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Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Justification for classification or non-classification

Carcinogenicity testing results indicate that repeated dermal exposure to petroleum naphtha streams similar to LOF causes skin tumors via a tumor promotion, likely secondary to repeated skin irritation or damage. As such, the available information indicate it is unlikely that LOF possesses inherent carcinogenic properties, and do not warrant classification as a carcinogen according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.

Additional information

The hydroformylation process, involves the preparation of oxygenated organic compounds by the reaction of carbon monoxide and hydrogen (synthesis gas) with olefinic carbon compounds. Olefins which do not react, and paraffins produced by side reactions are the primary components of Mixed LOF.

 

The oxo reaction is performed under hydroformylation conditions in the presence of a carbonylation catalyst or catalyst precursor such as dicobaltoctacarbonyl, and results in the formation of a compound (e.g. an aldehyde) which has one more carbon atom in its molecular structure than the feedstock. Subsequent hydrogenation of the hydroformylation product leads to formation of the desired product alcohols. By virtue of the nature of the feedstock commonly available to industry, and indeed of the catalyst and reaction parameters employed, the hydroformylation reaction inevitably yields a range of products due to the numerous secondary reactions which take place.

 

Mixed LOF (Alkenes, C6-10, hydroformylation products, low-boiling; no CAS RN; EC number 931-285-8) is a byproduct from C7-C11 alcohol production. In the hydroformylation process olefins (alkenes) are catalytically reacted with carbon monoxide and hydrogen, resulting in a range of products including primary alcohols. Alcohols are separated from the reaction mixture by distillation, with the remaining LOF containing unreacted olefins (alkenes) and paraffins (alkanes), frequently of the branched [iso-] form. Compositional analysis indicates Mixed LOF is approximately a 50/50% mixture of olefins and paraffins with a boiling point range of 102 – 182 ºC.

 

 While toxicity data are not available for LOF, based on composition and physical chemical characteristics it is appropriate to use data from naphtha petroleum streams with low levels of aromatic groups and carbon number ranges similar to C6-10. Naphtha streams are derived from the same original feedstock (crude petroleum) with a key process difference – feedstocks to the hydroformylation process (e.g., propylene, butene, and pentenes and combinations thereof) have very low to neglible aromatic material (e.g., benzene or toluene). Thus, use of naphtha streams can generally be considered a conservative read-across approach.

 

Light Catalytic Cracked Naphtha (LCCN; CAS No. 64741-55-5, consisting of hydrocarbons derived from a catalytic cracking process in the range of 4 to 11 carbons with a boiling range of approximately 65 to 230 degrees centigrade;) or Light Straight Run Naphtha (LSRN; CAS No. 64741-46-4, 64741-46-4, consisting predominantly of aliphatic [paraffinic and isoparaffinic] hydrocarbons in the range of 4 to 10 carbons and boiling between -20 to 180 degree centigrade) as read-across.

Available genetic toxicity data for petroleum naphtha similar to Alkenes, C6-10, hydroformylation products, low-boiling suggest that mutagenic properties are not present in these hydrocarbon streams, and therefore mutagenicity does not play a role in tumor development. The dermal tumors associated with repeated application of petroleum naphtha streams the consequence of repeated irritation and/or skin injury acting via a promotional process on pre-existing, spontaneously initiated cells (see summary of Przygoda et al., 1994 in the Specific Investigations: other studies section). Thus, skin tumors could be avoided by the use of good industrial hygiene practice to avoid excessive skin contact.

 

The chronic toxicity studies were conducted by standard procedures. While mice repeatedly exposed dermally to petroleum naphtha streams similar to Alkenes, C6-10, hydroformylation products, low boiling develop skin tumors, they appear to be secondary to irritation and/or skin damage and not an inherent hazard property. According to EU CLP Regulation (EC No. 1272/2008), the data do not support classification of Alkenes, C6-10, hydroformylation products, low-boiling for carcinogenic potential.


Justification for selection of carcinogenicity via dermal route endpoint:
Mutliple lifetime repeat dermal exposure studies reporting dermal carcinogenesis, but secondary to irritation.

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