Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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

Based on the assessment of the toxicological properties of the anionic surfactants (ANS) category performed under the high production volume (HPV) chemicals program of the Organisation for Economic Cooperation and Development (OECD) in 2007 at the OECD SIDS Initial Assessment Meeting (SIAM) 25 there are no reproductive toxicity studies available for either alkyl sulfates or alkane sulfonates that have been performed to standard protocols. A study available for C12 alkyl sulfate showed no adverse effects on epididymal spermatozoa and derived a NOAEL for male fertility of 1000 mg/kg bw/day. The results of several 90-day repeated dose toxicity studies performed using higher chain length alkyl sulfates gave no indication for adverse effects on reproductive organs at histopathological examinations.

In an extended 14-day repeated dose range finding study, C6 -8 alkane sulfonate was administered daily by gavage to CD® rats [LPT GmbH (2013) ]. The rats were treated with 100, 300 or 1000 mg/kg bw/day. The substance showed only limited signs of toxicity in this study up to the high dose of 1000 mg/kg bw/day and macroscopic post mortem examination did not reveal any test item-related changes at any dose level including in gonads, uterus and accessory reproductive organs. On the basis of these studies, the substance is not expected to cause adverse effects on fertility.

Effects on developmental toxicity

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Reference:
Composition 0
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
Limit test:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
According to guideline.
TEST ANIMALS
- Source: East Anglian Rabbitries, Colchester, UK
- Age at study initiation: no data
- Housing: individually in metal cages with wire mesh floors.
- Diet: ad libitum
- Water: ad libitum
- weight and age: according to guideline

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-2
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Prepared daily as a series of graded aqueous solutions so that all groups were dosed with a standard volume.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
According to guideline.
Duration of treatment / exposure:
Day 6-18 of pregnancy
Frequency of treatment:
Daily
Duration of test:
Day 1-29
Remarks:
Doses / Concentrations:
0, 0.2, 2, 300 and 600 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale:Lowest 2 doses selected to provide a factor of 1-2 and 10-20 times the likely maximum human intake. The highest 2 doses were considered likely to impair maternal economy and provoke some obvious adverse effects.
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:
Differences in group mean litter values were analysed by non-parametric methods (Wilcoxon test).
Historical control data:
No. of foetuses examined: 36,508
Major malformations (%): 0.74
Minor visceral anomalies (%): 2.53
Minor skeletal anomalies (%): 8.60
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Deaths: 2/13 (controls); 1/13 (- intubation error -2mg/kg bw); 1/13 (300 mg/kg bw); 11/13 (600 mg/kg bw)
Bodyweight: retarded gain at 0.2 and 300 mg/kg bw/day; loss at 600 mg/kg bw/day.
Total litter loss: 1 at 0.2 mg/kg bw/day and 2 at 300 mg/kg bw/day
Toxic effects were generally associated with a principal disturbance of the gastrointestinal tract. Affected rabbits showed diarrhoa, anorexia, weight loss and cachexia prior to death. Total litter loss (abortion and/or total resorption) tended to occur as a secondary consequence of the primary effect on the mother.
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
At maternally toxic doses there was an increased foetal loss and reduced litter size, due almost entirely to the total littler losses. That the latter were secondary consequence of maternal reaction was indicated by the fact that among rabbits bearing some young at termination litter parameters were comparable with (or not unduly different from) control values. At non-toxic dosages, or at dosages provoking only slight to moderate maternal reaction, values for litter size and foetal loss were essentially unaffected.
There wereno dose related increases in the number of abnormalities.
(please refer to attached tables)
Abnormalities:
not specified
Developmental effects observed:
not specified
Conclusions:
No maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day, respectively.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Species:
rabbit
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Additional information

The developmental toxicity of various alkyl sulfates (C12 ASO4 Na, C12–14 ASO4 Na, C12–15 ASO4, C13–15 ASO4 Na, C15–16 AS Na, C16–18 ASO4 Na) was tested on rats, rabbits and mice [OECD (2007); Wibbertmann et al. (2011)]. Principally, effects on litter parameters were restricted to doses causing significant maternal toxicity such as anorexia, weight loss, and death (doses between 300 and 500 mg a.i/kg bw/day for rats and 300 mg a.i./kg bw/day for mice and rabbits) and principal effects such as higher fetal loss and increased incidences of total litter losses. Apart from a higher incidence of delayed ossification or skeletal variation seen in mice at >500 mg a.i./kg bw/day which is indicative of delayed development, the incidences of malformations and visceral and skeletal anomalies were unaffected. The lowest reliable NOAEL for maternal toxicity is about 200 mg a.i./kg bw/day in rats, while the lowest NOAELs in offspring were 250 mg a.i./kg bw/day in rats and 300 mg a.i./kg bw/day for mice and rabbits. For a-olefin sulfonates, no adverse effects were reported in rats (dams and offspring) dosed with up to 600 mg a.i./kg bw/day of C14–16=/OHASO3 Na during days 6–15 of gestation, i.e. this value is the NOAEL both for maternal and developmental toxicity.From a parallel study performed with mice and rabbits, no clear NOAEL can be derived due to unusual intervals of the applied dose sizes (0, 0.2, 2 , 300 and 600 mg a.i./kg bw/day). At 2 mg a.i./kg bw/day, no adverse effects were found,while at 300 mg a.i./kg bw/day adverse effects both in dams and offspring were observed.

For alkane sulfonates, no data are available for developmental toxicity. However, due to similar toxicokinetic properties and a comparable metabolism of the alkyl sulfates and alkane sulfonates, the alkane sulfonates are not considered to be developmental toxicants

Justification for classification or non-classification

Based on the available data for members of the ANS category it is concluded that no classification for reproductive toxicity is warrented.