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Key value for chemical safety assessment

Effects on fertility

Description of key information

Various literature data were available in rats for the oral repeated dose toxicity of long chain alcohols (LCOH C16 and C18 chains), alkyl sulfates (AS C12 chain representing worst case situation for C14-C20). When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008) from NOAEL values of the components (C16 and C18 LCOH, C12 AS as worst case), this resulted in an oral reproductive NOAEL of 1357 mg/kg bw in rats. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is 1357 mg/kg bw.

Link to relevant study records

Referenceopen allclose all

Endpoint:
reproductive toxicity, other
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
- Short description of test conditions: The author studied possible effects on male fertility in Swiss albino mice after oral dosing via diet.
10 animals per dose group were dosed a.) with 1000 mg/kg bw/d over 2 weeks and fertility was assessed over the ensuing 3 week period or b.) with 100 mg/kg bw/d over 6 weeks to ensure that germ cells could be exposed to interference at any stage of development. 1, 2 or 3 weeks p.a. 6 animals of each group were paired.

GLP compliance:
no
Species:
mouse
Strain:
Swiss
Sex:
male
Route of administration:
oral: feed
Duration of treatment / exposure:
2 weeks or 6 weeks
Frequency of treatment:
continuously via diet
Dose / conc.:
1 other: % in diet
Remarks:
corresponds to 1000 mg/kg bw/d; 2 weeks exposure test
Dose / conc.:
0.1 other: % in diet
Remarks:
corresponds to 100 mg/kg bw/d; 6 weeks exposure test
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
a.) with 1000 mg/kg bw/d over 2 weeks and fertility was assessed over the ensuing 3 week period or
b.) with 100 mg/kg bw/d over 6 weeks to ensure that germ cells could be exposed to interference at any stage of development.
1, 2 or 3 weeks p.a. 6 animals of each group were paired.
Parental animals: Observations and examinations:
BODY WEIGHT: Yes
Body weight and weight changes:
effects observed, non-treatment-related
Description (incidence and severity):
Male mice fed diets containing 100 mg/kg bw/d for 6 weeks or 1000 mg/kg bw/d for 2 weeks experienced no impairment of epididymal spermatozoa, although at the highest dose the animals suffered a significant reduction of average body weight. At the highest dose level of 1000 mg/kg bw/d body weights were significantly decreased.
Reproductive performance:
no effects observed
Description (incidence and severity):
At the highest dose level of 1000 mg/kg bw/d body weights were significantly decreased, while the treatment caused no adverse effects on fertility (i.e. impairment of epididymal spermatozoa).
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: no adverse effects on fertility (i.e. impairment of epididymal spermatozoa)
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: no adverse effects on fertility (i.e. impairment of epididymal spermatozoa)
Critical effects observed:
no
Reproductive effects observed:
no
Conclusions:
Sodium dodecyl sulphate has no adverse effect on fertility, even when administered at concentrations sufficient to cause a significant reduction in body weight. A NOAEL of 1000 mg/kg bw/d was derived for this endpoint, using the following parameters: 25 g mice body weight and 2.5 g diet consumed per day.
Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study. Sodium dodecyl sulphate was administered to 10 male Swiss mice per dose group. The male mice were fed diets containing 100 mg/kg bw/d for 6 weeks or 1000 mg/kg bw/d for 2 weeks.

At the highest dose level of 1000 mg/kg bw/d body weights were significantly decreased, while the treatment caused no adverse effects on fertility (i.e. impairment of epididymal spermatozoa). Keeping in mind that the LOAEL for repeated dose toxicity for rats lies between 300 and 600 mg kg/day, the observed reduction in body weight is probably caused by the systemic toxicity of the substance.

In UNEP OECD SIDSInitial Assessment Report: Sodium Dodecyl Sulfate(1997), a NOAEL of 1000 mg/kg and day was derived for this endpoint, using the following parameters: 25 g mice body weight and 2.5 g diet consumed per day.

 

Reference: Hemsworth BN (1981) Male mouse fertility after ingestion of spermicidal detergents. Soc Occup Med 9, 243 – 244.

UNEP (1997) OECD SIDS Initial Assessment Report: Sodium Dodecyl Sulfate, http://www.chem.unep.ch/irptc/sids/OECDSIDS/151213.htm.

Endpoint:
fertility, other
Remarks:
28 days repeated dose study with histopathology of reproductive organs
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Version / remarks:
An in-house protocol based on OECD Guideline 407
GLP compliance:
not specified
Specific details on test material used for the study:
OTHER SPECIFICS: Tradename Lanette 16
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: M 84-98 g; F 81-93g
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
- Total volume applied: 5 mL/kg
- Doses: 0, 100, 500 and 1000 mg/kg/day

VEHICLE (olive oil)
- Concentration in vehicle: 0, 2, 10 or 20%
Duration of treatment / exposure:
27-28 days exposure (5 days/week)
Frequency of treatment:
dilay (5 days/week)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
10M+10F per dose level plus 5M+5F per dose level for reversibility.
Control animals:
yes, concurrent vehicle
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes / No / No data
- Time schedule:
- Cage side observations checked in table [No.?] were included.

CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily. Mortality: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Daily

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Weekly

OTHER:
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: At end of study

HAEMATOLOGY: Yes
- Time schedule for collection of blood: After 21/22 daily doses
- Parameters examined: Haematocrit, MCV, Hb, RBC, WBC, Thrombocytes, differential white count.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: After 21/22 daily doses
- Parameters examined: Serum Urea, creatinine, Na, K, calcium, alkaline phosphatase, ALAT, ASAT, GT, bilirubin, chloride, albumin, total protein, cholesterol.

URINALYSIS: No
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]

GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
Clinical signs:
no effects observed
Description (incidence and severity):
See chapter 7.5.1.
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
See chapter 7.5.1.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
See chapter 7.5.1.
Description (incidence and severity):
Water consumption was not affected.
Ophthalmological findings:
no effects observed
Description (incidence and severity):
See chapter 7.5.1.
Haematological findings:
effects observed, non-treatment-related
Description (incidence and severity):
Haematological parameters were not affected.
See chapter 7.5.1.
Clinical biochemistry findings:
effects observed, non-treatment-related
Description (incidence and severity):
See chapter 7.5.1.
Urinalysis findings:
not examined
Description (incidence and severity):
Reproductive tissues from the control and top dose animals (1000 mg/kg/day were examined histopathologically. In females examination of the ovaries, uterus and vagina and in males histopathological examination of the testes and prostate showed no difference between treated and control groups.
Dose descriptor:
NOAEL
Effect level:
ca. 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: highest dose tested
Critical effects observed:
no
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
ca. 1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Higest dose recevied
Critical effects observed:
no
Reproductive effects observed:
no
Conclusions:
The NOAEL for effects on the reproductive organs was considered to be 1000 mg/kg/day.
Executive summary:

Groups of 10M+10F Sprague-Dawley rats received daily doses of 0, 100, 500 and 1000 mg/kd Lanette 16 by gavage for 28 days. Full details of this study are reported in Chapter 7.5.1 Repeated dose toxicity: oral.

The testes and ovaries were weighed and these organs plus the prostate, uterus and vagina from all control and top dose animals were subject to histopathological examination.

There were no deaths among the test animals. Food intake, water consumption, body weight, organ weight, and haematological parameters were not affected.

The absolute and relative organ weights of the ovary and testes were determined and were comparable to controls.

Reproductive tissues from the control and top dose animals (1000 mg/kg/day) were examined histopathologically. In females examination of the ovaries, uterus and vagina and in males histopathological examination of the testes and prostate showed no difference between treated and control groups. The NOAEL for effects on the reproductive organs was considered to be 1000 mg/kg/day.

(Reference: Henkel KGaA. 1985a. Lanette 16: 28-Tage-Test mit wiederholter oraler Verabreichung an Ratten.November 1985.Report No. TBD 850499. With pathology report No. 840394)

Endpoint:
reproductive toxicity, other
Remarks:
Repeat dose study with histopathology of reproductive organs
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
no guideline available
Principles of method if other than guideline:
The results were reported to USEPA in accordance with TSCA 8(e).
GLP compliance:
no
Specific details on test material used for the study:
OTHER SPECIFICS: Tradename Alfol 16
Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: : Actual age not reported, described as young.
- Weight at study initiation: M 103.8 g; F 90.4 g
Route of administration:
oral: feed
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily in diet
Dose / conc.:
1 other: %
Remarks:
for 13 weeks. Actual dose received: M 723 mg/kg/day; F875 mg/kg/day
Dose / conc.:
2.5 other: %
Remarks:
for 13 weeks. Actual dose received: M1822 mg/kg, day; F 2064 mg/kg/day
Dose / conc.:
5 other: %
Remarks:
for 10 weeks , then 7.5% (week 11) and 10.0 % (weeks 12 & 13). Actual dose received: M 4257 mg/kg/day; F4567 mg/kg/day
No. of animals per sex per dose:
10M + 10F per test group, 20M + 20 F controls.
Parental animals: Observations and examinations:
CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily (5 days/week). Mortality: Daily (5 days/week)
Postmortem examinations (parental animals):
GROSS PATHOLOGY: Yes. Complete necropsy performed, organ weights measured were brain,thyroid, heart, liver, spleen, kidneys, adrenals, ovaries & testes.
HISTOPATHOLOGY: Yes. Tissues fixed: brain, thyroid, parathyroid, heart, lung, liver, spleen, stomach, small & large intestine, pancreas, kidney, urinary bladder, adrenals, ovaries, testes, lymph node,bone, bone marrow, muscle. All tissues from 5M+5F high dose and control animals were examined.
Statistics:
The original report indicates that a Chi square test was carried out on the organ:bodyweight ratio. It is not clear what statistical methods were used (if they were) for body weights, food consumption & haematological parameters. Subsequently The Weinberg Group Inc. used Tukeys test to re-analyse the organ weight data.
Clinical signs:
not specified
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significantly reduced (84.7 - 89.8% of controls) in top dose males for most study weeks, in mid dose females at weeks 4-13 and high dose females (81.7-89.7%) throughout the study. Changes were attributed at least in part to reduced food consumption and the high content of test material in the diet.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Significantly reduced (76.4 - 89.2% of controls) in top dose males at weeks 1 and 12, in mid dose males at week 13, in mid dose females at week 1 and high dose females weeks 1 and 12 (79.1 - 89.9% of controls).
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Clinical biochemistry findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
There were no treatment related histopathological changes in the control and top dose animals examined (including testes & ovaries).
Dose descriptor:
NOAEL
Effect level:
1 822 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: highest dose level tested
Dose descriptor:
NOAEL
Effect level:
4 567 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: highest dose level tested
Critical effects observed:
no
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 882 mg/kg bw/day
Based on:
test mat.
Sex:
male
Basis for effect level:
other: highest dose level tested
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
4 567 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: highest dose level tested
Critical effects observed:
no
Reproductive effects observed:
no
Conclusions:
The NOAEL for effects on the male reproductive organs can be considered as a dietary concentration of 2.5% (ca 2000 mg/kg/day) the NOAEL for the female reproductive organs is the highest dose level (ca 4000 mg/kg/day). Actual dose levels achieved at respective NOAELs, males 1822 mg/kg/day and females 4567 mg/kg/day.
Executive summary:

