Zinc dodecyl hydrogen disulphate

Endpoint summary

Description of key information

For all analogues of alkyl sulfates (AS) a NOAEL of 488 mg/kg bw/day for oral and dermal exposure was established.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: 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 Analogue Approach Justification document provided in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

LOAEL

Effect level:

1 016 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: systemic effects that could not be regarded solely as adaptive processess, i.e. increased testes weight in males

Remarks on result:

other: source CAS 68890-70-0, Unilever, 1976a

Key result

Dose descriptor:

NOAEL

Effect level:

488 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Remarks on result:

other: source CAS 68890-70-0, Unilever, 1976a

Dose descriptor:

NOAEL

Effect level:

482 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Only adaptive changes (elevated liver weights and hypertrophy of the liver) were observed.

Remarks on result:

other: source CAS 68955-20-4, Unilever, 1977b

Dose descriptor:

LOAEL

Effect level:

970 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: source CAS 68955-20-4, Unilever, 1977b

Dose descriptor:

NOAEL

Effect level:

460 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Only adaptive changes (elevated liver weights and hypertrophy of the liver) were observed.

Remarks on result:

other: source CAS 151-21-3, Unilever, 1976b

Dose descriptor:

LOAEL

Effect level:

920 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Significant decreased body weight and diffuse hepatocytic hypertrophy.

Remarks on result:

other: source CAS 151-21-3, Unilever, 1976b

Dose descriptor:

NOAEL

Effect level:

512 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Only adaptive changes (elevated liver weights and hypertrophy of the liver) were observed.

Remarks on result:

other: source CAS 86014-76-1, Unilever, 1977a

Dose descriptor:

LOAEL

Effect level:

1 007 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other:

Remarks on result:

other: source CAS 86014-76-1, Unilever, 1977a

Dose descriptor:

NOAEL

Effect level:

>= 201.28 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: overall effects

Remarks on result:

other: source CAS 68585-47-7, P&G, 1976

Dose descriptor:

NOAEL

Effect level:

>= 254.56 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

other: overall effects

Remarks on result:

other: source CAS 68585-47-7, P&G, 1976

Dose descriptor:

NOAEL

Effect level:

>= 430 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Only adaptive increases in liver weights in female animals.

Remarks on result:

other: source CAS 151-21-3, Walker, 1967

Critical effects observed:

not specified

Conclusions:

The NOAELs and LOAELs achieved within the different studies draw a coherent picture. The NOAEL of 254 mg/kg bw/d in the study of P&G (1976) represent unreasonably low doses for risk assessment. The relatively low values are due to the chosen dose level and the dose spacing, respectively. No effects were observed at this dose levels. The dietary NOAEL of 488 mg/kg bw/d (Unilever., 1976a) represents an average of all NOAEL and thus for C12-14AS Zn.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

488 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: dermal

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 Analogue Approach Justification document provided in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

not examined

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:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
One mouse treated with 12.5% died after 1 week due to dehydration and anorexia.

WATER CONSUMPTION
At 10% and above the water intake was increased.

HAEMATOLOGY
Haemoglobin levels reduced and wbc counts increased in high dose males.

ORGAN WEIGHTS
Absolute and relative heart weights were higher in high dose females. Relative liver weights were increased in both sexes at the 15% and in females at the 12.5% concentration. Increased absolute kidney weights (males) and relative kidney weights (females) were found at the 15% dose level.

GROSS PATHOLOGY & HISTOPATHOLOGY
Exudate adherent to skin (4/20) was observed at the 15% dose level. Loss of hair colour lateral and ventral to application site observed at all treatment levels. Extensive ulceration and necrosis of the epidermis of the decedent at the 12.5% treatment level. Dose-related ulceration of the epidermis (4/20) with inflammatory exudate (11/20) observed at 15% and 12.5% treatment levels.

OTHER FINDINGS
At concentrations of 12.5 and 15%, cytotoxic effects were found in the epidermis.

Dose descriptor:

NOAEL

Effect level:

10 other: %

Based on:

act. ingr.

Remarks:

corresponding to 400 mg/kg bw/day

Sex:

male/female

Basis for effect level:

dermal irritation

haematology

organ weights and organ / body weight ratios

Dose descriptor:

LOAEL

Effect level:

12.5 other: %

Based on:

act. ingr.

