublished studies in rats have also been conducted to investigate the potential for skin irritation of two C10-11 chlorinated paraffins which were 49 and 60% chlorinated. The protocols were as above except that single application tests were also conducted. No signs of irritation were noted following a single application of the higher chlorinated paraffin, although slight desquamation was noted in 2/6 rats, three to six hours after the treatment with the lower chlorinated paraffin. As above, both chlorinated paraffins produced slight erythema and/or slight desquamation with repeated applications, although neither study stated when such signs were first observed.

Two studies have also been conducted using rabbits and were reported in very brief unpublished summaries. A C10-13, 61% chlorinated paraffin and a 50% chlorinated short chain paraffin (Cereclor 50 HS), of unspecified carbon chain length, produced mild or a mild to moderate skin irritation, following a single occlusive application to intact and abraded skin. It was stated that "varying degrees of erythema persisted for 72

hours". No other information was available.

In contrast to the above studies, another two unpublished studies report more severe findings. One of these studies is a very brief summary which states that repeated occlusive application with a 50% chlorinated short chain paraffin (Cereclor 50 HS), of unspecified carbon chain length, resulted in moderately severe irritation with erythema, desquamation, thickening, cracking and scabbing of the skin being observed in rats. The second study reported slight erythema and desquamation after one 24-h application of the test substance applied under occlusive dressings. Following the third application, moderately severe desquamation, intracutaneous oedema with "extensive scratching" were reported and the study was terminated. However it was unclear if the test substance was a chlorinated paraffin or a solvent used in chlorinated paraffin formulations. Overall, due to uncertainties in the identification of the test substances and considering the weight of evidence, neither of these studies is considered to be reliable when assessing the skin irritation potential of the chlorinated paraffins under consideration

In humans, Cereclor 50 LV and 63 L (C10-13 chlorinated paraffins; 50 and 63% chlorination, respectively) were mildly irritating following 48 h occluded application to the upper arm of 26 healthy volunteers (MacDonald, 1975) [ICI, 1975], whereas Chlorowax 500C (a C12 chlorinated paraffin; 59% chlorination) did not produce local irritation when applied to the skin of 200 male and female volunteers (Howard et al. 1975). [See IUCLID Chapter 7.10.3 for further details of human data].

 

Eye irritation

No relevant human data are currently available.

In an assessment of its potential to induce eye irritation, a drop of undiluted C10-13 chlorinated paraffin (40% chlorinatation) was placed into the right eye of each of three rabbits and observations were made over a 3-day period. Mild congestion was evident after 1 h, but this had completely resolved within 24 h (McElligott, 1966) [ICI, 1966].

The eye irritation potential of C10-13, 40 to 52% chlorinated paraffins has been reported in a published study (Birtley et al., 1980). Three different C10-13 paraffins which were 63% chlorinated and which contained either 2.5 or 2% of two different additives or 0.7% of an epoxy stabiliser were tested in 2 studies. Both studies were conducted according to modern protocols with either 0.1 mL or "one drop" of the paraffin being instilled into one conjunctival sac of groups of three rabbits. Similar results were reported for all three formulations: "practically no" initial pain (2 on a 6 point scale) was noted. Slight irritation (3 on an 8 point scale), evidenced by redness and chemosis (only noted in the formulation containing the epoxy stabiliser) of the conjunctiva with some discharge, lasted for 24 hours. One drop of a 52% chlorinated paraffin, containing unspecified additives, was also tested as above, and slight, immediate irritation was followed by slight redness of the conjunctiva which, as above, lasted for 24 hours.

 

According to an expert review, citing a personal communication with industry, a single application of Chlorowax 500C (a C12 chlorinated paraffin; 58% chlorination) apparently produced a mild redness in the eyes of 4/6 rabbits (Howard et al., 1975). Similar results were obtained with another two chlorinated paraffins (Cereclor 50 HS, Hoechst 64 flussig), although the carbon chain length and/or percentage chlorination of these short chain paraffins was not identified. Although little information was provided, the earlier study apparently indicated the severity of the reactions observed did not increase with up to 5 daily instillations of the chlorinated paraffin (Hoechst AG, 1966; ICI, 1974).

 

Corrosivity

The studies in animals and humans (summarised above) indicate that SCCPs are not corrosive to the skin and eyes.

Respiratory irritation

There are no data in relation to respiratory irritation in humans or animals. However, the lack of any reports relating to this endpoint given the widespread use of these substances, suggests that they lack the potential to cause such an effect. The low skin and eye irritation potential, and generally unreactive nature of this group of substances, lends further support to this view.

References (for which a ESR has not been created - please move to reference list in CSR)

Hoechst AG (1966). 66.0053 (cited in EU, 2000).

 

ICI (1974). ICI Study Number CTL Z0548, 03.12.74 (cited in EU, 2000).


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Under the conditions of these studies, C10-13 chlorinated paraffins would not be classified as skin, eye or respiratory tract irritants according to EU CLP or DSD regulations.