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Key value for chemical safety assessment

Effects on fertility

Description of key information
OECD 416, rat, 2 gen, oral: not toxic to reproduction
NOAELrep = 300 mg/kg bw/day; LOAELrep > 300 mg/kg bw/day
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The whole data base is conclusive and of high quality.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

One study on reproductive toxicity is available for AES (C12-14) Na (CAS 68891-38-3). These data are also used to cover this endpoint for the other AES within the AES-category, i.e. AES (C9-11) NH4 (CAS 160901-27-9), AES (C8-10) NH4 (CAS 68891-29-2), AES (C12-14) NH4 (CAS 125301-88-4), AES (C12-14) MIPA (CAS 1187742-72-8), AES (C12-14) Mg (CAS 160104-51-8), AES (C10-16) Mg (CAS 67762-21-4), AES (C8-10) Na, AES (C9-11) Na (CAS 160901-28-0), AES (C10-12) Na (CAS 68610-66-2), AES (C12-13) Na (CAS161074-79-9), AES (C12-14) Na (CAS 68891-38-3) and AES (C12-18) Na (CAS 68081-91-4).

The AES reported within the category show similar structural, physico-chemical, environmental and toxicological properties. The approach of grouping different AES for the evaluation of their effects on human health and the environment was also made by the Danish EPA (2001) and HERA (2003), supporting the read-across approach between structurally related AES.

In a two-generation reproduction study with AES (C12-14) Na (CAS 68891-38-3, 27% a.i.) (BASF, 1999) Sprague Dawley rats were dosed via drinking water at 0, 0.03, 0.1 and 0.3%, which corresponded to daily doses of ca. 0, 30, 100 and 300 mg/kg bw/day. There were some changes indicative of parental toxicity in the group treated with 0.3% of the test substance. Slight but significantly reduced straight line velocity (VSL) of the sperm was without any significant effects on averaged path velocity (VAP) or total motility. Moreover, in the available subchronic and chronic toxicity studies on various AES the primary sex organs of the males and females did not show evidence for treatment-related adverse effects. The observed reduced triglyceride levels (female) and increased percentage neutrophil counts (males) were slight and within the range of the historical control data. The male F0 generation showed a small but significant reduction in body weight-liver weight ratios, but the corresponding brain related liver weights and the absolute liver weights developed not in a dose dependent way. For the F1 generation where similar results were reported, no dose-response relationship was detected either. No influence on liver weight development was seen in the F2 generation. None of the groups revealed any histopathological or clinical-chemical findings, which could be attributed to hepatotoxicity. This led to the conclusion that this untypical liver weight reduction was of no toxicological relevance, additionally underlined by the absence of such effects in the studies for subchronic toxicity mentioned above. There was evidence of toxicity on pup development at this dose level that was characterised by an increase in the time taken for sexual development of the male (not significant) and female (significant) offspring. This was investigated in more detail in the developmental toxicity study up to 1500 mg/kg bw/day (see "Developmental toxicity") and no effects were noted there.

Considering all these facts, the subchronic NOAEL for systemic toxicity can be set to greater than 300 mg/kg bw/day.

 

References:

Danish EPA - Environmental and Health Assessment of Substances in Household Detergents and Cosmetic Detergent Products (2001). Environmental Project No. 615, pp. 24-28

HERA (2003). Human & Environmental Risk Assessment on ingredients of European household cleaning products Alcohol Ethoxysulphates, Human Health Risk Assessment Draft, 2003. http: //www. heraproject. com.

Effects on developmental toxicity

Description of key information
OECD 414, rat, developmental toxicity, oral: not teratogenic
NOAELdev = 1000 mg/kg bw/day; LOAELdev > 1000 mg/kg bw/day
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The whole data base is conclusive and of high quality.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Data on developmental toxicity are available for AES (C12-14) Na (CAS 68891-38-3), AES (C12-15; 3 EO) Na (CAS 125301-92-0), AES (C10-16; 3 EO) Na (CAS 68585-34-2) and AES (C13-15; 2 EO) NH4 (CAS 162063-19-6). These data are also used to cover this endpoint for the other AES within the AES-category, i.e. AES (C9-11) NH4 (CAS 160901-27-9), AES (C8-10) NH4 (CAS 68891-29-2), AES (C12-14) NH4 (CAS 125301-88-4), AES (C12-14) MIPA (CAS 1187742-72-8), AES (C12-14) Mg (CAS 160104-51-8), AES (C10-16) Mg (CAS 67762-21-4), AES (C8-10) Na, AES (C9-11) Na (CAS 160901-28-0), AES (C10-12) Na (CAS 68610-66-2), AES (C12-13) Na (CAS161074-79-9), AES (C12-14) Na (CAS 68891-38-3) and AES (C12-18) Na (CAS 68081-91-4). The AES reported within the category show similar structural, physico-chemical, environmental and toxicological properties. The approach of grouping different AES for the evaluation of their effects on human health and the environment was also made by the Danish EPA (2001) and HERA (2003), supporting the read-across approach between structurally related AES.

The purpose of the key study (BASF, 1994b) was to assess the effects of orally administered AES (C12-14) Na (CAS 68891-38-3) on embryonic and foetal development in pregnant CD rats. The study followed OECD Guideline 414 and complied with the OECD principles of GLP. In this study, AES (C12-14) Na (CAS 68891-38-3) was administered orally by gavage at dose levels of 0, 100, 300, and 1000 mg/kg bw/day once daily on Day 6-15 of gestation. In summary, the results of the study showed that repeated oral administration of AES (C12-14; 2EO) Na (CAS 68891-38-3) to pregnant rats did not cause symptoms of cumulative toxicity up to a dose level of 1000 mg/kg bw/day. There were no treatment-related foetal abnormalities at necropsy and no treatment-related effects in the reproduction data. Thus, based on the available information, the NOAEL for teratogenicity and developmental toxicity is assessed to be greater than 1000 mg/kg bw/day.