Remarks:

corresponding to 500 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Extensive necrosis and ulceration of the skin, changes in haematology and organ weights.

Critical effects observed:

not specified

Conclusions:

Based on this study a NOAEL of 400 mg/kg bw/day was found and thus concluded for C12-14AS Zn.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subchronic

Species:

mouse

Repeated dose toxicity: dermal - local effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: dermal

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 Analogue Approach Justification document provided in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

not examined

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:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
One mouse treated with 12.5% died after 1 week due to dehydration and anorexia.

WATER CONSUMPTION
At 10% and above the water intake was increased.

HAEMATOLOGY
Haemoglobin levels reduced and wbc counts increased in high dose males.

ORGAN WEIGHTS
Absolute and relative heart weights were higher in high dose females. Relative liver weights were increased in both sexes at the 15% and in females at the 12.5% concentration. Increased absolute kidney weights (males) and relative kidney weights (females) were found at the 15% dose level.

GROSS PATHOLOGY & HISTOPATHOLOGY
Exudate adherent to skin (4/20) was observed at the 15% dose level. Loss of hair colour lateral and ventral to application site observed at all treatment levels. Extensive ulceration and necrosis of the epidermis of the decedent at the 12.5% treatment level. Dose-related ulceration of the epidermis (4/20) with inflammatory exudate (11/20) observed at 15% and 12.5% treatment levels.

OTHER FINDINGS
At concentrations of 12.5 and 15%, cytotoxic effects were found in the epidermis.

Dose descriptor:

NOAEL

Effect level:

10 other: %

Based on:

act. ingr.

Remarks:

corresponding to 400 mg/kg bw/day

Sex:

male/female

Basis for effect level:

dermal irritation

haematology

organ weights and organ / body weight ratios

Dose descriptor:

LOAEL

Effect level:

12.5 other: %

Based on:

act. ingr.

Remarks:

corresponding to 500 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Extensive necrosis and ulceration of the skin, changes in haematology and organ weights.

Critical effects observed:

not specified

Conclusions:

Based on this study a NOAEL of 400 mg/kg bw/day was found and thus concluded for C12-14AS Zn.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Study duration:

subchronic

Species:

mouse

Additional information

For analogues alkyl sulfates (AS) used as source substances, a NOAEL of 488 mg/kg bw/day was established.

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 analogues show structural similarity. The most important common structural feature of the members of the analogue approach 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 analogues in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS of the AS analogues have similar physicochemical, environmental and toxicological properties, validating the read-across approach. 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 program carrying out Human and Environmental Risk Assessments (HERA [2]), further supporting the read across approach between structurally related AS. A detailed justification for the analogue approach of alkyl sulfates is provided separately. Please refer for more details on the read-across also to the document “Analogue Approach Justification” attached in section 13 of IUCLID.

 

Therefore this endpoint is covered by read across to structurally related alkyl sulfates. Reliable repeated dose toxicity studies have been conducted with C12 AS Na (CAS 151-21-3), C10-16 AS Na (68585-47-7), C12-14 AS TEA (CAS 90583-18-9), C12-15 AS Na (CAS 68890-70-0), C16-18 AS Na (CAS 68955-20-4) and C13-15 AS Na (CAS 86014-79-1). Hence, alkyl sulfates with chain lengths between C10 and C18 have been tested.

Assessment of RDT of zinc

Zinc compounds are recognised as zinc category in the OECD HPV program [3]. The zinc category includes six compounds (zinc metal, zinc oxide, zinc distearate, zinc chloride, zinc sulphate, and trizinc bis(orthophosphate). Available data show that zinc salts have moderate effects upon acute oral application and may be irritating to skin and eyes. The repeated dose toxicity of zinc was evaluated in the SIDS for zinc [3]. “In repeated dose toxicity studies with rats and mice, oral zinc exposure resulted in copper deficiency and pathological changes in the pancreas and the spleen as the most sensitive effects, with a NOAEL of 13.3 mg Zn2+/kg bw/day. In studies with human volunteers, women appeared to be more sensitive than men to the effects of repeated zinc supplementation. In women, supplementation at a level of 150 mg Zn2+/day (2.5 mg/kg bw/day, based on a body weight of 60 kg; LOAEL) resulted in clinical signs such as headache, nausea and gastric discomfort, and in indications for disturbance of copper homeostasis. The NOAEL in women supplemented with zinc was 50 mg Zn2+/day (0.83 mg/kg bw/day). The background intake of zinc via food is approximately 10 mg/day.” Recalculating the effect levels to C12-14AS Zn in respect to the molecular weight this would lead to the following effect levels:

NOAEL (rat) = 121 mg/kg bw/day

LOAEL (human) = 22.76 mg/kg bw/day

NOAEL (human) = 7.55 mg/kg bw/day.