In a 13 week dietary feeding study in rats 10 male and 10 female rats per dose group (20 M and 20 F as controls) were dosed with Alfol 16 at dose levels of 1.0, 2.5 and 5% in the diet. The 5% dose was increased to 7.5% in week 11 and 10% in weeks 12 and 13.

At termination, all animals were necropsied and tissues from 5 males and 5 females (including gonads) of the high dose group and a similar number of controls were examined histopathologically. Testes and ovary weights were recorded together with other organ weights.

None of the animals displayed overt signs of intoxication due to oral exposure to hexadecanol during the 13 weeks of the experiment. Food consumption and body weights differed significantly for both males and females at various times in the intermediate and high dose levels. The relative testes weights were increased over control levels in all treatment groups reaching signficance in the low and high group according to the study report. The organ weight data were reanalysed by the Weinberg Associates using a Tukey test when significance was attained only at the high dose level. There were no significant changes in ovary weight. Histopathological examination revealed no treatment related changes in the ovaries or testes. The NOAEL for effects on the male reproductive organs can be considered as a dietary concentration of 2.5% (ca 2000 mg/kg/day) the NOAEL for the female reproductive organs is the highest dose level (ca 4000 mg/kg/day). Actual dose levels achieved at respective NOAELs, males 1822 mg/kg/day and females 4567 mg/kg/day.

(Reference: Scientific Associates, Inc. 1966a. Exhibit II. Final report on thirteen-week subacute feeding of Alfol 6 and Alfol 16 to rats.)

Endpoint:
reproductive toxicity, other
Remarks:
Combined repeat dose and Reproductive/Developmental screening study.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
according to guideline
Guideline:
other: Draft OECD 422 combined repeated dose and reproductive/developmental toxicity screening test
GLP compliance:
yes
Specific details on test material used for the study:
OTHER SPECIFICS: Octadecanol (112-92-5) (99% pure)
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 (males) - 9 (females) weeks at start of exposure
Route of administration:
oral: feed
Vehicle:
other: diet
Details on mating procedure:
- M/F ratio per cage: 1M+1F caged together
- Proof of pregnancy: vaginal plug. Inspection for vaginal plugs thrice daily.
- After 14 days of unsuccessful pairing replacement of first male by another male for 8 days.

Duration of treatment / exposure:
males 45 days, females up to 54 days
Frequency of treatment:
daily
Dose / conc.:
0 ppm
Remarks:
0 mg/kg bw/day
Dose / conc.:
1 500 ppm
Remarks:
ca. 100 mg/kg bw/day. Males: 99.25 mg/kg/day (mean of values reported for 2 weeks prior to matingand 3 weeks after mating). Females: 120 mg/kg/day (mean of values reported 2 weeks prior tomating)
Dose / conc.:
7 500 ppm
Remarks:
ca. 500 mg/kg bw/day. Males: 500.25 mg/kg/day (mean of values reported for 2 weeks prior to mating and 3 weeks after mating). Females: 625 mg/kg/day (mean of values reported 2 weeks prior to mating)
Dose / conc.:
30 000 ppm
Remarks:
ca. 2000 mg/kg bw/day. Males: 2146.5 mg/kg/day (mean of values reported for 2 weeks prior to mating and 3 weeks after mating) Females: 2435.5 mg/kg/day (mean of values reported 2 weeks prior to mating)
No. of animals per sex per dose:
12
Parental animals: Observations and examinations:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily. Mortality: Daily (Chapter 7.5.1)

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly (Chapter 7.5.1)

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Weekly (except during mating)

OTHER: See Chapter 7.5.1
HAEMATOLOGY: Yes
CLINICAL CHEMISTRY: Yes
URINALYSIS: No.


