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Carcinogenicity

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Description of key information

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

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
read-across source
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Diets were prepared by thoroughly mixing the appropriate quantity of Dobanol-25-sulphate HCB with a purified diet to provide feed containing the required amount of active ingredient, ie. the surfactant was not added to the diet as a part replacement for any ingredient, but was added “on top of the diet”. Rats were individually housed and provided with diet and water ad libitum. The animals were inspected daily for signs of ill-health while body weights, and food and water intakes, were measured weekly for the first 13 weeks, again at week 16, and thereafter at intervals of 4 weeks until the end of the study.
Route of administration:
oral: feed
Vehicle:
other: plain diet
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
Daily
Post exposure period:
none
Remarks:
Doses / Concentrations:0, 0.015, 0.15, 1.5% Basis:nominal in diet
Remarks:
Doses / Concentrations:0, 11, 113, 1125 mg/kg bwBasis:actual ingested
No. of animals per sex per dose:
45
Control animals:
yes, plain diet
Other examinations:
Animals dying or killed during the test received a full post-mortem examination at which tissues were taken for histological examination. Animals surviving to the end of the test were starved overnight and blood was taken under anaesthesia for haematology and biochemical measurements after which the animals were killed and a number of organs (heart, liver, spleen kidneys, testes, adrenals and brain) were removed and weighed. These organs and a range of other tissues from each rat were preserved for histological examination. Histological examination was undertaken on stained tissue sections from all animals fed the control diet and each dietary level of the test substances.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
The test materials used in the individual studies were prepared by two different production methods (high conversion bleached or HCB; and low conversion, unbleached or LCU). They differed slightly in chain length distribution, the latter having a slightly higher proportion of the C15 AS. 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 tumor incidence, nor any impact on tumor 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 was a decreased number of total tumors and tumor-bearing animals. Elevated serum GPT, LDH and AP were observed in high dose males.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.
Relevance of carcinogenic effects / potential:
The material was not tumorigenic at the any dose level, including the highest dose of 1.5%.
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: Effect type: carcinogenicity (migrated information)
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
Deviations:
yes
Remarks:
Some examinations like urinalysis are missing.
GLP compliance:
no
Remarks:
Tests were conducted prior to the implementation of GLP (1976-1978).
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Diets were prepared by thoroughly mixing the appropriate quantity of Dobanol-25-sulphate HCB with a purified diet to provide feed containing the required amount of active ingredient, ie. the surfactant was not added to the diet as a part replacement for any ingredient, but was added “on top of the diet”. Rats were individually housed and provided with diet and water ad libitum. The animals were inspected daily for signs of ill-health while body weights, and food and water intakes, were measured weekly for the first 13 weeks, again at week 16, and thereafter at intervals of 4 weeks until the end of the study.
Route of administration:
oral: feed
Vehicle:
other: plain diet
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
Daily
Post exposure period:
none
Remarks:
Doses / Concentrations:0, 0.015, 0.15, 1.5% Basis:nominal in diet
Remarks:
Doses / Concentrations:0, 11, 113, 1125 mg/kg bwBasis:actual ingested
No. of animals per sex per dose:
45
Control animals:
yes, plain diet
Other examinations:
Animals dying or killed during the test received a full post-mortem examination at which tissues were taken for histological examination. Animals surviving to the end of the test were starved overnight and blood was taken under anaesthesia for haematology and biochemical measurements after which the animals were killed and a number of organs (heart, liver, spleen kidneys, testes, adrenals and brain) were removed and weighed. These organs and a range of other tissues from each rat were preserved for histological examination. Histological examination was undertaken on stained tissue sections from all animals fed the control diet and each dietary level of the test substances.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
The test materials used in the individual studies were prepared by two different production methods (high conversion bleached or HCB; and low conversion, unbleached or LCU). They differed slightly in chain length distribution, the latter having a slightly higher proportion of the C15 AS. 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 tumor incidence, nor any impact on tumor 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 was a decreased number of total tumors and tumor-bearing animals. Elevated serum GPT, LDH and AP were observed in high dose males.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.
Relevance of carcinogenic effects / potential:
The material was not tumorigenic at the any dose level, including the highest dose of 1.5%.
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: Effect type: carcinogenicity (migrated information)
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 125 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The possibility of a read-across to 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 physicochemical, 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, neutralized 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 represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS 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.

A reliable combined chronic toxicity/carcinogenicity study was conducted with C12 -15AS Na (CAS 68890-70-0). For two combined chronic toxicity/carcinogenicity studies similar to OECD Guideline 453 C12-15AS 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.

REFERENCES

[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

Justification for classification or non-classification

The available data on carcinogenicity do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.