These effect levels are lower than found for the alkyl sulfates. Therefore, it has to be assumed that C12-14AS Zn has a NOAEL for repeated dose between 121 and 488 mg/kg bw/day in rats. Nevertheless, zinc salts are not classified regarding repeated dose toxicity and the estimated effect levels would not lead to a classification regarding repeated dose toxicity. However, the uncertainty will be considered when deriving a DNEL for C12-14AS Zn (CAS n.a.) and thus the lowest NOAEL of 7.55 mg/kg bw/day are used for DNEL derivation.

Oral gavage RDT

A 90% aqueous solution of C12 AS Na (CAS 151-21-3) was administered for 28 days by gavage to groups of five animals/sex/dose at dose levels of 30, 100 or 300/600 mg/kg bw/day (the dose of 300 mg/kg bw/day was changed into 600 mg/kg bw/day after 10 days of treatment). The study was performed in accordance with OECD 407 except for the functional observation battery and revealed a NOEL of 90 mg a.i./kg bw/day (BASF, 1987a). At the LOAEL (270/540 mg a.i./kg bw/day), feed intake and body weight gain were reduced and water intake increased. Bleeding and ulceration of the stomach, as well as transient alterations of the tongue and myocard were found. There was an increase in leucocytes and in alanine aminotransferase (ALT) activity, as well as a decrease in haematocrit and erythrocyte volume (MCV). Relative weights of adrenals, kidneys, brain, gonads and liver were increased; the relative thymus weight was decreased.

With the same study design (which meets all requirements of the OECD 407 except for functional observation battery tests), C12-14 AS TEA (CAS 90583-18-9) was administered by gavage as a ca. 40% aqueous solution at dose levels of 0, 70, 250 or 750 mg/kg bw/day (corresponding to 0, 29, 102 and 306 mg/kg bw/day active ingredient) to groups of five rats/sex/dose (BASF, 1988). At 250 mg/kg bw/day (i.e. 102 mg a.i./kg bw/day), signs of local irritation were found in the forestomach (inflammation, ulceration in some animals), but no indication of a systemic toxicity. Therefore, this level is considered as the systemic NOAEL. At 750 mg/kg bw/day (i.e. 306 mg a.s./kg bw/day), the severity of gastric irritation increased, and the animals showed leucocytosis (LOAEL).

In a 90 day gavage study, C16-18 AS Na (CAS 68955-20-4) was administered as 55% aqueous solution to groups of 10 rats/sex/dose at dose levels of 100, 300 and 900 mg/kg bw/day, corresponding to ca. 55, 165 and 495 mg a.s./kg bw/day (BASF, 1987b). The NOEL was established at 55 mg a.i./kg bw/day. At the next higher dose level (NOAEL, 165 mg a.i./kg bw/day) food consumption and body weight gain were reduced, and relative liver weight was increased. Other changes were non-specific and probably due to the irritant effect of the test substance to the stomach mucosa. At 495 mg/kg bw/day, there were clear signs of gastritis; absolute and relative liver weights were increased. No signs of toxicity were found in the kidney.

Oral feeding RDT 

C12 AS Na (CAS 151-21-3) was tested as well in a 90 day feeding study on rats (Walker et al., 1967). 12 male and 12 female rats/group were fed dietary levels of 40, 200, 1000 or 5000 ppm (corresponding to 3, 17, 86 or 430 mg/kg bw/day). The control group (18 males, 18 females) received the diet alone. Daily observations were made on health. Body weight and food intake were recorded weekly. Urine samples were obtained from the 5000 ppm and control groups during Week 12. The urine was examined for colour, pH, protein, reducing substances, bile salts and microscopic constituents. Terminal blood samples were taken by cardiac puncture and erythrocyte and leukocyte counts and determinations of haematocrit and haemoglobin were made. Total plasma protein and urea were determined. Gross pathological and histological examinations of a wide range of organs were made. The only effects observed occurred at 5000 ppm and comprised increases in liver weights in female animals. Regarding this as an adaptive effect, the NOAEL can be set at the highest dose level of 5000 ppm (430 mg/kg bw/day).

