Sulfuric acid, mono-C12-14(even numbered)-alkyl esters, ammonium salts

Carcinogenicity

Description of key information

No data are available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, read-across from a structural analogue substance has been applied.

equivalent or similar OECD 453, rat, combined chronic toxicity/carcinogenicity, oral: not carcinogenic
NOAEL = 1125 mg/kg bw/day; LOAEL > 1125 mg/kg bw/day

Read-across from structural analogue source substance Sulfuric acid, mono-C12-15-alkyl esters, sodium salts (CAS 68890-70-0).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Refer to the Category Approach Justification document provided in IUCLID6 Section 13

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOEL

Effect level:

> 1 125 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no neoplasm observed

Remarks on result:

other: Source, key, 68890-70-0, 1995a&b

Key result

Critical effects observed:

no

Conclusions:

Interpretation of results: negative. No neoplasms or other cricital effects have been observed.

Executive summary:

The carcinogenic potential of the target substance is estimated based on an adequate and reliable carcinogenicity feeding study of a structural analogue source substance. A NOEL of > 1125 mg/kg bw/day was determined and no neoplasms and other critical effects have been observed. Therefore, no hazard with regard to carcinogenicity is identified for the target substance. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the carcinogenic potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 125 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 2) study from a source substance with similar structures and intrinsic properties. Read-across is justified based on common physico-chemical, ecotoxicological and toxicological properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex X, 8.9.1, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on carcinogenicity obtainded with a structurally analogue substance do not meet the criteria for classification according to the CLP Regulation (EC) No. 1272/2008 and are, therefore, conclusive but not sufficient for classification. Based on read-across the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) is also not classified for carcinogenicity.

Additional information

No data regarding carcinogenic potential of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) are available. Therefore, read-across from the structural analogue substance sulfuric acid, mono-C12-15-alkyl esters, sodium salts (CAS 68890-70-0) has been applied. The possibility of a read-across from other alkyl sulfates in accordance with Regulation (EC) No. 1907/2006, Annex XI 1.5 “Grouping of substances and read-across approach” was assessed. In Annex XI 1.5 it is given that a read-across approach is possible for substances whose physico-chemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity. The AS reported within the AS category show structural similarity. The most important common structural feature of the category members is the presence of a predominantly linear aliphatic hydrocarbon chain with a polar sulfate group, neutralised with a counter ion. This structural feature confers the surfactant properties of the alkyl sulfates. The surfactant property of the members of the AS category in turn represents the predominant attribute in mediating effects on mammalian health. Therefore, the members of the AS category have similar physico-chemical, environmental and toxicological properties, validating the read-across approach within the category. The approach of grouping different AS for the evaluation of their effects on human health and the environment was also made by the OECD in the SIDS initial assessment profile [1] and by a voluntary industry programme carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read-across approach between structurally related AS.

Ammonium sulfate is used to produce AS NH4 within the current AS category. There is a substantial data base on ammonium sulfate online available. Ammonium sulfate is not listed in Annex VI of Regulation (EC) No. 1272/2008 (CLP). In addition, the effects of ammonium sulfate on human health were assessed by the OECD in the SIDS initial assessment report [3]. Ammonium sulfate gives no rise to concern of adverse effects on human health. Therefore, a contribution of ammonium sulfate to the effects on human health is considered to be negligible when assessing human health effects of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2).

Reliable combined chronic toxicity/carcinogenicity studies were conducted with C12 -15 AS Na (CAS 68890-70-0, Unilever, 1995a&b). For two combined chronic toxicity/carcinogenicity studies similar to OECD Guideline 453 C12-15 AS Na (CAS 68890-70-0) was prepared by two different production methods (high conversion bleached or HCB; and low conversion, unbleached or LCU). The substances of these different production methods differed slightly in chain length distribution, the latter having a slightly higher proportion of the C15AS Na. In both studies, the test material was dosed at 0, 0.015, 0.15 and 1.5% in the diet. There was no increase in tumour incidence, nor any impact on tumour type in either study. For both studies, approximately 70% of animals survived to study termination. Mortality was similar across dosage groups and controls. Animals in the 1.5% dose groups in both studies exhibited reduced food and water consumption, and slower growth rates. Within these high dose groups, there were a decreased number of total tumours and tumour-bearing animals.

Other pathological findings are summarized in the Section Repeated dose toxicity. Increased absolute liver weights and liver to body weight ratios, hypertrophy of the hepatic parenchyma, increased relative testicular weights, reduced incidence and severity of chronic nephropathy and nephrocalcinosis, and reduced arterial medial hypertrophy were among the findings at the higher dose levels.

Alkyl sulfates (AS) show a consistent absence of mutagenic activity when tested in in-vitro and in-vivo tests. Neither AS nor its metabolites possess electrophilic functional groups or functional groups associated with mutagenic activity. Taken together with the results of the carcinogenicity studies, AS are considered as non-carcinogenic.

 

[1] SIDS initial assessment profile, (2007); http://www.aciscience.org/docs/Alkyl_Sulfates_Final_SIAP.pdf

[2] (HERA Draft report, 2002); http://www.heraproject.com/files/3-HH-04-%20HERA%20AS%20HH%20web%20wd.pdf

[3] http://webnet.oecd.org/HPV/UI/SIDS_Details.aspx?Key=2c80d506-86bf-4719-be9b-d922022506ec&idx=0