 

AES (C12-14; 3 EO) Na (CAS 68891-38-3) was administered orally by gavage as well to pregnant Colworth-Wistar rats at dose levels of 0, 93, 187, 375 and 750 mg/kg bw/day from Day 6-15 of gestation (Unilever, 1981). The treatment induced some maternal toxicity at the dose level of 750 mg/kg bw/day. No evidence of treatment-related teratogenic effects or developmental toxicity was reported. This study was not conducted according to GLP or to any recognized guideline. However, the study appeared to be well-conducted, was well-documented and judged to be scientifically acceptable. Based on the available information the NOEL for maternal toxicity was determined to be 375 mg/kg bw/day and the NOAEL for teratogenic or developmental effects is estimated to be greater than 750 mg/kg bw/day.

 

AES (C12-15; 3 EO) Na (CAS 125301-92-0) was administered orally by gavage to pregnant Wistar rats at dose levels of 0, 375 and 750 mg/kg bw/day once daily on Day 6-15 of gestation (Unilever, 1986a). In summary, AES (C12-15; 3 EO) Na (CAS 125301-92-0) induced maternal toxicity, indicated by body weight changes and other clinical and behavioural observations at doses of 750 mg/kg bw/day. The authors were unable to detect any specific abnormality which would indicate a developmental toxicity or teratogenic response related to the treatment. This study was not conducted according to any recognized guideline. However, the study was conducted according to GLP, is well-documented and judged to be scientifically acceptable. Based on the available information, the NOEL for maternal toxicity was estimated to be 375 mg/kg bw/day and the NOAEL for teratogenic effects or developmental toxicity greater than 750 mg/kg bw/day.

 

AES (C12-15; 3 EO) Na (CAS 125301-92-0) was administered orally via the diet to pregnant Colworth-Wistar rats at dose levels of 0.375, 0.5, 1.0, 1.5% (corresponding to 0, 350, 450, 950 and 1500 mg/kg bw/day) once daily on Day 0-20 of gestation (Unilever, 1989b). In summary, maternal toxicity was revealed solely as a reduction in body weight gain at the 1.5 and 1% treatment levels; this was associated with reduced food intake. The increase in sternebrae variations in the 1.5% treatment group was probably related to maternal toxicity. This group also showed an increase in the number of foetuses with unossified phalanges. No other dose related defects were seen and it is considered that there is no indication of a teratogenic effect attributable to treatment with AES (C12-15, 3EO) Na (CAS 125301-92-0). Treatment throughout pregnancy at the highest dose level (1500 mg/kg bw/day) did not induce any teratogenic effects.

 

Pregnant albino rabbits, artificially inseminated, were administered AES (C10-16; 3 EO) Na (CAS 68585-34-2) by gavage at levels of 50, 100, or 300 mg/kg bw/day on Days 2-16 of gestation (P&G, 1972). No maternal deaths were attributable to the test substance and there were no significant differences in the number of corpora lutea, resorptions, implantations or live fetuses. The number of dead fetuses, 19 in the high level treatment group (300 mg/kg bw/day) and 17 in the control group, were higher than the remaining groups. All but four of these deaths occurred in just three litters. This lack of dose response indicated that something other than the test substance caused the deaths of these fetuses. In addition, no statistical differences were seen in the fetal weights of survivors or with regard to the number of fetuses with skeletal defects. The examination of fetuses from this study for soft-tissue abnormalities revealed only one instance of significant difference occurring in one litter of the low level treatment group. The lack of a dose response relationship between the levels of the test substance and the incidences of stressed bladder (five) indicate an isolated incidence of spontaneous malformations which have been seen in previous teratology studies. The NOAEL for the test substance was 300 mg/kg bw/day on the basis that the test substance did not produce any significant increases in the number of abnormal fetuses at any dose level. There were no significant test substance-related differences in the numbers of corpora lutea, implantation, resorptions or dead fetuses. Under the conditions of this study, the test substance, at the levels tested, was neither embryotoxic nor teratogenic.

 

AES (C13-15; 2 EO) NH4 (CAS 162063-19-6) was administered orally by gavage to pregnant Colworth-Wistar rats at dose levels of 0, 63, 125, 250 and 500 mg/kg bw/day from Day 6-15 of gestation (Unilever, 1986b). Some slight but statistically not significant signs of maternal toxicity indicated by body weight changes and other clinical observations (e.g. diarrhoea, respiratory wheeziness) were seen in rats with exposure to 250 and 500 mg/kg bw/day. No evidence of developmental toxicity or a teratogenic response to the treatment was reported at any dose level. The NOAELs for maternal toxicity and teratogenic effects or developmental toxicity were estimated to be greater than 500 mg/kg bw/day.

 

References:

Danish EPA - Environmental and Health Assessment of Substances in Household Detergents and Cosmetic Detergent Products (2001). Environmental Project No. 615, pp. 24-28

HERA (2003). Human & Environmental Risk Assessment on ingredients of European household cleaning products Alcohol Ethoxysulphates, Human Health Risk Assessment Draft, 2003. http: //www. heraproject. com.

Justification for classification or non-classification

The available data on toxicity to reproduction do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.