C12 AS Na (CAS 151-21-3) was also tested in a 13 week feeding study on rats by Unilever (1976b). Ten rats/sex/dose in the test groups and 20 rats/sex in the control group were administered dietary levels of 0, 0.07, 0.14, 0.28, 0.56, 1.13 and 2.25% (corresponding to 0, 58, 116, 230, 460, 920 and 1840 mg/kg bw/day). The control group received the diet alone. The NOAEL was set at 460 mg/kg bw/day since only adaptive changes were observed at this dose level.

Another subchronic feeding study was done with C10-16 AS Na (CAS 68585-47-7; P&G, 1976). Administration of 0, 0.25, 0.5 and 1% test substance in diet (corresponding to 0, 58, 118 and 228 mg/kg bw/day for males and females based on a.i.) to 20 Sprague-Dawley rats/sex/dose revealed no treatment-related effects either in-life or at necropsy. In addition, histopathological examinations did not show any changes considered to be related to compound administration. Hence, the NOAEL calculated by the mean food consumption was set at 254 mg/kg bw/day based on a.i. for females and 201 mg/kg bw/d based on a.i. for males.

C12-15 AS Na (CAS 68890-70-0) was investigated in a 13 week and in two 2 year studies with rats, all using the dietary route of exposure. When tested for 13 weeks at dietary concentrations of 0, 0, 0.07, 0.14, 0.28, 0.56, 1.13 or 2.25% in groups of ten rats/sex/dose in a study that meets current standards (except for neurotoxicity and immunotoxicity testing; Unilever, 1976a), the NOEL was set at 0.14% (122 mg/kg bw/day). Since the liver as the target organ showed only adaptive responses, the NOAEL was set at 0.56% (488 mg/kg bw/day). The adaptive changes included elevated relative liver weight due to a lower body weight and reduced food consumption, hepatic periportal hypertrophy as well as increased serum alkaline phosphatase (AP) activity. An increased serum AP activity is considered to represent a physiological adaptation resulting from changes in hepatic metabolism required for the breakdown and detoxification of the test material. Since AP is mainly localized in the hepatic parenchyma, enlargement of the hepatic parenchymal cells accompanied by an increased organ weight are an obvious consequence.

In the chronic dietary repeated dose toxicity studies the NOELs were set at 113 mg/kg bw/day (LOAELs = 1125 mg/kg bw/day; Unilever, 1995a,b). Animals in the high dose groups in both studies exhibited reduced food and water consumption and slower growth rates. Other pathological findings were 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.

In another subchronic study with C13-15 AS Na (CAS 86014-79-1; Unilever, 1977a), ten animals/sex/group were fed diets containing 0, 0.07, 0.14, 0.28, 0.56, 1.13 or 2.25% (corresponding to 0, 64, 134, 253, 512, 1007, or 2096 mg/kg bw/day), the NOAEL was established at 512 mg/kg bw/day since only adaptive changes (elevated liver weights and hypertrophy of the liver) were observed. At the LOAEL (1007 mg/kg bw/day) and higher dosages effects observed included enlargement of the kidneys without histological identifiable structural change, increased patency of intestinal lymphatics, decreased serum cholesterol concentration and elevated serum activity of the enzymes cholinesterase and glutamic-oxalacetic transaminase.

C16-18 AS Na (CAS 68955-20-4; subchronic, dietary study, Unilever, 1977b) shows an identical profile with a similar NOAEL (482 mg/kg bw/day) and LOAEL (970 mg/kg bw/day).

