Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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). However, there is a reliable OECD guideline study with the structural related analogue Alkyl Ether Sulfate (AES) substance Alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) available which has been used for read-across. For details, please refer to the discussion below.


equivalent or similar OECD 416, rat, 2-generation, oral: not reprotoxic
NOAEL reproduction > 300 mg/kg bw/day
NOAEL systemic > 300 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
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 justification provided in 'Attached justification'.
Reason / purpose for cross-reference:
read-across source
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
300 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxicity observed.
Remarks on result:
other: Source, key, 68891-38-3, 1999
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction
Effect level:
300 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxicity observed.
Remarks on result:
other: Source, key, 68891-38-3, 1999
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Generation:
F1
Effect level:
300 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxicity observed.
Remarks on result:
other: Source, key, 68891-38-3, 1999
Key result
Dose descriptor:
NOAEL
Remarks:
reproduction
Generation:
F1
Effect level:
300 mg/kg bw/day (nominal)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxicity observed.
Remarks on result:
other: Source, key, 68891-38-3, 1999
Reproductive effects observed:
no
Conclusions:
In summary, there was no effect of treatment at any dose level on reproduction of the parents or offspring (NOAEL >= 0.3 %; > 300 mg/kg/day).
Based on this study an overall NOAEL for systemic effects of 0.3 % (300 mg/kg bw) can be deduced.
Executive summary:

The reproductive toxicity of the target substance is estimated based on an adequate and reliable two-generation reproductive toxicity study of a structural analogue source substance. There was no effect of treatment at any dose level on reproduction of the parents or offspring (NOAEL >= 0.3 %; > 300 mg/kg/day). Based on this study an overall NOAEL for systemic effects of 0.3 % (300 mg/kg bw) can be deduced. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences with respect to toxicity to reproduction.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2) from an analogue source substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII - X, 8.7, in accordance
with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Relevant data from repeated dose toxicity and pre-natal developmental studies

No data on reproductive toxicity of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) and any other structurl alkyl sulfate (AS) analogue substance are available. In order to assess this endpoint, information from various repeated dose toxicity studies performed with a variety of structural analogue AS are considered. 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 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, 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 physicochemical, 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).

Repeated dose toxicity data

Subchronic repeated oral toxicity studies with sulfuric acid, mono-C12-15-alkyl esters, sodium salts (CAS 68890-70-0), sulfuric acid, mono-C16-18 (even-numbered)-alkyl esters, sodium salts (CAS 68955-20-4), sodium dodecyl sulfate (CAS 151-21-3), and sulfuric acid, mono-C13-15-alkyl esters, sodium dodecyl sulfate (CAS 86014-79-1) gave no indication of adverse effects on reproductive organs (Unilever 1976b, 1977a, 1977b, 1995a&b). At very high doses (around or above 1000 mg/kg bw/day) increases in relative (but not absolute) testes weights were noted. This effect was not considered as adverse but was attributed to a decreased body fat/body weight ratio. There were also no adverse histopathological findings at necropsy. The primary effect after application via gavage but not after application via the diet was gastrointestinal (GI) irritation, particularly of the forestomach. Moreover, it was impossible to differentiate between systemic effects as a consequence of the local irritation or due to specific substance properties. After dietary application 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 (refer to section 7.5 'Repeated dose toxicity' for details on study conduct and results). No adverse effect on fertility of male Swiss mice was observed within a feeding study with sodium dodecyl sulfate (CAS 151-21-3). 10 males were dosed either with 1 % test substance over 2 weeks and fertility was assessed over the ensuing 3 week period or with 0.1% test substance over 6 weeks and fertility was assessed 1, 2 or 3 weeks after termination of treatment with 6 animals. At the highest dose level body weights were significantly decreased, while the treatment caused no adverse effects on fertility. A NOAEL of 1000 mg/kg bw/d was derived for this endpoint in the OECD SIDS. Although the data are limited and are not sufficient for classification purposes the data support the assumption that fertility is not impaired by treatment with sodium dodecyl sulfate (CAS 151-21-3).

