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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

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
Remarks:
GLP study; considered as reliable by experts groups of HERA and CIR
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985
Reference Type:
publication
Title:
Human & Environmental Risk Assessment on Alcohol Ethoxylates
Author:
HERA Substance Team
Year:
2009
Bibliographic source:
Web Publication
Reference Type:
publication
Title:
Safety assessment of alkyl PEG ethers as used in cosmetics.
Author:
Cosmetic Ingredient Review (CIR) Expert Panel
Year:
2012
Bibliographic source:
Int J Toxicol. 2012 Sep-Oct;31(5 Suppl):169S-244S
Reference Type:
publication
Title:
Acute, Subchronic, and Reproductive Toxicity of a Linear Alcohol Ethoxylates Surfactant in the Rat
Author:
Gingell and Lu
Year:
1991
Bibliographic source:
Journal of the American College of Toxicology, Volume 10, Number 4, page 477-486

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: OECD 416
Deviations:
yes
Remarks:
Only 3 applications per week/ no treatment during mating
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
68439-46-3
EC Number:
614-482-0
Cas Number:
68439-46-3
IUPAC Name:
68439-46-3

Test animals

Species:
rat
Strain:
Fischer 344

Administration / exposure

Route of administration:
dermal
Vehicle:
water
Details on exposure:
Dose volume: 1 mL/kg bw
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
F0 generation: 119 days prior to mating
F1 generation: 133 days prior to mating
Frequency of treatment:
3/week (except during mating)
Duration of test:
P: 119 days of dosing
F1: 133 days of dosing
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 0% test material (w/v) in water
Dose / conc.:
10 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 1% test material (w/v) in water
Dose / conc.:
100 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 10% test material (w/v) in water
Dose / conc.:
250 mg/kg bw/day
Remarks:
dermal exposure to 1mL/kg of 25% test material (w/v) in water
No. of animals per sex per dose:
30 (P)
20/40 (male/female; F1)
Control animals:
yes, concurrent vehicle
Details on study design:
The P0 groups, consisting of 30 males and 30 females, were exposed dermally to 1 mL/kg of 0%, 1%, 10% or 25% w/v aqueous test material for 119 days prior to mating. The test site was shaved, but the application sites were not covered. The test material was not applied during mating to avoid ingestion. Among the F1 generation, groups of 20 males and 20 females per test group were mated. The male rats of both generations were killed following mating.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
effects observed, treatment-related
Description (incidence and severity):
No irritation was observed for any of the animals, but dry flaking skin was observed in the 10% and 25% dose groups.
Mortality:
mortality observed, non-treatment-related
Description (incidence):
Five death was observed in the F1 adult in the ctronol and treatment group, not treatment related
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Minimal decrease at 25%.
Organ weight findings including organ / body weight ratios:
effects observed, non-treatment-related
Description (incidence and severity):
Weight change in liver, lung, kidney and heart in P1/F1 animals
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed

Maternal developmental toxicity

Other effects:
no effects observed
Description (incidence and severity):
No effects regardin mating indices, fertility indices, or mean gestational length.

Effect levels (maternal animals)

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No significant effect up to the highest dose level
Remarks on result:
other:
Remarks:
The NOAEL obtained in a two generation reproduction toxicity study
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 250 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No significant effect up to the highest dose level
Remarks on result:
other:
Remarks:
The NOAEL obtained in a two generation reproduction toxicity study

Results (fetuses)

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Remarks:
developmental
Effect level:
>= 250 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: Up to 250 mg/kg bw no significant effect onthe growth and developmental of the offspring was found in the two generation reproduction toxicity study

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion

Executive summary:

In a GLP-compliant 2-generation reproduction study, groups of thirty weanling rats of each sex were treated dermally with 1 mL/kg bw of C9-11AE6 at concentration of 0, 1, 10 or 25% w/v (0, 10, 100 or 250 mg/kg bw/d) three times a week except during the mating periods. No compound related effects on litter size, number of live pubs and sex ratio of pups in the F1 and F2 generations were observed. Low incidences of foetal malformations were observed, but these were not dose related and considered to be of spontaneous nature. At necropsy, no effects were observed in the F1 pups. In the F2 pups, a significantly higher carcass weight in the females of the 250 mg/kg bw/d dose group was noted and some minor organ weight differences. Due to the lack of a doseresponse and no associated morphological findings, these effects were considered to be of no toxicological significance. It was concluded that dermal application of C9-11AE6 to rats did not induce any adverse effects on the growth and development of the offspring during two generations. The NOAEL of C9-11AE6 with respect to developmental and teratogenic toxicity can be assumed to be higher than the highest dose level dermally applied in this study (i.e., 250 mg/kg bw/d)