Oestrous cyclicity (parental animals):
Exposure was for 14 days premating covering at least 2 oestrous cycles. Ovaries were weighed and examined histopathologically at section (5 days after birth).
Sperm parameters (parental animals):
Exposure 14 days premating, no specific sperm analyses carried out, the testes & epididymes were weighed and examined histopathologically.
Postmortem examinations (parental animals):
- Organ weights P: liver, kidneys, thymus, testis, epididymes.
- Histopathology P: liver, kidneys, adrenals, brain, heart, spleen, ovaries, thymus, testes, epididymides and any organs showing abnormality on macroscopic examination were fixed. The above tissues from all controls and top dose treated rats (except the thymus) plus abnormalities were examined.
- Macroscopic P: Full macroscopic examination.
Postmortem examinations (offspring):
Offspring (and dams) were sacrificed on postnatal day 5 and the pups were weighed and examined for external malformations than sexed and examined for internal malformations.
Statistics:
Analysis of variance followed if significant differences were established by Dunnetts T-test to assess possible intergroup differences. For pregnancy rate a Qui2-test was carried out to confirm lack of significance.
Reproductive indices:
Pregancy rate, length of gestation, implantations, corpora lutea and resorptions were recorded.
Offspring viability indices:
Post natal survival until day 5
Clinical signs:
no effects observed
Description (incidence and severity):
See chapter 7.5.1
Mortality:
no mortality observed
Description (incidence):
See chapter 7.5.1
Body weight and weight changes:
no effects observed
Description (incidence and severity):
See chapter 7.5.1
Food consumption and compound intake (if feeding study):
effects observed, non-treatment-related
Description (incidence and severity):
See chapter 7.5.1
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Description (incidence and severity):
See chapter 7.5.1
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
The significance of changes in plasma free cholesterol, triglycerides and glucose is unclear, the changes were observed at all doses levels but were not dose related. They may be related to differences in dietary composition.
See chapter 7.5.1.
Urinalysis findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
There were no treatment related histopathological changes including no effects in the testes and ovaries.
Reproductive function: oestrous cycle:
not specified
Description (incidence and severity):
Ovarian primordial follicle counts: Not reported
Changes in lactation: Not reported
Changes in estrus cycles: Not reported
Description (incidence and severity):
Effects on sperm: Not reported
Reproductive performance:
no effects observed
Description (incidence and severity):
- Number of implantations: No significant differences in the numbers of implantations between treated and control groups.
Mean 13 in controls and low dose, 15 in mid and high dose groups.
Resorptions mean for controls and low dose 0, for mid and high dose 1.
- Number of corpora lutea: No significant differences between treated and control groups (mean controls 13, low and mid dose 14, high dose 15).



Dose descriptor:
NOAEL
Effect level:
ca. 2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: There were no statistically significant adverse effects on reproductive parameters .
Critical effects observed:
no
Description (incidence and severity):
Post natal survival until day 5: Similar in treated and control groups
Description (incidence and severity):
Litter size and weights: No effect of treatment (mean liter size 11.73, 10.0, 13.6 and 13.38 for controls, low, mid and high dose respectively).
Litter weights day 1 mean 69, 61, 75 and 75 g; Day 4 mean 96, 84, 101 and 101g for controls, low, mid and high dose respectively)
Description (incidence and severity):
- Sex and sex ratios: No treatment related effects.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
ca. 2 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: highest dose tested
Critical effects observed:
no
Reproductive effects observed:
no
Conclusions:
Parental NOAEL 2000 mg/kg/day changes in plasma free cholesterol, triglycerides and glucose were observed at all doses levels but were not dose related and may be due to differences in dietary composition. There were no statistically significant adverse effects on reproductive parameters and the NOAEL for reproductive and developmental effects can be considered as 2000 mg/kg/day (highest dose level).
Executive summary:

1-Octadenol was administered to groups of 12 male and 12 female Wistar rats in the diet for 45 days (males) and ca. 54 days (females) according to the Draft OECD 422 combined repeated dose and reproductive/developmental toxicity screening test.

Mortality and clinical signs were observed daily; body weight was observed weekly; food consumption was observed weekly (except during mating). Haematology and clinical chemistry were examined at day 37 in males only. Full necropsy was performed on all animals. Histopathological examination was carried out on all control and top dose animals plus any obvious lesions observed at necrospy. Organs examined were liver, kidneys, adrenals, brain, heart, spleen, ovaries or testes and epididymes.

Organ weights were recorded for liver, kidneys, thymus (females) liver, kidney, thymus, testes, epididymes (males).

There were no mortalities and no clinical signs reported.

There were no significant changes in body weight or body weight gain in the 3 weeks prior to mating for both sexes or in males after mating.

Food consumption was significantly increased in top dose males (p<0.001) and in mid dose females (p<0.05) at week 3. There were no other differences in food consumption or food conversion efficiency.

There were significant (but non-dose related) differences in free cholesterol (increased) and triglycerides (decreased) at all dose levels. Total cholesterol levels were not significantly increased. Plasma glucose was elevated with statistical significance in the low and mid-dose groups; only males were examined.

There were no statistically significant differences in haematology between treated and control groups (males only examined).

Gross pathology and histopathology were unremarkable.