As confirmed by literature (Mangelsdorf et al. 2003, Ulbrich and Palmer 1995, Janer et al. 2007, Dent 2007, Sanbuissho et al. 2009) histopathological examinations of reproductive tissues in repeated dose toxicity studies on rodents are of high value and high sensitivity for evaluation of reproductive toxicity in males and females. Moreover, histopathological changes on the reproductive organs in repeated dose toxicity studies are indicative of effects on fertility. Since histological examinations of the reproductive organs are covered in the studies described above, these repeated dose toxicity studies can be considered as sensitive and sufficient enough to evaluate toxicity on fertility. With additional respect to animal welfare, conducting additional reproductive toxicity studies appears scientifically not justified. This assumption is further supported by the results of a study during which whole body radiography on rats after i.p. injection of 35S-C10 AS K, C12 AS K and C18 AS K was performed. The aim was to follow the distribution of the labeled alkyl sulfates (AS) and/or their metabolites within the body as a function of time. For all compounds the only organs, where radioactivity was detected, were the liver and the kidney. The levels (not quantified) were highest 1 h after application (refer to section 7.1 'Toxicokinetics, metabolism and distribution' for details). Thus, within this study the AS did not reach the reproductive organs. This can explain why the only relevant effects after dietary application in the repeated dose toxicity studies referred to above were observed in the liver and why no treatment related effects on the reproductive organs were observed.

Within the repeated dose studies no histopathological findings on reproductive organs were observed. In addition, it is questionable whether AS reach the reproductive organs. Therefore, no effects on fertility are expected and conducting additional reproductive toxicity studies is not needed.

Pre-natal developmental toxicity data

The existing pre-natal developmental toxicity studies (OECD guideline 414) did not indicate adverse effects on the development of pups, when females were treated with different alkyl sulfates during pregnancy. The OECD 414 is the only guideline study gathering information on skeletal and visceral effects in the fetuses, but additionally provides further information on the development of pups. Within the study with sodium dodecyl sulfate (CAS 151-21-3; Unilever, 1976d), besides the common investigations of fetuses upon caesarian section, 5 mated rats from each of the treatment groups were selected by random for natural parturition. The observation period of pups of these litters was 21 days. No effect on litter size, pup weight, mortality and no clinical signs of toxicity in pups were observed. Thus, neither indication on developmental toxicity nor the early development of the pups post parturition (until day 21) was observed.

Based on these data, reproductive toxicity or toxic effects on fertility of target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) is very unlikely. To overcome remaining uncertainties a read-across from the structurally related anionic surfactant alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) was performed.

Read-across justification from structurally related alkyl ether sulfate (AES) substance alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3)

The target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2) and alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) are linear anionic surfactants. The surfactant properties of both substances are conferred by a hydrophobic carbon chain with a polar sulfate group. The carbon chain of the alkyl ether sulfate is ethoxlyated twice. The surfactant properties represent the predominant attribute in mediating effects on mammalian health. Next to the structural similarity, alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) additionally comprises 20% sodium dodecyl sulfate (CAS 151-21-3) and approximately 9% sodium tetradecyl sulfate. Thus, approximately 29% of the test item belong to the same chemical class as the target substance (i.e., alkyl sulfates, AS). If alkyl sulfates have a reproduction toxic potential, this considerable amount of alkyl sulfates can be expected to contribute to possible effects of the test substance. Therefore, the test item is also suited to assess the toxicity to reproduction of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Despite the structural similarity of the source and the target substance and the amount of alkyl sulfates within the test item, there are further reasons to perform a read-across from alkyl ether sulfates (AES) to alkyl sulfates (AS). Both linear anionic surfactants are absorbed readily in the gastrointestinal tract. Within the body, both substances are metabolised via omega and beta-oxidation of the carbon chain. The resulting C2-fragments enter the general C2 pool of the organism and will be either degraded within the citric acid cycle or used to produce ketone bodies. Short carbon chains linked to the sulfate group in case of alkyl sulfates or linked to the ethoxysulfate group in case of alkyl ether sulfates are rapidly urinary excreted. Thus, alkyl sulfates in principle comprise the same or comparable metabolites as alkyl ether sulfates. Based on the known metabolites a low systemic toxicity can be expected for both substances. This was proven by several repeated dose toxicity studies with alkyl sulfates and alkyl ether sulfates, respectively.

Summary of the 2-generation toxicity study performed with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) (based on the HERA Report, 2003)

Alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) (ethoxylation degree of 2) was applied to 30 Sprague Dawley rats of each sex via the drinking water at concentrations of 0.03, 0.1 and 0.3% according to OECD Guideline 416. The doses corresponded to daily doses of approximately 30, 100 and 300 mg/kg bw/day. Slight parental toxicity was observed at the top dose group of 0.3% of the test substance. Reduced triglyceride levels (female) and increased percentage neutrophil counts (males) were observed. Both effects were slight and within the range of the historical control data. The male F0 generation showed a small but significant reduction in relative liver weight, 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 effect on liver weight development was seen in the F2 generation. None of the groups revealed any histopathological or clinical-chemical findings. This led to the conclusion that this untypical liver weight reduction was of no toxicological relevance. This is underlined by the absence of such effects in the studies for subchronic toxicity. Therefore the systemic NOAEL can be established at 0.3%, corresponding to approx 300 mg/kg bw/day. Within the HERA-Report however a NOAEL of 0.1% for systemic toxicity was established. For the main purpose of the study (toxic effects on reproduction) this parameter does however not influence the overall conclusion.