Dermal RDT 

A repeated dose toxicity study with dermal application is also available. Dose levels employed in the 90 day study were 0, 5, 10, 12.5 and 15% C12-15 AS Na (CAS 68890-70-0) corresponding to 0, 200, 400, 500 and 600 mg/kg bw/day based on an average weight of 20 g bw/mouse and a 5 days/week treatment (Unilever, 1977). Ten C57BL mice per sex and group were treated with a dose volume of 0.2 mL with the control group being sterile water. An unknown area of all animals was with the appropriate dose two times per week. All animals were observed daily for signs of general health, mortality and gross skin irritation effects. Gross signs of toxicity and body weights were recorded on a weekly basis throughout the study. Effects at the site of application were consistent with the irritant properties of the test material. Dose-related ulceration of the epidermis with inflammatory exudate was observed at the 12.5% and 15% concentrations. Dose-dependent increases in edema, vascular dilatation, epidermal acanthosis, hyperkeratosis and hypergranulosis were prominent at the 10% treatment level and above. Haemoglobin levels were reduced and white blood cell counts increased in males of the high dose group. No clinical chemistry measurements were performed. Other noteworthy systemic effects included increases in liver-to-body weight ratios in both sexes at the 15% concentration, and in females at the 12.5% concentration. Absolute kidney weights increased in males and kidney weight-to-body weight ratios increased in females at the 15% treatment level. These target organs are consistent with those observed in the oral studies. Effects at these more distant organs suggest that a higher level of percutaneous absorption of the test material may have occurred at high doses with the longer duration of exposure in this study. The systemic NOAEL was set at 400 mg/kg bw/day. However, the dietary NOAEL of 488 mg/kg bw/day will be used for risk assessment. For details refer to the folowing discussion.

Conclusion 

In summary, gastrointestinal irritation, particularly of the forestomach, was the primary effect after application via gavage but not after application via the diet. This is consistent with the primary irritant properties of the AS and the bolus effect after application by gavage. Notably, gavage studies that included recovery groups indicated that systemic effects other than forestomach irritation were fully reversible. Moreover, administration via gavage (see developmental toxicity studies as well) does not allow differentiating between systemic effects as a consequence of the local irritation or due to specific substance properties (e.g. leucocytosis). The study investigating the dermal route resulted in significant local irritation. It provided some evidence of systemic toxicity however there is insufficient information to determine if these effects represented a direct toxic effect from systemic exposure to AS or if the response was associated with the significant dermal inflammation. Thus, the NOAEL used for the risk assessment should be based on a dietary study to assess potential systemic toxicity resulting from repeated exposures to AS. After administration in the diet, the liver was the only target organ identified. Adaptive effects on this organ included an increase in liver weight, enlargement of liver cells and elevated levels of liver enzymes. Liver effects were more apparent in dietary studies, partly because these allowed administration of higher doses of the test material with less GI tract injury.

The listing of all dietary NOAELs and LOAELs in Table 1 shows that the spacing of the concentrations in the chronic toxicity studies was very high. On the other hand, the NOAELs of the subchronic studies are all in the same range and about 4.5 times higher.

  

Table 1: NOAELs and LOAELs (for a.i.) for repeated dietary dose toxicity studies of AS in rats

Substance	Duration (weeks)	NOAEL (mg/kg bw/day)	LOAEL (mg/kg bw/day)	Reference
C12 AS Na	13	430	> 430	Walker et al. (1967)
C12 AS Na	13	460	920	Unilever (1976b)
C10-16 AS Na	13	201/254	> 201/>254	P&G (1976)
C12-15 AS Na	13	488	1016	Unilever (1976a)
C13-15 AS Na	13	512	1007	Unilever (1977a)
C16-18 AS Na	13	482	970	Unilever (1977b)
C12-15 AS Na	104	113	1125	Unilever (1995a,b)

 

The NOAELs and LOAELs achieved within the different studies draw a coherent picture. The NOAEL of the chronic toxicity study (113 mg/kg bw/d) as well as the NOAEL of 254 mg/kg bw/d in the study of P&G (1976) represent unreasonably low doses for risk assessment. The relatively low values are due to the chosen dose level and the dose spacing, respectively. No effects were observed at both dose levels. Since the subchronic and chronic LOAELs are in the same range and the subchronic NOAELs do not conflict with the chronic LOAEL, one of the subchronic NOAELs can be chosen as NOAEL for AS in rats. Based on the described effects and argumentations, the dietary NOAEL of 488 mg/kg bw/d (Unilever, 1976a) representing an average of all NOAEL was chosen as oral and dermal NOAEL in rats for AS.

[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] SIDS initial assessment profile, (2005);http://webnet.oecd.org/Hpv/UI/handler.axd?id=fddec5fa-9727-413a-9d67-41c2154cd362

Justification for classification or non-classification

The available data on repeated toxicity 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.