There was no statistically significant difference in pregnancy rates (confirmed using a Qui2-test) although they were reduced in treated groups (C: 92%, 100 & 500 mg/kg: 75%, 2000 mg/kg/day: 67%). These pregnancy rates were within the normal historical control range according to the authors (actual historical control data not presented).

There were no significant differences in the number of implantations or resorptions between treated and control groups.

There were no significant differences in the number of corpora lutea between treated and control groups.

There was no effect of treatment on litter size and litter weights.

Parental NOAEL for systemic toxicity was 2000 mg/kg/day based on changes in plasma free cholesterol, triglycerides and glucose. These changes were observed at all doses levels but were not dose related and may be due to differences in dietary composition.

There were no statistically significant adverse effects on reproductive parameters and the NOAEL for reproductive and developmental effects can be considered as 2000 mg/kg/day (highest dose level).

(Reference: Hansen, E. 1992b. Combined repeat dose and reproductive/developmental toxicity screening test on 1-octadecanol in rats. : of, National Food Agency, IT 911130.)

Endpoint:
reproductive toxicity, other
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
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
Dose descriptor:
NOAEL
Remarks:
oral in rats
Effect level:
>= 1 357
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
reproductive performance
Conclusions:
When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on NOAEL values of the components (C16 and C18 LCOH, C12 AS as worst case), this resulted in an oral reproductive NOAEL of at least 1357 mg/kg bw in rats; this is higher than the systemic NOAEL. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is at least 1357 mg/kg bw).
Executive summary:

When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on NOAEL values of the components (C16 and C18 LCOH, C12 AS as worst case), this resulted in an oral reproductive NOAEL of at least 1357 mg/kg bw in rats; this is higher than the systemic NOAEL. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is at least 1357 mg/kg bw).

Endpoint:
extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the extended one-generation reproductive toxicity study does not need to be conducted because there are no results from available repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity
Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 357 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Reliable, based on various studies
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 extra testing was performed as literature data were available as weight-of-evidence for the various components of the registered substances. A selection of most reliable sources (Klimisch 1-2) was made.

Toxicity to reproduction:

Various literature data were available in rats and dogs for the long chain alcohols (LCHO) with chain length C16 and C18, as summarised below.

-      For LCOH 16 (1-Hexadecanol; CAS 36653-82-4) a subacute toxicity study in rats treated by oral gavage for 27-28 days at doses levels of 1000, 500 and 1000 mg/kg resulted in a NOAEL >1000 mg/kg bw; no reproductive organs were affected (SIDS, 2006; Henkel, 1985a). A 13 week dietary subchronic toxicity study in rats dosed at 1.0, 2.5 and 5% (increased to 7.5% in week 11 and 10% in weeks 12-13) resulted in a NOAEL of ca. 750 (males 723, females 875) mg/kg bw; no reproductive organs were affected (SIDS, 2006; IUCLID 2000; Scientific Associates, Inc., 1996a). A 13 week dietary toxicity study in dogs dosed at 0.5, 1.0 and 3.0% resulted in a NOAEL of >1175 mg/kg bw for males and >1054 mg/kg/day for females, corresponding with highest dose level tested (3% in diet). Elevated ALAT (liver enzyme) values seen at 13 weeks in most test animals at all dose levels were apparently not dose related or accompanied by histopathological liver change: other markers of liver function appeared normal. (SIDS, 2006; IUCLID 2000; Scientific Associates, Inc., 1996b).

-      For LCOH 18 (1-Octadecanol; CAS 112-925) a study in rats treated by oral gavage for 27-28 days at doses levels of 1000, 500 and 1000 mg/kg resulted in a NOAEL >1000 mg/kg bw (SIDS 2006; Henkel, 1985a; Henkel 1999). In a combined repeated dose and reproductive screening study, rats treated in the diet for 45 days (males) and ca. 54 days (females) the reproductive NOAEL was 2000 mg/kg/day with a systemic NOEL of 100 mg/kg/day (SIDS 2006; Hansen, 1992b).

For the alkyl sulfates (AS), there were no data for the C14-C20 chain lengths, however literature data were available for the C12 chain length. The C12 AS can be considered as a worst case substance.

-      For C12-Alkylsulfate (CAS 151-21-3) a study in mice fed diets containing 100 mg/kg bw/d for 6 weeks or 1000 mg/kg bw/d for 2 weeks experienced no impairment of epidydimal spermatozoa. There were no adverse effects on fertility, even when administered at concentrations sufficient to cause a significant reduction in body weight (parental toxicity). The reproductive NOAEL was 1000 mg/kg bw (SIDS, 2007; Hemsworth, 1981).

For the sodium sulfate, no reliable literature data were available.

Conclusion:  When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008), based on NOAEL values of the components (C16 and C18 LCOH, C12 AS as worst case), this resulted in an oral reproductive NOAEL of 1357 mg/kg bw in rats, which is higher than the systemic NOAEL. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is at least 1357 mg/kg bw.).

