Registration Dossier

Administrative data

Endpoint:
three-generation reproductive toxicity
Type of 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: Well documented peer-reviewed publication.
Justification for type of information:
Category Approach; test material is reference substance LAS. LAS provides suitable read across for LAB Sulfonic Acids as both form the identical chemical species in aqueous solutions at neutral (physiological) pH, namely, the LAS ion (C10-13 linear alkyl benzene-SO3-) and would be expected to have similar toxicity properties.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1971

Materials and methods

Principles of method if other than guideline:
Na-LAS (chain length distribution C10-14) was fed for 84 days to 4 groups of weanling rats (3 dose levels, plus control), each dose consisting of 50 animals each of both sexes (PO-generation). When the P0 generation was 107-112 days old, 20 females from each dose group were mated with 20 males from the same group and maintained together for 17 days. The first litters of each generation (Fla- and F2a-generation) were sacrificed at 21 days of age. Ten days after the final litter was sacrificed, all females were remated with different males from the same group to obtain the F1b generation. From the Flb-generation, 20 males and females of each group were selected at weaning to continue their respective diets and to be used for further reproduction studies. Reproduction studies on the F1b and F2b generations were started when the rats were 80 to 85 days old, and were continued until the F3b generation was weaned.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium salt LAS (C10-14)
- Activity: 98.1% on an anhydrous basis (41.9% active)
- Impurities (identity and concentrations): unreacted alkylbenzene and Na2SO4

Test animals

Species:
rat
Strain:
other: Charles River
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: (P) weanling; (F1) 21 days
- Weight at study initiation: (P) Males: average 59.4-59.9 g; Females: average 57.0-57.3 g; (F1) Males: group weight 183.5-214.2 g; Females: group weight 157.8-193.2 g
- Housing: individual wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 76 +/- 3
- Humidity (%): 50 +/- 5
- Photoperiod (hrs dark / hrs light): 12/12 hrs

:

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: LAS was administered in feed (Purina Laboratory Meal) - no documentation of dilution prior to addition to meal
Details on mating procedure:
premating exposure period 84 days
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
2 years ( 3 generations)
Frequency of treatment:
continuous in feed
Details on study schedule:
- F1 parental animals not mated until 80-85 days old
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 107-112 days old
Doses / concentrations
Remarks:
Doses / Concentrations:
0.02, 0.1, 0.5% (14, 70, 350 mg/kg bw d)
Basis:
actual ingested
No. of animals per sex per dose:
50 males and 50 females per group.
Control animals:
yes, concurrent no treatment

Examinations

Litter observations:
Deformities and number of pups, average body weights, feed consumption, feed efficiency.
Postmortem examinations (parental animals):
Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
Postmortem examinations (offspring):
Necropsy, body weight, organ to body weight ratios, routine hematology and histology.
Reproductive indices:
fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
no effects to body weight were noted in the initial twelve weeks
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
no effects to body weight were noted in the initial twelve weeks
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Test substance intake: no effects to average food consumption were noted in the initial twelve weeks

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

No mortality or clinical signs were observed in parental animals. A statistically significant decrease in liver weights was noted in male rats at the low and mid dose levels at the 8 month sacrifice. As the decreased liver weight was within normal range, was not seen at the highest dose level, nor was seen at the 15 and 24 month sacrifices, it was not considered biologically significant. Body weight gains and organ to body weight ratios were normal. Gross examination revealed no abnormalities attributable to the test substance. General reproduction including fertility, gestation, parturition, neonatal viability, lactation, and post-weaning growth were normal for all test groups and did not vary from controls.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: 0.5%

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

Rats sacrificed at weaning were normal with respect to growth, organ to body weight ratios, gross pathology, and histology, and did not vary from controls. There were a number of statistically significant hematologic values, though these differences were small and did not indicate a trend or pattern.

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
350 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: 0.5%

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
350 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: 0.5%

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No significant effects on reproduction were observed at the highest concentration tested.
Executive summary:

Na-LAS was fed for 84 days to 4 groups of weanling rats for two years (three generations). No significant effects were observed at the highest dose tested and the resulting NOAEL for the parental and both offspring generations was 350 mg/kg bw (0.5%)