Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data regarding toxicity to reproduction is provided according to column 2, section 8.7.1 of Annex VIII, as a reliable and adequate pre-natal developmental toxicity study performed with an analogue source substance is available and data are read-across.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

No data regarding toxicity to reproduction is provided according to column 2, section 8.7.1 of Annex VIII, as a reliable and adequate pre-natal developmental toxicity study performed with an analogue source substance is available and data are read-across.

Effects on developmental toxicity

Description of key information

No data are available for the target substance Sulfuric acids, C9-11-iso-C10 rich, alkyl esters, sodium salt. Therefore, read-across from structural analogue substances has been applied.

OECD 414, rat, developmental toxicity, oral: not teratogenic, no effect on development

Maternal: NOAEL = 250 mg/kg bw/day; LOEL > 250 mg/kg bw/day
Developmental: NOAEL = 250 mg/kg bw/day; LOEL > 250 mg/kg bw/day

Read-across from source substance Sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8)

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
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
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Partially natural parturition.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
According to Guideline.
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Concentration in vehicle: 10%
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
According to Guideline.
Duration of treatment / exposure:
Day 6-15 of gestation.
Frequency of treatment:
Once daily.
Duration of test:
Day 21 and Post parturition
Dose / conc.:
63 mg/kg bw/day (nominal)
Dose / conc.:
125 mg/kg bw/day (nominal)
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
20 females (15 for dissection; 5 for natural parturition)
Control animals:
yes, concurrent vehicle
Maternal examinations:
Acording to Guideline, except for parturition. Except of killing one day prior to the expected day of delivery, five of 20 dams were allowed to natural parturition before sacrifice.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes

Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

- Other: Five mated rats from each of the treatment and ten from the control group were selected by random numbers for natural parturition. This enabled observations on litter size, weight and infant mortality to be recorded, together with any other observable postpartum expression of response to treatment for a period of 21 days (birth to weaning).
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Yes
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
At 500 mg/kg bw/day, the test substance produced maternal toxicity associated with severe diarrhoea, reduced food intake and reduced body weight gain. There was one death in this group and two animals were killed prior to full term. The survivors showed an increased number of intrauterine deaths and a reduction in live foetal body weight. These foetuses showed evidence of toxic retardation, with delayed ossification and also an increased incidence of supernumerary cervical ribs and shortened thoracic ribs. There were no gross external or visceral anomalies which could be attributed to treatment.
No maternal toxic effects were seen in the other treatment groups and there were no effects on live foetal numbers, body weight or crown-rump distance. There was no evidence of a specific external, gross visceral or skeletal defect which could be attributed to treatment.
There was no indication of a treatment effect on pups born by natural parturition and reared to weaning age of 21 days.
Dose descriptor:
NOAEL
Remarks:
maternal
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: no toxic effects
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Effects were only seen in the presence of maternal toxicity.
Dose descriptor:
NOAEL
Remarks:
development
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: no toxic effects
Developmental effects observed:
no
Conclusions:
Treatment of pregnant rats with the test substance 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 foetotoxicity and did not show teratogenic potential.
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Lack of details on test substance, intervals in dose range
GLP compliance:
no
Species:
rat
Strain:
other: CD
Details on test animals and environmental conditions:
According to guideline.
Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
According to guideline.
Duration of treatment / exposure:
Day 6-15 p.c.
Frequency of treatment:
Daily
Duration of test:
Day 20
Dose / conc.:
0.2 mg/kg bw/day (actual dose received)
Dose / conc.:
2 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
Dose / conc.:
600 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20
Control animals:
yes, concurrent vehicle
Maternal examinations:
According to guideline.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: No data
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Yes.
Details on maternal toxic effects:
Maternal toxic effects:yes
Dose descriptor:
NOAEL
Remarks:
maternal
Effect level:
300 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: retarded body weight gain
Dose descriptor:
LOAEL
Remarks:
maternal
Effect level:
600 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
mortality
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
> 600 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: no significant higher incidences of malfurmations
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
At 600 mg/kg bw no developmental toxicity was detected. Maternal toxicity was present at 600 mg/kg bw.
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
lack of details on test substance, intervals in dose range
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
According to guideline.
Route of administration:
oral: gavage
Vehicle:
water
Details on mating procedure:
According to guideline.
Duration of treatment / exposure:
Day 6-18
Frequency of treatment:
Daily
Duration of test:
Day 1-29
Dose / conc.:
0.2 mg/kg bw/day (actual dose received)
Dose / conc.:
2 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
Dose / conc.:
600 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle
Maternal examinations:
According to guideline.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: No data
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Yes.
Details on maternal toxic effects:
Maternal toxic effects:yes
Dose descriptor:
NOAEL
Remarks:
maternal
Effect level:
300 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: retarded body weight gain
Dose descriptor:
LOAEL
Remarks:
maternal
Effect level:
600 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
mortality
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
> 600 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: no significant higher incidences of malformations in a dose-response way
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
No maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day, respectively.
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Method: other
GLP compliance:
no
Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
Age: 16 - 18 weeks
Route of administration:
oral: gavage
Details on mating procedure:
Virgin female rats were taken at random from a stock  cage and recaged in groups of 3 with each of 15 virgin male rats of the  same age and from the same colony. The dropping trays were examined each  morning thereafter for ejected vaginal plugs, and when these were found  the female rats were removed and individually examined for evidence of  mating. Confirmation of mating was established by microscopically  examination of the vaginal mucus for the presence of spermatozoa.
Duration of treatment / exposure:
Days 6 - 15 of gestation
Frequency of treatment:
daily
Duration of test:
Termination on Day 21 of gestation or up to weaning Day 21.
Dose / conc.:
63 mg/kg bw/day (actual dose received)
Dose / conc.:
125 mg/kg bw/day (actual dose received)
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
15 rats (10 for dissection, 5 for  natural parturition)
Control animals:
yes
Details on study design:
negative control: saline 
positive control: aspirin 250 mg/kg  s.c.
Maternal examinations:
-body weight: daily
-maternal food intake: daily
Ovaries and uterine content:
- mean gravid uterus weight & mean weight of uterine tissue
- intrauterine mortality 
- mean response per pregnancy
Fetal examinations:
- mean foetal body weight, crown  rump distance and mean placental weight
-  % incidence of external and  gross visceral observations of foetuses
- incidence of skeletal  variants/anomalies of foetuses
- incidence and distribution of other  anomalies
- post-partum mortalities
- mean body weight of pups (at birth  and on days 7, 14 and 21)
- weaned of born
- incidence of external and  gross visceral variations of pups
- incidence of skeletal variations of  pups
Details on maternal toxic effects:
Maternal toxic effects: yes