Effects on developmental toxicity

Link to relevant study records

Referenceopen allclose all

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no
Species:
mouse
Strain:
CD-1
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: no data
Details on mating procedure:
no further specified
Duration of treatment / exposure:
day 6 - 15 of gestation
Frequency of treatment:
daily
Duration of test:
sacrifice at day 17 of gestation
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:
-Clinical observations:
Animals were observed daily for signs of toxicity and were weighed regularly throughout gestation.
- Organs examined at necropsy (macroscopic and microscopic):
All animals, including those that died during the study, were dissected and examined for macroscopic changes immediately after sacrifice.
Ovaries and uterine content:
Uteri were dissected and the contents examined to determine the numbers of implantations, viable young and embryonic deaths.
Fetal examinations:
Fetuses were examined for visceral anomalies, or dissected and examined followed by clearing, alizarin staining and skeletal examination.
Statistics:
Wilcoxon test
Description (incidence):
300 mg/kg: mortality 1/20
600 mg/kg: mortality 4/20
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
ca. 2 mg/kg bw/day (actual dose received)
Basis for effect level:
other: no effects observed
Dose descriptor:
LOAEL
Remarks:
maternal toxicity
Effect level:
ca. 300 mg/kg bw/day (actual dose received)
Basis for effect level:
mortality
Description (incidence and severity):
<= 300 mg/kg: no adverse effects on foetal morphogenesis
600 mg/kg: total resorption and/or increased incidence of litter loss
Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Effect level:
ca. 300 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
other: resorption
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
300 mg/kg bw/day
Treatment related:
yes

Observation

Dose (mg/kg bw)

0

0.2

2

300

600

mated

20

20

20

20

20

died

0

0

0

1

4

non-pregnant

2

2

3

4

2

total litter loss

0

2

2

2

4

With viable young

18

16

15

13

10

Conclusions:
Under the present test conditions the following effect levels were established:
NOAEL maternal toxicity= 2 mg/kg bw
NOAEL teratogenicity= 300 mg/kg bw
LOAEL maternal toxicity = 300 mg/kg bw
Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study.

Sodium dodecyl sulphate was administered to 20 female CD-1 mice per dose group.

The mice were dosed by gavage with water as vehicle once daily at 0, 0.2, 2, 300 or 600 mg /kg bw/d from days 6- 15 of gestation.

The animals were observed daily for signs of toxicity and were weighed regularly throughout gestation and were sacrificed at day 17 of gestation.

All animals, including those that died during the study, were dissected and examined for macroscopic changes immediately after sacrifice.

Uteri were dissected and the contents examined to determine the numbers of implantations, viable young and embryonic deaths.

Fetuses were examined for visceral anomalies, or dissected and examined followed by clearing, alizarin staining and skeletal examination.

Viable young were weighed and examined for external abnormalities.

 

Maternal data:

300 mg/kg: mortality 1/20

600 mg/kg: mortality 4/20

 

Offspring:

<= 300 mg/kg: no adverse effects on foetal morphogenesis

600 mg/kg: total resorption and/or increased incidence of litter loss

 

The following effect levels were established:

NOAEL maternal toxicity= 2 mg/kg bw

NOAEL teratogenicity= 300 mg/kg bw

LOAEL maternal toxicity = 300 mg/kg bw

 

Reference:

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part I - LAS, AS and CLD. Toxicology 3, 91 - 106

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part II - AOS. Toxicology 3, 107 – 113

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
13 animals/group
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Concentration in vehicle: no data
Duration of treatment / exposure:
day 6 - 18 of gestation
Frequency of treatment:
daily
Duration of test:
sacrifice at day 29 of gestation
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
Description (incidence and severity):
>= 300 mg/kg: diarrhoea, anorexia, cachexia,
Description (incidence):
300 mg/kg: mortality 1/13
600 mg/kg: mortality 11/13
Description (incidence and severity):
>= 300 mg/kg: weight loss
Details on maternal toxic effects:
>= 300 mg/kg: foetal loss
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
ca. 2 mg/kg bw/day (actual dose received)
Basis for effect level:
other: no effects observed
Dose descriptor:
LOAEL
Remarks:
maternal toxicity
Effect level:
ca. 300 mg/kg bw/day (actual dose received)
Basis for effect level:
body weight and weight gain
mortality
Details on embryotoxic / teratogenic effects:
<= 300 mg/kg: no adverse effects on foetal morphogenesis
600 mg/kg: abortion, total resorption and/or increased incidence of litter loss
Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Effect level:
ca. 300 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
external malformations
skeletal malformations
visceral malformations
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: not specified
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
600 mg/kg bw/day
Treatment related:
yes

Observation

Dose (mg/kg bw)

0

0.2

2

300

600

mated

13

13

13

13

13

died

2

0

1*

1

11

non-pregnant

1

1

2

1

0

total litter loss

0

1

0

2

0

With viable young

10

11

10

9

2

* intubation error

Conclusions:
Under the present test conditions the following effect levels were established:
NOAEL maternal toxicity= 2 mg/kg bw
NOAEL teratogenicity= 300 mg/kg bw
LOAEL maternal toxicity = 300 mg/kg bw
Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study.

Sodium dodecyl sulphate was administered to 13 female New Zealand White rabbits per dose group.

The rabbits were dosed by gavage with water as vehicle once daily at 0, 0.2, 2, 300 or 600 mg /kg bw/d from days 6- 18 of gestation.

