Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Well documented peer-reviewed journal article
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Refer to Section 13.2 for read-across justification document.

Data source

Reference
Reference Type:
publication
Title:
Assessment of the teratogenic potential of surfactants. Part I - LAS, AS, and CLD
Author:
Palmer, A.K., Readshaw, M.A., and Neuff, A.M.
Year:
1975
Bibliographic source:
Toxicology. 3:91-106

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Twenty female rats were administered 0.2, 2.0, 300 or 600 mg/kg bw of LAS by gavage at days 6-15 of gestation. All animals were sacrificed on day 20 of pregnancy.
GLP compliance:
no
Remarks:
Study pre-dated GLP
Limit test:
no

Test material

Constituent 1
Reference substance name:
Linear Alkylbenzene Sulphonate (LAS)
IUPAC Name:
Linear Alkylbenzene Sulphonate (LAS)
Details on test material:
Supplied by Lion Fat & Oil Co., Tokyo

Test animals

Species:
rat
Strain:
other: CD
Details on test animals or test system and environmental conditions:
Source: Charles River Breeding Laboratories, Wilmingoton, Mass., USA.
Rats were housed 5 per cage in opaque plastic cages, and maintained under environmental conditions of 20 +/- 1°C and 50 +/- 5% RH. All animals were allowed free access to drinking water and food (Spratt’s Laboratory Diet No. 1).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
For administration each material was prepared daily as a series of graded aqueous solutions so that within each study animals in all groups were dosed orally by intragastric intubation at a standard volume. Control animals were dosed with water.
Duration of treatment / exposure:
days 6 - 15 of pregnancy
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
0.2 mg/kg bw/day
Dose / conc.:
2 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
600 mg/kg bw/day
No. of animals per sex per dose:
20 female rats per dose
Control animals:
yes, concurrent no treatment

Examinations

Maternal examinations:
The day of mating as judged by the detection of the vaginal plug in rats was considered day 0; dosing commenced on day 6 and continued daily up to and including day 15.
Throughout the experiment all animals were observed daily for signs of malreaction and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.
At termination (days 20) rats were euthanised by carbon dioxide euthanasia. The uteri were immediately dissected and the contents examined to determine the numbers of {a) implantations, (b) viable young, (c) embryonic deaths (abortion or resorption sites).
Ovaries and uterine content:
Ovaries were examined and the number of corpora lutea counted.
Fetal examinations:
Viable young were weighed and carefully examined for external abnormalities. Following weighing and examination for external malformations, one third of the foetuses were fixed in Bouin's fluid for subsequent free hand sectioning to detect visceral anomalies, and the remaining two thirds fixed in alcohol for subsequent dissection and examination followed by clearing, alizarin staining and skeletal examination.
Statistics:
In assessing results group mean values were calculated from the individual litter data in two ways. Mean A: includes all surviving animals showing evidence of implantation, including those with total litter loss. Mean B: includes only animals bearing viable young at termination.
Mean B has more meaning when only the occasional animal shows total litter loss, Mean A provides a better index when several animals show total litter loss.
Differences in mean values were statistically analysed by non-parametric methods (Wilcoxon test) since litter values rarely, if ever, follow a normal (Gaussian) distribution; in all analyses the litter was considered as the basic sample unit.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Toxic effects were generally associated with a principal disturbance of the gastrointestinal tract.
Mortality:
mortality observed, treatment-related
Description (incidence):
a single mortality was observed at 600 mg/kg bw/d. No evidence was offered as to whether this was related to test item dosing or an isolated incident.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significant body weight gain reduction was seen at 600 mg/kg bw/d.
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
not specified
Early or late resorptions:
not specified
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
no effects observed
Other effects:
no effects observed
Details on maternal toxic effects:
Body weight gain was retarded in the highest dose group from the start of dosing and showed partial recovery toward the end of the dosing period. One animal died in this group but it could not be conclusively related to treatment. The toxic effects were associated with disturbance of the gastrointestinal tract.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
not specified
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
Details on embryotoxic / teratogenic effects:
No differences were observed among dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post implantation embryonic loss, major malformations, minor visceral or embryonic loss, major malformations, minor visceral or skeletal anomalies or incidence of pups with extra ribs.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
>= 600 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to adverse toxic effects at highest dose / concentration tested

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Any other information on results incl. tables

Summary of adult performance

 Observation Number of animals at dosage
 mg/kg bw/d  0  0.2  2  300  600
 Mated  20  20  20  20  20
 Died  0  0  0  0  1
 Non-pregnant  5  5  2  4  3
 Total litter loss  0  1  0  0  0
 With viable young  15  14  18  16  16
 Bodyweight change  -  -  -  -  Retarded weight gain

Group mean incidence of major malformations and minor anomalies

 Dosage  Number of Young  Incidence of pups with extra ribs *
  Major malformations Minor anomalies    
   Examined  Affected     Gross or visceral    Skeletal      Mean %   
 (mg/kg)    Total number  Mean %  Examined  Total Number Affected  Mean % Affected  Examined  Total Number Affected  Mean % Affected  Cervical  Lumbar
 0  149  0  0  33  1  2.2  116  2  2.0    18.6
 0.2  137  0  0  26  0  0  111  2  1.7  

 33.1
 2  147  0  0  22  0  0  125  5  3.5    21.3
 300  153  1  0.6  30  0  0  122  4  3.6    12.9
 600 (M)  166  0 0   34  1  6.7  132  2  1.8  

 15.3

* Young showing major malformations excluded

(M) denotes minor maternal toxicity

Group Litter Data

              Embryonic Loss (%)    
 Dosage (mg/kg)  Number of Litters  Litter Size and Viable Young  Embryonic Deaths  Implantations  Corpora Lutea  Pre-Implantation  Post-Implantation  Litter Weight (g)  Foetal Weight (g)
 0  15  9.9  0.3  10.3  12.5  18.1  2.8  36.15  3.66
 0.2  14  9.8  0.6  10.4  12.8  18.4  6.1  37.14  3.84 (a)
 2  18  8.2  0.6  8.8  13.9  36.9  5.9  31.62  3.94 (b)
 300  16  9.6  0.4  10.0  12.4  15.6  3.6  35.72  3.78
 600 (M)  16  10.4  0.4  10.8  13.9  20.3  3.1  37.49  3.64

Differences from controls statistically significant at Wilcoxon test (a) P < 0.05; (b) P < 0.001

(M) denotes minor maternal toxicity

Applicant's summary and conclusion

Conclusions:
Based on the results of the study, the maternal NOAEL = 300 mg/kg bw/d and the developmental NOAEL = 600 mg/kg bw/d.
Executive summary:

Pregnant female rats (20 animals per group) were exposed to LAS via gavage on days 6 -15 of gestation.

Maternal toxicity:


Body weight gain was retarded in the highest dose group from the start of dosing and showed partial recovery toward the end of the dosing period. One animal died in this group but it could not be conclusively related to treatment. The toxic effects were associated with disturbance of the gastrointestinal tract. Pregnancy rate was comparable at all dosages.

Teratogenicity:


No differences were observed among dose groups and the control group with respect to number of litters, viable young, litter weight, foetal weight, embryonic deaths, implantations, corpora lutea, pre- and post implantation embryonic loss, major malformations, minor visceral or embryonic loss, major malformations, minor visceral or skeletal anomalies or incidence of pups with extra ribs.

Based on the results of the study, the maternal NOAEL = 300 mg/kg bw/d and the developmental NOAEL = 600 mg/kg bw/d.