Details on maternal toxic effects:
General health: All animals at 500 mg/kg bw/day had diarrhoea, which continued until cessation  of treatment. With successive treatments the passage of the cannula down  the oesophagus became more difficult suggesting a dryness of the  membranes, and the demeanour of the animals became more aggressive. Between the 4th and 8th dose 4 of the animals of this group died and 1  was sacrificed because of its condition. A further animal aborted on the 14th  day of gestation having received 9 treatments. All the animals which died  showed evidence of gastrointestinal irritation and diffuse haemorrhage of  the stomach. In 3 instances there was also congestion of the lungs. Mean maternal body weight gain: Treatment with 500 mg/kg bw/day induced a significant (p = < 0.05) reduction in  maternal body weight gain during the period of treatment. Food consumption: Rats treated with 500 mg/kg bw/day consumed significantly (p=<0.05) less food  than controls Intrauterine mortality: No significant differences between treatment and control Mean response per pregnancy: Treatment did not adversely affect the pre- or post-implantation loss
Dose descriptor:
NOAEL
Remarks:
maternal
Effect level:
250 mg/kg bw/day
Basis for effect level:
other: diarrhoea, gastrointestinal irritation and diffuse haemorrhage of  the stomach
Dose descriptor:
LOAEL
Remarks:
maternal
Effect level:
500 mg/kg bw/day
Basis for effect level:
other: diarrhoea, gastrointestinal irritation and diffuse haemorrhage of  the stomach
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Foetal and placental size: The mean placental weight for male and female foetuses combined and  considered separately were significantly lower in animals fed 500 mg/kg bw/day (p= 0.05). Incidence of gross variants/anomalies: No significant differences between treatment groups and control group Incidence of skeletal anomalies: No significant differences between treatment groups and control group Incidence of foetal variations, minor anomalies and major malformations: Malformations were found in 3 foetuses from dams treated with 500 mg/kg bw/day -  protruding tongue, gross oedema and shortening of the pubic bone;  agenesis of eyelids and cleft palate; unossified metatarsus and claw in  left hind foot. The foetuses were all taken from separate pregnancies. A  single live foetus with a malformation was also found after treatment  with 250 mg/kg bw/day (hermi-centric lumbar centra with asymmetry and reduced  ossification of the 6th lumbar arch and scoliosis) and 63 mg/kg bw/day (unossified and dumbbell shaped thoracic centrae associated with branched  ribs) Rats allocated to natural parturition: Post-partum mortalities: No significant differences between treatment and controls. Incidence of skeletal defects in rat pups: No significant differences between treatment groups and control group.
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
>= 500 mg/kg bw/day
Basis for effect level:
other: no effects observed
Abnormalities:
no effects observed
Developmental effects observed:
no
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
Method: other
GLP compliance:
no
Species:
rat
Strain:
Wistar
Route of administration:
oral: gavage
Duration of treatment / exposure:
Day 6 - 15 of gestation
Frequency of treatment:
daily
Duration of test:
termination on GD 21 or up to weaning day 21
Dose / conc.:
112 mg/kg bw/day (actual dose received)
Dose / conc.:
225 mg/kg bw/day (actual dose received)
Dose / conc.:
450 mg/kg bw/day (actual dose received)
Dose / conc.:
675 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
15 females per dose group: 10 for dissection and 5  for natural parturition
Control animals:
yes, concurrent vehicle
Dose descriptor:
NOAEL
Remarks:
maternal
Effect level:
225 mg/kg bw/day
Basis for effect level:
clinical signs
body weight and weight gain
Dose descriptor:
LOAEL
Remarks:
maternal
Effect level:
450 mg/kg bw/day
Basis for effect level:
clinical signs
body weight and weight gain
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
675 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: no effects observed
Dose descriptor:
LOAEL
Remarks:
develoopmental
Effect level:
> 675 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: no effects observed
Abnormalities:
no effects observed
Developmental effects observed:
no