The animals were observed daily for signs of toxicity and were weighed regularly throughout gestation and were sacrificed at day 29 of gestation.

All animals, including those that died during the study, were dissected and examined for macroscopic changes immediately after sacrifice.

Uteri were dissected and the contents examined to determine the numbers of implantations, viable young and embryonic deaths.

Ovaries were examined and the number of corpora lutea were counted.

Fetuses then were dissected and examined for abnormalities of internal organs, sex determination, and clearing, alizarin staining and skeletal examination.

Viable young were weighed and examined for external abnormalities.

 

Maternal data:

300 mg/kg: mortality 1/13

>= 300 mg/kg: diarrhoea, anorexia, weight loss, cachexia, foetal loss

600 mg/kg: mortality 11/13

 

Offspring:

<= 300 mg/kg: no adverse effects on foetal morphogenesis

600 mg/kg: abortion, total resorption and/or increased incidence of litter loss

 

The following effect levels were established:

NOAEL maternal toxicity= 2 mg/kg bw

NOAEL teratogenicity= 300 mg/kg bw

LOAEL maternal toxicity = 300 mg/kg bw

 

Reference:

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part I - LAS, AS and CLD. Toxicology 3, 91 - 106

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part II - AOS. Toxicology 3, 107 – 113

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: CD
Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
-Total volume applied: no data

VEHICLE
- Concentration in vehicle: no data
Details on mating procedure:
no further specified
Duration of treatment / exposure:
day 6 - 15 of gestation
Frequency of treatment:
daily
Duration of test:
sacrifice at day 20 of gestation
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:
-Clinical observations:
Animals were observed daily for signs of toxicity and were weighed regularly throughout gestation.
- Organs examined at necropsy (macroscopic and microscopic):
All animals, including those that died during the study, were dissected and examined for macroscopic changes immediately after sacrifice.
Ovaries and uterine content:
Uteri were dissected and the contents examined to determine the numbers of implantations, viable young and embryonic deaths. Ovaries were examined and the number of corpora lutea were counted.
Fetal examinations:
Viable young were weighed and examined for external abnormalities.
Fetuses were examined for visceral anomalies, or dissected and examined followed by clearing, alizarin staining and skeletal examination.
Statistics:
Wilcoxon test
Description (incidence and severity):
>= 300 mg/kg: slight to moderate toxicity (anorexia, weight loss, cachexia, abortion)
Description (incidence):
600 mg/kg: mortality 3/20
Description (incidence and severity):
>= 300 mg/kg: slight to moderate toxicity (abortion)
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
ca. 2 mg/kg bw/day (actual dose received)
Basis for effect level:
other: no effects observed
Dose descriptor:
LOAEL
Remarks:
maternal toxicity
Effect level:
ca. 300 mg/kg bw/day (actual dose received)
Basis for effect level:
number of abortions
Details on embryotoxic / teratogenic effects:
600 mg/kg: no adverse effects
Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Effect level:
ca. 600 mg/kg bw/day (actual dose received)
Sex:
male/female
Basis for effect level:
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
external malformations
skeletal malformations
visceral malformations
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
600 mg/kg bw/day
Treatment related:
yes

Observation

Dose (mg/kg bw)

0

0.2

2

300

600

mated

20

20

20

20

20

died

0

0

0

0

3

non-pregnant

3

1

2

1

0

total litter loss

0

0

0

0

0

With viable young

17

19

18

19

17

Conclusions:
Under the present test conditions the following effect levels were established:
NOAEL maternal toxicity= 2 mg/kg bw
NOAEL teratogenicity= 600 mg/kg bw
LOAEL maternal toxicity = 300 mg/kg bw
Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study.

Sodium dodecyl sulphate was administered to 20 female CD rats per dose group.

The rats were dosed by gavage with water as vehicle once daily at 0, 0.2, 2, 300 or 600 mg /kg bw/d from days 6- 15 of gestation.

The animals were observed daily for signs of toxicity and were weighed regularly throughout gestation and were sacrificed at day 20 of gestation.

All animals, including those that died during the study, were dissected and examined for macroscopic changes immediately after sacrifice.

Uteri were dissected and the contents examined to determine the numbers of implantations, viable young and embryonic deaths.

Ovaries were examined and the number of corpora lutea were counted.

Fetuses were examined for visceral anomalies, or dissected and examined followed by clearing, alizarin staining and skeletal examination.

Viable young were weighed and examined for external abnormalities.