A slight but significantly reduced straight line velocity (VSL) of the sperm was observed in males of the top dose which was rather significant by chance than to reflect a treatment related effect. This is also supported by available subchronic and chronic toxicity studies on various AES where no adverse effects on the primary sex organs of males and females were observed.

At the top dose an increased time needed for sexual development of the male (not significant) and the female (significant) offspring was observed. This effect was investigated in more detail in a developmental toxicity study with alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) up to 1000 mg/kg bw/day and no effects were noted there. Therefore, this finding is considered to be incidental.

Based on the available data the NOAEL for reproduction toxicity can be set to greater than 0.3%, corresponding to approx. 300 m/kg bw/day. This is in agreement with the NOAEL established in the HERA report.

Conclusion on reproductive toxicity

Due to structural similarities, common metabolites, identical human hazard profiles and the composition of alcohols, C12-14, ethoxylated, sulfates, sodium salts (CAS 68891-38-3) the data obtained with the substance reflect also the hazard potential of the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, the read-across from the AES substance is well suited and also indicated by the 3R concept to close the data gap of the target substance. The absence of any reproduction toxicity of the target substance is further supported by the known ubiquitously occurring metabolites of sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2), the repeated dose toxicity data of structurally analogue alkyl sulfate (AS) substances investigating reproductive organs and the developmental studies with several AS substances. In consequence, no hazard for reproductive toxicity is expected for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2).

[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

Mangelsdorf, I., Buschmann, J., Orthen, B., 2003. Some aspects relating to the evaluation of the effects of chemicals on male fertility. Regulatory Toxicology and Pharmacology 37, 356–369

Ulbrich, B. and Palmer, A.K. (1995). Detection of effects on male reproduction: a literature survey. J. Am. College of Toxicology 14, 293–327

Janer G, Hakkert BC, Slob W, Vermeire T, Piersma AH. 2007. A retrospective analysis of the two-generation study: What is the added value of the second generation? Reprod Toxicol 24:97-102.

Dent MP. 2007. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility. Regul Toxicol Pharmacol. 2007 Aug; 48(3):241-58. Epub 2007 Apr 12.

Sanbuissho A, Yoshida M, Hisada S, et al., 2009. Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Toxicol Sci 2009.:SP1-22.

Effects on developmental toxicity

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 structural analogue substances has been applied.

Developmental toxicity (equivalent or similar OECD 414, rat, oral): not teratogenic
Maternal: NOEL = 250 mg/kg bw/day; LOEL > 250 mg/kg bw/day
Developmental: NOEL = 250 mg/kg bw/day; LOEL > 250 mg/kg bw/day

Developmental toxicity (equivalent or similar OECD 414, rabbit, oral): not teratogenic

Maternal: NOAEL = 300 mg/kg bw/day

Developmental: NOAEL > 600 mg/kg bw/day

Read-across of key information from source substance sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8; rat) and sodium dodecyl sulfate (CAS 151-21-3; rabbit), supported by additional studies performed with various structural analogue substances.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
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
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:
NOEL
Remarks:
systemic (rat)
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: No toxic effects.
Remarks on result:
other: Source, key, 85586-07-8, 1987
Key result
Dose descriptor:
NOAEL
Remarks:
systemic (rabbit)
Effect level:
300 mg/kg bw/day (actual dose received)
Remarks on result:
other: Source, key, 151-21-3, 1975a
Key result
Dose descriptor:
NOEL
Remarks:
development (rat)
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxic effects.
Remarks on result:
other: Source, key, 85586-07-8, 1987
Key result
Dose descriptor:
NOAEL
Remarks:
development (rabbit)
Effect level:
> 600 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: No effects observed
Remarks on result:
other: Source, key, 151-21-3, 1975a
Developmental effects observed:
yes
Lowest effective dose / conc.:
500 mg/kg bw/day (actual dose received)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects
Conclusions:
Treatment of pregnant rats with the test substance sulfuric acid, mono-C12-14-alkyl esters, sodium salts at 500 mg/kg bw/day induced a maternal toxic response and this was reflected in the conception which showed toxic retardation. At 250, 125 and 63 mg/kg bw/day, the test substance did not cause maternal toxicity or feototoxicity and did not show teratogenic potential. In rabbits, no maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day of sodium dodecyl sulfate, respectively, were observed.
Executive summary:

The developmental toxicity of the target substance is estimated based adequate and reliable pre-natal developmental toxicity studies of a structural analogue source substance conducted in rat and rabbit, respectively. Treatment of pregnant rats with the test substance sulfuric acid, mono-C12-14-alkyl esters, sodium salts at 500 mg/kg bw/day induced a maternal toxic response which was reflected in the conception that showed toxic retardation. At 250, 125 and 63 mg/kg bw/day, the test substance did not cause maternal toxicity or fetotoxicity and did not show teratogenic potential. In rabbits, no maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day of sodium dodecyl sulfate, respectively, were observed. 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 developmental toxicity / teratogenicity.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on common physico-chemical, ecotoxicological and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex X, 8.7.2, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.
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

There are no data on developmental toxicity / teratogenicity available for the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2). Therefore, these endpoints are covered by read-across from structurally related alkyl sulfates (AS). 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).

In the developmental toxicity study using rats which was chosen as key study sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8) was administered orally by gavage to pregnant Wistar rats at dose levels of 0, 63, 125, 250 and 500 mg/kg bw/day once daily from Day 6 to 15 of gestation (Unilever, 1987). In summary, the test item induced maternal toxicity, indicated by body weight decrease, diarrhoea and increased mortality, when administered at doses of 500 mg/kg bw/day. Developmental toxicity could be seen by an increased number of intrauterine deaths, a decreased live foetal body weight and toxic retardation with delayed ossification and increased incidence of supernumerary cervical ribs and shortened thoracic rib at 500 mg/kg bw/day. Based on the available information the NOEL for maternal toxicity and developmental toxicity is set at 250 mg/kg bw/day.

The purpose of the studies conducted by Palmer (key, 1975a, in rabbit; supporting, 1975b, in rat) was to assess the effects of orally administered sodium dodecyl sulfate (CAS 151-21-3) on embryonic and foetal development in pregnant CD-rats and NZW-rabbits. In this study, the test item was administered orally by gavage at dose levels of 0, 0.2, 2, 300 and 600 mg/kg bw/day once daily from Day 6 to Day 15 (rat) / Day 19 (rabbit) of gestation. In summary, the results of the studies showed that repeated oral administration of sodium dodecyl sulfate (CAS 151-21-3) to pregnant rats and rabbits did not cause symptoms of cumulative maternal toxicity up to a dose level of 300 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 are assessed to be greater than 600 mg/kg bw/day.

 

The effect of sodium dodecyl sulfate (CAS 151-21-3) on embryonic and foetal development was also assessed by Unilever (1976d) in Wistar rats in another supporting study. The test substance was administered by gavage at dose levels of 0, 63, 125, 250 and 500 mg/kg bw/day once daily from Day 6 to 15 of gestation. No cumulative maternal toxicity was seen up to a dose level of 250 mg/kg bw/day. At 500 mg/kg bw/day dams showed significant decreased body weight and food consumption together with corresponding clinical signs like diarrhoea. No treatment-related foetal abnormalities or effects in the reproduction data were observed at 500 mg/kg bw/day. Thus, the NOAEL for teratogenicity and developmental toxicity are assessed to be greater than 500 mg/kg bw/day.

Finally, embryonic and foetal development was examined after administration of sulfuric acid, mono-C16-18-alkyl esters, sodium salts (CAS 68955-20-4; Unilever, 1978). The alkyl sulfate was administered by gavage at dose levels of 0, 112, 225, 450 and 675 mg/kg bw/day once daily from Day 6 to 15 of gestation. At 450 mg/kg bw/day and higher dams showed significant decreased body weight gain together with diarrhoea. No treatment-related foetal abnormalities or effects in the reproduction data were observed at 675 mg/kg bw/day. Thus, the NOAEL for teratogenicity and developmental toxicity are assessed to be greater than 675 mg/kg bw/day.

 

Conclusion

In the repeated dose studies performed with a variety of structural analogue alkyl sulfates (AS) it was observed that the primary effect after application via gavage is gastrointestinal irritation. This is consistent with the primary irritant properties of the AS and the bolus effect after application by gavage. Moreover, it was impossible to differentiate between systemic effects as a consequence of the local irritation or due to specific substance properties. In the developmental toxicity study which revealed teratogenic effects (Unilever, 1987), these occurred only at the highest dose level after oral gavage. However, at this dose level signs of marked maternal toxicity, i.e., increased mortality was also observed. It is important to note that not teratogenicity was observed at dose levels inducing no maternal toxicity. Thus, based on the experimental findings, AS substances, including the target substance sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, ammonium salts (CAS 90583-11-2), are not considered to exhibit a teratogenic potential.

 

[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

Justification for classification or non-classification

The available data on reproductive and developmental toxicity as well as teratogenicity obtainded with structurally analogue substances 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 reproductive toxicity.

Additional information