Maternal effects:
General health: Treatment with 675 mg/kg bw/day induced diarrhoea in 4/15 females

after the third dose day (day 9 of gestation)
Mean maternal body weight gain: the mean maternal body weight gain in rats 

fed 675 mg/kg bw/day on days 6-10 and rats fed 450 mg/kg bw/day on days 10-15 of gestation 

were significantly lower (p = < 0.05) than controls
Food consumption: no significant differences between treatment and control groups
Intrauterine mortality: no significant differences between treatment and control
Mean response per pregnancy: When data for live foetuses was analysed there

was significantly less (p=<0.05) live foetuses in the 675 mg/kg group 

than the controls. This was not attributable, however, to a significant 

decrease in viable female foetuses in this group, but purely a chance 

occurrence of a high number of female foetuses in the controls.

Offspring:
Foetal and placental size: Only significant effect when data for the 

separate males and females was analysed which revealed a significantly 

lower (p= <0.05) mean placental weight for the male foetuses in the 450 

mg/kg bw/day group
Incidence of gross variants/anomalies: No explanation could be given for 

the incidence of macroscopically observed haemorrhage under the capsule 

of the kidney in some foetuses in the 3 lower treatment groups (3.66% of 

foetuses at 450 mg/kg bw/day; 3.73% at 225 mg/kg bw/day; 4.95% at 112 mg/kg bw/day).
Incidence of skeletal anomalies: Analysis of the data relating to 

vertebral and head variations/anomalies revealed a significant (p=<0.05) 

increase in the foetuses from mothers treated with 112 mg/kg bw/day

Rats allocated to natural parturition
Post-partum mortalities: In the 675 mg/kg bw/day treatment group 5/6 

pups were partially cannibalised during post-partum days 1-3 and all came 

from a single litter. Two pups from a single litter were also cannibalised 

in the 450 mg/kg bw/day treatment group.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
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

No data regarding developmental toxicity of Sulfuric acids, C9-11-iso-C10 rich, alkyl esters, sodium salt are available. Therefore, read-across from the structural analogue substance Sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8) has been applied in accordance with Regulation (EC) No 1907/2006 Annex XI 1.5 “Grouping of substances and read-across approach”. 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 read-across approach show structural similarity. The most important common structural feature of the source and target substances 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 source and target substances in turn represent the predominant attribute in mediating effects on mammalian health. Therefore, the AS have similar physico-chemical, environmental and toxicological properties. 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.

Regarding developmental toxicity / teratogenicity one relevant key study with Sulfuric acid, mono-C12-14-alkyl esters, sodium salts (C12-14 AS Na, CAS 85586-07-8) and further supporting studies with structurally analogue read-across source substances Sodium dodecyl sulfate (C12 AS Na, CAS 151-21-3) and Sulfuric acid, mono-C16-18-alkyl esters, sodium salts (C16-18 AS Na, CAS 68955-20-4) are available.

In the developmental toxicity study which was chosen as key study C12-14 AS Na (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, C12-14 AS Na (CAS 85586-07-8) 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 NOAEL for maternal toxicity and developmental toxicity is set at 250 mg/kg bw/day.

The purpose of the studies conducted by Palmer (1975a&b) was to assess the effects of orally administered C12 AS Na (CAS 151-21-3) on embryonic and foetal development in pregnant CD-rats and NZW-rabbits. In this study, C12 AS Na (CAS 151-21-3) 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 study showed that repeated oral administration of C12 AS Na (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 C12 AS Na (CAS 151-21-3) on embryonic and foetal development was as well assessed by Unilever (1976c) in Wistar rats. 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 C16-18 AS Na (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 key developmental toxicity study with the analogue substance Sulfuric acid, mono-C12-14-alkyl esters, sodium salts (CAS 85586-07-8), developmental effects were noticed, which however occurred at a dose level which clearly was found to be toxic to the dams. Thus the findings do not provide any evidence for the test item to be potentially toxic to development and/or teratogenic. Thus, AS, including the target substance Sulfuric acids, C9-11-iso-C10 rich, alkyl esters, sodium salt are considered to be not teratogenic.

 

[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 reproductive toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.