 

Maternal data:

>= 300 mg/kg: slight to moderate toxicity (anorexia, weight loss, cachexia, abortion)

600 mg/kg: mortality 3/20

 

Offspring:

600 mg/kg: no adverse effects

 

The following effect levels were established:

NOAEL maternal toxicity= 2 mg/kg bw

NOAEL teratogenicity= 600 mg/kg bw

LOAEL maternal toxicity = 300 mg/kg bw

 

Reference:

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part I - LAS, AS and CLD. Toxicology 3, 91 - 106

-Palmer AK, Readshaw MA & Neuff AM (1975) Assessment of the teratogenic potential of surfactants. Part II - AOS. Toxicology 3, 107 - 113

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
15 animals/group (10 for dissection, 5 for natural parturition)
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 16 - 18 weeks
Route of administration:
oral: gavage
Vehicle:
not specified
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:
once 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)
Remarks:
test substance
Dose / conc.:
125 mg/kg bw/day (actual dose received)
Remarks:
test substance
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Remarks:
test substance
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Remarks:
test substance
No. of animals per sex per dose:
15 rats per dose group (10 for dissection, 5 for natural parturition)
Control animals:
yes
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; 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;
Fetal examinations:
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
Description (incidence and severity):
All animals at 500 mg/kg 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 killed 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.
Description (incidence):
Between the 4th and 8th dose 4 of the animals of the 500 mg/kg dose group died and 1 was killed because of its condition.
Description (incidence and severity):
Treatment with 500 mg/kg induced a significant (p = < 0.05) reduction in maternal body weight gain during the period of treatment.
Description (incidence and severity):
Rats treated with 500 mg/kg consumed significantly (p=<0.05) less food than controls.
Description (incidence and severity):
Treatment did not adversely affect the pre- or post-implantation loss.
Description (incidence and severity):
Intrauterine mortality: No significant differences between treatment and control
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
ca. 250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: no effects observed
Dose descriptor:
LOAEL
Remarks:
maternal toxicity
Effect level:
ca. 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
gross pathology
other: placental weight
Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Effect level:
ca. 500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
changes in sex ratio
fetal/pup body weight changes
changes in litter size and weights
external malformations
skeletal malformations
visceral malformations
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
500 mg/kg bw/day
Treatment related:
yes

Maternal data

General health:

All animals at 500 mg/kg 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 killed 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 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 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

 

Offspring:

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 (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 - 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 (hermi-centric lumbar centra with asymmetry and reduced ossification of the 6th lumbar arch and scoliosis) and 63 mg/kg (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.

Conclusions:
Under the present test conditions the following effect levels were established:
NOAEL maternal toxicity= 250 mg/kg bw
NOAEL teratogenicity= 500 mg/kg bw
LOAEL maternal toxicity = 500 mg/kg bw

Executive summary:

The IUCLID dataset of C12-Alkylsulfate (CAS 151-21-3) in the OECD SIDS Initial Assessment Profile on Sodium dodecyl sulfate (SDS) describes the following Klimisch 2 study.

Sodium dodecyl sulphate was administered to 15 female Wistar rats per dose group (10 for dissection, 5 for natural parturition). The rats were dosed by gavage once daily at 0, 63, 125, 250 or 500 mg test substance/kg bw/d from days 6- 15 of gestation.

The following observations were performed:

-body weight: daily

-maternal food intake: daily

-mean gravid uterus weight & mean weight of uterine tissue; intrauterine mortality; mean response per pregnancy; 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

All maternal animals at 500 mg/kg 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 killed 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.

Treatment with 500 mg/kg induced a significant (p = < 0.05) reduction in maternal body weight gain during the period of treatment.

Rats treated with 500 mg/kg consumed significantly (p=<0.05) less food than controls.

No significant differences in intrauterine mortality were observed between treatment and control animals.

Treatment did not adversely affect the pre- or post-implantation loss.

 

The mean placental weight for male and female foetuses combined and considered separately were significantly lower in animals fed 500 mg/kg (p= 0.05).

No significant differences in incidence of gross variants/anomalies and skeletal anomalies between treatment groups and control group in the offspring.

Malformations were found in 3 foetuses from dams treated with 500 mg/kg: 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 (hermi-centric lumbar centra with asymmetry and reduced ossification of the 6th lumbar arch and scoliosis) and 63 mg/kg (unossified and dumbbell shaped thoracic centrae associated with branched ribs).

 

In the rats allocated to natural parturition, no significant differences in post-partum mortalities and incidence of skeletal defects in rat pups were observed between treatment and controls.

The following effect levels were established:

NOAEL maternal toxicity= 250 mg/kg bw

NOAEL teratogenicity= 500 mg/kg bw

LOAEL maternal toxicity = 500 mg/kg bw

 

Reference: Unilever Research (1976) Mutagenicity and teratology of alternative surfactants. IV. Teratology of sodium lauryl sulphate: oral administration in the rat (Unpublished Report No. PCW 76 1593). Unilever Research, Colworth/Welwyn. 70 pp.

Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Conclusions:
When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008) from NOAEL values of the components (C16 and C18 LCOH; C12 AS as worst case), this resulted in an oral reproductive NOAEL of 1200 mg/kg bw in rats. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is 1200 mg/kg bw.
Executive summary:

When the NOAEL of the target substance was calculated by concentration addition based on the general equation as presented in the CLP regulation on mixtures (2008) from NOAEL values of the components (C16 and C18 LCOH; C12 AS as worst case), this resulted in an oral reproductive NOAEL of 1200 mg/kg bw in rats. It can therefore be concluded that the oral reproductive NOAEL of the registered substance is 1200 mg/kg bw.

Justification for classification or non-classification

Based on these results and according to CLP (No. 1272/2008 of 16 December 2008), the registered substance does not have to be classified and has no obligatory labelling requirement for reproductive toxicity.

 

Additional information